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Congenital human cytomegalovirus (HCMV) infection causes severe damage to the fetal brain, and the underlying mechanisms remain elusive. Cytokine signaling is delicately controlled in the fetal central nervous system to ensure proper development. Here we show that suppressor of cytokine signaling 3 (SOCS3), a negative feedback regulator of the IL-6 cytokine family signaling, was upregulated during HCMV infection in primary neural progenitor cells (NPCs) with a biphasic expression pattern. From viral protein screening, pUL97 emerged as the viral factor responsible for prolonged SOCS3 upregulation. Further, by proteomic analysis of the pUL97-interacting host proteins, regulatory factor X 7 (RFX7) was identified as the transcription factor responsible for the regulation. Depletion of either pUL97 or RFX7 prevented the HCMV-induced SOCS3 upregulation in NPCs. With a promoter-luciferase activity assay, we demonstrated that the pUL97 kinase activity and RFX7 were required for SOCS3 upregulation. Moreover, the RFX7 phosphorylation level was increased by either UL97-expressing or HCMV-infection in NPCs, suggesting that pUL97 induces RFX7 phosphorylation to drive SOCS3 transcription. We further revealed that elevated SOCS3 expression impaired NPC proliferation and migration in vitro and caused NPCs migration defects in vivo. Taken together, these findings uncover a novel regulatory mechanism of sustained SOCS3 expression in HCMV-infected NPCs, which perturbs IL-6 cytokine family signaling, leads to NPCs proliferation and migration defects, and consequently affects fetal brain development.
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Infecciones por Citomegalovirus , Citomegalovirus , Humanos , Citomegalovirus/fisiología , Interleucina-6/metabolismo , Proteómica , Factores de Transcripción/metabolismo , Células Madre , Proteína 3 Supresora de la Señalización de Citocinas/metabolismoRESUMEN
The presence of human cytomegalovirus (HCMV) in glioblastoma (GBM) and improved outcomes of GBM patients receiving therapies targeting the virus have implicated HCMV in GBM progression. However, a unifying mechanism that accounts for the contribution of HCMV to the malignant phenotype of GBM remains incompletely defined. Here we have identified SOX2, a marker of glioma stem cells (GSCs), as a key determinant of HCMV gene expression in gliomas. Our studies demonstrated that SOX2 downregulated promyelocytic leukemia (PML) and Sp100 and consequently facilitated viral gene expression by decreasing the amount of PML nuclear bodies in HCMV-infected glioma cells. Conversely, the expression of PML antagonized the effects of SOX2 on HCMV gene expression. Furthermore, this regulation of SOX2 on HCMV infection was demonstrated in a neurosphere assay of GSCs and in a murine xenograft model utilizing xenografts from patient-derived glioma tissue. In both cases, SOX2 overexpression facilitated the growth of neurospheres and xenografts implanted in immunodeficient mice. Lastly, the expression of SOX2 and HCMV immediate early 1 (IE1) protein could be correlated in tissues from glioma patients, and interestingly, elevated levels of SOX2 and IE1 were predictive of a worse clinical outcome. These studies argue that HCMV gene expression in gliomas is regulated by SOX2 through its regulation of PML expression and that targeting molecules in this SOX2-PML pathway could identify therapies for glioma treatment.
