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Family history (FH) of cancer and polygenic risk scores (PRS) are pivotal for cancer risk assessment, yet their combined impact remains unclear. Participants in the UK Biobank (UKB) were recruited between 2006 and 2010, with complete follow-up data updated until February 2020 for Scotland and January 2021 for England and Wales. Using UKB data (N = 442,399), we constructed PRS and incidence-weighted overall cancer PRS (CPRS). FH was assessed through self-reported standardized questions. Among 202,801 men (34.6% with FH) and 239,598 women (42.0% with FH), Cox regression was used to examine the associations between FH, PRS, and cancer risk. We found a significant dose-response relationship between FH of cancer and corresponding cancer risk (Ptrend < .05), with over 10 significant pairs of cross-cancer effects of FH. FH and PRS are positively correlated and independent. Joint effects of FH of cancer (multiple cancers) and PRS (CPRS) on corresponding cancer risk were observed: for instance, compared with participants with no FH of cancer and low PRS, men with FH of cancer and high PRS had the highest risk of colorectal cancer (hazard ratio [HR]: 3.69, 95% confidence interval [CI]: 3.01-4.52). Additive interactions were observed in prostate and overall cancer risk for men and breast cancer for women, with the most significant result being a relative excess risk of interaction (RERI) of 2.98, accounting for ~34% of the prostate cancer risk. In conclusion, FH and PRS collectively contribute to cancer risk, supporting their combined application in personalized risk assessment and early intervention strategies.
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AIM: This study explored the role of the Hedgehog pathway in epithelial cells during cervical cancer [CC] progression, providing new insights for improving current CC treatment. BACKGROUND: Abnormal activation of the Hedgehog signaling pathway is associated with the malignant transformation of CC epithelial cells. Single-cell atlas of CC and the role of Hedgehog pathway in epithelial cells during CC progression remain to be explored. OBJECTIVE: To comprehensively analyze the mechanism of Hedgehog pathway activation in CC epithelial cells and its impact on tumor progression by applying single-cell RNA sequencing [scRNA-seq] analysis. METHODS: The scRNA-seq data were acquired from the Gene Expression Omnibus [GEO] database and then processed with the Seurat package. FindNeighbors and Find- Clusters functions were applied to cluster the cells. The CellMarker database was used for subgroup annotation. Differentially expressed genes [DEGs] in each cell subgroup were filtered by FindAllMarkers function. Biological function analysis for the gene set of interest was performed using Clusterprofiler package. AUCell function was employed to calculate the score of the Hedgehog pathway. The differentiation trajectory in epithelial cell subtypes was generated by performing Pseudotime analysis. Finally, protein-protein network [PPI] was used to investigate the interactions between the Hedgehog pathway and other pathways enriched in the gene set of interest. RESULTS: A total of 9 major cell subpopulations were classified and the proportion of epithelial cells was the highest in CC samples. Further analysis revealed that the Hedgehog pathway was abnormally activated in STYK1+ and TP73+ epithelial cell subtypes. Pseudo-time trajectory analysis showed that the differentiation trajectory of STYK1+ epithelial cells gradually transformed into defense-to-virus cells or into proliferation cells, while TP73+ epithelial cells eventually differentiated into two branches of response to estrogen and virus-induced proliferation. PPI analysis showed that the Hedgehog pathway was involved in the proliferation and viral process of epithelial cells in CC. CONCLUSION: The current study comprehensively analyzed the features of CC samples and differentiation trajectories of epithelial cell subtypes, as well as the role of the Hedgehog pathway in epithelial cells during CC progression. More importantly, effective target genes were discovered for the molecular diagnosis and precise treatment of CC.
