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In recent years, the rotational Doppler effect (RDE) has been widely used in rotational motion measurement. However, the performance of existing detection systems based on the RDE are generally limited by the drastic reduction of signal-to-noise ratio (SNR) due to the influence of atmospheric turbulence, partial obscuration of the vortex beam (VB) during propagation, and misalignment between the optical axis of VB and the rotational axis of the object, which poses a challenge for practical applications. In this paper, we proposed a coherent detection method of the RDE measurement based on triple Fourier transform. First, the weak RDE signal in backscattered light is amplified by using the balanced homodyne detection method, and the amplified signal still retains the same characteristic of severe broadening in the frequency domain as the original signal. Furthermore, we proposed the triple Fourier transform to extract the broadened RDE frequency shift signal after the coherent amplification. The proposed method significantly improves the SNR of RDE measurement and facilitates the accurate extraction of rotational speed, which helps to further improve the RDE detection range and promote its practical application.
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In multiple clinical trials, immune checkpoint blockade-based immunotherapy has shown significant therapeutic efficacy in bladder cancer (BCa). Sex is closely related to the incidence rate and prognosis of BCa. As one of the sex hormone receptors, the androgen receptor (AR) is a well-known key regulator that promotes the progression of BCa. However, the regulatory mechanism of AR in the immune response of BCa is still unclear. In this study, the expression of AR and programmed death ligand 1 (PD-L1) was negatively correlated in BCa cells, clinical tissues, and tumor data extracted from The Cancer Genome Atlas Bladder Urothelial Carcinoma cohort. A human BCa cell line was transfected to alter the expression of AR. The results show that AR negatively regulated PD-L1 expression by directly binding to AR response elements on the PD-L1 promoter region. In addition, AR overexpression in BCa cells significantly enhanced the antitumor activity of cocultured CD8+ T cells. Injection of anti-PD-L1 monoclonal antibodies into C3H/HeN mice significantly suppressed tumor growth, and stable expression of AR dramatically enhanced the antitumor activity in vivo. In conclusion, this study describes a novel role of AR in regulating the immune response to BCa by targeting PD-L1, thus providing potential therapeutic strategies for immunotherapy in BCa.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Animais , Humanos , Camundongos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/tratamento farmacológico , Camundongos Endogâmicos C3H , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Receptores Androgênicos/uso terapêutico , Neoplasias da Bexiga Urinária/patologiaRESUMO
PURPOSE: This study assessed the vertigo/dizziness in patients following COVID-19 vaccination. PATIENTS AND METHODS: From July 2021 to June 2022, totaling 50 patients with dizzy spells following COVID-19 vaccination by AZ (AstraZeneca-Oxford University, AZD1222), BNT (Pfizer-BioNTech, BNT162b2) or Moderna (Moderna, mRNA-1273) vaccine were enrolled in this study. The interval from vaccination to the onset of vertigo/dizziness was compared with inter-episodic interval of vertigo/dizziness in the same patients, but without vaccination, during past one year (2020). RESULTS: The incidences of severe systemic complication per 106 shots were 0.86 for Moderna vaccine, 1.22 for AZ vaccine, and 1.23 for BNT vaccine. Conversely, rate of post-vaccination vertigo/dizziness was noted in the Moderna group (66 %), followed by the AZ group (20 %) and the BNT (14 %) group, meaning that type of COVID-19 vaccine may affect various organ systems. The median time to the onset of vertigo/dizziness following vaccination is 10d, which is consistent with the onset of IgG production, and significantly less than inter-episodic interval (84d) in the same patients without vaccination. CONCLUSION: Post-vaccination vertigo/dizziness can manifest as exacerbation of previous neurotological disorder. The median time to the onset of vertigo/dizziness following COVID-19 vaccination is 10d. Since the outcome is fair after supportive treatment, the immunomodulatory effect of the vaccines does not undermine the necessity of the COVID-19 vaccination.
