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As one of the most successful pathogenic organisms, Vibrio cholerae (V. cholerae) has evolved sophisticated regulatory mechanisms to overcome host stress. During long-term colonization by V. cholerae in adult mice, many spontaneous nonmotile mutants (approximately 10% at the fifth day post-infection) were identified. These mutations occurred primarily in conserved regions of the flagellar regulator genes flrA, flrC, and rpoN, as shown by Sanger and next-generation sequencing, and significantly increased fitness during colonization in adult mice. Intriguingly, instead of key genes in DNA repair systems (mutS, nfo, xthA, uvrA) or ROS and RNS scavenging systems (katG, prxA, hmpA), which were generally thought to be associated with bacterial mutagenesis, we found that deletion of the cyclin gene dps significantly increased the mutation rate (up to 53% at the fifth day post-infection) in V. cholerae. We further determined that the dpsD65A and dpsF46E point mutants showed a similar mutagenesis profile as the Δdps mutant during long-term colonization in mice, which strongly indicated that the antioxidative function of Dps directly contributes to the development of V. cholerae nonmotile mutants. Methionine metabolism pathway may be one of the mechanism for ΔflrA, ΔflrC and ΔrpoN mutant increased colonization in adult mice. Our results revealed a new phenotype in which increased fitness of V. cholerae in the host gut via spontaneous production nonmotile mutants regulated by cyclin Dps, which may represent a novel adaptation strategy for directed evolution of pathogens in the host.
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Vibrio cholerae , Animais , Camundongos , Vibrio cholerae/genética , Vibrio cholerae/metabolismo , Adaptação ao Hospedeiro , Mutação , Ciclinas/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão GênicaRESUMO
Working to all orders in dimensionally regularized QCD with massless quarks, we study the radiation of a photon whose energy is much lower than that of external partons. The conventional soft photon theorem receives corrections at leading power in the photon energy, associated with soft virtual loops of massless fermions. These additive corrections give an overall factor times the nonradiative amplitude that is infrared finite and real to all orders in α_{s}. Based on recent calculations of the three-loop soft gluon current, we identify the lowest-order three-loop correction.
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OBJECTIVES: The European Kidney Function Consortium (EKFC) developed two novel equations in 2023 for estimating glomerular filtration rate (GFR): one sex-free cystatin C-based equation (EKFCCys) and one creatinine-cystatin C combined equation (EKFCCr-Cys). This study compared their performance with the previous creatinine-based EKFC equation (EKFCCr) and commonly used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study (BIS) equations in Chinese adults. METHODS: A total of 2,438 Chinese adults (mean age=53.04 years) who underwent the 99mTc-DTPA renal dynamic imaging for reference GFR (rGFR) were included. Diagnostic value was evaluated using correlation coefficients, sensitivity, specificity, and area under the receiver operating characteristic curve (ROCAUC). Performance was assessed in terms of bias, precision (interquartile range of the median difference [IQR]), accuracy (percentage of estimates ±30â¯% of rGFR [P30], and root-mean-square error [RMSE]) across age, sex, and rGFR subgroups. Gender differences in bias and P30 were also analyzed. RESULTS: Average rGFR was 73.37â¯mL/min/1.73â¯m2. EKFC equations showed stronger correlations and larger AUCs compared to the parallel CKD-EPI equations, with EKFCCr-Cys demonstrating the greatest improvement (R=0.771, ROCAUC=0.913). Concerning bias, precision, and accuracy, EKFC equations consistently outperformed CKD-EPI equations. EKFCCr-Cys and EKFCCr performed acceptably well in the entire population and were equivalent to BIS equations in the elderly. All equations, including EKFCCys, showed similar P30 accuracy across sexes. CONCLUSIONS: EKFC equations provided a reasonable alternative for estimating GFR in the Chinese adult population. While EKFCCys did not outperform EKFCCr, EKFCCr-Cys improved the accuracy of single-marker equations.