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Monotherapy, especially the use of antibodies targeting vascular endothelial growth factor (VEGF), has shown limitations in treating choroidal neovascularization (CNV) since reactive oxygen species (ROS) also exacerbate CNV formation. Herein, we developed a combination therapy based on a DNA origami platform targeting multiple components of ocular neovascularization. Our study demonstrated that ocular neovascularization was markedly suppressed by intravitreal injection of a rectangular DNA origami sheet modified with VEGF aptamers (Ap) conjugated to an anti-VEGF antibody (aV) via matrix metalloproteinase (MMP)-cleavable peptide linkers in a mouse model of CNV. Typically, the DNA origami-based therapeutic platform selectively accumulates in neovascularization lesions owing to the dual-targeting ability of the aV and Ap, followed by the cleavage of the peptide linker by MMPs to release the antibody. Together, the released antibody and Ap inhibited VEGF activity. Moreover, the residual bare DNA origami could effectively scavenge ROS, reducing oxidative stress at CNV sites and thus maximizing the synergistic effects of inhibiting neovascularization.
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Neovascularización Coroidal , ADN , Factor A de Crecimiento Endotelial Vascular , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/metabolismo , Animales , Ratones , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/química , ADN/química , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno/metabolismo , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/farmacología , Metaloproteinasas de la Matriz/metabolismo , Metaloproteinasas de la Matriz/química , Anticuerpos/químicaRESUMEN
BACKGROUND: The association between sleep patterns and young students' mental health, which is crucial for their development, remains understudied in rural China. Therefore, the relationship between sleep patterns and mental health among primary and junior high school students in rural China was examined. METHOD: A total of 1592 primary and junior high school students from rural areas of Gansu Province were surveyed, and the Depression Anxiety and Stress Scale (DASS) was utilized to assess mental health, alongside self-reported data on their daily sleep patterns. RESULTS: Significant sleep inadequacies were identified: 28% of students received less than 8 h of sleep on weekdays, and 19% went to bed later than recommended. On weekends, 38% of students had delayed bedtimes, though only 7.2% received less than 8 h of sleep. Notably, a "U-shaped" relationship was uncovered between sleep duration and mental health for students on weekends, with optimal mental health correlated with receiving 10-11 h of sleep, while both shorter and longer sleep durations on weekends worsened outcomes. This pattern is absent on weekdays. Additionally, adequate sleep and an earlier bedtime was linked to a 6-8% decrease in mental health risks. CONCLUSIONS: These findings provide valuable insights for policymakers seeking to enhance student mental well-being in rural settings, emphasizing the importance of implementing measures that promote balanced sleep habits among young students.
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Precision spectroscopy of hyperfine splitting (HFS) is a crucial tool for investigating the structure of nuclei and testing quantum electrodynamics. However, accurate theoretical predictions are hindered by two-photon exchange (TPE) effects. We propose a novel formalism that accounts for nuclear excitations and recoil in TPE, providing a model-independent description of TPE effects on HFS in light ordinary and muonic atoms. Combining our formalism with pionless effective field theory at next-to-next-to-leading order, the predicted TPE effects on HFS are 41.7(4.4) kHz and 0.117(13) meV for the 1S state in deuterium and the 2S state in muonic deuterium. These results align within 1σ and 1.3σ from recent measurements and highlight the importance of nuclear structure effects on HFS and indicate the value of more precise measurements in future experiments.
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BACKGROUND: Right ventricular (RV) fibrosis is an important pathological change that occurs during the development of right heart failure (RHF) induced by pulmonary hypertension (PH). Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has been shown to play a major role in left heart failure, but it is unclear whether it has a positive effect on RHF. This study aimed to clarify the effect of DAPA on PH-induced RHF and investigate the underlying mechanisms. METHODS: We conducted experiments on two rat models with PH-induced RHF and cardiac fibroblasts (CFs) exposed to pathological mechanical stretch or transforming growth factor-beta (TGF-ß) to investigate the effect of DAPA. RESULTS: In vivo, DAPA could improve pulmonary hemodynamics and RV function. It also attenuated right heart hypertrophy and RV fibrosis. In vitro, DAPA reduced collagen expression by increasing the production of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9). Additionally, DAPA was found to reduce reactive oxygen species (ROS) levels in CFs and the right heart in rats. Similar to DAPA, the ROS scavenger N-acetylcysteine (NAC) exerted antifibrotic effects on CFs. Therefore, we further investigated the mechanism by which DAPA promoted collagen degradation by reducing ROS levels. CONCLUSIONS: In summary, we concluded that DAPA ameliorated PH-induced structural and functional changes in the right heart by increasing collagen degradation. Our study provides new ideas for the possibility of using DAPA to treat RHF.