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Glioma , Proteínas Inmediatas-Precoces , Animales , Humanos , Ratones , Citomegalovirus/fisiología , Regulación hacia Abajo , Expresión Génica , Glioma/genética , Glioma/patología , Proteínas Inmediatas-Precoces/metabolismo , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, and recent epidemiological studies suggested type 2 diabetes mellitus (T2DM) is an independent risk factor for the development of AF. Zinc finger and BTB (broad-complex, tram-track and bric-a-brac) domain containing 16 (Zbtb16) serve as transcriptional factors to regulate many biological processes. However, the potential effects of Zbtb16 in AF under T2DM condition remain unclear. Here, we reported that db/db mice displayed higher AF vulnerability and Zbtb16 was identified as the most significantly enriched gene by RNA sequencing (RNA-seq) analysis in atrium. In addition, thioredoxin interacting protein (Txnip) was distinguished as the key downstream gene of Zbtb16 by Cleavage Under Targets and Tagmentation (CUT&Tag) assay. Mechanistically, increased Txnip combined with thioredoxin 2 (Trx2) in mitochondrion induced excess reactive oxygen species (ROS) release, calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation, and spontaneous Ca2+ waves (SCWs) occurrence, which could be inhibited through atrial-specific knockdown (KD) of Zbtb16 or Txnip by adeno-associated virus 9 (AAV9) or Mito-TEMPO treatment. High glucose (HG)-treated HL-1 cells were used to mimic the setting of diabetic in vitro. Zbtb16-Txnip-Trx2 signaling-induced excess ROS release and CaMKII activation were also verified in HL-1 cells under HG condition. Furthermore, atrial-specific Zbtb16 or Txnip-KD reduced incidence and duration of AF in db/db mice. Altogether, we demonstrated that interrupting Zbtb16-Txnip-Trx2 signaling in atrium could decrease AF susceptibility via reducing ROS release and CaMKII activation in the setting of T2DM.
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Fibrilación Atrial , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animales , Ratones , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Proteínas Portadoras/genética , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Proteína de la Leucemia Promielocítica con Dedos de Zinc , Especies Reactivas de Oxígeno , Tiorredoxinas/genéticaRESUMEN
During the layer-by-layer (LBL) processing of polymer solar cells (PSCs), the swelling and molecule interdiffusion are essential for achieving precise, controllable vertical morphology, and thus efficient PSCs. However, the influencing mechanism of material properties on morphology and correlated device performance has not been paid much attention. Herein, a series of fluorinated/non-fluorinated polymer donors (PBDB-T and PBDB-TF) and non-fullerene acceptors (ITIC, IT-2F, and IT-4F) are employed to investigate the performance of LBL devices. The impacts of fluorine substitution on the repulsion and miscibility between the donor and acceptor, as well as the molecular arrangement of the donor/acceptor and the vertical distribution of the LBL devices are systematically explored by the measurement of donor/acceptor Flory-Huggins interaction parameters, spectroscopic ellipsometry, and neutron reflectivity, respectively. With efficient charge transfer due to the ideal vertical and horizon morphology properties, devices based on PBDB-TF/IT-4F exhibit the highest fill factors (FFs) as well as champion power conversion efficiencies (PCEs). With this guidance, high-performance LBL devices with PCE of 17.2%, 18.5%, and 19.1% are obtained by the fluorinated blend of PBDB-TF/Y6, PBDB-TF/L8-BO, and D18/L8-BO respectively.
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Human cytomegalovirus (HCMV) is a leading cause of congenital birth defects. Though the underlying mechanisms remain poorly characterized, mouse models of congenital CMV infection have demonstrated that the neuronal migration process is damaged. In this study, we evaluated the effects of HCMV infection on connexin 43 (Cx43), a crucial adhesion molecule mediating neuronal migration. We show in multiple cellular models that HCMV infection downregulated Cx43 posttranslationally. Further analysis identified the immediate early protein IE1 as the viral protein responsible for the reduction of Cx43. IE1 was found to bind the Cx43 C terminus and promote Cx43 degradation through the ubiquitin-proteasome pathway. Deletion of the Cx43-binding site in IE1 rendered it incapable of inducing Cx43 degradation. We validated the IE1-induced loss of Cx43 in vivo by introducing IE1 into the fetal mouse brain. Noteworthily, ectopic IE1 expression induced cortical atrophy and neuronal migration defects. Several lines of evidence suggest that these damages result from decreased Cx43, and restoration of Cx43 levels partially rescued IE1-induced interruption of neuronal migration. Taken together, the results of our investigation reveal a novel mechanism of HCMV-induced neural maldevelopment and identify a potential intervention target. IMPORTANCE Congenital CMV (cCMV) infection causes neurological sequelae in newborns. Recent studies of cCMV pathogenesis in animal models reveal ventriculomegaly and cortical atrophy associated with impaired neural progenitor cell (NPC) proliferation and migration. In this study, we investigated the mechanisms underlying these NPC abnormalities. We show that Cx43, a critical adhesion molecule mediating NPC migration, is downregulated by HCMV infection in vitro and HCMV-IE1 in vivo. We provide evidence that IE1 interacts with the C terminus of Cx43 to promote its ubiquitination and consequent degradation through the proteasome. Moreover, we demonstrate that introducing IE1 into mouse fetal brains led to neuronal migration defects, which was associated with Cx43 reduction. Deletion of the Cx43-binding region in IE1 or ectopic expression of Cx43 rescued the IE1-induced migration defects in vivo. Our study provides insight into how cCMV infection impairs neuronal migration and reveals a target for therapeutic interventions.
