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We report an H-bond donor controlled diastereoselective switchable intramolecular aza-Henry reaction of ketimines derived from α-ketoesters and 2-(2-nitroethyl)anilines, allowing facile access to chiral tetrahydroquinolines bearing an aza-quaternary carbon stereocenter, which are privileged scaffold for medicinal researches. While newly developed cinchona alkaloid derived phosphoramide-bearing quaternary ammonium salt C2 selectively give cis-adducts in up to 20:1 dr and 99% ee, the corresponding urea-bearing analogue C8 preferentially give trans-adducts in up to 20:1 dr and 99% ee.
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Global climate change is leading to rapid and drastic shifts in environmental conditions, posing threats to biodiversity and nearly all life forms worldwide. Forest trees serve as foundational components of terrestrial ecosystems and play a crucial and leading role in combating and mitigating the adverse effects of extreme climate events, despite their own vulnerability to these threats. Therefore, understanding and monitoring how natural forests respond to rapid climate change is a key priority for biodiversity conservation. The recent progress of evolutionary genomics, primarily driven by cutting-edge multi-omics technologies, offer powerful new tools to address several key issues. These include the precise delineation of species and evolutionary units, inference of past evolutionary histories and demographic fluctuations, identification of environmental adaptive variants, and measurement of genetic load levels. As the urgency to deal with more extreme environmental stresses grows, understanding the genomics of evolutionary history, local adaptation, future responses to climate change, and the conservation and restoration of natural forest trees will be critical for research at the nexus of global change, population genomics and conservation biology. In this review, we explore the application of evolutionary genomics to assess the effects of global climate change using multi-omics approaches and discuss the outlook for breeding climate-adapted trees.
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In this paper, we introduced a novel phase-transfer strategy tailored for the efficient batch detection of ascorbic acid in vitamin C tablets. This method entailed the reaction between ascorbic acid and an excess of potassium permanganate. Subsequent reaction of the residual potassium permanganate with sodium oxalate in an acidic medium led to the generation of carbon dioxide. The quantification of the produced carbon dioxide was achieved using headspace GC, enabling the indirect measurement of ascorbic acid. The obtained findings revealed that the headspace method exhibited satisfied precision with a relative standard deviation of less than 2.11% and high sensitivity with a limit of quantitation of 0.27 µmol. These results firmly establish the reliability of this innovative approach for determining ascorbic acid. In addition, the highly automated feature of headspace method significantly enhances the efficiency of batch sample detection and reduces the errors caused by human operation. Thus, the adoption of the transformed phase strategy has demonstrated its effectiveness in assessing ascorbic acid, especially for large-scale sample analysis in industrial applications, owing to its efficiency, precision, and sensitivity.
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OBJECTIVE: The reported impact of age on the effectiveness of emerging immunotherapies in patients with advanced non-small cell lung cancer (NSCLC) has been inconsistent in clinical trials, largely due to an underrepresentation of older individuals. This meta-analysis aimed to evaluate the efficacy of immune checkpoint inhibitor (ICI) in older patients with NSCLC. MATERIALS AND METHODS: The literature up to April 2024 was reviewed to identify articles meeting the criteria for inclusion. Hazard ratios (HRs) for overall survival (OS) across various age groups were examined. The ratio of HR (RHR) was computed and combined for each study. RESULTS: A preliminary search identified 118 articles, with 13 being phase II or III randomized clinical trials comparing the efficacy of nivolumab, avelumab, ipilimumab, pembrolizumab, atezolizumab, and chemotherapy with or without antiangiogenic therapy. The analysis revealed that the HR for OS was 0.75 (95 % CI: 0.70-0.80, P=0.080) in patients aged under 75 years and 0.87 (95 % CI: 0.74-1.01, P=0.913) in patients aged 75 years and older. The combined RHR for patients aged 75 years and above versus those aged under 75 years was 1.14 (95 % CI: 0.97-1.34, P=0.697). There was no significant difference in OS benefit between patients over 75 years and younger patients (P=0.105). Subgroup analyses indicated that the benefit of OS was consistent across all subgroups and age groups. CONCLUSIONS: Our investigation found no significant differences in the efficacy of immunotherapy for patients with NSCLC aged 75 years and older compared to those under 75 years old. This suggests that the efficacy of immunotherapy against NSCLC is consistent across age groups.
