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To better understand the migration behavior of plastic fragments in the environment, development of rapid non-destructive methods for in-situ identification and characterization of plastic fragments is necessary. However, most of the studies had focused only on colored plastic fragments, ignoring colorless plastic fragments and the effects of different environmental media (backgrounds), thus underestimating their abundance. To address this issue, the present study used near-infrared spectroscopy to compare the identification of colored and colorless plastic fragments based on partial least squares-discriminant analysis (PLS-DA), extreme gradient boost, support vector machine and random forest classifier. The effects of polymer color, type, thickness, and background on the plastic fragments classification were evaluated. PLS-DA presented the best and most stable outcome, with higher robustness and lower misclassification rate. All models frequently misinterpreted colorless plastic fragments and its background when the fragment thickness was less than 0.1mm. A two-stage modeling method, which first distinguishes the plastic types and then identifies colorless plastic fragments that had been misclassified as background, was proposed. The method presented an accuracy higher than 99% in different backgrounds. In summary, this study developed a novel method for rapid and synchronous identification of colored and colorless plastic fragments under complex environmental backgrounds.
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Monitoramento Ambiental , Aprendizado de Máquina , Plásticos , Espectroscopia de Luz Próxima ao Infravermelho , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Monitoramento Ambiental/métodos , Plásticos/análise , Análise dos Mínimos Quadrados , Análise Discriminante , CorRESUMO
Chemodynamic therapy (CDT), an emerging cancer treatment modality, uses multivalent metal elements to convert endogenous hydrogen peroxide (H2O2) to toxic hydroxyl radicals (â¢OH) via a Fenton or Fenton-like reaction, thus eliciting oxidative damage of cancer cells. However, the antitumor potency of CDT is largely limited by the high glutathione (GSH) concentration and low catalytic efficiency in the tumor sites. The combination of CDT with chemotherapy provides a promising strategy to overcome these limitations. In this work, to enhance antitumor potency by tumor-targeted and GSH depletion-amplified chemodynamic-chemo therapy, the hyaluronic acid (HA)/polydopamine (PDA)-decorated Fe2+-doped ZIF-8 nano-scaled metal-organic frameworks (FZ NMs) were fabricated and utilized to load doxorubicin (DOX), a chemotherapy drug, via hydrophobic, π-π stacking and charge interactions. The attained HA/PDA-covered DOX-carrying FZ NMs (HPDFZ NMs) promoted DOX and Fe2+ release in weakly acidic and GSH-rich milieu and exhibited acidity-activated â¢OH generation. Through efficient CD44-mediated endocytosis, the HPDFZ NMs internalized by CT26 cells not only prominently enhanced â¢OH accumulation by consuming GSH via PDA-mediated Michael addition combined with Fe2+/Fe3+ redox couple to cause mitochondria damage and lipid peroxidation, but also achieved intracellular DOX release, thus eliciting apoptosis and ferroptosis. Importantly, the HPDFZ NMs potently inhibited CT26 tumor growth in vivo at a low DOX dose and had good biosafety, thereby showing promising potential in tumor-specific treatment.
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Doxorrubicina , Glutationa , Ácido Hialurônico , Indóis , Ferro , Estruturas Metalorgânicas , Polímeros , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Doxorrubicina/farmacologia , Doxorrubicina/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Glutationa/metabolismo , Glutationa/química , Indóis/química , Indóis/farmacologia , Humanos , Animais , Polímeros/química , Polímeros/farmacologia , Camundongos , Ferro/química , Ferro/metabolismo , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Propriedades de Superfície , Portadores de Fármacos/química , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Tamanho da Partícula , Nanopartículas/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/químicaRESUMO
The global prevalence of the XBB lineage presents a formidable challenge posed by the recombinant SARS-CoV-2 virus. The understanding of SARS-CoV-2's recombination preference assumes utmost significance in predicting future recombinant variants and adequately preparing for subsequent pandemics. Thus, an urgent need arises to establish a comprehensive landscape concerning SARS-CoV-2 recombinants worldwide and elucidate their evolutionary mechanisms. However, the initial step, involving the detection of potential recombinants from a vast pool of over 10 million sequences, presents a significant obstacle. In this study, we present CovRecomb, a lightweight methodology specifically designed to effectively identify and dissect interlineage SARS-CoV-2 recombinants. Leveraging CovRecomb, we successfully detected 135,567 putative recombinants across the entirety of 14.5 million accessed SARS-CoV-2 genomes. These putative recombinants could be classified into 1451 distinct recombination events, of which 206 demonstrated transmission spanning multiple countries, continents, or globally. Hotspot regions were identified in six specific areas, with prominence observed in the latter halves of the N-terminal domain and receptor-binding domain within the spike (S) gene. Epidemiological investigations revealed extensive recombination events occurring among different SARS-CoV-2 (sub)lineages, independent of lineage prevalence frequencies.