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Vacinas contra COVID-19 , COVID-19 , Humanos , Vacinas contra COVID-19/efeitos adversos , Vacina BNT162 , ChAdOx1 nCoV-19 , COVID-19/prevenção & controle , Vacinação/efeitos adversos , Vertigem/etiologiaRESUMO
Neuropathic pain takes a heavy toll on individual well-being, while current therapy is far from desirable. Herein, we assessed the analgesic effect of ß-elemene, a chief component in the traditional Chinese medicine Curcuma wenyujin, and explored the underlying mechanisms at the level of spinal dorsal horn (SDH) under neuropathic pain. A spared nerve injury (SNI)-induced neuropathic pain model was established in rats. Intraperitoneal injection (i.p.) of ß-elemene was administered for 21 consecutive days. Mechanical allodynia was explored by von Frey filaments. The activation of the mitogen-activated protein kinase (MAPK) family (including ERK, p38, and JNK) in spinal neurons, astrocytes, and microglia was evaluated using immunostaining 29 days after SNI surgery. The expression of GFAP, Iba-1, p-ERK, p-JNK, and p-p38 within the SDH was measured using immunoblotting. The levels of proinflammatory cytokines (including TNF-α, IL-1ß, and IL-6) were measured with ELISA. The levels of oxidative stress indicators (including MDA, SOD, and GSH-PX) were detected using biochemical tests. Consecutive i.p. administration of ß-elemene relieved SNI-induced mechanical allodynia (with an EC50 of 16.40 mg/kg). SNI significantly increased the expression of p-ERK in spinal astrocytes but not microglia on day 29. ß-elemene reversed spinal astrocytic ERK activation and subsequent upregulation of proinflammatory cytokines in SNI rats, with no effect on the expression of p38 and JNK in spinal glia. ß-elemene also exerted antioxidative effects by increasing the levels of SOD and GSH-PX and decreasing the level of MDA. Our results suggest that SNI induces robust astrocytic ERK activation within the SDH in the late phase of neuropathic pain. ß-elemene exerts remarkable analgesic effects on neuropathic pain, possibly by inhibiting spinal astrocytic ERK activation and subsequent neuroinflammatory processes. Our findings suggest that ß-elemene might be a promising analgesic for the treatment of chronic pain.
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Hiperalgesia , Neuralgia , Analgésicos/metabolismo , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hiperalgesia/complicações , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Ratos , Ratos Sprague-Dawley , Sesquiterpenos , Medula Espinal/metabolismo , Corno Dorsal da Medula Espinal/metabolismo , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: As an antioxidant, hydrogen (H2) can selectively react with the highly toxic hydroxyl radical (·OH) in tumor cells to break the balance of reactive oxygen species (ROS) and cause oxidative stress. However, due to the high diffusibility and storage difficulty of hydrogen, it is impossible to achieve long-term release at the tumor site, which highly limited their therapeutic effect. RESULTS: Photosynthetic bacteria (PSB) release a large amount of hydrogen to break the balance of oxidative stress. In addition, as a nontoxic bacterium, PSB could stimulate the immune response and increase the infiltration of CD4+ and CD8+ T cells. More interestingly, we found that hydrogen therapy induced by our live PSB did not lead to the up-regulation of PD-L1 after stimulating the immune response, which could avoid the tumor immune escape. CONCLUSION: Hydrogen-immunotherapy significantly kills tumor cells. We believe that our live microbial hydrogen production system provides a new strategy for cancer hydrogen treatment combining with enhanced immunotherapy without up-regulating PD-L1.