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Conexina 43 , Infecciones por Citomegalovirus , Citomegalovirus , Proteínas Inmediatas-Precoces , Animales , Humanos , Recién Nacido , Ratones , Conexina 43/genética , Conexina 43/metabolismo , Citomegalovirus/fisiología , Infecciones por Citomegalovirus/metabolismo , Proteínas Inmediatas-Precoces/genética , Proteínas Inmediatas-Precoces/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismoRESUMEN
Polarization singularities that exist in momentum space have brought new opportunities in various fields such as enhanced optical nonlinearity, structured laser sources, and light field manipulation. However, previous researches have predominantly focused on the polarization singularities above the light line, because they have no leakage and are referred to bound states in the continuum. Here, by extending the polarization fields to Fourier components of the evanescent field on a dielectric metasurface, polarization singularities of different Fourier orders are discovered below the light line. When continuously changing the geometrical parameters of the metasurface, a Fourier order transition process of the polarization singularity is observed through the bandgap closing at the boundary of the Brillouin zone, which finally leads to the annihilation of two singularities with opposite topological charges below the light line. These findings expand the understanding of polarization singularities in the near-field region and may find applications in light field manipulation and light-matter interaction.
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BACKGROUND: The abnormality of chromosomal karyotype is one factor causing poor prognosis of lymphoma. In the analysis of abnormal karyotype of lymphoma patients, three smallest overlap regions were found, in which MYCT1 was located. MYCT1 is the first tumor suppressor gene cloned by our research team, but its studies relating to the occurrence and development of lymphoma have not been reported. METHODS: R banding analyses were employed to screen the abnormality of chromosomal karyotype in clinical specimen and MYCT1 over-expression cell lines. FISH was to monitor MYCT1 copy number aberration. RT-PCR and Western blot were to detect the mRNA and protein levels of the MYCT1 and RUNX1 genes, respectively. The MYCT1 and RUNX1 protein levels in clinical specimen were evaluated by immunohistochemical DAB staining. The interaction between MYCT1 and MAX proteins was identified via Co-IP and IF. The binding of MAX on the promoter of the RUNX1 gene was detected by ChIP and Dual-luciferase reporter assay, respectively. Flow cytometry and CCK-8 assay were to explore the effects of MYCT1 and RUNX1 on the cell cycle and proliferation, respectively. RESULTS: MYCT1 was located in one of three smallest overlap regions of diffuse large B-cell lymphoma, it altered chromosomal instability of diffuse large B-cell lymphoma cells. MYCT1 negatively correlated with RUNX1 in lymphoma tissues of the patients. MAX directly promoted the RUNX1 gene transcription by binding to its promoter region. MYCT1 may represses RUNX1 transcription by binding MAX in diffuse large B-cell lymphoma cells. MYCT1 binding to MAX probably suppressed RUNX1 transcription, leading to the inhibition of proliferation and cell cycle of the diffuse large B-cell lymphoma cells. CONCLUSION: This study finds that there is a MYCT1-MAX-RUNX1 signaling pathway in diffuse large B-cell lymphoma. And the study provides clues and basis for the in-depth studies of MYCT1 in the diagnosis, treatment and prognosis of lymphoma.