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PURPOSE: This retrospective study was conducted to evaluate the effectiveness and safety of a new combination therapy of radiotherapy (RT), hepatic arterial infusion chemotherapy (HAIC), tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) for hepatocellular carcinoma (HCC) patients involving portal vein tumor thrombus (PVTT). METHODS: A total of 71 HCC patients with PVTT were retrospectively analyzed: 45 patients were treated by 'HAIC + TKI + ICI' therapy and 26 patients by the new combination therapy. The primary outcomes were overall survival (OS), progression-free survival (PFS), and cumulative survival rate. RESULTS: The PFS in the 'New combination therapy' group was longer than that in the 'HAIC + TKI + ICI' group (HR 0.459, 95%CI 0.253-0.832; P = 0.008). Meanwhile, the OS in the 'New combination therapy' group was also longer than that in the 'HAIC + TKI + ICI' group (HR 0.420, 95%CI 0.198-0.894; P = 0.024). Compared with 'HAIC + TKI + ICI' group patients, the 'New combination therapy' group patients had higher 1-year PFS rate and 1-year OS rate (P = 0.029; P = 0.015). There was no significant difference in the incidence of adverse events between the two groups. CONCLUSION: The new combination therapy was an effective and safe non-surgical treatment for HCC patients with PVTT and could be considered a preferred therapy option.
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In the context of oxygen evolution reaction (OER), the construction of high-valent transition metal sites to trigger the lattice oxygen oxidation mechanism is considered crucial for overcoming the performance limitations of traditional adsorbate evolution mechanism. However, the dynamic evolution of lattice oxygen during the reaction poses significant challenges for the stability of high-valent metal sites, particularly in high-current-density water-splitting systems. Here, we have successfully constructed Co-O-Fe catalytic active motifs in cobalt-iron Prussian blue analogs (CoFe-PBA) through oxygen plasma bombardment, effectively activating lattice oxygen reactivity while sustaining robust stability. Our spectroscopic and theoretical studies reveal that the Co-O-Fe bridged motifs enable a unique double-exchange interaction between Co and Fe atoms, promoting the formation of high-valent Co species as OER active centers while maintaining Fe in a low-valent state, preventing its dissolution. The resultant catalyst (CoFe-PBA-30) requires an overpotential of only 276 mV to achieve 1000 mA cm-2. Furthermore, the assembled alkaline exchange membrane electrolyzer using CoFe-PBA-30 as anode material achieves a high current density of 1 A cm-2 at 1.76 V and continuously operates for 250 hours with negligible degradation. This work provides significant insights for activating lattice oxygen redox without compromising structure stability in practical water electrolyzers.
