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Aflatoxin B1 (AFB1), a widespread contaminant in food and feeds, poses a threat to the health of animals and humans. Consequently, it is significant to develop a rapid, precise and highly sensitive analytical method for the detection of AFB1. Herein, we developed an immunochromatographic strip (ICS) based on a tetrahedral DNA (TDN) immunoprobe for AFB1 determination in rice bran oil. Three sizes of TDN immunoprobes (AuNP-TDN13bp-mAb, AuNP-TDN17bp-mAb, AuNP-TDN26bp-mAb) were constructed, and the performance of these three immunoprobes, including the effective antibody labeling density and immunoaffinity, was measured and compared with that of the immunoprobe (AuNP-mAb) developed using the physical adsorption method. Subsequently, the optimal TDN immunoprobe, namely AuNP-TDN13bp-mAb, was selected to prepare the immunochromatographic strip (ICS) for the qualitative and quantitative detection of AFB1 in rice bran oil. The visual limits of detection (vLODs) of the ICS based on AuNP-TDN13bp-mAb and AuNP-mAb were 0.2 ng/mL and 2 ng/mL, with scanning quantitative limits (sLOQs) of 0.13 ng/mL and 1.4 ng/mL, respectively. The ICS demonstrated a wide linear range from 0.02 ng/mL to 0.5 ng/mL, with good specificity, accuracy, precision, repeatability, and stability. Moreover, a high consistency was observed between the constructed ICS and ultra-high-performance liquid chromatography (UPLC) in the quantification of AFB1. The results indicated that the introduction of TDN was beneficial for promoting efficient antibody labeling, protecting the bioactivity of immunoprobes, and increasing the sensitivity of detection, which would provide new perspectives for the achievement of the highly sensitive detection of mycotoxins.
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BACKGROUND: Late-onset Pompe disease (LOPD) is mainly characterized by progressive limb-girdle muscle weakness and respiratory impairment, whereas stroke and cerebrovascular abnormalities have been insufficiently studied in LOPD. This study aimed to evaluate the frequency and pattern of intracranial artery and brain parenchyma abnormalities in LOPD patients. RESULTS: Neuroimaging data from 30 Chinese adult LOPD patients were collected from our center. Seven patients (7/30) had acute cerebral infarction or hemorrhage. Brain magnetic resonance angiography (MRA) or computed tomography angiography (CTA) revealed artery abnormalities in 23 patients (23/30). Dilative arteriopathy was found in 19 patients (19/30), with vertebrobasilar dolichoectasia found in 17 patients and dilatation of the anterior circulation arteries found in 8 patients. The maximum diameter of the basilar artery was correlated with disease duration (p < 0.05). In addition, aneurysms (7/30) and fenestrations (3/30) were discovered. There were 14 patients with arterial stenosis (14/30), and both anterior and posterior circulation involvement occurred in 9 patients (9/14). Stenosis and dilative arteriopathy simultaneously occurred in 10 patients (10/30). White matter hyperintensities were present in 13 patients (13/28). Microbleeds, predominantly located in the cerebellum and brainstem, were detected in 7 patients (7/22) via susceptibility-weighted imaging. CONCLUSIONS: Intracranial vasculopathy involving both large arteries and small vessels is an important organ damage in LOPD patients. LOPD should be considered a key differential diagnosis in young adults with cryptogenic stroke, and a series of imaging evaluations of the brain and intracranial blood vessels is recommended as a routine workup in adult LOPD patients.
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Enfermedad del Almacenamiento de Glucógeno Tipo II , Humanos , Masculino , Femenino , Adulto , Enfermedad del Almacenamiento de Glucógeno Tipo II/patología , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico por imagen , Adulto Joven , Persona de Mediana Edad , Angiografía por Resonancia Magnética , AdolescenteRESUMEN
Deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON) and 15-acetyldeoxynivalenol (15-ADON) belong to type B trichothecenes that are widely detected in agricultural products as one of the most common classes of mycotoxins. In the present study, we aimed to characterize the alteration of lipid metabolism in normal human hepatocytes by poisoning with DON and its acetylated derivatives. After verifying the hepatotoxicity of the three toxins, DON, 15-ADON, and 3-ADON, the mRNA expression was determined by transcriptomics, and the results showed that DON and 15-ADON had a significant regulatory effect on the transcriptome, in which glycerophospholipid metabolism pathway and phospholipase D signaling pathways have not been reported in studies of DON and its acetylated derivatives. For further validation, we explored lipid metabolism in depth and found that PC (15:0/16:0), PC (16:1/18:3), PC (18:1/22:6), PC (16:0/16:0), PC (16:0/16:1), PC (16:1/18:1), PC (14:0/18:2), PE (14:0/16:0) and PE (18:1/18:3) were downregulated for all nine lipids. Combined with the transcriptome results, we found that hepatic steatosis induced by the three toxins, DON, 15-ADON and 3-ADON, was associated with altered expression of genes related to lipid oxidation, lipogenesis and lipolysis, and their effects on lipid metabolism in L-02 cells were mainly realized through the PC-PE cycle.