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Plastic nanoparticles are extensively used in various products, leading to inevitable pollution in soil. Understanding their transport in soils where various organic substances exist is crucial. This study examined the impact of low-molecular-weight organic acids (LMWOAs) on the transport of polystyrene nanoplastics (PS-NPs) through saturated quartz sand. The experiments involved three dibasic acids-malonic acid (MA1), malic acid (MA2) and tartaric acid (TA) - and four monobasic acids- formic acid (FA), acetic acid (AA), propanoic acid (PA) and glycolic acid (GA) -under different pH levels (4.0, 5.5, 7.0) and in the presence of cations (Na+, Ca2+). The results demonstrated that in the presence of Na+, dibasic acids significantly enhanced PS-NPs transport, with TA being the most effective, followed by MA2 and MA1. This enhancement is attributed to the adsorption of LMWOAs onto the nanoparticles and sand, creating a more negative ζ-potential, which increases the electrostatic repulsion and decreases the PS-NPs deposition, thereby facilitating the transport. Applying the Derjaguin-Landau-Verwey-Overbeek theory, higher pH levels increased the energy barrier and secondary energy minimum, decreasing PS-NPs deposition. Moreover, dibasic acids significantly enhanced the hydrophilicity of PS-NPs. Conversely, monobasic acids, except for GA, slightly reduced the hydrophilicity of PS-NPs, as indicated by a small increase in the water contact angle, hereby minimally affecting PS-NPs transport. As for GA, although it is a monobasic acid, the additional -OH group in its molecular structure promoted PS-NPs transport, similar to dibasic acids. For example, GA also significantly enhanced the hydrophilicity of PS-NPs. In the presence of Ca2+, the enhancement of PS-NPs transport by LMWOAs was comparable to that with Na+, primarily due to the complex-forming and bridging effects of Ca2+ with the organic acids and PS-NPs. These findings provide important insights into predicting and analyzing the transport behaviors of PS-NPs.
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Harnessing the photoinduced phase transitions in organic crystals, especially the changes in shape and structure across various dimensions, offers a fascinating avenue for exact spatiotemporal control, which is crucial for developing future smart devices. In our study, we report a new photoactive molecular crystal made from (E)-2-(3-phenyl-allylidene)malonate ((E)-PADM). When exposed to ultraviolet (UV) light at 365 nm, this compound experiences an E-to-Z photoisomerization in liquid solution and a crystal-to-liquid phase transition in solid crystals. Remarkably, nanoscopic crystalline rods boost their melting rate and degree compared to bulk crystals, indicating that miniaturization enhances the photoinduced melting effect. Our results demonstrate a simple approach to rapidly drive molecular crystals into liquids via photochemical reactions and phase transitions.
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Habitual daytime napping is a common behavioral and lifestyle practice in particular countries and is often considered part of a normal daily routine. However, recent evidence suggests that the health effects of habitual daytime napping are controversial. We systematically searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to March 9, 2024, to synthesize cohort studies of napping and health outcome risk. A total of 44 cohort studies with 1,864,274 subjects aged 20-86 years (mean age 56.4 years) were included. Overall, habitual napping increased the risk of several adverse health outcomes, including all-cause mortality, cardiovascular disease, metabolic disease, and cancer, and decreased the risk of cognitive impairment and sarcopenia. Individuals with a napping duration of 30 min or longer exhibited a higher risk of all-cause mortality, cardiovascular disease, and metabolic disease, whereas those with napping durations less than 30 min had no significant risks. No significant differences in napping and health risks were observed for napping frequency, percentage of nappers, sample size, sex, age, body mass index, follow-up years, or comorbidity status. These findings indicate that individuals with a long napping duration should consider shortening their daily nap duration to 30 min or less.
