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The SARS-CoV-2 Omicron variant sparked the largest wave of infections worldwide. Mainland China eased its strict COVID-19 measures in late 2022 and experienced two nationwide Omicron waves in 2023. Here, we investigated lineage distribution and virus evolution in Guangdong, China, 2022-2023 by comparing 5813 local viral genomes with the datasets from other regions of China and worldwide. Additionally, we conducted three large-scale serological surveys involving 1696 participants to measure their immune response to the BA.5 and XBB.1.9 before and after the corresponding waves. Our findings revealed the Omicron variants, mainly the BA.5.2.48 lineage, causing infections in over 90% of individuals across different age groups within a month. This rapid spread led to the establishment of widespread immunity, limiting the virus's ability to further adaptive mutation and dissemination. While similar immune responses to BA.5 were observed across all age groups after the initial wave, children aged 3 to 11 developed a stronger cross immune response to the XBB.1.9 strain, possibly explaining their lower infection rates in the following XBB.1 wave. Reinfection with Omicron XBB.1 variant triggered a more potent neutralizing immune response among older adults. These findings highlight the impact of age-specific immune responses on viral spread in potential future waves.
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COVID-19 , Genoma Viral , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/inmunología , SARS-CoV-2/genética , China/epidemiología , Niño , Preescolar , Adulto , Adolescente , Persona de Mediana Edad , Adulto Joven , Genoma Viral/genética , Masculino , Femenino , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Epidemiología Molecular , Lactante , Anciano , Pandemias , FilogeniaRESUMEN
Infection with severe acute respiratory syndrome coronavirus 2 Omicron variants still causes neurological complications in elderly individuals. However, whether and how aging brains are affected by Omicron variants in terms of neuroinvasiveness and neurovirulence are unknown. Here, we utilize resected paracarcinoma brain tissue from elderly individuals to generate primary brain spheroids (BSs) for investigating the replication capability of live wild-type (WT) strain and Omicron (BA.1/BA.2), as well as the mechanisms underlying their neurobiological effects. We find that both WT and Omicron BA.1/BA.2 are able to enter BSs but weakly replicate. There is no difference between Omicron BA.1/BA.2 and WT strains in neurotropism in aging BSs. However, Omicron BA.1/BA.2 exhibits ameliorating neurological damage. Transcriptional profiling indicates that Omicron BA.1/BA.2 induces a lower neuroinflammatory response than WT strain in elderly BSs, suggesting a mechanistic explanation for their attenuated neuropathogenicity. Moreover, we find that both Omicron BA.1/BA.2 and WT strain infections disrupt neural network activity associated with neurodegenerative disorders by causing neuron degeneration and amyloid-ß deposition in elderly BSs. These results uncover Omicron-specific mechanisms and cellular immune responses associated with severe acute respiratory syndrome coronavirus 2-induced neurological complications.
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Hand, Foot and Mouth Disease (HFMD) is a highly contagious viral illness primarily affecting children globally. A significant epidemiological transition has been noted in mainland China, characterized by a substantial increase in HFMD cases caused by non-Enterovirus A71 (EV-A71) and non-Coxsackievirus A16 (CVA16) enteroviruses (EVs). Our study conducts a retrospective examination of 36,461 EV-positive specimens collected from Guangdong, China, from 2013 to 2021. Epidemiological trends suggest that, following 2013, Coxsackievirus A6 (CVA6) and Coxsackievirus A10 (CVA10) have emerged as the primary etiological agents for HFMD. In stark contrast, the incidence of EV-A71 has sharply declined, nearing extinction after 2018. Notably, cases of CVA10 infection were considerably younger, with a median age of 1.8 years, compared to 2.3 years for those with EV-A71 infections, possibly indicating accumulated EV-A71-specific herd immunity among young children. Through extensive genomic sequencing and analysis, we identified the N136D mutation in the 2 A protein, contributing to a predominant subcluster within genogroup C of CVA10 circulating in Guangdong since 2017. Additionally, a high frequency of recombination events was observed in genogroup F of CVA10, suggesting that the prevalence of this lineage might be underrecognized. The dynamic landscape of EV genotypes, along with their potential to cause outbreaks, underscores the need to broaden surveillance efforts to include a more diverse spectrum of EV genotypes. Moreover, given the shifting dominance of EV genotypes, it may be prudent to re-evaluate and optimize existing vaccination strategies, which are currently focused primarily target EV-A71.