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BACKGROUND: Histone deacetylase (HDAC), a kind of protease that regulates gene expression by modifying protein acetylation levels, is usually aberrantly activated in tumors. The approved pan-HDAC inhibitors (HDACi) have exhibited clinical benefits for hematopoietic malignancies. Recently, HDACis have emerged as enhancers of antitumor immunity. However, the effect of HDACs on the tumor immune microenvironment of lung adenocarcinoma (LUAD) and the underlying mechanism is largely unknown. METHODS: C57BL/6J and BALB/c nude mice with subcutaneous tumors were used for in vivo therapeutic effects and mechanistic investigations. Flow cytometry was used to measure the toxicity and exhaustion of human CD8+T cells after co-culturing with tumor cells and to determine the immunophenotype of tumor-infiltrating CD8+T cells. A series of experimental techniques, including RNA sequencing, quantitative PCR, western blot, ELISA, mass spectrometry, co-immunoprecipitation, chromatin immunoprecipitation and immunohistochemistry, were used to explore the underlying molecular mechanism. RESULTS: The pan-HDACi vorinostat (SAHA) promoted CD8+T cell infiltration and effector function in LUAD through suppressing FGL1, a newly identified major ligand of LAG-3. Mechanistically, SAHA inhibited the activity of HDAC1, an essential deacetylase of JAK1. This increased the acetylation level of JAK1 at lysine 1109, thus promoting its proteasomal degradation and subsequently reducing STAT3-driven FGL1 transcription. The combination regimen of SAHA and anti-LAG-3 therapy was further explored in an immunocompetent LUAD mouse model. Compared with those receiving control or single agent treatments, mice receiving combination therapy exhibited a lower tumor burden and superior CD8+T-cell-killing activity. CONCLUSIONS: Our results revealed a novel mechanism by which the HDACi SAHA potentiates CD8+T-cell-mediated antitumor activity through the HDAC1/JAK1/FGL1 axis, providing a rationale for the combined use of HDACis and immunotherapy.
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Adenocarcinoma de Pulmão , Histona Desacetilase 1 , Inibidores de Histona Desacetilases , Janus Quinase 1 , Neoplasias Pulmonares , Animais , Camundongos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Histona Desacetilase 1/metabolismo , Histona Desacetilase 1/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/imunologia , Janus Quinase 1/metabolismo , Vorinostat/farmacologia , Vorinostat/uso terapêutico , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Camundongos Nus , Camundongos Endogâmicos C57BL , FemininoRESUMO
The clinical efficacy of immunotherapy for hepatocellular carcinoma (HCC) is significantly limited by the low immunogenicity of the tumor. Recent studies have revealed that both pyroptosis and photothermal therapy can effectively induce tumor immunogenic cell death (ICD) in liver cancer cells. Polyphyllin II (PPII), the major active component of Rhizoma Paridis, has been demonstrated for the first time to induce pyroptosis in tumor cells, while IR780 is activated by 808 nm laser to transform light energy into heat energy, effectively eliminating tumor cells. However, both PPII and IR780 are afflicted with challenges such as low solubility and poor targeting, significantly limiting their utilization. To address these problems, the pyroptosis inducer PPII and photosensitizer IR780 were co-loaded in PLGA nanoparticles by precipitation method, and the aptamer AS1411 was modified on the surface of nanoparticles to construct the targeting nanoparticles (Apt/PPII/IR780-NPs). The nanoparticles exhibit a pH/NIR dual-response intelligent release feature, which realizes the targeted and controlled release of drugs in tumor site. Furthermore, it can rapidly release PPII to induce cell pyroptosis under laser irradiation, combining with IR780-based photothermal therapy exert a significant synergistic anti-tumor effect in vitro and in vivo. This process not only promotes maturation of DCs and activates effector T cells, thereby initiating adaptive immunity, but also generates enduring and effective immune memory. In addition, Apt/PPII/IR780-NPs significantly improved the Anti-PD-1 efficacy. In summary, chemo-photothermal therapy based on Apt/PPII/IR780-NPs can significantly enhance tumor ICD, which provides a promising new strategy for HCC immunotherapy.