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Cistatina C , Taxa de Filtração Glomerular , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Cistatina C/sangue , Adulto , Idoso , Creatinina/sangue , Testes de Função Renal/métodos , Testes de Função Renal/normas , China , Povo Asiático , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Rim/fisiologia , Curva ROC , População do Leste AsiáticoRESUMO
OBJECTIVES: Glomerular filtration rate (GFR) estimating equations based on rescaled serum creatinine (SCr/Q) have shown better performance, where Q represents the median SCr for age- and sex-specific healthy populations. However, there remains a scarcity of investigations in China to determine this value. We aimed to develop Chinese age- and sex-specific reference intervals (RIs) and Q-values for SCr and to validate the equations incorporating new Q-values. METHODS: We included 117,345 adults from five centers for establishing RIs and Q-values, and 3,692 participants with reference GFR (rGFR, 99mTc-DTPA renal dynamic imaging measurement) for validation. Appropriate age partitioning was determined using the decision tree method. Lower and upper reference limits and medians were calculated using the refineR algorithm, and Q-values were determined accordingly. We evaluated the full age spectrum (FAS) and European Kidney Function Consortium (EKFC) equations incorporating different Q-values considering bias, precision (interquartile range, IQR), and accuracy (percentage of estimates within ±20â¯% [P20] and ±30â¯% [P30] of rGFR). RESULTS: RIs for males were: 18-79 years, 55.53-92.50⯵mol/L; ≥80 years, 54.41-96.43⯵mol/L. RIs for females were: 18-59 years, 40.42-69.73⯵mol/L; 60-79 years, 41.16-73.69⯵mol/L; ≥80 years, 46.50-73.20⯵mol/L. Q-values were set at 73.82⯵mol/L (0.84â¯mg/dL) for males and 53.80⯵mol/L (0.61â¯mg/dL) for females. After validation, we found that the adjusted equations exhibit less bias, improved precision and accuracy, and increased agreement of GFR categories. CONCLUSIONS: We determined Chinese age- and sex-specific RIs and Q-values for SCr. The adjustable Q-values provide an effective alternative to obtain valid equations for estimating GFR.
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Creatinina , Mineração de Dados , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Creatinina/sangue , Adulto , Idoso , Valores de Referência , Adolescente , Adulto Jovem , Mineração de Dados/métodos , Idoso de 80 Anos ou mais , ChinaRESUMO
First-principles calculations were employed to investigate the impact of quantum ionic fluctuations and lattice anharmonicity on the crystal structure and superconductivity of Pm3Ì AlM(M = Hf, Zr)H6 at pressures of 0.3-21.2 GPa (AlHfH6) and 4.7-39.5 GPa (AlZrH6) within the stochastic self-consistent harmonic approximation. A correction is predicted for the crystal lattice parameters, phonon spectra, and superconducting critical temperatures, previously estimated without considering ionic fluctuations on the crystal structure and assuming the harmonic approximation for lattice dynamics. The findings suggest that quantum ionic fluctuations have a significant impact on the crystal lattice parameters, phonon spectra, and superconducting critical temperatures. Based on our anharmonic phonon spectra, the structures will be dynamically stable at 0.3 GPa for AlHfH6 and 6.2 GPa for AlZrH6, â¼6 and 7 GPa lower than pressures given by the harmonic approximation, respectively. Due to the anharmonic correction of their frequencies, the electron-phonon coupling constants (λ) are suppressed by 28% at 11 GPa for AlHfH6 and 22% at 30 GPa for AlZrH6, respectively. The decrease in λ causes Tc to be overestimated by â¼12 K at 11 GPa for AlHfH6 and 30 GPa for AlZrH6. Even if the anharmonic and quantum effects are not as strong as those of Pm3Ìn-AlH3, our results also indicate that metal hydrides with hydrogen atoms in interstitial sites are subject to anharmonic effects. Our results will inevitably stimulate future high-pressure experiments on synthesis, structural, and conductivity measurements.