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Antígeno B7-H1 , Neoplasias , Linfócitos T CD8-Positivos , Humanos , Hidrogênio/uso terapêutico , Imunoterapia , Neoplasias/tratamento farmacológicoRESUMO
SUMOylation of proteins regulates cell behaviors and is reversibly removed by small ubiquitin-like modifier (SUMO)-specific proteases (SENPs). The SENP family member SENP3 is involved in SUMO2/3 deconjugation and has been reported to sense cell stress and accumulate in several human cancer cells and macrophages. We previously reported that Senp3-knockout heterozygous mice showed smaller liver, but the pertinent mechanisms of SENP3 and SUMOylated substrates remain unclear. Thus, in this study, we investigated the interacting proteins with SENP3 and the alteration in hepatocytes treated with the xenobiotic diethylnitrosamine (DEN), which is specifically transformed in the liver and induces DNA double-strand breaks. Our data revealed that a certain amount of SENP3 was present in normal, untreated hepatocytes; however, DEN treatment promoted rapid SENP3 accumulation. SENP3 was mainly localized in the nuclei, and its level was significantly increased in the cytoplasm after 2 h of DEN treatment. The application of the recent proximity-dependent biotinylation (BioID) method led to the identification of 310 SENP3-interacting proteins that were involved in not only gene transcription but also RNA splicing, protein folding, and metabolism. Furthermore, after DEN exposure for a short duration, ribosomal proteins as well as proteins associated with mitochondrial ATP synthesis, membrane transport, and bile acid synthesis, rather than DNA repair proteins, were identified. This study provides insights into the diverse regulatory roles of SENP3, and the BioID method seems to be efficient for identifying physiologically relevant insoluble proteins.
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Alquilantes/farmacologia , Bioensaio/métodos , Biotinilação/métodos , Cisteína Endopeptidases/metabolismo , Dietilnitrosamina/farmacologia , Hepatócitos/metabolismo , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Hepatócitos/efeitos dos fármacos , Humanos , Ligação Proteica , Mapas de Interação de Proteínas/efeitos dos fármacos , SumoilaçãoRESUMO
BACKGROUND: Progressive fibrosis is the underlying pathophysiological process of CKD, and targeted prevention or reversal of the profibrotic cell phenotype is an important goal in developing therapeutics for CKD. Nanoparticles offer new ways to deliver antifibrotic therapies to damaged tissues and resident cells to limit manifestation of the profibrotic phenotype. METHODS: We focused on delivering plasmid DNA expressing bone morphogenetic protein 7 (BMP7) or hepatocyte growth factor (HGF)-NK1 (HGF/NK1) by encapsulation within chitosan nanoparticles coated with hyaluronan, to safely administer multifunctional nanoparticles containing the plasmid DNA to the kidneys for localized and sustained expression of antifibrotic factors. We characterized and evaluated nanoparticles in vitro for biocompatibility and antifibrotic function. To assess antifibrotic activity in vivo, we used noninvasive delivery to unilateral ureteral obstruction mouse models of CKD. RESULTS: Synthesis of hyaluronan-coated chitosan nanoparticles containing plasmid DNA expressing either BMP7 or NGF/NKI resulted in consistently sized nanoparticles, which-following endocytosis driven by CD44+ cells-promoted cellular growth and inhibited fibrotic gene expression in vitro. Intravenous tail injection of these nanoparticles resulted in approximately 40%-45% of gene uptake in kidneys in vivo. The nanoparticles attenuated the development of fibrosis and rescued renal function in unilateral ureteral obstruction mouse models of CKD. Gene delivery of BMP7 reversed the progression of fibrosis and regenerated tubules, whereas delivery of HGF/NK1 halted CKD progression by eliminating collagen fiber deposition. CONCLUSIONS: Nanoparticle delivery of HGF/NK1 conveyed potent antifibrotic and proregenerative effects. Overall, this research provided the proof of concept on which to base future investigations for enhanced targeting and transfection of therapeutic genes to kidney tissues, and an avenue toward treatment of CKD.