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Genoma Viral , Genotipo , Enfermedad de Boca, Mano y Pie , Filogenia , China/epidemiología , Humanos , Enfermedad de Boca, Mano y Pie/epidemiología , Enfermedad de Boca, Mano y Pie/virología , Preescolar , Lactante , Estudios Retrospectivos , Femenino , Masculino , Niño , Epidemiología Molecular , Enterovirus/genética , Enterovirus/clasificación , Enterovirus/aislamiento & purificación , Enterovirus Humano A/genética , Enterovirus Humano A/aislamiento & purificación , Genómica , Incidencia , Adolescente , Infecciones por Enterovirus/epidemiología , Infecciones por Enterovirus/virologíaRESUMEN
AIMS: Immunotherapy has brought a new era to cancer treatment, yet we lack dependable predictors for its effectiveness. This study explores the predictive significance of intratumour stroma proportion (iTSP) for treatment success and prognosis in non-small cell lung cancer (NSCLC) patients undergoing treatment with immune check-point inhibitors (ICIs) together with chemotherapy. METHODS AND RESULTS: We retrospectively collected data from patients with unresectable stage IIIB-IV NSCLC who were treated with first-line ICIs and chemotherapy. Each patient received a confirmed pathological diagnosis, and the pathologist evaluated the iTSP on haematoxylin and eosin (H&E)-stained sections of diagnostic tissue slides. Among the 102 H&E-stained biopsy samples, 61 (59.8%) were categorised as stroma-L (less than 50% iTSP), while 41 (40.2%) were classified as stroma-H (more than 50% iTSP). We observed that the stroma-L group exhibited a significantly better objective response rate (ORR) (72.1 versus 51.2%, P = 0.031) and deeper response depth (DpR) (-50.49 ± 28.79% versus -35.83 ± 29.91%, P = 0.015) compared to the stroma-H group. Furthermore, the stroma-L group showed longer median progression-free survival (PFS) (9.6 versus 6.0 months, P = 0.011) and overall survival (OS) (24.0 versus 12.2 months, P = 0.001) compared to the stroma-H group. Multivariate Cox proportional hazards regression analysis indicated that iTSP was a highly significant prognostic factor for both PFS [hazard ratio (HR) = 1.713; P = 0.030] and OS (HR = 2.225; P = 0.003). CONCLUSION: Our findings indicate that a lower iTSP corresponds to improved clinical outcomes and greater DpR in individuals with stage IIIB-IV NSCLC treated with first-line ICIs and chemotherapy. The iTSP could potentially serve as a predictive biomarker for ICIs therapy response.
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Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Femenino , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Masculino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Pronóstico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estadificación de Neoplasias , Anciano de 80 o más Años , Resultado del TratamientoRESUMEN
Destruction of erythropoiesis process leads to various diseases, including thrombocytopenia, anaemia, and leukaemia. miR-429-CT10 regulation of kinase-like (CRKL) axis involved in development, progression and metastasis of cancers. However, the exact role of miR-429-CRKL axis in leukaemic cell differentiation are still unknown. The current work aimed to uncover the effect of miR-429-CRKL axis on erythropoiesis. In the present study, CRKL upregulation was negatively correlated with miR-429 downregulation in both chronic myeloid leukaemia (CML) patient and CR patient samples. Moreover, CRKL expression level was significantly decreased while miR-429 expression level was increased during the erythroid differentiation of K562 cells following hemin treatment. Functional investigations revealed that overexpression and knockdown of CRKL was remarkably effective in suppressing and promoting hemin-induced erythroid differentiation of K562 cells, whereas, miR-429 exhibited opposite effects to CRKL. Mechanistically, miR-429 regulates erythroid differentiation of K562 cells by downregulating CRKL via selectively targeting CRKL-3'-untranslated region (UTR) through Raf/MEK/ERK pathway. Conversely, CRKII had no effect on erythroid differentiation of K562 cells. Taken together, our data demonstrated that CRKL (but not CRKII) and miR-429 contribute to development, progression and erythropoiesis of CML, miR-429-CRKL axis regulates erythropoiesis of K562 cells via Raf/MEK/ERK pathway, providing novel insights into effective diagnosis and therapy for CML patients.