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Carcinoma Hepatocelular , Imunoterapia , Indóis , Neoplasias Hepáticas , Nanopartículas , Terapia Fototérmica , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Piroptose , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Animais , Imunoterapia/métodos , Piroptose/efeitos dos fármacos , Camundongos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Humanos , Nanopartículas/química , Indóis/química , Indóis/farmacologia , Terapia Fototérmica/métodos , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Myocardial ischemia/reperfusion (I/R) injury stands as a primary contributor to ischemic heart disease. Sevoflurane (SEVO), a commonly used inhalation anesthetic, has been shown to exert a direct protective effect on ischemic heart injury. However, the specific mechanism by which it exerts the protective effect remains unclear. This study was designed to investigate the role of SEVO in myocardial I/R injury and its potential molecular mechanisms. METHODS: Blood samples were collected from patients with acute myocardial infarction (AMI) (n = 20) and healthy volunteers (n = 20). The human cardiomyocytes AC16 models of I/R injury were induced by hypoxia/reoxygenation. The mRNA expression levels of growth differentiation factor 11 (GDF11) in the cells and blood were determined by reverse transcription quantitative real-time PCR (RT-qPCR). The cell proliferation was detected by Cell Counting Kit-8 (CCK-8). Enzyme-Linked Immunosorbent Assay (ELISA) was utilized to detect the levels of inflammatory factors interleukin (IL)-8, IL-1ß and IL-6 in the cells. And biochemical assay kits were applied for the measurement of the activity of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) as well as the malondialdehyde (MDA) level in the cells. Moreover, western blot was employed to evaluate the levels of the p-serine-threonine protein kinase (AKT), AKT, and phosphatidylinositol 3-kinase (PI3K), protein expression in the cells. RESULTS: The GDF11 expression was decreased in the blood of AMI patients and cardiomyocytes induced by I/R (p < 0.01). Besides, 1% SEVO was presented to promote cardiomyocyte proliferation, inhibit apoptosis, oxidative stress and inflammation, and activate the PI3K/AKT signaling pathway through up-regulation of GDF11 expression (p < 0.01). CONCLUSION: SEVO promotes proliferation and inhibits inflammatory response, apoptosis, and oxidative stress of I/R-treated cardiomyocytes by elevating GDF11 expression, thereby reducing myocardial I/R injury. Notably, the mechanism underlying the alleviation of the I/R injury may involve the activation of PI3K/AKT signaling pathway.
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Fatores de Diferenciação de Crescimento , Traumatismo por Reperfusão Miocárdica , Miócitos Cardíacos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Sevoflurano , Transdução de Sinais , Humanos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Sevoflurano/farmacologia , Fatores de Diferenciação de Crescimento/metabolismo , Fatores de Diferenciação de Crescimento/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Masculino , Regulação para Cima/efeitos dos fármacos , Feminino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/sangue , Linhagem Celular , Estresse Oxidativo/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proteínas Morfogenéticas ÓsseasRESUMO
BACKGROUND: There is controversy about the relationship between type 1 diabetes and vitamin A (VA) levels in the body. Through meta-analysis, the results of related studies can be aggregated to more accurately estimate the relationship between type 1 diabetes mellitus (T1DM) patients and the level of VA in the body. METHODS: Our purpose is to review the study to investigate VA levels in type T1DM patients and to provide recommendations for future studies. Until January 2024, we searched the National Library of Medicine (PubMed), Cochrane Library, Embase Databases, Web of Sciences, Scopus, China National Knowledge Infrastructure (CNKI), VIP databases (VIP) and WAN FANG databases. After a systematic search, 8 case-control studies were included in our meta-analysis. In the process of data inclusion and extraction, the 2 reviewers selected literature independently of each other. In this study, RevMan5.3 software was used for meta-analysis. RESULTS: Eight case-control studies involving 689 participants were screened. The results after meta-analysis showed that there was a significant difference in serum VA between the patients with T1DM and the control group (standardized mean difference [SMD]â =â -0.82, 95% CI [-1.29, -0.36], Pâ <â .001, random effects model) with significant heterogeneity among these studies (Pâ <â .001, I2â =â 84%). Similarly, the difference in the high-performance liquid chromatography (HPLC) subgroup on serum VA (SMDâ =â -0.99, 95% CI [-1.60, -0.38], Pâ =â .002) as well as the difference in the countries of Asia and Europe subgroup on serum VA (SMDâ =â -0.60, 95% CI [-1.15, -0.05], Pâ =â .03; SMDâ =â -1.06, 95% CI [-1.88, -0.24], Pâ =â .01) were suggested to be statistically significant. A significant result was also observed in the National Diabetes Data Group (NDDG) criteria subgroup (SMDâ =â -0.48, 95% CI [-0.85, -0.12]). CONCLUSION: Serum VA levels seem to have decreased in T1DM patients. Further research is needed to strengthen this finding and clarify possible impact mechanisms.