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Antifibrinolíticos/administração & dosagem , Proteína Morfogenética Óssea 7/genética , Técnicas de Transferência de Genes , Fator de Crescimento de Hepatócito/genética , Nanopartículas Multifuncionais , Insuficiência Renal Crônica/terapia , Animais , Técnicas de Cultura de Células , Quitosana , Modelos Animais de Doenças , Ácido Hialurônico , Camundongos , PolímerosRESUMO
Fibrosis is characterized by excessive production of disorganized collagen- and fibronectin-rich extracellular matrices (ECMs) and is driven by the persistence of myofibroblasts within tissues. A key protein contributing to myofibroblast differentiation is extra domain A fibronectin (EDA-FN). We sought to target and interfere with interactions between EDA-FN and its integrin receptors to effectively inhibit profibrotic activity and myofibroblast formation. Molecular docking was used to assist in the design of a blocking polypeptide (antifibrotic 38-amino-acid polypeptide, AF38Pep) for specific inhibition of EDA-FN associations with the fibroblast-expressed integrins α4ß1 and α4ß7. Blocking peptides were designed and evaluated in silico before synthesis, confirmation of binding specificity, and evaluation in vitro. We identified the high-affinity EDA-FN C-C' loop binding cleft within integrins α4ß1 and α4ß7. The polypeptide with the highest predicted binding affinity, AF38Pep, was synthesized and could achieve specific binding to myofibroblast fibronectin-rich ECM and EDA-FN C-C' loop peptides. AF38Pep demonstrated potent myofibroblast inhibitory activity at 10 µg/mL and was not cytotoxic. Treatment with AF38Pep prevented integrin α4ß1-mediated focal adhesion kinase (FAK) activation and early signaling through extracellular-signal-regulated kinases 1 and 2 (ERK1/2), attenuated the expression of pro-matrix metalloproteinase 9 (MMP9) and pro-MMP2, and inhibited collagen synthesis and deposition. Immunocytochemistry staining revealed an inhibition of α-smooth muscle actin (α-SMA) incorporation into actin stress fibers and attenuated cell contraction. Increases in the expression of mRNA associated with fibrosis and downstream from integrin signaling were inhibited by treatment with AF38Pep. Our study suggested that AF38Pep could successfully interfere with EDA-FN C-C' loop-specific integrin interactions and could act as an effective inhibitor of fibroblast of myofibroblast differentiation.
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Desenho de Fármacos , Fibroblastos/efeitos dos fármacos , Fibronectinas/metabolismo , Fibrose/tratamento farmacológico , Integrinas/metabolismo , Miofibroblastos/efeitos dos fármacos , Peptídeos/farmacologia , Sítios de Ligação , Diferenciação Celular , Matriz Extracelular/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibronectinas/química , Fibrose/metabolismo , Fibrose/patologia , Humanos , Integrinas/química , Pulmão/citologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Simulação de Acoplamento Molecular , Miofibroblastos/citologia , Miofibroblastos/metabolismo , Ligação Proteica , Domínios Proteicos , Transdução de SinaisRESUMO
Multifunctional tissue adhesives with excellent adhesion, antibleeding, anti-infection, and wound healing properties are desperately needed in clinical surgery. However, the successful development of multifunctional tissue adhesives that simultaneously possess all these properties remains a challenge. We have prepared a novel chitosan-based hydrogel adhesive by integration of hydrocaffeic acid-modified chitosan (CS-HA) with hydrophobically modified chitosan lactate (hmCS lactate) and characterized its gelation time, mechanical properties, and microstructure. Tissue adhesion properties were evaluated using both pigskin and intestine models. In situ antibleeding efficacy was demonstrated via the rat hemorrhaging liver and full-thickness wound closure models. Good antibacterial activity and anti-infection capability toward S. aureus and P. aeruginosa were confirmed using in vitro contact-killing assays and an infected pigskin model. The result of coculturing with 3T3 fibroblast cells indicated that the hydrogels have no significant cytotoxicity. Most importantly, the biocompatible and biodegradable CS-HA/hmCS lactate hydrogel was able to close the wound in a sutureless way and promote wound healing. Our results demonstrate that this hydrogel has great promise for sutureless closure of surgical incisions.
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Quitosana , Adesivos Teciduais , Adesivos/farmacologia , Animais , Antibacterianos/farmacologia , Hidrogéis/farmacologia , Ratos , Staphylococcus aureus , Adesivos Teciduais/farmacologiaRESUMO
PM2.5 particles are regarded as prominent risk factors that contribute to the development of atherosclerosis. However, the composition of PM2.5 is rather complicated. This study aimed to provide a model particle that simulates the behavior of actual PM2.5, for subsequent use in exploring mechanisms and major complications arising from PM2.5. To establish model particles of PM2.5, a series of monodisperse SiO2 microspheres with different average grain diameters were mixed according to the size distribution of actual PM2.5. The organic carbon (OC) was removed from PM2.5 and coated onto the SiO2 model particle, to formulate simulant PM2.5. Results showed that the size distribution of the model particle was highly approximate to that of the PM2.5 core. The polycyclic aromatic hydrocarbon (PAHs) composition profile of the simulated PM2.5 were approximate to PM2.5, and loading efficiency was approximately 80%-120%. Furthermore, compared to the control, SiO2-only model particle had negligible cytotoxicity on cell viability and oxidative stress of HUVECs, and marginal effect on the lipid metabolism and atherosclerotic plaque formation in ApoE-/- mice. In contrast, simulated PM2.5 exhibited similar cytotoxic and detrimental effects on lipid metabolism and atherosclerotic plaque formation with actual PM2.5. Traffic-related PM2.5 had negative effects on endothelial function and led to the formation of atherosclerosis via oxidative stress. The simulated PM2.5 simulated the outcomes of actual PM2.5 exposure. Here, we show that SiO2 particle model cores coated with OC could significantly assist in the evaluation of the effects of specific organic compositions bound on PM2.5, specifically in the context of environmental health and safety.
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Poluentes Atmosféricos/toxicidade , Apolipoproteínas E/deficiência , Material Particulado/química , Placa Aterosclerótica/induzido quimicamente , Dióxido de Silício/química , Poluentes Atmosféricos/química , Animais , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Material Particulado/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/química , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Dióxido de Silício/toxicidade , Emissões de Veículos/toxicidadeRESUMO
Metal,N-codoped carbon (M-N-C) nanostructures are promising electrocatalysts toward oxygen reduction reaction (ORR) or other gas-involved energy electrocatalysis. Further creating pores into M-N-C nanostructures can increase their surface area, fully expose the active sites, and improve mass transfer and electrocatalytic efficiency. Nonetheless, it remains a challenge to fabricate M-N-C nanomaterials with both well-defined morphology and hierarchical porous structures. Herein, high-quality 2D Cu-N-C nanodisks (NDs) with biomimic stomata-like interconnected hierarchical porous topology are synthesized via carbonization of Cu-tetrapyridylporphyrin (TPyP)-metal-organic frameworks (MOFs) precursors and followed by etching the carbonization product (Cu@Cu-N-C) along with re-annealing treatment. Such hierarchical porous Cu-N-C NDs possess high specific surface area (293 m2 g-1 ) and more exposed Cu single-atom sites, different from their counterparts (Cu@Cu-N-C) and pure N-C control catalysts. Electrochemical tests in alkaline media reveal that they can efficiently catalyze ORR with a half-wave potential of 0.85 V (vs reversible hydrogen electrode), comparable to Pt/C and outperforming Cu@Cu-N-C, N-C, Cu-TPyP-MOFs, and most other reported M-N-C catalysts. Moreover, their stability and methanol-tolerant capability exceed Pt/C. This work may shed some light on optimizing 2D M-N-C nanostructures through bio-inspired pore structure engineering, and accelerate their applications in fuel cells, artificial photosynthesis, or other advanced technological fields.
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Nanostructures and nanomaterials based on peptide self-assembly have attracted tremendous interests due to the functionalities of peptide molecules. Furthermore, the self-assembled peptide nanostructures are also adopted to fabricate nanomaterials and nanodevices. In this work, the intramolecular folding and self-assembly of a ß-hairpin peptide CBHH were first studied under the regulation of platinum ion. And then, platinum nanostructures were synthesized through the reduction of platinum ions templated with peptide self-assemblies. The results of circular dichroism spectroscopy, UV-vis spectroscopy, isothermal titration calorimetry, and atomic force microscopy observation showed that platinum ions could promote the conversion of peptide CBHH secondary structure from a random coil to a ß-sheet through coordination with histidine residues. Platinum nanostructures including nanorods and one dimensionally aligned nanorods were synthesized through in situ reduction with CBHH self-assembled nanofiber as the templates. And the synthesized platinum nanostructures showed excellent electrocatalytic activities.