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The concept of a healthy lifestyle is receiving increasing attention. This study sought to identify an optimal healthy lifestyle profile associated with sleep health in general population of China. An online cross-sectional survey was conducted from June to July 2022. Six healthy lifestyle factors were assessed: healthy diet, regular physical exercise, never smoking, never drinking alcohol, low sedentary behavior, and normal weight. Participants were categorized into the healthy lifestyle (5-6 factors), average (3-4 factors), and unhealthy lifestyle groups (0-2 factors). The study's primary outcome was sleep health, which included sleep quality, duration, pattern, and the presence of any sleep disorder or disturbance, including insomnia, excessive daytime sleepiness, obstructive apnea syndrome, and narcolepsy. Multivariable logistic regression analysis was applied to explore lifestyles associated with the selected sleep health outcomes. 41,061 individuals were included, forming 18.8% healthy, 63.8% average, and 17.4% unhealthy lifestyle groups. After adjusting for covariates, participants with healthy lifestyle were associated with a higher likelihood of good sleep quality (OR = 1.56, 95% CI = 1.46-1.68), normal sleep duration (OR = 1.60, 95% CI = 1.49-1.72), healthy sleep pattern (OR = 2.15, 95% CI = 2.00-2.31), and lower risks of insomnia (OR = 0.66, 95% CI = 0.61-0.71), excessive daytime sleepiness (OR = 0.66, 95% CI = 0.60-0.73), and obstructive apnea syndrome (OR = 0.40, 95% CI = 0.37-0.43), but not narcolepsy (OR = 0.92, 95% CI = 0.83-1.03), compared to those with unhealthy lifestyle. This large cross-sectional study is the first to our knowledge to quantify the associations of a healthy lifestyle with specific aspects of sleep health. The findings offer support for efforts to improve sleep health by modulating lifestyle.
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Estilo de Vida Saudável , Humanos , Masculino , Estudos Transversais , Feminino , China/epidemiologia , Pessoa de Meia-Idade , Adulto , Estilo de Vida , Qualidade do Sono , Transtornos do Sono-Vigília/epidemiologia , Idoso , Exercício Físico , Adulto Jovem , AdolescenteRESUMO
Background: Dihydroartemisinin (DHA), a derivative of Artemisia annua, has been shown to possess anti-inflammatory properties. Besides, Yes-associated protein 1 (YAP1) plays a crucial role in maintaining liver homeostasis. Methods: This study used Yap1 Flox/Flox, Albumin-Cre mice with hepatocyte-specific Yap1 knockout (referred to as Yap1 LKO) and their control mice (Yap1 Flox/Flox, referred to as Yap1 Flox). The effect of Yap1 on lipid metabolism homeostasis was investigated through non-targeted metabolomic analysis of mouse liver. Subsequently, DHA was administered to Yap1 LKO mice to assess its potential as a treatment. Liver pathology was evaluated via H&E staining, and the levels of AST, ALT, and TG were quantified using biochemical assays. The contents of arachidonic acid (AA), prostaglandin E1 (PGE1), and leukotrienes (LT) in the liver were measured using ELISA, while the protein expressions of PLIN2, 5-lipoxygenase (5-LOX), and cyclooxygenase-2 (COX-2) were analyzed through IHC staining. Results: Hepatocyte-specific Yap1 knockout activated the AA metabolic pathway, resulting in increased elevated levels of AA, PGE1, and LT levels, along with inflammatory cytokine infiltration. DHA mitigated the elevation of metabolites such as PGE1 and LT caused by the AA metabolic pathway activation by down-regulating the levels of COX-2 and 5-LOX in the liver of Yap1 LKO mice. Moreover, it alleviated the accumulation of lipid vacuoles and reduced triglyceride (TG) and perilipin-2 (PLIN2) levels in the liver of Yap1 LKO mice. Conclusions: Excessively low YAP1 expression induces liver inflammation and disturbances in lipid metabolism, whereas DHA modulated AA metabolism and mitigated liver inflammation by inhibiting the activation of 5-LOX and COX-2.