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Proteínas Adaptadoras Transductoras de Señales , Diferenciación Celular , Células Eritroides , Hemina , Leucemia Mielógena Crónica BCR-ABL Positiva , MicroARNs , Proteínas Proto-Oncogénicas c-crk , Humanos , Regiones no Traducidas 3' , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Diferenciación Celular/efectos de los fármacos , Células Eritroides/metabolismo , Células Eritroides/efectos de los fármacos , Células Eritroides/patología , Células Eritroides/citología , Eritropoyesis/genética , Eritropoyesis/efectos de los fármacos , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Hemina/farmacología , Células K562 , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-crk/metabolismo , Proteínas Proto-Oncogénicas c-crk/genéticaRESUMEN
BACKGROUND: After the adjustment of COVID-19 epidemic policy, mainland China experienced two consecutive waves of Omicron variants within a seven-month period. In Guangzhou city, as one of the most populous regions, the viral infection characteristics, molecular epidemiology, and the dynamic of population immunity are still elusive. METHODS: We launched a prospective cohort study in the Guangdong Provincial CDC from December 2022 to July 2023. Fifty participants who received the same vaccination regimen and had no previous infection were recruited. RESULTS: 90% of individuals were infected with Omicron BA.5* variants within three weeks in the first wave. Thirteen cases (28.26%) experienced infection with XBB.1* variants, occurring from 14 weeks to 21 weeks after the first wave. BA.5* infections exhibited higher viral loads in nasopharyngeal sites compared to oropharyngeal sites. Compared to BA.5* infections, the XBB.1* infections had significantly milder clinical symptoms, lower viral loads, and shorter durations of virus positivity. The infection with the BA.5* variant elicited varying levels of neutralizing antibodies against XBB.1* among different individuals, even with similar levels of BA.5* antibodies. The level of neutralizing antibodies specific to XBB.1* determined the risk of reinfection. CONCLUSIONS: The rapid large-scale infections of the Omicron variants have quickly established herd immunity among the population in mainland China. In the future of the COVID-19 epidemic, a lower infection rate but a longer duration can be expected. Given the large population size and ongoing diversified herd immunity, it remains crucial to closely monitor the molecular epidemiology of SARS-CoV-2 for the emergence of new variants of concern in this region. Additionally, the timely evaluation of the immune status across different age groups is essential for informing future vaccination strategies and intervention policies.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , SARS-CoV-2 , Carga Viral , Humanos , COVID-19/epidemiología , COVID-19/virología , COVID-19/inmunología , China/epidemiología , SARS-CoV-2/genética , SARS-CoV-2/inmunología , SARS-CoV-2/clasificación , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Estudios Prospectivos , Anticuerpos Antivirales/sangre , Estudios de Cohortes , Adulto Joven , AncianoRESUMEN
Global COVID-19 vaccination programs effectively contained the fast spread of SARS-CoV-2. Characterizing the immunity status of returned populations will favor understanding the achievement of herd immunity and long-term management of COVID-19 in China. Individuals were recruited from 7 quarantine stations in Guangzhou, China. Blood and throat swab specimens were collected from participants, and their immunity status was determined through competitive ELISA, microneutralization assay and enzyme-linked FluoroSpot assay. A total of 272 subjects were involved in the questionnaire survey, of whom 235 (86.4%) were returning Chinese individuals and 37 (13.6%) were foreigners. Blood and throat swab specimens were collected from 108 returning Chinese individuals. Neutralizing antibodies against SARS-CoV-2 were detected in ~90% of returning Chinese individuals, either in the primary or the homologous and heterologous booster vaccination group. The serum NAb titers were significantly decreased against SARS-CoV-2 Omicron BA.5, BF.7, BQ.1 and XBB.1 compared with the prototype virus. However, memory T-cell responses, including specific IFN-γ and IL-2 responses, were not different in either group. Smoking, alcohol consumption, SARS-CoV-2 infection, COVID-19 vaccination, and the time interval between last vaccination and sampling were independent influencing factors for NAb titers against prototype SARS-CoV-2 and variants of concern. The vaccine dose was the unique common influencing factor for Omicron subvariants. Enhanced immunity against SARS-CoV-2 was established in returning Chinese individuals who were exposed to reinfection and vaccination. Domestic residents will benefit from booster homologous or heterologous COVID-19 vaccination after reopening of China, which is also useful against breakthrough infection.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19 , Anticuerpos Neutralizantes , China/epidemiologíaRESUMEN
Pulmonary sarcomatoid carcinoma (PSC) is an uncommon variant of non-small cell lung cancer (NSCLC), known for its unfavorable prognosis. Previous studies have elucidated that PSC generally exhibits a significant expression of programmed death-ligand 1 (PD-L1), an elevated tumor mutation burden, and marked vascular invasion. These factors imply the possible effectiveness of treatments like immunotherapy and anti-angiogenic therapy. The subject of this case was a 65-year-old male diagnosed with advanced PSC, characterized by high PD-L1 expression and devoid of known driver gene mutations. Owing to the restrictions imposed by the COVID-19 pandemic, the patient initially underwent home-based treatment with anlotinib, which led to symptomatic improvement after a single treatment cycle. Subsequent hospitalization allowed for the administration of anlotinib plus Pembrolizumab, resulting in a partial response. Radiotherapy was necessitated due to local disease progression. But after 15 cycles of treatment with Pembrolizumab, hyperprogression was observed. The patient's overall survival spanned 14 months, with no evident adverse reactions to the medications. Genomic analysis revealed potential associations between treatment efficacy and mutations in the TP53, NF1, and MET genes. This case underscores the effectiveness and safety of a first-line treatment regimen combining pan-target anti-angiogenic therapy (anlotinib) with anti-tumor immunotherapy.
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The chemically synthesized polymer polyacrylamide (HPAM) has achieved excellent oil displacement in conventional reservoirs, but its oil displacement is poor in extreme reservoir environments. To develop a biopolymer oil flooding agent suitable for extreme reservoir conditions, the viscosity changes and rheological properties of three biopolymers, diutan gum, xanthan gum, and scleroglucan, were studied under extreme reservoir conditions (high salt, high temperature, strong acid, and alkali), and the effects of temperature, mineralization, pH, and other factors on their viscosities and long-term stability were analyzed and compared. The results show that the three biopolymers had the best viscosity-increasing ability at temperatures of 90 °C and below. The viscosity of the three biopolymers was 80.94 mPa·s, 11.57 mPa·s, and 59.83 mPa·s, respectively, when the concentration was 1500 mg/L and the salinity 220 g/L. At the shear rate of 250 s-1, 100 °C~140 °C, scleroglucan had the best viscosification. At 140 °C, the solution viscosity was 19.74 mPa·s, and the retention rate could reach 118.27%. The results of the long-term stability study showed that the solution viscosity of scleroglucan with a mineralization level of 220 mg/L was 89.54% viscosity retention in 40 days, and the diutan gum could be stabilized for 10 days, with the viscosity maintained at 90 mPa·s. All three biopolymers were highly acid- and alkali-resistant, with viscosity variations of less than 15% in the pH3~10 range. Rheological tests showed that the unique double-helix structure of diutan gum and the rigid triple-helix structure of scleroglucan caused them to have better viscoelastic properties than xanthan gum. Therefore, these two biopolymers, diutan gum, and scleroglucan, have the potential for extreme reservoir oil displacement applications. It is recommended to use diutan gum for oil displacement in reservoirs up to 90 °C and scleroglucan for oil displacement in reservoirs between 100 °C and 140 °C.