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Hepatocitos , Metabolismo de los Lípidos , Tricotecenos , Humanos , Tricotecenos/toxicidad , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Células CultivadasRESUMEN
Ferroptosis is a way of cell death mainly due to the imbalance between the production and degradation of lipid reactive oxygen species, which is closely associated with various diseases. Endogenous hypochlorous acid (HOCl) mainly produced in mitochondria is regarded as an important signal molecule of ferroptosis. Therefore, monitoring the fluctuation of endogenous HOCl is beneficial to better understand and treat ferroptosis-related diseases. Inspired by the promising aggregation-induced emission (AIE) properties of tetraphenylethene (TPE), herein, we rationally constructed a novel AIE-based fluorescent probe, namely QTrPEP, for HOCl with nice mitochondria-targeting ability and high sensitivity and selectivity. Probe QTrPEP consisted of phenylborate ester and the AIE fluorophore of quinoline-conjugated triphenylethylene (QTrPE). HOCl can brighten the strong fluorescence through a specific HOCl-triggered cleavage of the phenylborate ester bond and release of QTrPE, which has been demonstrated by MS, HPLC, and DLS experiments. In addition, combining QTrPE-doped test strips with a smartphone-based measurement demonstrated the excellent performance of the probe to sense HOCl. The obtained favorable optical properties and negligible cytotoxicity allowed the use of this probe for tracking of HOCl in three different cells. In particular, this work represents the first AIE-based mitochondria-targeting fluorescent probe for monitoring the fluctuation of HOCl in ferroptosis.
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Ferroptosis , Colorantes Fluorescentes , Ácido Hipocloroso , Mitocondrias , Ácido Hipocloroso/análisis , Ácido Hipocloroso/metabolismo , Colorantes Fluorescentes/química , Mitocondrias/metabolismo , Ferroptosis/efectos de los fármacos , Humanos , Espectrometría de Fluorescencia/métodos , Imagen Óptica/métodosRESUMEN
Acute myeloid leukemia (AML) is a malignant disease that is difficult to completely cure. Polyphyllin I (PPI), a steroidal saponin isolated from Paris polyphylla, has exhibited multiple biological activities. Here, we discovered the superior cytotoxicity of PPI on AML cells MOLM-13 with an IC50 values of 0.44 ± 0.09 µM. Mechanically, PPI could cause ferroptosis via the accumulation of intracellular iron concentration and triggering lipid peroxidation. Interestingly, PPI could induced stronger ferroptosis in a short time of about 6 h compared to erastin. Furthermore, we demonstrate that PPI-induced rapid ferroptosis is due to the simultaneous targeting PI3K/SREBP-1/SCD1 axis and triggering lipid peroxidation, and PI3K inhibitor Alpelisib can enhance the activity of erastin-induced ferroptosis. Molecular docking simulations and kinase inhibition assays demonstrated that PPI is a PI3K inhibitor. In addition, PPI significantly inhibited tumor progression and prolonged mouse survival at 4 mg/kg with well tolerance. In summary, our study highlights the therapeutic potential of PPI for AML and shows its unique dual mechanism.