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The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) has been clinically shown to effectively slow down the progression of chronic kidney disease (CKD) and has demonstrated significant anti-fibrosis effects in experimental CKD model. However, the specific active ingredients and underlying mechanism are still unclear. The active ingredients of A&P were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-HR-MS). A mouse model of CKD was constructed by 5/6 nephrectomy. Renal function was assessed by creatinine and urea nitrogen. Real-time PCR and Western Blot were performed to detect the mRNA and protein changes in kidney and cells. An in vitro fibrotic cell model was constructed by TGF-ß induction in TCMK-1 cells. The results showed that thirteen active ingredients of A&P were identified by UPLC-HR-MS, nine of which were identified by analysis with standards, among which the relative percentage of NOB was high. We found that NOB treatment significantly improved renal function, pathological damage and reduced the expression level of fibrotic factors in CKD mice. The results also demonstrated that Lgals1 was overexpressed in the interstitial kidney of CKD mice, and NOB treatment significantly reduced its expression level, while inhibiting PI3K and AKT phosphorylation. Interestingly, overexpression of Lgals1 significantly increased fibrosis in TCMK1 cells and upregulated the activity of PI3K and AKT, which were strongly inhibited by NOB treatment. NOB is one of the main active components of A&P. The molecular mechanism by which NOB ameliorates renal fibrosis in CKD may be through the inhibition of Lgals1/PI3K/AKT signaling pathway.
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Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Fibrose , Flavonas , Rim , Panax notoginseng , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Insuficiência Renal Crônica , Transdução de Sinais , Animais , Camundongos , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Panax notoginseng/química , Flavonas/farmacologia , Flavonas/uso terapêutico , Rim/patologia , Rim/efeitos dos fármacos , Astrágalo/química , Camundongos Endogâmicos C57BL , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta PressãoRESUMO
Alzheimer's disease (AD) is a severe threat to human health and one of the three major causes of human death.Double-stranded RNA-dependent protein kinase (PKR) is an interferon-induced protein kinase involved in innate immunity.In the occurrence and development of AD,PKR is upregulated and continuously activated.On the one hand,the activation of PKR triggers an integrated stress response in brain cells.On the other hand,it indirectly upregulates the expression of ß-site amyloid precursor protein cleaving enzyme 1 and facilitates the accumulation of amyloid-ß protein (Aß),which could activate PKR activator to further activate PKR,thus forming a sustained accumulation cycle of Aß.In addition,PKR can promote Tau phosphorylation,thereby reducing microtubule stability in nerve cells.Inflammation in brain tissue,neurotoxicity resulted from Aß accumulation,and disruption of microtubule stability led to the progression of AD and the declines of memory and cognitive function.Therefore,PKR is a key molecule in the development and progression of AD.Effective PKR detection can aid in the diagnosis and prediction of AD progression and provide opportunities for clinical treatment.The inhibitors targeting PKR are expected to control the activity of PKR,thereby controlling the progression of AD.Therefore,PKR could be a target for the development of therapeutic drugs for AD.
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Doença de Alzheimer , eIF-2 Quinase , Doença de Alzheimer/metabolismo , Humanos , eIF-2 Quinase/metabolismo , Peptídeos beta-Amiloides/metabolismo , Proteínas tau/metabolismo , Fosforilação , Encéfalo/metabolismo , Precursor de Proteína beta-Amiloide/metabolismoRESUMO
In aquatic ecosystems with low nutrient levels, organic aggregates (OAs) act as nutrient hotspots, hosting a diverse range of microbial species compared to those in the water column. Lake eutrophication, marked by intensified and prolonged cyanobacterial blooms, significantly impacts material and energy cycling processes, potentially altering the ecological traits of both free-living (FL) and particle-attached (PA) bacteria. However, the extent to which observed patterns of FL and PA bacterial diversity, community assembly, and stability extend to hypereutrophic lakes remains understudied. To address this gap, we investigated bacterial diversity, composition, assembly processes, and stability within hypereutrophic Lake Xingyun. Our results revealed that FL bacterial communities exhibited higher α-diversity than PA counterparts, coupled with discernible taxonomic compositions. Both bacterial communities showed distinct seasonality, influenced by cyanobacterial bloom intensity. Environmental factors accounted for 71.1% and 54.2% of the variation among FL and PA bacteria, respectively. The assembly of the PA bacterial community was predominantly stochastic, while FL assembly was more deterministic. The FL network demonstrated greater stability, complexity, and negative interactions, indicative of competitive relationships, while the PA network showed a prevalence of positive correlations, suggesting mutualistic interactions. Importantly, these findings differ from observations in oligotrophic, mesotrophic, and eutrophic lakes. Overall, this research provides valuable insights into the interplay among bacterial fractions, enhancing our understanding of nutrient status and cyanobacterial blooms in shaping bacterial communities.