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BACKGROUND: Epidemiological studies have shown that sarcopenia was associated with depression among older adults. However, most of these investigations used a cross-sectional design, limiting the ability to establish a causal relation, the present study examined whether sarcopenia was associated with incident depressive symptoms. METHODS: This is a prospective cohort study with participants from the Western China Health and Aging Trends (WCHAT) study. Participants could complete anthropometric measurements and questionnaires were included. The exposure was sarcopenia, defined according to the Asian Working Group for Sarcopenia in 2019, the outcome was depressive symptoms, evaluated by GDS-15. We excluded depression and depressive symptoms at baseline and calculated the risk of incident depressive symptoms during the follow-up year. RESULTS: A total of 2612 participants (mean age of 62.14 ± 8.08 years) were included, of which 493 with sarcopenia. 78 (15.82%) participants with sarcopenia had onset depressive symptoms within the next year. After multivariable adjustment, sarcopenia increased the risk of depressive symptoms (RR = 1.651, 95%CI = 1.087-2.507, P = 0.0187) in overall participants. Such relationship still exists in gender and sarcopenia severity subgroups. Low muscle mass increased the risk of depressive symptoms (RR = 1.600, 95%CI = 1.150-2.228, P = 0.0053), but low muscle strength had no effect (RR = 1.250, 95%CI = 0.946-1.653, P = 0.117). CONCLUSIONS: Sarcopenia is an independent risk factor for depressive symptoms, Precautions to early detect and targeted intervene for sarcopenia should continue to be employed in adult with sarcopenia to achieve early prevention for depression and reduce the incidence of adverse clinical outcomes.
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Sarcopenia , Humanos , Idoso , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Sarcopenia/complicações , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/etiologia , Estudos Transversais , Estudos Prospectivos , Força Muscular/fisiologia , Força da MãoRESUMO
Polymers of intrinsic microporosity (PIMs) have been used as precursors for the fabrication of porous carbon molecular sieve (CMS) membranes. PIM-1, a prototypical PIM material, uses a fused-ring structure to increase chain rigidity between spirobisindane repeat units. These two factors inhibit effective chain packing, thus resulting in high free volume within the membrane. However, a decrease of pore size and porosity was observed after pyrolytic conversion of PIM-1 to CMS membranes, attributed to the destruction of the spirocenter, which results in the "flattening" of the polymer backbone and graphite-like stacking of carbonaceous strands. Here, a spirobifluorene-based polymer of intrinsic microporosity (PIM-SBF) was synthesized and used to fabricate CMS membranes that showed significant increases in p-xylene permeability (approximately four times), with little loss in p-xylene/o-xylene selectivity (13.4 versus 14.7) for equimolar xylene vapor separations when compared to PIM-1-derived CMS membranes. This work suggests that it is feasible to fabricate such highly microporous CMS membranes with performances that exceed current state-of-the-art zeolites at high xylene loadings.
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Intranasal (i.n.) immunization is a promising vaccination route for infectious respiratory diseases such as influenza. Recombinant protein vaccines can overcome the safety concerns and long production phase of virus-based influenza vaccines. However, soluble protein vaccines are poorly immunogenic if administered by an i.n. route. Here, we report that polyethyleneimine-functionalized graphene oxide nanoparticles (GP nanoparticles) showed high antigen-loading capacities and superior immunoenhancing properties. Via a facile electrostatic adsorption approach, influenza hemagglutinin (HA) was incorporated into GP nanoparticles and maintained structural integrity and antigenicity. The resulting GP nanoparticles enhanced antigen internalization and promoted inflammatory cytokine production and JAWS II dendritic cell maturation. Compared with soluble HA, GP nanoparticle formulations induced significantly enhanced and cross-reactive immune responses at both systemic sites and mucosal surfaces in mice after i.n. immunization. In the absence of any additional adjuvant, the GP nanoparticle significantly boosted antigen-specific humoral and cellular immune responses, comparable to the acknowledged potent mucosal immunomodulator CpG. The robust immune responses conferred immune protection against challenges by homologous and heterologous viruses. Additionally, the solid self-adjuvant effect of GP nanoparticles may mask the role of CpG when coincorporated. In the absence of currently approved mucosal adjuvants, GP nanoparticles can be developed into potent i.n. influenza vaccines, providing broad protection. With versatility and flexibility, the GP nanoplatform can be easily adapted for constructing mucosal vaccines for different respiratory pathogens.