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Nanoestruturas/química , Peptídeos/síntese química , Platina/química , Adsorção , Íons/química , Tamanho da Partícula , Peptídeos/química , Estrutura Secundária de Proteína , Propriedades de SuperfícieRESUMO
Objective/Hypothesis: This study correlated stage of Meniere's disease (MD) with MR imaging of endolymphatic hydrops (EH) to assess the role of MD staging in modern era. Study Design: Retrospective study. Methods: Fifty-four MD patients (60 ears) underwent an inner ear test battery and were further confirmed by MR imaging. Sixty MD ears were divided into stages I-IV, and hydrops MR images at each stage were compared. Results: Hydrops MRI demonstrated that EH at the cochlea with respective Grades 0/I/II were 3/7/1 ears for stage I, 0/5/3 ears for stage II, 1/6/26 ears for stage III and 0/2/6 ears for stage IV. Significant relationship was not identified between MD stage and grades of cochlear hydrops. Similarly, no significant relationship was shown between MD stage and grades of vestibular (saccular/utricular) hydrops. The optimal cutoff value of four-tone average for predicting severe type (Grade II-III) cochlear/vestibular EH was 48 dB, which was within the stage III. Hence, prevalence of severe type (Grade II) cochlear EH in stages III (79%) and IV (75%) was significantly higher than stages I (9%) and II (38%). Similarly, severe type saccular/utricular EH in stages III (64%) and IV (75%) also showed significantly higher than stages I (18%) and II (25%). Conclusion: Although conventional MD staging fails to correlate with the grades of EH on hydrops MRI, late-stage MD may indicate heightened EH severity in the cochlea and vestibule. Level of Evidence: 4.
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The cyanobacterial response to flow velocity or light intensity deviates from the combined effect of both factors. The responses of Microcystis aeruginosa to different combinations of flow velocities and light intensities were tested. Growth (OD730 and protein), stress (catalase, ascorbate peroxidase, and glutathione peroxidase), and photosynthetic ability (chlorophyll-a and fluorescence) parameters of M. aeruginosa were measured to evaluate the effects of different combinations. Exposure to different flow velocity-light combinations significantly affected the growth and physiology of M. aeruginosa. Flow velocities of 0.4 m s-1 showed a prominent influence on most of the measured parameters compared with no flow velocity or higher flow velocity conditions. The 1.2-m s-1 flow velocity and high light intensity (1200 µmol m-2 s-1 ) exposure caused a significant elevation in oxidative stress. Lower velocities are beneficial for M. aeruginosa at light stress, whereas extreme velocities are adverse and elevate the stress. Two categories of light-velocity combinations were identified as preferred and extreme categories, depending on whether they suppressed or supported M. aeruginosa growth. In controlling cyanobacteria blooms using flow or high-intensity light, it is imperative to consider the interaction of these two factors, as their combined effects can significantly vary the stress levels in cyanobacteria. A new system, designed to minimize mechanical damage on M. aeruginosa, was used to generate flow velocities. Additionally, the combined effects of flow velocities and light intensities have been considered for the first time. PRACTITIONER POINTS: Flow velocity can influence the effect of light on Microcystis aeruginosa. High light exposure effect on Microcystis aeruginosa can be reduced by low flow velocity. High flow velocity and high light exposure increase the stress on Microcystis aeruginosa. Different light intensities and flow velocity combinations changed Microcystis aeruginosa stress physiology.
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Cianobactérias , Microcystis , Cianobactérias/metabolismo , Clorofila A , LuzRESUMO
Cancer immunotherapy has shown to be a promising method in treating hepatocellular carcinoma (HCC), but suboptimal responses in patients are attributed to cellular and molecular heterogeneity. Iron metabolism-related genes (IRGs) are important in maintaining immune system homeostasis and have the potential to help develop new strategies for HCC treatment. Herein, we constructed and validated the iron-metabolism gene prognostic index (IPX) using univariate Cox proportional hazards regression and LASSO Cox regression analysis, successfully categorizing HCC patients into two groups with distinct survival risks. Then, we performed single-sample gene set enrichment analysis, weighted correlation network analysis, gene ontology enrichment analysis, cellular lineage analysis, and SCENIC analysis to reveal the key determinants underlying the ability of this model based on bulk and single-cell transcriptomic data. We identified several driver transcription factors specifically activated in specific malignant cell sub-populations to contribute to the adverse survival outcomes in the IPX-high subgroup. Within the tumor microenvironment (TME), T cells displayed significant diversity in their cellular characteristics and experienced changes in their developmental paths within distinct clusters identified by IPX. Interestingly, the proportion of Treg cells was increased in the high-risk group compared with the low-risk group. These results suggest that iron-metabolism could be involved in reshaping the TME, thereby disrupting the cell cycle of immune cells. This study utilized IRGs to construct a novel and reliable model, which can be used to assess the prognosis of patients with HCC and further clarify the molecular mechanisms of IRGs in HCC at single-cell resolution.