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Diosgenina , Ferroptosis , Leucemia Mieloide Aguda , Peroxidación de Lípido , Fosfatidilinositol 3-Quinasas , Animales , Humanos , Ratones , Línea Celular Tumoral , Diosgenina/farmacología , Diosgenina/análogos & derivados , Diosgenina/uso terapéutico , Ferroptosis/efectos de los fármacos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas/metabolismoRESUMEN
OBJECTIVE: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. METHODS: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. RESULTS: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46). The median duration of response was 9.6 months (95% confidence interval [CI]=5.5-not estimable). The median progression-free survival was 8.1 months (95% CI=5.7-14.0). Forty-five (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). CONCLUSION: QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can't tolerate bevacizumab, which needs to be further verified in phase III confirmatory study. Trial RegistrationClinicalTrials.gov Identifier: NCT04864782.
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Ultrasound-mediated transdermal drug delivery exhibits various advantages such as biocompatibility, controllability and safety, which attracts plenty of interests within biomedical field. Current researches mostly emphasizes the acoustic cavitation generated by planar or focused waves while neglecting other physics that occur during transportation. Our experimental study illustrates the presence of an acoustic vortex (AV) beam that exhibits a lower acoustic intensity and typically means a lower dose of inertial cavitation, yet achieves a more efficient delivery. Such a result calls for the fundamental mechanism of ultrasound-mediated transdermal transfer using the AV beam. In this work, according to our knowledge, the AV beam is firstly introduced to ultrasound-mediated transdermal medication delivery. The transversal acoustic radiation force (T-ARF), which is the primary characteristic carried by the acoustic vortex beam, and its contribution to the transport enhancement are investigated. It is shown that a focused AV (FAV) beam with a maximal acoustic pressure of 200 kPa induces a pN-level T-ARF, which promotes the enlargement of pores on the stratum corneum and thereby enhances the permeability, as compared with a zero-order (non-vortex) counterpart. This contribution of the T-ARF is validated by the experimental transport on the cellulose membrane, which exhibits a significantly increased membrane porosity and delivery efficiency. The favorable results introduce the new degree of freedom into the ultrasound-mediated transdermal drug transport based on AV beam, and thereby promotes the development of a combined control strategy for more precise and efficient transdermal drug delivery in conjunction with the administration of acoustic cavitation.
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Administración Cutánea , Sistemas de Liberación de Medicamentos , Sistemas de Liberación de Medicamentos/métodos , Acústica , Animales , Absorción Cutánea , Piel/metabolismo , Piel/diagnóstico por imagen , Ondas Ultrasónicas , Permeabilidad , PorcinosRESUMEN
BACKGROUND: The gene cell division cycle associated 5 (CDCA5), also called sororin, has oncogenic characteristics and is upregulated in various carcinomas. Nevertheless, the involvement of CDCA5 in ovarian cancer (OC), a highly aggressive form of cancer, and the underlying mechanism of metastasis remain inadequately investigated. RESULTS: The bioinformatics data revealed a negative correlation between the patient's survival and CDCA5 expression, which was overexpressed in OC. Functional assays also confirmed high expression levels of CDCA5 in OC tissues and cells. This suggests that CDCA5 may potentially enhance the motility, migration, and proliferation of OC cells invitro. It impedes DNA damage and apoptosis in OC cells, inhibiting xenograft development in nude mice. The RNA sequencing results suggest CDCA5 is majorly associated with biological functions related to the extracellular matrix (ECM) and influences the transforming growth factor (TGF) signaling pathway. Moreover, subsequent functional investigations elucidated that CDCA5 facilitated the migration and invasion of OC cells viathe TGF-ß1/Smad2/3 signaling pathway activation. CONCLUSIONS: CDCA5 may be a strong potential therapeutic target for the treatment and management of OC.
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Neoplasias Ováricas , Factor de Crecimiento Transformador beta1 , Animales , Ratones , Humanos , Femenino , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Ratones Desnudos , Línea Celular Tumoral , Neoplasias Ováricas/patología , Ciclo Celular , Proliferación Celular , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismoRESUMEN
In this article, we propose a lightweight and flexible enhanced Tai Chi training system composed of multiple standalone virtual reality (VR) devices. The system aims to enable a hyper-realistic multi-user action training platform at low cost by displaying real-time action guidance trajectories, providing real-world impossible visual effects and functions, and rapidly enhancing movement precision and communication interest for learners. We objectively evaluate participants' action quality at different levels of immersion, including traditional coach guidance (TCG), VR, and mixed reality (MR), along with subjective measures like motion sickness, quality of interaction, social meaning, presence/immersion to comprehensively explore the system's feasibility. The results indicate VR performs the best in training accuracy, but MR provides superior social experience and relatively high accuracy. Unlike TCG, MR offers hyper-realistic hand movement trajectories and Tai Chi social references. Compared with VR, MR provides more realistic avatar companions and a safer environment. In summary, MR balances accuracy and social experience.