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Compuestos de Bencidrilo , Colágeno , Fibrosis , Glucósidos , Insuficiencia Cardíaca , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno , Animales , Glucósidos/farmacología , Glucósidos/uso terapéutico , Compuestos de Bencidrilo/farmacología , Compuestos de Bencidrilo/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Especies Reactivas de Oxígeno/metabolismo , Ratas , Colágeno/metabolismo , Masculino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Metaloproteinasa 9 de la Matriz/metabolismo , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/patología , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Metaloproteinasa 2 de la Matriz/metabolismo , Modelos Animales de EnfermedadRESUMEN
To reveal the connections between the 2024 moment magnitude (Mw) 7.5 Noto earthquake in Japan and the seismicity swarms that preceded it, we investigated its rupture process through near-source waveform analysis and source imaging techniques, combining seismic and geodetic datasets. We found notable complexity in the initial rupture stages. A strong fault asperity, which remained unbroken in preceding seismic swarms, slowed down the rupture. Then, a second rupture initiated at the opposite edge of the asperity, and the asperity succumbed to double-pincer rupture fronts. The failure of this high-stress drop asperity drove the earthquake into a large-scale event. Our observations help unravel the crucial role of fault asperities in controlling swarm migration and rupture propagation and underscore the need for detailed seismological and interdisciplinary studies to assess seismic risk in swarm-prone regions.
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Constrained many-objective optimization problems (CMaOPs) have gradually emerged in various areas and are significant for this field. These problems often involve intricate Pareto frontiers (PFs) that are both refined and uneven, thereby making their resolution difficult and challenging. Traditional algorithms tend to over prioritize convergence, leading to premature convergence of the decision variables, which greatly reduces the possibility of finding the constrained Pareto frontiers (CPFs). This results in poor overall performance. To tackle this challenge, our solution involves a novel dual-population constrained many-objective evolutionary algorithm based on reference point and angle easing strategy (dCMaOEA-RAE). It relies on a relaxed selection strategy utilizing reference points and angles to facilitate cooperation between dual populations by retaining solutions that may currently perform poorly but contribute positively to the overall optimization process. We are able to guide the population to move to the optimal feasible solution region in a timely manner in order to obtain a series of superior solutions can be obtained. Our proposed algorithm's competitiveness across all three evaluation indicators was demonstrated through experimental results conducted on 77 test problems. Comparisons with ten other cutting-edge algorithms further validated its efficacy.
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At present, no consensus has been reached on the generation mechanism of anisotropy in materials fabricated by laser powder bed fusion (LPBF), and most attention has been focused on crystallographic texture. In this paper, an analysis and test were carried out on the hardness, defect distribution, residual stress distribution, and microstructure of WE43 magnesium alloy fabricated by LPBF. The results indicate that LPBF WE43 exhibits obvious anisotropy-the hardness HV of X-Z surface (129.9 HV on average) and that of Y-Z surface (130.7 HV on average) are about 33.5% higher than that of X-Y surface (97.6 HV on average), and the endurable load is smaller in the stacking direction Z compared to the X and Y directions. The factors contributing more to the anisotropy are listed as follows in sequence. Firstly, the defect area of the X-Y projection surface is about 13.2% larger than that of the other two surfaces, so this surface shows greatly reduced mechanical properties due to the exponential relationship between the material strength and the number of defects. Secondly, for laser scanning in each layer/time, the residual stress accumulation in the Z direction is higher than that in the X and Y directions, which may directly reduce the mechanical properties of the material. Finally, more fine grains are distributed in X-Z and Y-Z surfaces when comparing them with those in an X-Y surface, and this fine-grain strengthening mechanism also contributes to the anisotropy. After T5 aging heat treatment (250 °C/16 h), a stronger crystallographic texture is formed in the <0001> direction, with the orientation density index increasing from 10.92 to 21.38, and the anisotropy disappearing. This is mainly caused by the enhancement effect of the texture in the <0001> direction on the mechanical properties in the Z direction cancelling out the weakening effect of the defects in the X-Y surface in the Z direction.