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Subunidad alfa 2 del Factor de Unión al Sitio Principal , Linfoma de Células B Grandes Difuso , Humanos , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Regiones Promotoras Genéticas , Linfoma de Células B Grandes Difuso/genética , Hematopoyesis , Línea Celular Tumoral , Proteínas Nucleares/metabolismoRESUMEN
Glioblastoma (GBM) is the most prevalent primary intracranial tumor. Temozolomide (TMZ) is the first-line chemotherapy for GBM. Nonetheless, the development of TMZ resistance has become a main cause of treatment failure in GBM patients. Evidence suggests that neuropilin-1 (NRP-1) silencing can attenuate GBM cell resistance to TMZ. This study aims to determine potential mechanisms by which NRP-1 affects TMZ resistance in GBM. The parental U251 and LN229 GBM cells were exposed to increasing concentrations of TMZ to construct TMZ-resistant GBM cells (U251/TMZ, LN229/TMZ). BALB/c nude mice were injected with U251/TMZ cells to establish the xenograft mouse model. Functional experiments were carried out to examine NRP-1 functions. Western blotting and real-time quantitative polymerase chain reaction were used to evaluate molecular protein and mRNA expression, respectively. Immunohistochemical staining showed NRP-1 and STAT1 expression in mouse tumors. The results showed that NRP-1 was highly expressed in TMZ-resistant cells. Moreover, knocking down NRP-1 attenuated the TMZ resistance of U251/TMZ cells, while upregulating NRP-1 enhanced TMZ resistance of the parental cells. NRP-1 silencing elevated GBM cell sensitivity to TMZ in tumor-bearing mice. Depleting NRP-1 reduced STAT1, p53, and p21 expression in U251/TMZ cells. STAT1 depletion offset NRP-1 silencing evoked attenuation of GBM cell resistance to TMZ. Collectively, our study reveals that NRP-1 enhances TMZ resistance in GBM possibly by regulating the STAT1/p53/p21 axis.
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Antineoplásicos Alquilantes , Neoplasias Encefálicas , Resistencia a Antineoplásicos , Glioblastoma , Ratones Endogámicos BALB C , Ratones Desnudos , Neuropilina-1 , Factor de Transcripción STAT1 , Temozolomida , Proteína p53 Supresora de Tumor , Temozolomida/farmacología , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Glioblastoma/metabolismo , Glioblastoma/genética , Animales , Resistencia a Antineoplásicos/efectos de los fármacos , Neuropilina-1/metabolismo , Neuropilina-1/genética , Humanos , Factor de Transcripción STAT1/metabolismo , Antineoplásicos Alquilantes/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Línea Celular Tumoral , Ratones , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Parkinson's disease (PD) is the second most prevalent dementia in the world. Wearable technology has been useful in the computer-aided diagnosis and long-term monitoring of PD in recent years. The fundamental issue remains how to assess the severity of PD using wearable devices in an efficient and accurate manner. However, in the real-world free-living environment, there are two difficult issues, poor annotation and class imbalance, both of which could potentially impede the automatic assessment of PD. To address these challenges, we propose a novel framework for assessing the severity of PD patient's in a free-living environment. Specifically, we use clustering methods to learn latent categories from the same activities, while latent Dirichlet allocation (LDA) topic models are utilized to capture latent features from multiple activities. Then, to mitigate the impact of data imbalance, we augment bag-level data while retaining key instance prototypes. To comprehensively demonstrate the efficacy of our proposed framework, we collected a dataset containing wearable-sensor signals from 83 individuals in real-life free-living conditions. The experimental results show that our framework achieves an astounding 73.48% accuracy in the fine-grained (normal, mild, moderate, severe) classification of PD severity based on hand movements. Overall, this study contributes to more accurate PD self-diagnosis in the wild, allowing doctors to provide remote drug intervention guidance.