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Reações Cruzadas/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Nanopartículas/química , Infecções por Orthomyxoviridae/imunologia , Administração Intranasal , Animais , Linhagem Celular , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Grafite/química , Grafite/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Imunidade Humoral/efeitos dos fármacos , Imunidade Humoral/imunologia , Imunidade nas Mucosas/efeitos dos fármacos , Imunidade nas Mucosas/imunologia , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/fisiologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/química , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Oligodesoxirribonucleotídeos/química , Oligodesoxirribonucleotídeos/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/virologia , Polietilenoimina/química , Vacinação/métodosRESUMO
The fruits of Cornus officinalis are used not only as a popular health food to tonify the liver and kidney, but also as staple materials to treat dementia and other age-related diseases. The pharmacological function of C. officinalis fruits with or without seeds is controversial for treating some symptoms in a few herbal prescriptions. However, the related metabolite and pharmacological information between its pericarps and seeds are largely deficient. Here, comparative metabolomics analysis between C. officinalis pericarps and seeds were conducted using an ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, and therapeutic effects were also evaluated using several in vitro bioactivity arrays (antioxidant activity, α-glucosidase and cholinesterase inhibitory activities, and cell inhibitory properties). A total of 499 secondary metabolites were identified. Thereinto, 77 metabolites were determined as key differential metabolites between C. officinalis pericarps and seeds, and the flavonoid biosynthesis pathway was identified as the most significantly different pathway. Further, 47 metabolites were determined as potential bioactive constituents. In summary, C. officinalis seeds, which demonstrated higher contents in total phenolics, stronger in vitro antioxidant activities, better α-glucosidase and butyrylcholinesterase inhibitory activities, and stronger anticancer activities, exhibited considerable potential for food and health fields. This work provided insight into the metabolites and bioactivities of C. officinalis pericarps and seeds, contributing to their precise development and utilization.
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Cornus , Frutas , Butirilcolinesterase , alfa-Glucosidases , Sementes , Compostos Fitoquímicos/farmacologiaRESUMO
Various physiological activities and metabolic reactions of cells need to be carried out under the corresponding pH environment. Intracellular GSH as an acid tripeptide and an important reducing substance also plays an important role in maintaining cellular acid-base balance and redox balance. Therefore, developing a method to monitor pH and GSH and their changes in cells is necessary. Herein, we developed a novel turn-on fluorescent silicon nanoparticles (SiNPs) using N-(2-aminoethyl)-3-aminopropyltrimethoxysilane as the silicon source and dithiothreitol as the reducing agent via a one-pot hydrothermal method. It was worth mentioning that the fluorescence intensity of the SiNPs increased along with the acidity increase, making the SiNPs have excellent pH and GSH sensing capability. Furthermore, the pH and GSH sensing performance of the SiNPs in the cell was verified by confocal imaging and flow cytometry experiment. Based on the above, the prepared SiNPs had the potential to be used as an intracellular pH and GSH multimode fluorescent sensing platform and exhibited the ability to distinguish between normal cells and cancer cells.
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Nanopartículas , Silício , Silício/química , Nanopartículas/química , Corantes Fluorescentes/química , Concentração de Íons de HidrogênioRESUMO
The epidemics caused by the influenza virus are a serious threat to public health and the economy. Adding appropriate adjuvants to improve immunogenicity and finding effective mucosal vaccines to combat respiratory infection at the portal of virus entry are important strategies to boost protection. In this study, a novel type of core/shell protein nanoparticle consisting of influenza nucleoprotein (NP) as the core and NA1-M2e or NA2-M2e fusion proteins as the coating antigens by SDAD hetero-bifunctional crosslinking is exploited. Immune-stimulating complexes (ISCOMs)/monophosphoryl lipid A (MPLA) adjuvants further boost the NP/NA-M2e SDAD protein nanoparticle-induced immune responses when administered intramuscularly. The ISCOMs/MPLA-adjuvanted protein nanoparticles are delivered through the intranasal route to validate the application as mucosal vaccines. ISCOMs/MPLA-adjuvanted nanoparticles induce significantly strengthened antigen-specific antibody responses, cytokine-secreting splenocytes in the systemic compartment, and higher levels of antigen-specific IgA and IgG in the local mucosa. Meanwhile, significantly expanded lung resident memory (RM) T and B cells (TRM /BRM ) and alveolar macrophages population are observed in ISCOMs/MPLA-adjuvanted nanoparticle-immunized mice with a 100% survival rate after homogeneous and heterogeneous H3N2 viral challenges. Taken together, ISCOMs/MPLA-adjuvanted protein nanoparticles could improve strong systemic and mucosal immune responses conferring protection in different immunization routes.