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BACKGROUND: The SPHERe (Supervised Pulmonary Hypertension Exercise Rehabilitation) trial is a multi-centre, pragmatic, randomised controlled trial assessing the clinical and cost-effectiveness of supervised exercise rehabilitation with psychosocial and motivational support compared to best-practice usual care for people with pulmonary hypertension (PH). The original protocol was published in BMC Pulmonary Medicine (accessible online). We randomised our first participant in January 2020. In response to the COVID-19 pandemic, the trial was stopped in March 2020. In person delivery of the SPHERe intervention to a vulnerable population was not possible during the COVID-19 pandemic. We describe here how trial procedures and intervention delivery were adapted in response to the COVID-19 pandemic. METHODS: Restrictions imposed by the COVID-19 pandemic on the clinically vulnerable PH population meant that trial delivery was changed from a centre-based rehabilitation programme to remotely delivered group online sessions. This led to minor alterations to the eligibility criteria. These changes followed a consultation process with stakeholders and people with PH and were approved by the funder and independent trial committees. CONCLUSIONS: We describe the modified SPHERe trial protocol in response to restrictions imposed by the COVID-19 pandemic. SPHERe is the first randomised controlled trial to assess the clinical and cost-effectiveness of an online group rehabilitation programme for people with PH compared to usual care. TRIAL REGISTRATION: ISRCTN no. 10608766. Prospectively registered on 18th March 2019, updated 16th August 2023.
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COVID-19 , Análisis Costo-Beneficio , Terapia por Ejercicio , Hipertensión Pulmonar , Humanos , COVID-19/rehabilitación , COVID-19/epidemiología , Terapia por Ejercicio/métodos , Terapia por Ejercicio/economía , Hipertensión Pulmonar/rehabilitación , Hipertensión Pulmonar/economía , Estudios Multicéntricos como Asunto , Ensayos Clínicos Pragmáticos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , SARS-CoV-2 , Resultado del TratamientoRESUMEN
This paper address the performance optimization of the battery heat sink module by analyzing the lattice structure of the battery heat sink module through in-depth modeling and simulation, and combining the laser powder bed fusion (LPBF)-forming technology with mechanical and corrosion resistance experiments for a comprehensive study. It is found that the introduction of the lattice skeleton significantly improves the thermal conductivity of the phase change material (PCM), realizing the efficient distribution and fast transfer of heat in the system. At the same time, the lattice skeleton makes the heat distribution in the heat exchanger more uniform, improves the utilization rate of the PCM, and helps to maintain the stability of the cell temperature. In addition, the melting of PCM in the lattice heat exchanger is more uniform, thus maximizing its latent heat capacity. In summary, by optimizing the lattice structure and introducing the lattice skeleton, this study successfully improves the performance of the battery heat dissipation system, which provides a strong guarantee for the high efficiency and stable operation of the battery, and provides new ideas and references for the development of the battery heat dissipation technology.