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Molecular behavior of rhamnolipid mixed with a biobased zwitterionic surfactant at an n-hexadecane/water interface has been studied, and the effects of a rhamnose moiety and composition are evaluated. Results showed that rhamnolipid abundantly interacts with biobased surfactant EAB by means of hydrophobic interactions between aliphatic tails and electrostatic interactions between headgroups, including the attractive interaction between COO- of rhamnolipids and N+ of biobased surfactants and the repulsive interaction between COO- of both surfactants. Dirhamnolipid has a larger number of bound Na+ and a more stable bound structure of COO- â¼ Na+, which screens the repulsive interaction between two kinds of surfactants and shows a more homogeneous distribution with biobased surfactants. The interfacial tension between n-hexadecane and water has been synergistically reduced by dirhamnolipids mixed with biobased surfactants at a higher molar ratio of biobased surfactants. Monorhamnolipids show a strengthened interaction with N+ of biobased surfactants and a more stable hydrogen bond with water relative to that of dirhamnolipids, and there is no synergistic effect in lowering the interfacial tension for the mixture of monorhamnolipids and biobased surfactants. The present work provides details of the molecular behavior of biosurfactant rhamnolipids mixed with biobased surfactants and obtains the key factor in affecting the interfacial properties of the binary system.
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OBJECTIVE: HNRNPA2B1, one of the regulator of m6A methylation, is involved in a wide range of physiological processes. However, the aberrant expression of HNRNPA2B1 in Breast Cancer (BC) and its clinical significance still need to be further studied. METHODS: We used related databases to analyze the relationship between HNRNPA2B1 and BC by bioinformatics. Then, we further detected the expression of HNRNPA2B1 by immunohistochemical method, and analyzed the relationship between it and the prognosis of breast cancer by COX regression method. RESULTS: In the study, we found that the expression level of HNRNPA2B1 in breast cancer (BC) was significantly higher than that in normal breast tissues. In addition, the expression level of HNRNPA2B1 in BC samples was significantly correlated with clinical indexes such as TNM stage. The Cox analysis revealed that the expression of HNRNPA2B1 in BC had significant clinical prognostic value. The results of immune infiltration of HNRNPA2B1 showed that there was a significant correlation between HNRNPA2B1 and immune cell subsets. CONCLUSION: Our results show that the expression of HNRNPA2B1 in BC has important clinical diagnostic significance and high expression may be related with poor clinical outcome of BC. This helps to provide us with a new direction of BC targeted therapy.
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Relevancia Clínica , Neoplasias , Biomarcadores , Biología Computacional , Bases de Datos Factuales , PronósticoRESUMEN
A terahertz beam imaging method was proposed that involves scanning a reflecting echelon with temporal-spatial mapping inversion based on self-developed translation-scan and rotation-scan temporal-spatial mapping (TTSM and RTSM) algorithms. The beam characteristics of a terahertz time-domain spectroscopy (TDS) system, such as its size, shape, and energy distribution, were obtained. Besides the weak terahertz beam emitted from a TDS system, this scheme is also suitable for imaging large-size terahertz or laser beams in time-domain systems where existing beam imaging is impractical.
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Biosurfactants have significant applications in various industries, including microbial-enhanced oil recovery (MEOR). While the state-of-the-art genetic approaches can generate high-yield strains for biosurfactant production in fermenters, there remains a critical challenge in enhancing biosurfactant-producing strains for use in natural environments with minimal ecological risks. The objectives of this work are enhancing the strain's capacity for rhamnolipids production and exploring the genetic mechanisms for its improvement. In this study, we employed atmospheric and room-temperature plasma (ARTP) mutagenesis to enhance the biosynthesis of rhamnolipids in Pseudomonas sp. L01, a biosurfactant-producing strain isolated from petroleum-contaminated soil. Following ARTP treatment, we identified 13 high-yield mutants, with the highest yield of 3.45 ± 0.09 g/L, representing a 2.7-fold increase compared to the parent strain. To determine the genetic mechanisms behind the enhanced rhamnolipids biosynthesis, we sequenced the genomes of the strain L01 and five high-yield mutants. A comparative genomic analysis suggested that mutations in genes related to the synthesis of lipopolysaccharides (LPS) and the transport of rhamnolipids may contribute to the improved biosynthesis. To the best of our knowledge, this is the first instance of utilizing the ARTP approach to improve rhamnolipid production in Pseudomonas strains. Our study provides valuable insights into the enhancement of biosurfactant-producing strains and the regulatory mechanisms of rhamnolipids biosynthesis.