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ISCOMs , Vacinas contra Influenza , Nanopartículas , Animais , Camundongos , Imunidade nas Mucosas , Complexo Antígeno-Anticorpo , Vírus da Influenza A Subtipo H3N2 , Adjuvantes Imunológicos , Camundongos Endogâmicos BALB CRESUMO
Cells are compartmentalized by numerous membrane-bounded organelles and membraneless organelles (MLOs) to ensure temporal and spatial regulation of various biological processes. A number of MLOs, such as nucleoli, nuclear speckles and stress granules, exist as liquid droplets within the cells and arise from the condensation of proteins and RNAs via liquid-liquid phase separation (LLPS). By concentrating certain proteins and RNAs, MLOs accelerate biochemical reactions and protect cells during stress, and dysfunction of MLOs is associated with various pathological processes. With the development in this field, more and more relations between the MLOs and diseases have been described; however, these results have not been made available in a centralized resource. Herein, we build MloDisDB, a database which aims to gather the relations between MLOs and diseases from dispersed literature. In addition, the relations between LLPS and diseases were included as well. Currently, MloDisDB contains 771 curated entries from 607 publications; each entry in MloDisDB contains detailed information about the MLO, the disease and the functional factor in the relation. Furthermore, an efficient and user-friendly interface for users to search, browse and download all entries was provided. MloDisDB is the first comprehensive database of the relations between MLOs and diseases so far, and the database is freely accessible at http://mlodis.phasep.pro/.
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Citoplasma/metabolismo , Bases de Dados Factuais , Doença , Organelas/metabolismo , Proteínas/metabolismo , HumanosRESUMO
Sensing and resisting oxidative stress is critical for Vibrio cholerae to survive in either the aquatic environment or the gastrointestinal tract. Previous studies mainly focused on the mechanisms of oxidative stress response regulation that rely on enzymatic antioxidant systems, while functions of non-enzymatic antioxidants are rarely discussed in V. cholerae. For the first time, we investigated the role of hydrogen sulfide (H2S), the simplest thiol compound, in protecting V. cholerae against oxidative stress. We found that degradation of L-cysteine by putative cystathionine ß-synthase (CBS) is the major source of endogenous H2S in V. cholerae. Our results indicate that intracellular H2S level has a positive correlation with cbs expression, while the enhanced H2S production can render V. cholerae cells less susceptible to H2O2 in vitro. Using proteome analysis and real-time qPCR assay, we found that cbs expression could stimulate the expression of several enzymatic antioxidants, including reactive oxygen species (ROS) detoxifying enzymes SodB, KatG and AhpC, the DNA protective protein DPS and the protein redox regulator Trx1. Assays of ROS detoxification capacities revealed that CBS-derived H2S could promote catalase activity at the post-translational level, especially for KatB, which serves as an important way that endogenous H2S participates in H2O2 detoxification. The enhancement of catalase activity by H2S is achieved through facilitating the uptake of iron. Adult mice experiments showed that cbs mutant has colonization defect, while either complementation of cbs or exogenous supplement of N-Acetyl-L-Cysteine restores its fitness in the host environment. Herein, we proposed that V. cholerae regulates CBS-dependent H2S production for better survival and proliferation under ROS stress.