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To explore the size, morphology, and distribution patterns of internal pore defects in WE43 magnesium alloy formed by laser powder bed fusion (LPBF), as well as their impact on its mechanical properties, computer tomography (CT), metallographic microscopy, and scanning electron microscopy were used to observe the material's microstructure and the morphology of tensile test fractures. The study revealed that a large number of randomly distributed non-circular pore defects exist internally in the LPBF-formed WE43 magnesium alloy, with a defect volume fraction of 0.16%. Approximately 80% of the defects had equivalent diameters concentrated in the range of 10â¼40 µm, and 56.2% of the defects had sphericity values between 0.65â¼0.7 µm, with the maximum defect equivalent diameter being 122 µm. There were a few spherical pores around 20 µm in diameter in the specimens, and unfused powder particles were found in pore defects near the edges of the parts. Under the test conditions, the fusion pool structure of LPBF-formed WE43 magnesium alloy resembled a semi-elliptical shape with a height of around 66 µm, capable of fusion three layers of powder material in a single pass. Columnar grains formed at the edge of individual fusion pools, while the central area exhibited equiaxed grains. The "scale-like pattern" formed by overlapping fusion pool structures resulted in the microstructure of LPBF-formed WE43 magnesium alloy mainly consisting of fine equiaxed grains with a size of 2.5 µm and columnar grains distributed in a band-like manner.
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BACKGROUND: Psoriasis refers to a highly prevalent and immunologically mediated dermatosis with considerable deterioration in life quality. Wogonin, a sort of flavonoid, has been mentioned to elicit protective activities in skin diseases. However, whether Wogonin is implicated in the treatment of psoriasis and its specific mechanisms are not fully understood. AIM: The present work attempted to elaborate the role of Wogonin during the process of psoriasis and to concentrate on the associated action mechanism. METHODS: Cell counting kit-8 (CCK-8) method was initially applied to assay the viability of human keratinocyte HaCaT cells treated by varying concentrations of Wogonin. To mimic psoriasis in vitro, HaCaT cells were exposed to M5 cytokines. CCK-8 and 5-Ethynyl-2'-deoxyuridine assays were adopted for the measurement of cell proliferation. Inflammatory levels were examined with enzyme-linked immunosorbent assay. Immunofluorescence staining tested nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) and Caspase-1 expressions. Western blot examined the protein expressions of proliferation-, inflammation-, pyroptosis-associated factors, and NLRP3. RESULTS: Wogonin treatment antagonized the proliferation, inflammatory response, and NLRP3/caspase-1/Gasdermin-D (GSDMD)-mediated pyroptosis in M5-challenged HaCaT cells. Besides, NLRP3 elevation partially abrogated the effects of Wogonin on M5-induced proliferation, inflammatory response, and NLRP3/caspase-1/GSDMD-mediated pyroptosis in HaCaT cells. CONCLUSION: In a word, Wogonin might exert anti-proliferation, anti-inflammatory and anti-pyroptosis activities in M5-induced cell model of psoriasis and the blockade of NLRP3/Caspase-1/GSDMD pathway might be recognized as a potential mechanism underlying the protective mechanism of Wogonin in psoriasis, suggesting Wogonin as a prospective anti-psoriasis drug.
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Caspasa 1 , Proliferación Celular , Flavanonas , Queratinocitos , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Transducción de Señal , Humanos , Flavanonas/farmacología , Piroptosis/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Proliferación Celular/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Caspasa 1/metabolismo , Transducción de Señal/efectos de los fármacos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Psoriasis/tratamiento farmacológico , Psoriasis/metabolismo , Psoriasis/patología , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Células HaCaT , Línea Celular , Gasderminas , Proteínas de Unión a FosfatoRESUMEN
Herein, we report a DNA origami plasmonic nanoantenna for the programmable surface-enhanced Raman scattering (SERS) detection of cytokine release syndrome (CRS)-associated cytokines (e.g., tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)) in cancer immunotherapy. Typically, the nanoantenna was made of self-assembled DNA origami nanotubes (diameter: â¼19 nm; length: â¼90 nm) attached to a silver nanoparticle-modified silicon wafer (AgNP/Si). Each DNA origami nanotube contains one miniature gold nanorod (AuNR) inside (e.g., length: â¼35 nm; width: â¼7 nm). Intriguingly, TNF-α and IFN-γ logically regulate the opening of the nanotubes and the dissociation of the AuNRs from the origami structure upon binding to their corresponding aptamers. On this basis, we constructed a complete set of Boolean logic gates that read cytokine molecules as inputs and return changes in Raman signals as outputs. Significantly, we demonstrated that the presented system enables the quantification of TNF-α and IFN-γ in the serum of tumor-bearing mice receiving different types of immunotherapies (e.g., PD1/PD-L1 complex inhibitors and STING agonists). The sensing results are consistent with those of the ELISA. This strategy fills a gap in the use of DNA origami for the detection of multiple cytokines in real systems.