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Diabetes Mellitus Tipo 1 , Vitamina A , Humanos , Diabetes Mellitus Tipo 1/sangue , Vitamina A/sangue , Estudos de Casos e Controles , Deficiência de Vitamina A/sangueRESUMO
Since the onset of COVID-19, respiratory diseases have emerged as a focal concern within the field of public health. This study aims to reveal the prevalence of acute respiratory infectious diseases by screening antipyretic, antiviral, and antibiotic biomarkers through wastewater analysis. Samples were collected over a seven-day period each year in 2022, 2023, and 2024 from a northern city in China, assessing the concentrations of two antipyretics (paracetamol and ibuprofen), one antiviral drug (oseltamivir), eleven antibiotics, and three pathogens (influenza A, influenza B, and Mycoplasma pneumoniae). The usage of most antipyretics and antibiotics was higher in 2023 and 2024, primarily due to the outbreak of COVID-19 in 2023 and the prevalence of influenza A, influenza B, and Mycoplasma pneumoniae in 2024. The prevalence assessed using antipyretics (2.68 %) and pathogens (2.70 %) demonstrated a high degree of consistency, whereas the prevalence estimated using antibiotics and antiviral drugs was only 0.53 % and 0.36 %, respectively. Antibiotics are generally used to treat a broad spectrum of bacterial infections rather than targeting a specific pathogen, so their presence in wastewater may not directly reflect the prevalence of a particular disease. In contrast, antipyretics and specific pathogens exhibit a stronger correlation, suggesting that they may serve as more reliable biomarkers than antiviral and antibiotic drugs. The research findings offer alternative biomarkers, such as antipyretics, aside from pathogens, for the assessment of acute respiratory infectious diseases.
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The system-bath entanglement theorem (SBET) was established in terms of linear response functions [Du et al., J. Chem. Phys. 152, 034102 (2020)] and generalized to correlation functions [Su et al., J. Chem. Phys. 160, 084104 (2024)] in our previous studies. This theorem connects the entangled system-bath properties to the local system and bare-bath ones. In this work, we extend the SBET to field-dressed conditions with multiple baths at different temperatures. As in reality, the external fields may interact with not only the system but also environments. The extended SBET facilitates, for example, photo-acoustic, photo-thermal, pump-probe related studies. The theorem under the field-free condition (multiple baths) and its counterpart in the classical limit is also presented.
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BACKGROUND: Chest compression at a rate of 100-120 compressions per minute (cpm) during cardiopulmonary resuscitation (CPR) is associated with the highest survival rates. Performing compressions at a faster rate may exhaust the rescuers. OBJECTIVES: To compare a new cue of 'two compressions per second' to the traditional cue of '100-120 compressions per minute' on compression rate in CPR training. METHODS: In this cluster-randomized study, students from two senior high schools were assigned into two groups. For the experimental group, the cue for the compression rate was 'two compressions per second'. For the control group, the cue was '100-120 cpm'. Except the different cues, all participants underwent the same standardized CPR training program. Verbal compression rate-related feedback was not obtained during practice. Quality indicators of chest compressions were recorded by a sensorized manikin. The primary outcome measure was mean compression rate at course conclusion. The secondary outcome measures were individual compression quality indicators at course conclusion and 3 months after training. RESULTS: We included 164 participants (85 participants, experimental group; 79 participants, control group). Both groups had similar characteristics. The experimental group had a significantly lower mean compression rate at course conclusion (144.3 ± 16.17 vs. 152.7 ± 18.38 cpm, p = 0.003) and at 3 months after training (p = 0.09). The two groups had similar mean percentage of adequate compression rate (≥ 100 cpm), mean compression depth, and mean percentage of complete recoil at course conclusion and 3 months after training. CONCLUSION: The new cue of 'two compressions per second' resulted in participants having a lower compression rate, although it still exceeded 120 cpm.