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Microbial remediation has been regarded as one of the most promising decontamination techniques for crude oil pollution. However, there are few studies on the interaction of bacteria in the microbial community during bioremediation. The aim of this work was to research the promotion of defined co-culture of Bacillus subtilis SL and Pseudomonas aeruginosa WJ-1 for biodegradation of crude oil. After 7 days of incubation, the analysis of residual oil, saturated and aromatic fraction in the samples showed that the degradation efficiency of them was significantly improved. The degradation efficiency of crude oil was enhanced from 32.61% and 54.35% in individual culture to 63.05% by the defined co-culture of strains SL and WJ-1. Furthermore, it was found that the defined co-culture system represented relatively excellent performance in bacterial growth, cell surface hydrophobicity (CSH) and emulsification activity. These results indicated that the combination of Bacillus subtilis and Pseudomonas aeruginosa can effectively promote the degradation and utilization of crude oil, which may provide a new idea for the improvement of bioremediation strategies. GRAPHICAL ABSTRACT.
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Potentially toxic elements in soils (SPTEs) from industrial and mining sites (IMSs) often cause public health issues. However, previous studies have either focused on SPTEs in agricultural or urban areas, or in a single or few IMSs. A systematic assessment of the pollution and risk levels of SPTEs from IMS at the national scale is lacking. Here, we obtained SPTE (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) concentrations from IMSs across China based on 188 peer-reviewed articles published between 2004 and 2022 and quantified their pollution and risk levels using the pollution index and risk assessment model, respectively. The results indicated that the average concentrations of the eight SPTEs were 4.42-270.50 times the corresponding background values, and 19.58% of As, 14.39% of Zn, 12.79% of Pb, and 8.03% of Cd exceeded the corresponding soil risk screening values in these IMSs. In addition, 27.13% of the examined IMS had one or more SPTE pollution, mainly distributed in the southwest and south central China. On the examined IMSs, 81.91% had moderate or severe ecological risks, which were mainly caused by Cd, Hg, As, and Pb; 23.40% showed non-carcinogenic risk and 11.70% demonstrated carcinogenic risk. The primary exposure pathways of the former were ingestion and inhalation, while that for the latter was ingestion. A Monte Carlo simulation also confirmed the health risk assessment results. As, Cd, Hg, and Pb were identified as priority control SPTEs, and Hunan, Guangxi, Guangdong, Yunnan, and Guizhou were selected as the key control provinces. Our results provide valuable information for public health and soil environment management in China.
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Mercurio , Metales Pesados , Contaminantes del Suelo , Suelo , Monitoreo del Ambiente/métodos , Cadmio , Plomo , Metales Pesados/análisis , China , Contaminantes del Suelo/análisis , Medición de RiesgoRESUMEN
OBJECTIVE: To determine the function of the YAP-JNK-mitophagy signalling pathway in gastric cancer (GC). STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Seventh People's Hospital of Shanghai University of TCM (Traditional Chinese Medicine), between June 2019 and June 2021. METHODOLOGY: Tissues from 30 cases of gastric cancer and corresponding adjacent tissues were collected. RT-qPCR was employed to detect the expression of YAP and JNK in GC samples. MTT, Wound healing and Transwell assays were used to detect changes in GC cell proliferation, migration, and invasion under different stimulation. LC3 immunofluorescence and mitochondrial membrane potential detection were used to analyse the occurrence of mitochondrial autophagy. RESULTS: The expression of YAP and JNK were significantly increased in GC tissues (p=0.024, 0.033). YAP knockdown inhibited GC cell proliferation, migration, and invasion. Further studies showed that YAP affects GC cell function by targeting JNK. In addition, YAP-JNK signalling was found to regulate GC cell proliferation, migration, and invasion mainly through regulating the occurrence of mitophagy. CONCLUSION: These findings revealed that YAP-JNK promotes the development of GC by targeting mitophagy. KEY WORDS: Gastric cancer, YAP, JNK, Autophagy.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Mitofagia , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Línea Celular Tumoral , China , Proliferación Celular/fisiologíaRESUMEN
Understanding terrestrial ecosystem dynamics requires a comprehensive examination of vegetation changes. Remote sensing technology has been established as an effective approach to reconstructing vegetation change history, investigating change properties, and evaluating the ecological effects. However, current remote sensing techniques are primarily focused on break detection but ignore long-term trend analysis. In this study, we proposed a novel framework based on a change detection algorithm and a trend analysis method that could integrate both short-term disturbance detection and long-term trends to comprehensively assess vegetation change. With this framework, we characterized the vegetation changes in Zhejiang Province from 1990 to 2020 using Landsat and landcover data. Benefiting from combining break detection and long-term trend analysis, the framework showcased its capability of capturing a variety of dynamics and trends of vegetation. The results show that the vegetation was browning in the plains while greening in the mountains, and the overall vegetation was gradually greening during the study period. By comparison, detected vegetation disturbances covered 57.71% of the province's land areas (accounting for 66.92% of the vegetated region) which were mainly distributed around the built-up areas, and most disturbances (94%) occurred in forest and cropland. There were two peak timings in the frequency of vegetation disturbances: around 2003 and around 2014, and the proportions of more than twice disturbances in a single location were low. The results illustrate that this framework is promising for the characterization of regional vegetation growth, including long-term trends and short-term features. The proposed framework enlightens a new direction for the continuous monitoring of vegetation dynamics.