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Enfermedad de Parkinson , Dispositivos Electrónicos Vestibles , Humanos , Enfermedad de Parkinson/diagnóstico , Movimiento , Índice de Severidad de la Enfermedad , Extremidad SuperiorRESUMEN
BACKGROUND: Early referral to palliative care has been viewed as providing opportunity for accomplishing end-of-life care goals of life closure, comfortable dying and effective grieving. However, previous studies have shown that palliative care referrals are being made too late. Healthcare providers play important role in helping terminally ill patients to early access and being referred to palliative care. It is necessary to understand healthcare providers' attitudes on palliative care referral and associated factors regarding referrals. OBJECTIVES: This review aimed to identify and synthesise healthcare providers' attitudes and associated factors on palliative care referrals systematically. DESIGN: A systematic review of qualitative evidence and meta-aggregation was conducted and guided according to PRISMA guideline. DATA SOURCES: PubMed, CINAHL, PsycINFO, EMBASE, Web of Science and Cochrane databases from inception to 24 October 2022. RESULTS: Database searches yielded 5856 references. Twenty-two studies met eligibility criteria and of moderate to high methodological quality were included. Studies occurred in USA, UK, Australia and France with 716 healthcare providers participants were included. A total of 378 codings were finally extracted and integrated into 41 categories, forming three synthesised findings: (1) Healthcare providers' attitudes towards palliative care referrals, (2) the influence of subjective norms on palliative care referral behaviour and (3) perceived behavioural control on palliative care referral behaviour. CONCLUSION: This review demonstrates a series of factors that affect the palliative care referrals, including the attitudes of healthcare providers, the participation of patients and families, the support of colleagues and supervisors, inter-professional collaboration, the availability of hospice resource, disease trajectory and socio-economic factors. Further research that addresses these factors and design relevant trainings on improving healthcare providers' attitudes, enhancing patient and family engagement, strengthening support networks and optimising resource allocation may aid to meet increasing demands of patients. RELEVANCE TO CLINICAL PRACTICE: This review not only guides healthcare providers in making better decisions about patient referrals by identifying and addressing barriers but also aids in the development of effective interventions that facilitate the early initiation of referrals. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.
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Actitud del Personal de Salud , Personal de Salud , Cuidados Paliativos , Derivación y Consulta , Humanos , Derivación y Consulta/estadística & datos numéricos , Personal de Salud/psicología , Investigación Cualitativa , Masculino , FemeninoRESUMEN
Objective To gain an in-depth understanding of the motivations,patterns,and related factors in family decision-making regarding the referral of terminal patients in tertiary hospitals. Methods Using purposive sampling,terminal patients and their family members from three tertiary hospitals in Beijing were selected as subjects.Semi-structured interviews were conducted,and the interview data were subjected to thematic analysis. Results Following the saturation principle,a total of 11 patients and 15 family members were included.The interview data were organized and analyzed,yielding six major themes:decision premises,decision patterns,family support,support from the referring hospital's medical team,referral channel conditions,and involvement of volunteer teams and social support.Based on these findings,a flowchart illustrating the family decision-making process for the referral of terminal patients was constructed. Conclusions The study provides a comprehensive analysis of various factors influencing family decision-making in the referral of terminal patients in tertiary hospitals.The results underscore the significance of internal and external factors,emphasizing the integrated impact of decision patterns,family support,medical team support,referral channel conditions,and the involvement of volunteer teams and social support.The research offers profound insights into improving the referral process for terminal patients and enhancing the quality of family decision-making.It provides valuable recommendations for future improvements in medical services and decision support.