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Bactérias , Biodiversidade , Cianobactérias , Eutrofização , Lagos , Microbiota , Lagos/microbiologia , Cianobactérias/genética , Cianobactérias/classificação , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , RNA Ribossômico 16S/genética , Estações do Ano , Ecossistema , ChinaRESUMO
We report a case of a 72-year-old female who presented with fever, abdominal pain, and diarrhea accompanied by leukopenia, anemia, and thrombocytopenia. The diagnosis of acute aplastic anemia was confirmed through bone marrow aspiration. Treatment included glucocorticoids, immunoglobulin therapy, and plasma exchange. Subsequently, the patient developed gastrointestinal bleeding and abdominal Computed Tomography (CT) revealed perforation of the transverse colon. Pathological examination of surgically removed diseased tissue confirmed mucor infection. Despite receiving antifungal therapy with amphotericin B, the patient's condition deteriorated due to the sepsis progression. Mucor infection in immunocompromised patients should be vigilant, and early diagnosis may help improve prognosis.
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Systemic administration of adeno-associated virus (AAV) vectors for spinal cord gene therapy has challenges including toxicity at high doses and pre-existing immunity that reduces efficacy. Intrathecal (IT) delivery of AAV vectors into cerebral spinal fluid can avoid many issues, although distribution of the vector throughout the spinal cord is limited, and vector entry to the periphery sometimes initiates hepatotoxicity. Here we performed biopanning in non-human primates (NHPs) with an IT injected AAV9 peptide display library. We identified top candidates by sequencing inserts of AAV DNA isolated from whole tissue, nuclei, or nuclei from transgene-expressing cells. These barcoded candidates were pooled with AAV9 and compared for biodistribution and transgene expression in spinal cord and liver of IT injected NHPs. Most candidates displayed increased retention in spinal cord compared with AAV9. Greater spread from the lumbar to the thoracic and cervical regions was observed for several capsids. Furthermore, several capsids displayed decreased biodistribution to the liver compared with AAV9, providing a high on-target/low off-target biodistribution. Finally, we tested top candidates in human spinal cord organoids and found them to outperform AAV9 in efficiency of transgene expression in neurons and astrocytes. These capsids have potential to serve as leading-edge delivery vehicles for spinal cord-directed gene therapies.
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Dependovirus , Terapia Genética , Vetores Genéticos , Medula Espinal , Dependovirus/genética , Animais , Medula Espinal/metabolismo , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Humanos , Terapia Genética/métodos , Transgenes , Técnicas de Transferência de Genes , Capsídeo/metabolismo , Distribuição Tecidual , Injeções Espinhais , Transdução Genética , Macaca mulatta , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismoRESUMO
Oligotrophic deep-water lakes are unique and sensitive ecosystems with limited nutrient availability. Understanding bacterial communities within these lakes is crucial for assessing ecosystem health, biogeochemical cycling, and responses to environmental changes. In this study, we investigated the seasonal and vertical dynamics of both free-living (FL) and particle-attached (PA) bacteria in Lake Fuxian, a typical oligotrophic deep freshwater lake in southeast China. Our findings revealed distinct seasonal and vertical dynamics of FL and PA bacterial communities, driven by similar physiochemical environmental factors. PA bacteria exhibited higher α- and ß-diversity and were enriched with Proteobacteria, Cyanobacteria, Firmicutes, Patescibacteria, Planctomycetota, and Verrucomicrobiota, while FL bacteria were enriched with Actinobacteria and Bacteroidota. FL bacteria showed enrichment in putative functions related to chemoheterotrophy and aerobic anoxygenic photosynthesis, whereas the PA fraction was enriched with intracellular parasites (mainly contributed by Rickettsiales, Chlamydiales, and Legionellales) and nitrogen metabolism functions. Deterministic processes predominantly shaped the assembly of both FL and PA bacterial communities, with stochastic processes playing a greater role in the FL fraction. Network analysis revealed extensive species interactions, with a higher proportion of positively correlated edges in the PA network, indicating mutualistic or cooperative interactions. Cyanobium, Comamonadaceae, and Roseomonas were identified as keystone taxa in the PA network, underscoring potential cooperation between autotrophic and heterotrophic bacteria in organic particle microhabitats. Overall, the disparities in bacterial diversity, community composition, putative function, and network characteristics between FL and PA fractions highlight their adaptation to distinct ecological niches within these unique lake ecosystems.IMPORTANCEUnderstanding the diversity of microbial communities, their assembly mechanisms, and their responses to environmental changes is fundamental to the study of aquatic microbial ecology. Oligotrophic deep-water lakes are fragile ecosystems with limited nutrient resources, rendering them highly susceptible to environmental fluctuations. Examining different bacterial types within these lakes offers valuable insights into the intricate mechanisms governing community dynamics and adaptation strategies across various scales. In our investigation of oligotrophic deep freshwater Lake Fuxian in China, we explored the seasonal and vertical dynamics of two bacterial types: free-living (FL) and particle-attached (PA). Our findings unveiled distinct patterns in the diversity, composition, and putative functions of these bacteria, all shaped by environmental factors. Understanding these subtleties provides insight into bacterial interactions, thereby influencing the overall ecosystem functioning. Ultimately, our research illuminates the adaptation and roles of FL and PA bacteria within these unique lake environments, contributing significantly to our broader comprehension of ecosystem stability and health.