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Cistationina beta-Sintase/metabolismo , Interações Hospedeiro-Patógeno/fisiologia , Sulfeto de Hidrogênio/metabolismo , Cinesinas/metabolismo , Vibrio cholerae/metabolismo , Animais , Proteínas de Bactérias/metabolismo , Catalase/metabolismo , Cólera/metabolismo , Camundongos , Estresse Oxidativo/fisiologia , Vibrio cholerae/patogenicidadeRESUMO
Wideband microwave absorbers, especially those with high optical transparency, are significantly used in civil and military fields. This paper proposes an ultra-wideband optically transparent metamaterial absorber (MMA) with causal optimal thickness and high angular stability. Based on the equivalent circuits model of the MMA, a genetic algorithm is adopted to identify the best circuit parameters that can realize broadband microwave absorption. High transparent indium tin oxide and poly-methyl methacrylate are utilized to realize the absorber. Optimization and simulation results show that the designed MMA presents a high microwave absorption above 90%, covering a wide frequency of 2.05-15.5â GHz with an impressive FBW of 153.3%. The proposed MMA exhibits extraordinary angular stability. For TM polarization, it can still maintain a fractional bandwidth (FBW) over 114.5% at an incidence angle of 70° and over 142% at an incidence angle of 60°, while the FBW of both TE polarization and TM polarization exceeds 150% when the incidence angle is below 45°. Furthermore, the proposed absorber has the advantages of high transparency and polarization insensitiveness. A prototype of the proposed MMA is fabricated and experimentally tested. The measured results are in excellent agreement with the optimized design and the full-wave simulation results, demonstrating its excellent performance. Most significantly, the overall thickness of the absorber is 0.102 λ at the lowest working frequency and only 1.08 times the causality-dictated minimum sample thickness. The MMA proposed herein provides methods to achieve high compatibility with wideband microwave absorption, optical transparency, and wide-angle incidence, thus enabling a wide range of applications in stealth, electromagnetic pollution reduction, and electromagnetic compatible facilities.
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To explore new therapeutic options for cervical cancer, the inhibitory effect on cervical cancer of targeted CD133-loaded sPD1 gene microbubbles (MBs) combined with low-frequency ultrasound was studied and its mechanism was explored. We prepared microbubbles conjugated with anti-CD133 antibody to deliver the sPD1 gene and determined concentration, particle size, and potentials of MBs. In addition, we verified that CD133 targeted-MBs could specifically bind to U14 cervical cancer cells in vitro. A mouse model of subcutaneous xenograft cervical cancer was established and mice were divided into a control group, an non-targeted microbubble group, a CD133-MBs group, an sPD1-MBs group and a CD133/sPD1-MBs group. Compared with the control group, tumor growth was inhibited in each group, with the CD133/sPD1 group showing the strongest inhibitory effect after treatment. The tumor volume and weight inhibition rates in the CD133/sPD1-MBs group were 78.01% and 72.25% respectively, which were statistically different from the other groups (P < 0.05), and HE staining and TUNEL immunofluorescence showed necrosis and apoptosis in tumor tissue. Flow cytometry, lactate dehydrogenase, and indirect immunofluorescence experiments showed that T lymphocytes were activated and a large number of CD8-positive T cells infiltrated the tumor tissue after treatment, with the CD133/sPD1-MBs group showing the most prominent effects (P < 0.05). The combination of ultrasound with anti- CD133 antibody-conjugated microbubbles loaded with the sPD1 gene can inhibit the growth of cervical cancer, suggesting that the immunosuppressive microenvironment of the tumor is improved after treatment.
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Microbolhas , Neoplasias do Colo do Útero , Feminino , Humanos , Animais , Camundongos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/terapia , Ultrassonografia , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Artificial intelligence (AI) is a field of computer science that involves the development of programs designed to replicate human cognitive processes and the analysis of complex data. In dermatology, which is predominantly a visual-based diagnostic field, AI has become increasingly important in improving professional processes, particularly in the diagnosis of psoriasis. In this review, we summarized current AI applications in psoriasis: (i) diagnosis, including identification, classification, lesion segmentation, lesion severity and area scoring; (ii) treatment, including prediction treatment efficiency and prediction candidate drugs; (iii) management, including e-health and preventive medicine. Key challenges and future aspects of AI in psoriasis were also discussed, in hope of providing potential directions for future studies.