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Toma de Decisiones , Familia , Derivación y Consulta , Centros de Atención Terciaria , Humanos , Familia/psicología , Femenino , Masculino , Cuidado Terminal/psicología , Persona de Mediana Edad , Apoyo Social , AdultoRESUMEN
Terminally ill patients face multiple difficulties in home care.Home-based palliative care adhering to the concept of whole-person,whole-family,whole-team,and whole-course care is able to meet the needs of terminally ill patients and their families.In this paper,we reported the care history and home-based palliative care process of a patient with end-stage breast tumor and summarized the experience,aiming to provide reference for the future work of home-based palliative care.
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Cuidados Paliativos , HumanosRESUMEN
Human cytomegalovirus (HCMV) has a large (â¼235 kb) genome with more than 200 predicted open reading frames that exploits numerous cellular factors to facilitate its replication. A key feature of HCMV-infected cells is the emergence of a distinctive membranous cytoplasmic compartment termed the virion assembly compartment (vAC). Here, we report that host protein WD repeat domain 11 (WDR11) plays a key role in vAC formation and virion morphogenesis. We found that WDR11 was upregulated at both mRNA and protein levels during HCMV infection. At the late stage of HCMV replication, WDR11 relocated to the vAC and colocalized with markers of the trans-Golgi network (TGN) and vAC. Depletion of WDR11 hindered HCMV-induced membrane reorganization of the Golgi and TGN, altered vAC formation, and impaired HCMV secondary envelopment and virion morphogenesis. Further, motifs critical for the localization of WDR11 in TGN were identified by alanine-scanning mutagenesis. Mutation of these motifs led to WDR11 mislocation outside the TGN and loss of vAC formation. Taken together, these data indicate that host protein WDR11 is required for efficient viral replication at the stage of virion assembly, possibly by facilitating the remodeling of the endomembrane system for vAC formation and virion morphogenesis. IMPORTANCE During the late phase of human cytomegalovirus (HCMV) infection, the endomembrane system is dramatically reorganized, resulting in the formation of a unique structure termed the virion assembly compartment (vAC), which is critical for the assembly of infectious virions. The mechanism of HCMV-induced vAC formation is still not fully understood. In this report, we identified a host factor, WDR11, that plays an important role in vAC formation. Our findings argue that WDR11 contributes to the relocation of the Golgi and trans-Golgi network to the vAC, a membrane reorganization process that appears to be required for efficient virion maturation. The present work provides new insights into the vAC formation and HCMV virion morphogenesis and a potential novel target for antiviral treatment.
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Infecciones por Citomegalovirus , Citomegalovirus , Interacciones Microbiota-Huesped , Repeticiones WD40 , Citomegalovirus/genética , Citomegalovirus/metabolismo , Infecciones por Citomegalovirus/fisiopatología , Infecciones por Citomegalovirus/virología , Humanos , Morfogénesis , Virión/metabolismo , Ensamble de Virus/genética , Replicación Viral/genética , Repeticiones WD40/genética , Red trans-Golgi/metabolismoRESUMEN
BACKGROUND: Thymic carcinoma (TC) is a rare type of a malignant tumor. The optimal treatment for Masaoka-Koga stage IVB TC patients is controversial due to the rarity of the disease. Chemotherapy is still the preferred option, but the outcomes are unsatisfactory. Whether radiotherapy combined with chemotherapy could improve prognosis remains unclear. METHODS: Untreated stage IVB TC patients who have received first-line chemotherapy were included in the present study. The patients who have undergone surgery were excluded. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). RESULTS: Sixty-seven patients were included in the study. A total of 31 patients received chemoradiotherapy (ChemoRT cohort), and the remaining 36 patients only received chemotherapy (Chemo cohort). The median follow-up period was 40.3 months. The ORR for the ChemoRT and Chemo cohorts was 61.3 and 27.8%, respectively (Pâ¯= 0.006). Furthermore, PFS (Pâ¯= 0.003) and OS (Pâ¯= 0.046) were significantly superior in the ChemoRT cohort. Radiotherapy maintained a significant favorable effect on PFS in multivariate analysis (Pâ¯= 0.014), but the effect on OS was insignificant (Pâ¯= 0.249). There was no advantage in PFS (Pâ¯= 0.302) in the ChemoRT cohort in patients who received < 4 cycles of chemotherapy. In contrast, radiotherapy significantly improved PFS (Pâ¯= 0.005) in patients who received ≥ 4 cycles of chemotherapy. CONCLUSIONS: Chemoradiotherapy used as the first-line treatment improved ORR and PFS in Masaoka-Koga stage IVB TC patients. Patients receiving more cycles of chemotherapy may have a better chance to benefit from chemoradiotherapy.