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Reanimação Cardiopulmonar , Manequins , Humanos , Reanimação Cardiopulmonar/educação , Reanimação Cardiopulmonar/métodos , Reanimação Cardiopulmonar/normas , Masculino , Feminino , Sinais (Psicologia) , Parada Cardíaca Extra-Hospitalar/terapia , Adolescente , Adulto Jovem , Fatores de Tempo , Massagem Cardíaca/métodos , Massagem Cardíaca/normasRESUMO
BACKGROUND: This study examines global trends in acquired immune deficiency syndrome (AIDS) incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2019, focusing on regional disparities in AIDS incidence, mortality, and DALYs across various levels of socio-demographic index (SDI). It also investigates variations in AIDS incidence, mortality, and DALYs across different age groups, and projects specific trends for the next 25 years. METHODS: Comprehensive data on AIDS from 1990 to 2019 in 204 countries and territories was obtained from a GBD study. This included information on AIDS incidence, mortality, DALYs, and age-standardized rates (ASRs). Projections for AIDS incidence and mortality over the next 25 years were generated using the Bayesian age-period-cohort model. RESULTS: From 1990 to 2019, the global incidence of HIV cases increased from 1,989,282 to 2,057,710, while the age-standardized incidence rate (ASIR) decreased from 37.59 to 25.24 with an estimated annual percentage change (EAPC) of -2.38. The ASIR exhibited an upward trend in high SDI and high-middle SDI regions, a stable trend in middle SDI regions, and a downward trend in low-middle SDI and low SDI regions. In regions with higher SDI, the ASIR was higher in males than in females, while the opposite was observed in lower SDI regions. Throughout 1990 to 2019, the age-standardized death rate (ASDR) and age-standardized DALY rate remained stable, with EAPCs of 0.24 and 0.08 respectively. Countries with the highest HIV burden affecting women and children under five years of age are primarily situated in lower SDI regions, particularly in sub-Saharan Africa. Projections indicate a significant continued decline in the age-standardized incidence and mortality rates of AIDS over the next 25 years, for both overall and by gender. CONCLUSIONS: The global ASIR decreased from 1990 to 2019. Higher incidence and death rates were observed in the lower SDI region, indicating a greater susceptibility to AIDS among women and < 15 years old. This underscores the urgent need for increased resources to combat AIDS in this region, with focused attention on protecting women and < 15 years old as priority groups. The AIDS epidemic remained severe in sub-Saharan Africa. Projections for the next 25 years indicate a substantial and ongoing decline in both age-standardized incidence and mortality rates.
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Síndrome da Imunodeficiência Adquirida , Anos de Vida Ajustados por Deficiência , Carga Global da Doença , Humanos , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/mortalidade , Carga Global da Doença/tendências , Masculino , Feminino , Incidência , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Anos de Vida Ajustados por Deficiência/tendências , Saúde Global/estatística & dados numéricos , Pré-Escolar , Previsões , Criança , Lactente , Idoso , Teorema de BayesRESUMO
Neutrophil extracellular traps (NETs) formation, namely NETosis, is implicated in antiphospholipid syndrome (APS)-related thrombosis in various autoimmune disorders such as systemic lupus erythematosus (SLE) and APS. Human parvovirus B19 (B19V) infection is closely associated with SLE and APS and causes various clinical manifestations such as blood disorders, joint pain, fever, pregnancy complications, and thrombosis. Additionally, B19V may trigger the production of autoantibodies, including those against nuclear and phospholipid components. Thus, exploring the connection between B19V, NETosis, and thrombosis is highly relevant. An in vitro NETosis model using differentiated HL-60 neutrophil-like cells (dHL-60) was employed to investigate the effect of B19V-VP1u IgG on NETs formation. A venous stenosis mouse model was used to test how B19V-VP1u IgG-mediated NETs affect thrombosis in vivo. The NETosis was observed in the dHL-60 cells treated with rabbit anti-B19V-VP1u IgG and was inhibited in the presence of either 8-Br-cAMP or CGS216800 but not GSK484. Significantly elevated reactive oxygen species (ROS), myeloperoxidase (MPO), and citrullinated histone (Cit-H3) levels were detected in the dHL60 treated with phorbol myristate acetate (PMA), human aPLs IgG and rabbit anti-B19V-VP1u IgG, respectively. Accordingly, a significantly larger thrombus was observed in a venous stenosis-induced thrombosis mouse model treated with PMA, human aPLs IgG, rabbit anti-B19V-VP1u IgG, and human anti-B19V-VP1u IgG, respectively, along with significantly increased amounts of Cit-H3-, MPO- and CRAMP-positive infiltrated neutrophils in the thrombin sections. This research highlights that anti-B19V-VP1u antibodies may enhance the formation of NETosis and thrombosis and implies that managing and treating B19V infection could lower the risk of thrombosis.