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Ecosistema , Monitoreo del Ambiente , Factores de Tiempo , Monitoreo del Ambiente/métodos , Bosques , Tecnología de Sensores Remotos , Cambio Climático , ChinaRESUMEN
In fringe projection profilometry (FPP), the luminance nonlinearity generated by the superimposed γ effect of the projector and camera can lead to distortion of the intensity of the sinusoidal phase-shift fringe, resulting in a reduction of measurement precision and resolution. Traditional phase error compensation and γ-correction methods need to focus on the projector's optimal performance. However, commercial projectors often have huge apertures and are, therefore, unable to project a perfectly focused sinusoidal fringe image. This paper proposes an easy-to-implement active projection error correction method with high precision that is insensitive to projector defocus. After calibrating the projector to establish the nonlinear γ-response model of the optical measurement system, inverse γ compensation is performed. By generating and projecting a set of precorrected sinusoidal fringes, the camera can capture the high-quality sinusoidal fringe image and decrease the phase measurement error caused by the nonlinear γ effect of the FPP system. Computer simulations and experiments verify the effectiveness and feasibility of the proposed method for estimating and correcting the nonlinear γ distortion of the FPP system. The experimental results show that using the proposed active projection method to compensate for the error of the three-step phase-shift algorithm can achieve a high-precision measurement, and the influence of the system's nonlinear γ effect on the measurement accuracy is significantly suppressed.
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Background: Non-small cell lung cancer, comprising lung adenocarcinoma (LUAD) and lung squamous cell carcinoma, is one of the leading causes of cancer-related mortality. Pyroptosis is a new form of programmed cell death involved in cancer development. The relationship between LUAD and pyroptosis is unclear. This research aims to investigate this relationship and develop a stratified clinical model based on pyroptosis-related genes (PRGs). Methods: We analyzed the data of LUAD from The Cancer Genome Atlas (TCGA) and evaluated the expression of 48 PRGs to identify the differentially expressed genes. Then, constructing the risk model using the least absolute shrinkage and selection operator and the Cox regression method to find the gene signatures. The functional enrichment, immune cell infiltration, tumor mutational burden (TMB), and expression of immune checkpoints were compared to investigate the potential mechanism. The IC50 of common drugs was evaluated and compared. The inflammasome activation assay and lactate dehydrogenase (LDH) assay of NLR-family CARD-containing protein 4 (NLRC4) were also performed to confirm the role of pyroptosis in LUAD. Results: The pyroptosis-related model accurately predicted the prognosis of patients with LUAD, with the low-risk group exhibiting a higher survival probability. The risk score was an independent prognostic factor for survival. The stratified patients exhibited distinct tumor microenvironments, TMB, and drug sensitivity. The validation experiments of NLRC4 confirmed its role in inducing pyroptosis via promoting IL-1 maturation. Conclusion: PRGs regulated the tumor microenvironment and influenced the outcome of LUAD. NLRC4 may function as a hub gene in the process of LUAD.