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Técnicas Biosensibles , Citocinas , ADN , Oro , Inmunoterapia , Nanopartículas del Metal , Espectrometría Raman , Animales , Ratones , ADN/química , Citocinas/metabolismo , Citocinas/sangre , Oro/química , Nanopartículas del Metal/química , Humanos , Plata/química , Nanotubos/química , Neoplasias , Interferón gamma/sangre , Interferón gamma/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
The heat shock protein 70 family contains the stress proteins ubiquitous in plants. These proteins are involved in the responses to different abiotic stress conditions and have highly conserved gene sequences. However, little is known about the molecular mechanisms of Fritillaria cirrhosa in response to high-temperature stress. Here, 26 HSP70s, FcHSP70-1 to FcHSP70-26, were identified from the transcriptome data of root, bulb, stem, leaf, and fruit samples of F. cirrhosa. The proteins encoded by FcHSP70s had the lengths ranging from 560 aa to 944 aa, with the molecular weight of 61.64-100.01 kDa and the theoretical isoelectric point between 5.00 and 6.59. The secondary structural elements of HSP70s were mainly random coils and α-helixes. Subcellular localization prediction revealed that FcHSP70s were distributed in mitochondria, chloroplasts, nuclei, endoplasmic reticulum, and cytoplasm. The phylogenetic tree showed that 7 members of the HSP70 family belonged to the Dnak subfamily and 19 members belonged to the HSP110/SSE subfamily. In addition, the qRT-PCR results showed that the expression of FcHSP70-5, FcHSP70-8, FcHSP70-17, FcHSP70-18, and FcHSP70-23 in F. cirrhosa was significantly up-regulated at 35 â, which indicated that these genes might play a role in the response to high temperature stress. In addition, compared with other tissues, stems and leaves were sensitive to high temperature stress, with the expression of 18 genes up-regulated by 18.18 and 8.03 folds on average, respectively. These findings provide valuable information about the molecular mechanism of HSP70s of F. cirrhosa in response to high temperature stress.
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Fritillaria , Regulación de la Expresión Génica de las Plantas , Proteínas HSP70 de Choque Térmico , Filogenia , Proteínas de Plantas , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas HSP70 de Choque Térmico/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Fritillaria/genética , Fritillaria/química , Calor , Estrés Fisiológico/genética , Perfilación de la Expresión Génica , Familia de MultigenesRESUMEN
MicroRNAs (miRNA) are endogenously produced small, non-coded, single-stranded RNAs. Due to their involvement in various cellular processes and cross-communication with extracellular components, miRNAs are often coined the "grand managers" of the cell. miRNAs are frequently involved in upregulation as well as downregulation of specific gene expression and thus, are often found to play a vital role in the pathogenesis of multiple diseases. Central nervous system (CNS) diseases prove fatal due to the intricate nature of both their development and the methods used for treatment. A considerable amount of ongoing research aims to delineate the complex relationships between miRNAs and different diseases, including each of the neurological disorders discussed in the present review. Ongoing research suggests that specific miRNAs can play either a pathologic or restorative and/or protective role in various CNS diseases. Understanding how these miRNAs are involved in various regulatory processes of CNS such as neuroinflammation, neurovasculature, immune response, blood-brain barrier (BBB) integrity and angiogenesis is of empirical importance for developing effective therapies. Here in this review, we summarized the current state of knowledge of miRNAs and their roles in CNS diseases along with a focus on their association with neuroinflammation, innate immunity, neurovascular function and BBB.