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Timoma , Neoplasias del Timo , Humanos , Timoma/patología , Timoma/cirugía , Estudios Retrospectivos , Estadificación de Neoplasias , Quimioradioterapia , Neoplasias del Timo/patología , Neoplasias del Timo/cirugíaRESUMEN
In a non-line-of sight reflective underwater wireless optical communications (UWOC) link, the transmitted beam relies on reflections from the sea surface to propagate to the underwater receiver. Most previous research on reflective channels has sufficiently considered single reflections from a smooth or rough surface, while ignoring the effect of multiple reflections. In fact, a rough sea surface may cause the reflected photons to hit the sea surface again, which is referred as a multiple reflection process. To make up for deficiencies in the existing literature, we first construct a capillary waves rough sea surface model, and then present a multiple reflection channel model with the help of the Monte Carlo ray tracing approach. The path loss and channel impulse response (CIR) were further evaluated based on the model for different communications scenarios. Numerical results suggest that multiple reflections increase the path loss by more than about 5 dB, and reduce the CIR amplitude to less than one-third compared to a single reflection. The work done in this paper aims to provide theoretical support for UWOC system design.
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BACKGROUND: Most Chinese patients chose to die at home, therefore there is a reliance on the family caregivers to be involved in their palliative care. The needs and coping strategies of family caregivers in home-based palliative care are rooted in culture. Little is known about the needs and coping strategies of family caregivers taking care of dying patients at home. METHODS: A field study using semi-structured interview, participant observation, documents and records collection was employed. The study was conducted in two palliative care outpatient departments in tertiary hospitals and four communities in Beijing, China from March 2021 to July 2022. Using purposive sampling, twenty-five family caregivers were recruited. All collected data were analyzed using content analysis approach. RESULTS: Five themes emerged, including three care needs and two coping strategies. Family caregivers need to learn care skills and acquire care resources, including (i) decision-making about home-based palliative care, (ii) improving patient's quality of life, and (iii) signs of final hours and funeral procedures. In facing the care burden, family caregivers coped by (iv) balancing the roles of caregivers and individuals: giving priority to patient care while maintaining their own normal life. In facing the death of a loved one, family caregivers responded by (v) making room for coming death by facing death indirectly and "rescuing" patients for consolation while preparing for the coming death. CONCLUSION: Family caregivers strive to balance the roles of being caregivers and being themselves. As caregivers, they actively prepare patients for good death with no regrets. As individuals, they preserve themselves from being hurt to maintain normal life. The needs of family caregivers focus on caregiver role and are manifested in care skills and resources. TRIAL REGISTRATION: Not registered.