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Bactérias , Lagos , Microbiota , Lagos/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , China , Ecossistema , Estações do AnoRESUMO
Background: Thyroid cancer, a leading type of endocrine cancer, accounts for 3-4% of all cancer diagnoses. This study aims to analyse and compare thyroid cancer patterns in China and the Group twenty (G20) countries, and predict these trend for the upcoming two decades. Methods: This observational longitudinal study utilised data from the Global Burden of Disease (GBD) study 2019. We used metrics including incidence, mortality, mortality-incidence ratio (MIR), age-standardised rate (ASR) and average annual percent change (AAPC) to examine thyroid cancer trends. Joinpoint regression analysis was used to identify periods manifesting notable changes. The association between sociodemographic index (SDI) and AAPC were investigated. The autoregressive integrated moving average (ARIMA) model was used to predict thyroid cancer trends from 2020 to 2040. Results: From 1990 to 2019, thyroid cancer incidence cases in China increased by 289.6%, with a higher AAPC of age-standardised incidence rate (ASIR) in men. Contrastingly, the G20 demonstrated a smaller increase, particularly among women over 50. Despite the overall age-standardised mortality rate (ASMR) was higher in the G20, the increase in mortality was less pronounced than in China. Age-standardised incidence rate increased across all age groups and genders, with a notable rise among men aged 15-49. ASMR decreased in specific age groups and genders, especially among women. Conversely, the ASMR significantly increased in group aged over 70. The MIR exhibited a declining trend, but this decrease was less noticeable in men and the group aged over 70. Joinpoint analysis pinpointed significant shifts in overall ASIR and ASMR, with the most pronounced increase in ASIR during 2003-2011 in China and 2003-2010 in the G20. Predictions suggested a continual ASIR uptrend, especially in the 50-69 age group, coupled with a predicted ASMR downturn among the elderly by 2040. Moreover, the proportion of thyroid cancer deaths attributable to high body mass index (BMI) escalated, with significant increase in Saudi Arabia and a rise to 7.4% in China in 2019. Conclusions: Thyroid cancer cases in incidence and mortality are escalating in both China and the G20. The increasing trend may be attributed to factors beyond overdiagnosis, including environmental and genetic factors. These findings emphasise the necessity for augmenting prevention, control, and treatment strategies. They also highlight the significance of international collaboration in addressing the global challenge posed by thyroid cancer.