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We propose an ultra-compact mode filtering wavelength demultiplexer design with a footprint of 3µm×3µm. Our device can route input T E 1 mode signals at 1310 nm and 1550 nm to different output ports while simultaneously blocking fundamental transverse electric (T E 0) mode input. Our device is designed based on the topology optimization algorithm, which results in an ultra-compact footprint combining wavelength routing and mode filtering functions for the first time, to the best of our knowledge. Our final optimized devices demonstrated insertion losses of 1.26 dB and 1.47 dB for the C- and O-band output ports, respectively, with inter-port crosstalk as low as -21.25d B and -30.99d B. The extinction ratios between T E 1 mode and T E 0 mode are 24.02 dB and 30.12 dB at the 1310 nm and 1550 nm output ports. The combination of small footprint, broad transmission bandwidth, T E 1 to T E 0 mode selectively filtering, and C- and O-band T E 1 mode demultiplexing functions make this a uniquely versatile device that can play an important role in future high density mode-wavelength multiplexing systems.
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OBJECTIVE: This purpose of this study is to investigate the effectiveness and safety of utilizing the arterial spin-labeling (ASL) combined with diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) combined with DWI double mismatch in the endovascular treatment of patients diagnosed with wake-up stroke (WUS). METHODS: In this single-center trial, patients diagnosed with WUS underwent thrombectomy if acute ischemic lesions were observed on DWI indicating large precerebral circulation occlusion. Patients with no significant parenchymal hypersignal on FLAIR and ASL imaging showing a hypoperfusion tissue to infarct core volume ratio of at least 1.2 were included. The participants were divided into groups receiving endovascular thrombectomy plus medical therapy or medical therapy alone, based on their subjective preference. Functional outcomes were assessed using the ordinal score on the modified Rankin scale (mRs) at 90 days, along with the rate of functional independence. RESULTS: In this study, a total of 77 patients were included, comprising 38 patients in the endovascular therapy group and 39 patients in the medical therapy group. The endovascular therapy group exhibited more favorable changes in the distribution of functional prognosis measured by mRs at 90 days, compared to the medical therapy group (adjusted common odds ratio, 3.25; 95% CI, 1.03 to 10.26; P < 0.01). Additionally, the endovascular therapy group had a higher proportion of patients achieving functional independence (odds ratio, 4.0; 95% CI, 1.36 to 11.81; P < 0.01). Importantly, there were no significant differences observed in the incidence of intracranial hemorrhage or mortality rates between the two groups. CONCLUSION: Guided by the ASL-DWI and FLAIR-DWI double mismatch, endovascular thrombectomy combined with standard medical treatment appears to yield superior functional outcomes in patients with WUS and large vessel occlusion compared to standard medical treatment alone.
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Imagen de Difusión por Resonancia Magnética , Procedimientos Endovasculares , Marcadores de Spin , Trombectomía , Humanos , Trombectomía/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Masculino , Femenino , Procedimientos Endovasculares/métodos , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Anciano de 80 o más Años , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/cirugía , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/cirugía , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/fisiopatologíaRESUMEN
Background: Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer. Methods: Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence by genetic risk group among 374,463 participants from the UK Biobank. We generated PhenoAge using chronological age and nine biomarkers, PhenoAgeAccel after subtracting the effect of chronological age by regression residual, and an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific polygenic risk scores (PRSs). Results: Compared with biologically younger participants, those older had a significantly higher risk of overall cancer, with hazard ratios (HRs) of 1.22 (95% confidence interval, 1.18-1.27) in men, and 1.26 (1.22-1.31) in women, respectively. A joint effect of genetic risk and PhenoAgeAccel was observed on overall cancer risk, with HRs of 2.29 (2.10-2.51) for men and 1.94 (1.78-2.11) for women with high genetic risk and older PhenoAge compared with those with low genetic risk and younger PhenoAge. PhenoAgeAccel was negatively associated with the number of healthy lifestyle factors (Beta = -1.01 in men, p<0.001; Beta = -0.98 in women, p<0.001). Conclusions: Within and across genetic risk groups, older PhenoAge was consistently related to an increased risk of incident cancer with adjustment for chronological age and the aging process could be retarded by adherence to a healthy lifestyle. Funding: This work was supported by the National Natural Science Foundation of China (82230110, 82125033, 82388102 to GJ; 82273714 to MZ); and the Excellent Youth Foundation of Jiangsu Province (BK20220100 to MZ).