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Cuidadores , Servicios de Atención de Salud a Domicilio , Humanos , Calidad de Vida , Cuidados Paliativos/métodosRESUMEN
The Li dendrite issue is the major barrier that limits the implement of Li metal anode practically, especially at high current density. From the perspective of the nucleation and growth mechanism of the Li dendrite, we rationally develop a novel Prussian blue analogues (PBA)-derived separator, where tuning the metal ions bestows the PBAs with open metal site to confine anion movement and thereby afford a high Li+ transference number (0.78), and PBA with ordered micropores could act as an ionic sieve to selectively extract Li+ and thereby homogenize Li+ flux. This demonstrates a highly reversible Li plating/stripping cycling for 3000 h at a practically high current density (5.0 mA cm-2). Consequently, a high loading Li||LiFeO4 battery (â¼10.0 mg cm-2) demonstrates ultralong cycling life at high current densities (â¼5.1 mA cm-2). This work highlights the prospect of optimizing PBAs in regulating ion transport behavior to enable high-power Li metal batteries.
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Suministros de Energía Eléctrica , Litio , Ferrocianuros , IonesRESUMEN
Purpose: To explore the death experiences of nursing students in their personal lives. Methods: This study employed a qualitative descriptive design using the semi-structured interview approach. A purposive sampling method was used to recruit 24 nursing students from September 2020 to July 2022. Data were analyzed using Colaizzi's analysis method. Lincoln and Guba's criteria was used to evaluate the trustworthiness of the data. Results: Four main themes emerged from the interviews: (a) reactions to encounters with death; (b) adjustment strategies; (c) personal growth induced by the death experiences; and (d) professional reflections for preparing nurse role. Conclusions: Although the death of a loved one makes nursing students suffer from grief and emotional distress, we show that the experience promotes the personal growth and professional competencies of nursing students and thereby, developing their overall aptitude towards the profession. Death experiences of nursing students have shown to allow them to reflect on both life and death, to consider the demands of the nursing profession, and to provide foundation for nursing students to be more empathetic and compassionate when facing death in the future. Exploring death experiences of nursing students is vital in better providing better quality education and personal support for nursing students.
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Lithium metal batteries hold great promise for promoting energy density and operating at low temperatures, yet they still suffer from insufficient Li compatibility and slow kinetic, especially at ultra-low temperatures. Herein, we rationally design and synthesize a new amphiphilic solvent, 1,1,2,2-tetrafluoro-3-methoxypropane, for use in battery electrolytes. The lithiophilic segment is readily to solvate Li+ to induce self-assembly of the electrolyte solution to form a peculiar core-shell-solvation structure. Such unique solvation structure not only largely improves the ionic conductivity to allow fast Li+ transport and lower the desolvation energy to enable facile desolvation, but also leads to the formation of a highly robust and conductive inorganic SEI. The resulting electrolyte demonstrates high Li efficiency and superior cycling stability from room temperature to -40 °C at high current densities. Meanwhile, anode-free high-voltage cell retains 87 % capacity after 100 cycles.
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The high local electron density and efficient charge carrier separation are two important factors to affect photocatalytic activity, especially for the CO2 photoreduction reaction. However, the systematic studies on the structure-functional relationship regarding the above two factors based on precisely structure model are rarely reported. Herein, as a proof-of-concept, we developed a new strategy on the evaluation of local electron density by controlling the relative electron-deficient (ED) and electron-rich (ER) intensity of monomer at a molecular level based on three rational-designed vinylene-linked sp2 carbon-covalent organic frameworks (COFs). As expected, the as-prepared vinylene-linked sp2 carbon-conjugated metal-covalent organic framework (MCOFs) (VL-MCOF-1) with molecular junction exhibited excellent activities for CO2 -to-HCOOH conversion (283.41â µmol g-1 h-1 ) and high selectivity of 97.1 %, much higher than the VL-MCOF-2 and g-C34 N6 -COF, which is due to the synergistic effect of the multi-electronic metal clusters (Cu3 (PyCA)3 ) (PyCA=pyrazolate-4-carboxaldehyde) as strong ER roles and cyanopyridine units as ED roles and active sites, as well as the boosted photo-induced charge separation efficiency of vinyl connection and increased light utilization ability. These results not only provide a strategy for regulating the electron-density distribution of photocatalysts at the molecular level but also offers profound insights for metal clusters-based COFs to effective CO2 conversion.