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Armadilhas Extracelulares , Neutrófilos , Parvovirus B19 Humano , Trombose , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/imunologia , Humanos , Animais , Camundongos , Parvovirus B19 Humano/imunologia , Trombose/virologia , Trombose/patologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Proteínas do Capsídeo/imunologia , Proteínas do Capsídeo/metabolismo , Células HL-60 , Espécies Reativas de Oxigênio/metabolismo , Modelos Animais de Doenças , Infecções por Parvoviridae/imunologia , Infecções por Parvoviridae/complicações , Infecções por Parvoviridae/virologia , Imunoglobulina G/imunologia , MasculinoRESUMO
Proton exchange membrane (PEM) electrolysis holds great promise for green hydrogen production, but suffering from high loading of platinum-group metals (PGM) for large-scale deployment. Anchoring PGM-based materials on supports can not only improve the atomic utilization of active sites but also enhance the intrinsic activity. However, in practical PEM electrolysis, it is still challenging to mediate hydrogen adsorption/desorption pathways with high coverage of hydrogen intermediates over catalyst surface. Here, operando generated stable palladium (Pd) hydride nanoclusters anchored on tungsten carbide (WCx) supports were constructed for hydrogen evolution in PEM electrolysis. Under PEM operando conditions, hydrogen intercalation induces formation of Pd hydrides (PdHx) featuring weakened hydrogen binding energy (HBE), thus triggering reverse hydrogen spillover from WCx (strong HBE) supports to PdHx sites, which have been evidenced by operando characterizations, electrochemical results and theoretical studies. This PdHx-WCx material can be directly utilized as cathode electrocatalysts in PEM electrolysis with ultralow Pd loading of 0.022â mg cm-2, delivering the current density of 1â A cm-2 at the cell voltage of ~1.66â V and continuously running for 200â hours without obvious degradation. This innovative strategy via tuning the operando characteristics to mediate reverse hydrogen spillover provide new insights for designing high-performance supported PGM-based electrocatalysts.
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Due to the heterogeneity of the tumor microenvironment, the clinical efficacy of tumor treatment is not satisfied, highlighting the necessity for new strategies to tackle this issue. To effectively treat breast tumors by tumor-targeted chemo/chemodynamic therapy, herein, the Fe3+-rich MIL-88B nanobullets (MNs) covered with hyaluronic acid (HA) were fabricated as vehicles of zoledronic acid (ZA). The attained ZA@HMNs showed a high ZA payload (ca 29.6 %), outstanding colloidal stability in the serum-containing milieu, and accelerated ZA as well as Fe3+ release under weakly acidic and glutathione (GSH)-rich conditions. Also, the ZA@HMNs consumed GSH by GSH-mediated Fe3+ reduction and converted H2O2 into OH via Fenton or Fenton-like reaction with pH reduction. After being internalized by 4T1 cells upon CD44-mediated endocytosis, the ZA@HMNs depleted intracellular GSH and degraded H2O2 into OH, thus eliciting lipid peroxidation and mitochondria damage to suppress cell proliferation. Also, the ZA@HMNs remarkably killed macrophage-like RAW 264.7 cells. Importantly, the in vivo studies and ki67 and GPX4 staining of tumor sections demonstrated that the ZA@HMNs efficiently accumulated in 4T1 tumors to hinder tumor growth via ZA chemotherapy combined with OH-mediated ferroptosis. This work presents a practicable strategy to fabricate ZA@HMNs for breast tumor-targeted chemo/chemodynamic therapy with potential clinical translation.