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PURPOSE: This study seeks to examine the influence of the heartbeat on the position, volume, and shape of the heart and its substructures during various breathing states. The findings of this study will serve as a valuable reference for dose-volume evaluation of the heart and its substructures in radiotherapy for treating thoracic tumors. METHODS: Twenty-three healthy volunteers were enrolled in this study, and cine four-dimensional magnetic resonance images were acquired during periods of end-inspiration breath holding (EIBH), end-expiration breath holding (EEBH), and deep end-inspiration breath holding (DIBH). The MR images were used to delineate the heart and its substructures, including the heart, pericardium, left ventricle (LV), left ventricular myocardium, right ventricle (RV), right ventricular myocardium (RVM), ventricular septum (VS), atrial septum (AS), proximal and middle portions of the left anterior descending branch (pmLAD), and proximal portion of the left circumflex coronary branch (pLCX). The changes in each structure with heartbeat were compared among different respiratory states. RESULTS: Compared with EIBH, EEBH increased the volume of the heart and its substructures by 0.25-3.66%, while the average Dice similarity coefficient (DSC) increased by - 0.25 to 8.7%; however, the differences were not statistically significant. Conversely, the VS decreased by 0.89 mm in the left-right (LR) direction, and the displacement of the RV in the anterior-posterior (AP) direction significantly decreased by 0.76 mm (p < 0.05). Compared with EIBH and EEBH, the average volume of the heart and its substructures decreased by 3.08-17.57% and 4.09-20.43%, respectively, during DIBH. Accordingly, statistically significant differences (p < 0.05) were observed in the volume of the heart, pericardium, LV, RV, RVM, and AS. The average DSC increased by 0-37.04% and - 2.6 to 32.14%, respectively, with statistically significant differences (p < 0.05) found in the right ventricular myocardium and interatrial septum. Furthermore, the displacements under DIBH decreased in the three directions (i.e.,- 1.73 to 3.47 mm and - 0.36 to 2.51 mm). In this regard, the AP displacement of the heart, LV, RV, RVM, LR direction, LV, RV, and AS showed statistically significant differences (p < 0.05). The Hausdorff distance (HD) of the heart and its substructures under the three breathing states are all greater than 11 mm. CONCLUSION: The variations in the displacement and shape alterations of the heart and its substructures during cardiac motion under various respiratory states are significant. When assessing the dose-volume index of the heart and its substructures during radiotherapy for thoracic tumors, it is essential to account for the combined impacts of cardiac motion and respiration.
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Coração , Neoplasias Torácicas , Humanos , Frequência Cardíaca , Respiração , Ventrículos do Coração , Suspensão da Respiração , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
The inheritance of recurrent patellar dislocation (RPD) is known, but the susceptible gene remains unidentified. Here, we performed the first whole exome sequencing (WES) cohort study to identify the susceptible genes. The results showed eight genes were associated with this disease. Notably, the carboxypeptidase D (CPD) gene showed the highest relevance based on its gene function and tissue expression. Single-cell sequencing results indicate that the CPD gene is involved in the pathophysiological process of RPD through granulocytes. Implicated pathways include nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and Wnt/ß-catenin signaling, potentially influencing CPD's role in RPD pathogenesis. This study identified the susceptible gene and investigates the potential pathogenesis of RPD, which provided a new prospect for the understanding of RPD. Besides, it would offer the theoretical basis for disease prevention and genetic counseling.