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Neoplasias da Glândula Tireoide , Humanos , China/epidemiologia , Masculino , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/mortalidade , Feminino , Pessoa de Meia-Idade , Adulto , Incidência , Idoso , Estudos Longitudinais , Saúde Global/estatística & dados numéricos , Adolescente , Adulto Jovem , Previsões , Carga Global da Doença/tendênciasRESUMO
OBJECTIVE: Hepatocellular carcinoma, characterized by high mortality rates, often exhibits limited responsiveness to conventional treatments such as surgery, radiotherapy, and chemotherapy. Therefore, identifying a sensitizer for cisplatin has become crucial. Dihydroartemisinin, known for its potent role of tumor treatment, arises as a prospective candidate for cisplatin sensitization in clinical settings. METHODS: A mouse model of liver tumor was established through chemical induction of DEN/TCPOBOP. Upon successful model establishment, ultrasound was employed to detect tumors, Hematoxylin and eosin staining was conducted for observation of liver tissue pathology, and ELISA was utilized to assess cytokine changes (IFN-γ, IL-2, IL-4, IL-10, TGF-ß, IL-1ß, CCL2, and CCL21) in peripheral blood, para-tumor tissues, and tumor tissues. The infiltration of CD8+T cells and macrophages in tumor tissue sections was detected by immunofluorescence. RESULTS: Dihydroartemisinin combined with cisplatin obviously restrained the growth of liver tumors in mice and improved the weight and spleen loss caused by cisplatin. Cisplatin treatment of liver tumor mice increased the content of CCL2 and the number of macrophages in tumor tissues and promoted the formation of an immunosuppressive microenvironment. The combination therapy decreased the content of TGF-ß in tumor tissues while increasing CCL2 levels in para-tumor tissues. Both combination therapy and cisplatin alone increased the number of CD8+T cells in tumor tissue, but there was no difference between them. CONCLUSION: Dihydroartemisinin combined with cisplatin obviously prevented the deterioration of liver tumor in hepatocellular carcinoma mice and improve the therapeutic effect of cisplatin by improving the immunosuppressive microenvironment induced by cisplatin. Our findings provide a theoretical basis for considering dihydroartemisinin as an adjuvant drug for cisplatin in the treatment of hepatocellular carcinoma in the future.
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Artemisininas , Carcinoma Hepatocelular , Cisplatino , Neoplasias Hepáticas , Microambiente Tumoral , Animais , Cisplatino/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Camundongos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Microambiente Tumoral/efeitos dos fármacos , Masculino , Antineoplásicos/farmacologia , Quimiocina CCL2/metabolismo , Citocinas/metabolismoRESUMO
This study investigates the presence of plastic and non-plastic microparticles in the gastrointestinal tracts of two deep-sea sharks, Etmopterus molleri (n = 118) and Squalus mitsukurii (n = 6), bycatch from the East China Sea continental shelf. We found a total of 117 microparticles, predominantly fibres (67.52 %), with blue (31.62 %) and black (23.94 %) being the most prevalent colours. E. molleri contained 70 microparticles (0.63 ± 0.93 items/shark), 61.42 % non-plastics like viscose and cotton, while plastics included polyethylene, polyethylene terephthalate, and acrylic. Despite S. mitsukurii's limited sample size, the results show that it takes in a lot of microparticles (47 microparticles, 7.83 ± 2.64 items/shark), 57.44 % non-plastics (viscose, cotton, and ethyl cellulose), and 42.56 % plastics. A positive correlation between microparticle presence and total length was observed for E. molleri. These results provide initial data on microparticle ingestion by these species, highlighting potential ecological risks and trophic transfer implications in deep-sea ecosystems.
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Monitoramento Ambiental , Plásticos , Tubarões , Animais , China , Estômago , Oceanos e MaresRESUMO
While the world struggles to recover from the devastation wrought by the widespread spread of COVID-19, monkeypox virus has emerged as a new global pandemic threat. In this paper, a high precision and lightweight classification network MpoxNet based on ConvNext is proposed to meet the need of fast and safe detection of monkeypox classification. In this method, a two-branch depth-separable convolution residual Squeeze and Excitation module is designed. This design aims to extract more feature information with two branches, and greatly reduces the number of parameters in the model by using depth-separable convolution. In addition, our method introduces a convolutional attention module to enhance the extraction of key features within the receptive field. The experimental results show that MpoxNet has achieved remarkable results in monkeypox disease classification, the accuracy rate is 95.28%, the precision rate is 96.40%, the recall rate is 93.00%, and the F1-Score is 95.80%. This is significantly better than the current mainstream classification model. It is worth noting that the FLOPS and the number of parameters of MpoxNet are only 30.68% and 31.87% of those of ConvNext-Tiny, indicating that the model has a small computational burden and model complexity while efficient performance.