Assuntos
Neoplasias da Mama , Ácido Hialurônico , Nanopartículas , Ácido Zoledrônico , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Animais , Camundongos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Ácido Zoledrônico/farmacologia , Ácido Zoledrônico/química , Nanopartículas/química , Células RAW 264.7 , Linhagem Celular Tumoral , Humanos , Compostos Férricos/química , Compostos Férricos/farmacologia , Proliferação de Células/efeitos dos fármacos , Peróxido de Hidrogênio/química , Glutationa/metabolismoRESUMO
Accelerating perovskite solid solution discovery and sustainable synthesis is crucial for addressing challenges in wireless communication and biosensors. However, the vast array of chemical compositions and their dependence on factors such as crystal structure, and sintering temperature require time-consuming manual processes. To overcome these constraints, we introduce an automated materials discovery approach encompassing machine learning (ML) assisted material screening, robotic synthesis, and high-throughput characterization. Our proposed platform for rapid sintering and dielectric analysis streamlines the characterization of perovskites and the discovery of disordered materials. The setup has been successfully validated, demonstrating processing materials within minutes, in stark contrast to conventional procedures that can take hours or days. Following setup validation with established samples, we showcase synthesizing single-phase solid solutions within the barium family, such as (BaxSr1-x)CeO3, identified through ML-guided chemistry.
RESUMO
Inefficient active site utilization of oxygen evolution reaction (OER) catalysts have limited the energy efficiency of proton exchange membrane (PEM) water electrolysis. Here, an atomic grid structure is demonstrated composed of high-density Ir sites (≈10 atoms per nm2) on reactive MnO2-x support which mediates oxygen coverage-enhanced OER process. Experimental characterizations verify the low-valent Mn species with decreased oxygen coordination in MnO2-x exert a pivotal impact in the enriched oxygen coverage on the surface during OER process, and the distributed Ir atomic grids, where highly electrophilic IrâO(II-δ)- bonds proceed rapidly, render intense nucleophilic attack of oxygen radicals. Thereby, this metal-support cooperation achieves ultra-low overpotentials of 166 mV at 10 mA cm-2 and 283 mV at 500 mA cm-2, together with a striking mass activity which is 380 times higher than commercial IrO2 at 1.53 V. Moreover, its high OER performance also markedly surpasses the commercial Ir black catalyst in PEM electrolyzers with long-term stability.
RESUMO
Methods used to monitor anaerobic digestion (AD) indicators are commonly based on wet chemical analyses, which consume time and materials. In addition, physical disturbances, such as floating granules (FGs), must be monitored manually. In this study, we present an eco-friendly, high-throughput methodology that uses near-infrared hyperspectral imaging (NIR-HSI) to build a machine-learning model for characterizing the chemical composition of the digestate and a target detection algorithm for identifying FGs. A total of 732 digestate samples were used to develop and validate a model for calculating total nitrogen (TN), total organic carbon (TOC), total ammonia nitrogen (TAN), and chemical oxygen demand (COD), which are the chemical indicators of responses to disturbances in the AD process. Among these parameters, good model performance was obtained using the dried digestates data set, where the coefficient of determination (R2test) and the root-mean-square error (RMSEtest) were 0.82 and 1090 mg/L for TOC, and 0.86 and 690 mg/L for TN, respectively. Furthermore, the unique spectral features of the FGs in reactors with a lipid-rich substrate meant that they could also be identified by the HSI system. Based on these findings, developing NIR-HSI solutions to monitor the digestate properties in AD plants has great potential for industrial application.
Assuntos
Imageamento Hiperespectral , Anaerobiose , Imageamento Hiperespectral/métodos , Nitrogênio , Análise da Demanda Biológica de OxigênioRESUMO
Semiaquilegia danxiashanensis is currently known only from the type locality, Danxia Mountain, characterized by its spectacular red sandstone cliffscape. In this study, we assembled the complete chloroplast genome sequence of S. danxiashanensis and inferred its phylogenetic relationships. Total length of the chloroplast genome was 160,548 bp, with an overall GC content of 39%. The chloroplast genome had typical quadripartite structure and contained one LSC region (89,882 bp) and one SSC region (17,386 bp), which were separated by two IRs regions (26,640 bp, respectively). It comprised 133 genes, including 84 protein coding genes, 41 tRNA genes and eight rRNA genes. The maximum likelihood phylogenetic analysis indicated that S. danxiashanensis was sister to S. adoxoides; meanwhile, Semiaquilegia was closely related to both Urophysa and Aquilegia in Ranunculaceae. This study sheds light on the evolutionary history of Semiaquilegia and provides preliminary data for future comparative analysis of chloroplast genomes.