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Vascular injury is central to the pathogenesis and progression of cardiovascular diseases, however, fostering alternative strategies to alleviate vascular injury remains a persisting challenge. Given the central role of cell-derived nitric oxide (NO) in modulating the endogenous repair of vascular injury, NO-generating proteolipid nanovesicles (PLV-NO) are designed that recapitulate the cell-mimicking functions for vascular repair and replacement. Specifically, the proteolipid nanovesicles (PLV) are versatilely fabricated using membrane proteins derived from different types of cells, followed by the incorporation of NO-generating nanozymes capable of catalyzing endogenous donors to produce NO. Taking two vascular injury models, two types of PLV-NO are tailored to meet the individual requirements of targeted diseases using platelet membrane proteins and endothelial membrane proteins, respectively. The platelet-based PLV-NO (pPLV-NO) demonstrates its efficacy in targeted repair of a vascular endothelium injury model through systemic delivery. On the other hand, the endothelial cell (EC)-based PLV-NO (ePLV-NO) exhibits suppression of thrombosis when modified onto a locally transplanted small-diameter vascular graft (SDVG). The versatile design of PLV-NO may enable a promising therapeutic option for various vascular injury-evoked cardiovascular diseases.
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Óxido Nítrico , Proteolipídeos , Lesões do Sistema Vascular , Óxido Nítrico/metabolismo , Animais , Lesões do Sistema Vascular/metabolismo , Proteolipídeos/metabolismo , Modelos Animais de Doenças , Camundongos , Humanos , Nanopartículas/química , MasculinoRESUMO
Mercury (Hg) in coastal wetlands is of great concern due to its acute toxicity. We measured the total Hg content (THg) from a 210Pb-dated sediment core obtained from the Futian mangrove wetland in Shenzhen Bay, South China to explore the historical variation and possible sources. Our results extend the sediment THg record back to 1960 and reveal three distinct intervals. Interval I (1960-1974) has low and increasing THg values, averaging 83.0 µg/kg; Interval II (1975-1984) witnesses a remarkably increase, peaking in 1980 (261.6 µg/kg) then remaining elevated; Interval III (1985-2014) shows a steady reduction, averaging 118.4 µg/kg. The good correlation among THg, TOC, and Hg/TOC, and the downstream decrease in monitoring sediment THg consistently suggest that the bulk THg are mainly sourced from the Shenzhen River discharge. The different timing in industrial development attributes the elevated THg concentrations during 1975-1984 to Hong Kong industrial sewage pollution.
Assuntos
Mercúrio , Poluentes Químicos da Água , Mercúrio/análise , Áreas Alagadas , Hong Kong , Desenvolvimento Industrial , Sedimentos Geológicos , Monitoramento Ambiental , China , Poluentes Químicos da Água/análiseRESUMO
Cyanobacteria are a significant primary producer and pioneer species that play a vital role in ecological reconstruction, especially in aquatic environments. Cyanobacteria have excellent recovery capacity from significant stress exposure and are thus suggested as bioreserves, even for space colonization programs. Few studies have been conducted on the recovery capacity after experiencing stress. Long-duration darkness or insufficient light is stressful for photosynthetic species, including cyanobacteria, and can cause chlorosis. Cyanobacterial recovery after extensive exposure to darkness has not yet been studied. In this experiment, Microcystis aeruginosa and Pseudanabaena foetida were subjected to a year-long darkness treatment, and the change in recovery capacity was measured in monthly samples. Cyanobacterial growth, chlorophyll-a concentration, oxidative stress, and photosynthetic capacity were evaluated. It was found that the rapid recovery capacity of the two species remained even after one year of darkness treatment. However, the H2O2 content of recovered samples of both M. aeruginosa and P. foetida experienced significant changes at six-seven months, although the photosynthetic capacity of both cyanobacteria species was maintained within the healthy range. The chlorophyll-a and carotenoid content of the recovered samples also changed with increasing darkness. The results showed that long-term dark treatment had time-dependent effects but different effects on M. aeruginosa and P. foetida. However, both cyanobacteria species can recover rapidly after one year of dark treatment.