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Inteligência Artificial , Psoríase , Humanos , Aprendizado de Máquina , Psoríase/terapiaRESUMO
It is essential to identify the neuronal mechanisms of Alzheimer's Disease (AD)-associated neuropsychiatric symptoms, e.g., apathy, before improving the life quality of AD patients. Here, we focused on the nucleus accumbens (NAc), a critical brain region processing motivation, also known to display AD-associated pathological changes in human cases. We found that the synaptic calcium permeable (CP)-AMPA receptors (AMPARs), which are normally absent in the NAc, can be revealed by acute exposure to Aß oligomers (AßOs), and play a critical role in the emergence of synaptic loss and motivation deficits. Blockade of NAc CP-AMPARs can effectively prevent AßO-induced downsizing and pruning of spines and silencing of excitatory synaptic transmission. We conclude that AßO-triggered synaptic insertion of CP-AMPARs is a key mechanism mediating synaptic degeneration in AD, and preserving synaptic integrity may prevent or delay the onset of AD-associated psychiatric symptoms.
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Doença de Alzheimer , Receptores de AMPA , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Cálcio/metabolismo , Humanos , Motivação , Núcleo Accumbens/metabolismo , Receptores de AMPA/metabolismo , Receptores de Detecção de Cálcio , Sinapses/metabolismo , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol PropiônicoRESUMO
AIM: To investigate the relationship of the glycation gap (GGap) with all-cause and cardiovascular (CV) mortality in US adults. METHODS: This was a retrospective cohort study comprising 12 909 individual participant data from the National Health and Nutrition Examination Survey from 1999 to 2004 and their mortality data through 31 December 2019. Weighted Cox proportional hazards regression models and restricted cubic splines were used to investigate the associations between GGap and mortality. RESULTS: During a median follow-up of 16.8 years, 3528 deaths occurred, including 1140 CV deaths. The associations of GGap with risk of all-cause and CV mortality were U-shaped (both P for non-linearity < .001). Compared with individuals with a GGap of 0.09%-0.38% (61st-80th centiles), the multivariable-adjusted HRs and 95% CIs for individuals with a GGap less than -0.83% (first-fifth centiles) and individuals with a GGap greater than 0.90% (96th-100th centiles) were 1.36 (1.10, 1.69) and 1.21 (1.00, 1.45) for all-cause mortality, and 1.77 (1.16, 2.71) and 1.43 (1.04, 1.95) for CV mortality. The GGap value associated with the lowest risk of all-cause and CV mortality was 0.38% in the general population and 0.78% among individuals with diabetes. CONCLUSIONS: We found a U-shaped association between GGap and all-cause and CV mortality, with significant positive or negative GGap values associated with increased mortality risk, probably because of glycaemic variability and fructosamine-3-kinase activity.
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Doenças Cardiovasculares , Reação de Maillard , Humanos , Adulto , Estudos de Coortes , Inquéritos Nutricionais , Estudos RetrospectivosRESUMO
Herein, we report an unprecedented asymmetric guanidinium polyiodate, namely, C(NH2)3(I3O8)(HI3O8)(H2I2O6)(HIO3)4·3H2O (1). The title compound was obtained via the hybridization of polyiodate anions and planar π-conjugated C(NH2)3+; meanwhile, its strong second-harmonic-generation (SHG) response (2.1 × KDP, where KDP = KH2PO4) and wide band gap (3.89 eV) were mainly dominated by the synergy effect of the aforementioned structural units.
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Developing strategies to rational design noncentrosymmetric structure still attract much interest for their applications in nonlinear optical and piezoelectric materials. Two noncentrosymmetric (NCS) alkaline earth metal bismuth phosphates have been successfully achieved via partial replacement of Bi3+ with Ca2+ or Sr2+ ions. BiCa(H0.5PO4)2 (designated as CaBiPO) and BiSr(H0.5PO4)2 (designated as SrBiPO), together with their solid solution Bi(Sr1-xCax)(H0.5PO4)2 (0 < x ≤ 0.5), crystallize in the NCS space group C2. Both CaBiPO and SrBiPO exhibit ultraviolet nonlinear optical (NLO) properties, and their second-harmonic generation effects belong to type-II phase matching. Meanwhile, they could also act as photoluminescence hosts in which the Eu3+-doping samples SrBiPO:xEu3+ (x = 0.02-0.2) emit orange light. The effect of different radius ions on the derivative structures and the structure-NLO property relationship has also been discussed in detail.