Age is a major risk factor for cancer. Other factors, such as lifestyle or environmental exposures, may increase or mitigate cancer risks. Biological age, which considers accelerated aging processes, may, however, better predict cancer risk than chronological age. Some scientists propose using biological aging measures as an alternative for assessing cancer and other age-related disease risks, as these markers may provide a more accurate assessment of the various factors contributing to cancer risk. PhenoAge, a measure of biological aging processes in the body, could provide an alternative way to assessing aging-related cancer risks. This tool utilizes an individual's chronological age and nine biomarkers of aging processes. It has the potential to identify individuals whose aging process is accelerated compared to their peers, potentially indicating an increased cancer risk. This information may empower them to make lifestyle changes that could significantly reduce their risk. To assess the suitability of PhenoAge, Bian, Ma et al. used nine clinical chemistry biomarkers and chronological age to calculate PhenoAge in 374,463 participants from the UK Biobank. Their findings revealed that people with older PhenoAges regardless of their genetic risk profiles have an increased risk of cancer. Individuals with higher PhenoAge scores, indicating accelerated biological aging, had a roughly 25 percent higher risk of developing cancer. Individuals with both a high genetic risk and higher PhenoAge score had roughly double the risk of cancer. People with lower PhenoAges were more likely to have healthier lifestyles. These results suggest that adopting healthier lifestyles may slow the aging process and reduce cancer risk. While the analyses conducted by Bian, Ma et al. provide promising insights, they also underscore the need for further research. PhenoAge may offer a way to assess biological aging and identify individuals at higher risk of cancer. Those with higher PhenoAge scores may benefit from earlier cancer screening, and adopting a healthier lifestyle could potentially slow down the aging process and reduce their cancer risk. However, more studies in more diverse cohorts of people are needed to confirm that PhenoAge is a reliable marker for cancer risk and to test interventions to slow aging and reduce cancer risks in individuals with accelerated aging.
Asunto(s)
Envejecimiento , Neoplasias , Fenotipo , Humanos , Neoplasias/genética , Neoplasias/epidemiología , Masculino , Femenino , Envejecimiento/genética , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Incidencia , Factores de Riesgo , Predisposición Genética a la Enfermedad , Reino Unido/epidemiología , Adulto , Modelos de Riesgos ProporcionalesRESUMEN
Enterovirus C116 (EV-C116) is a new member of the enterovirus C group which is closely associated with several infectious diseases. Although sporadic studies have detected EV-C116 in clinical samples worldwide, there is currently limited information available. In this study, two EV-C-positive fecal specimens were detected in apparently healthy children, which harbored low abundance, through meta-transcriptome sequencing. Based on the prototypes of several EV-Cs, two lineages were observed. Lineage 1 included many types that could not cause EV-like cytopathic effect in cell culture. Three genogroups of EV-C116 were divided in the maximum likelihood tree, and the two strains in this study (XZ2 and XZ113) formed two different lineages, suggesting that EV-C116 still diffuses worldwide. Obvious inter-type recombination events were observed in the XZ2 strain, with CVA22 identified as a minor donor. However, another strain (XZ113) underwent different recombination situations, highlighting the importance of recombination in the formation of EV-Cs biodiversity. The EV-C116 strains could propagate in rhabdomyosarcoma cell cultures at low titer; however, EV-like cytopathic effects were not observed. HEp-2, L20B, VERO, and 293T cell lines did not provide an appropriate environment for EV-C116 growth. These results challenge the traditional recognition of the uncultured nature of EV-C116 strains and explain the difficulty of clinical detection.