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Realidad Aumentada , Taichi Chuan , Humanos , Gráficos por Computador , MovimientoRESUMEN
Triple-negative breast cancer (TNBC) is the most aggressive and lethal clinical subtype and lacks effective targeted therapies at present. Isobavachalcone (IBC), the main active component of Psoralea corylifolia L., has potential anticancer effects. Herein, we identified IBC as a natural sirtuin 2 (SIRT2) inhibitor and characterized the potential mechanisms underlying the inhibition of TNBC. Molecular dynamics analysis, enzyme activity assay, and cellular thermal shift assay were performed to evaluate the combination of IBC and SIRT2. The therapeutic effects, mechanism, and safety of IBC were analyzed in vitro and in vivo using cellular and xenograft models. IBC effectively inhibited SIRT2 enzyme activity with an IC50 value of 0.84 ± 0.22 µM by forming hydrogen bonds with VAL233 and ALA135 within its catalytic domain. In the cellular environment, IBC bound to and stabilized SIRT2, consequently inhibiting cellular proliferation and migration, and inducing apoptosis and cell cycle arrest by disrupting the SIRT2/α-tubulin interaction and inhibiting the downstream Snail/MMP and STAT3/c-Myc pathways. In the in vivo model, 30 mg/kg IBC markedly inhibited tumor growth by targeting the SIRT2/α-tubulin interaction. Furthermore, IBC exerted its effects by inducing apoptosis in tumor tissues and was well-tolerated. IBC alleviated TNBC by targeting SIRT2 and triggering the reactive oxygen species ROS/ß-catenin/CDK2 axis. It is a promising natural lead compound for future development of SIRT2-targeting drugs.
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Chalconas , Sirtuina 2 , Neoplasias de la Mama Triple Negativas , Humanos , Sirtuina 2/farmacología , Línea Celular Tumoral , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Tubulina (Proteína)/farmacología , Tubulina (Proteína)/uso terapéutico , Proliferación Celular , ApoptosisRESUMEN
In this study, a type of luminescent porous coordination network-224 (PCN-224) in alkaline conditions was synthesized with the dramatic fluorescence enhancement by 20.4 times, which was explained by the fact that the decrease of Zr4+ content in alkaline conditions resulted in the partial recovery of the electron cloud density of 4,4',4'',4'''-(Porphine-5,10,15,20-tetrayl) tetrakis(benzoic acid) (TCPP). Given the large overlap between the excitation spectrum of PCN-224 and the absorption band of Ag nanoparticles (Ag NPs), the coating of the Ag layer on PCN-224 triggered the fluorescence quenching effect, which was applied to "turn off" fluorescence immunoassay for sensitive detection of Escherichia coli O157:H7 (E. coli O157:H7) in milk. The proposed immunoassay reached a low limit of detection (LOD) of 3.3 × 102 CFU mL-1, 29.7 times more sensitive than the conventional ELISA. It will provide a novel alternative strategy for sensitively detecting pathogenic bacteria in the field of food safety.
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Escherichia coli O157 , Nanopartículas del Metal , Animales , Leche/microbiología , Plata , Inmunoensayo/métodos , Microbiología de AlimentosAsunto(s)
Cistitis , Laparoscopía , Humanos , Cistectomía , Vejiga Urinaria/cirugía , Cistitis/etiología , Cistitis/cirugíaRESUMEN
Organophosphate flame retardants (OPFRs), a novel class of persistent pollutants, are widely distributed in the environment, and their potential health risks have garnered significant global attention in recent years. Crayfish is a popular freshwater crustacean product in China primarily sourced from the middle and lower reaches of the Yangtze River. The purpose of this study was to investigate the exposure levels of OPFRs in crayfish, assess the health and safety risks associated with crayfish consumption, and explore the bioaccumulation of OPFRs in environmental water and sediment on crayfish. Ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed to analyze 7 common OPFRs in 106 crayfish samples and 76 environmental samples. The results revealed that OPFRs were detected at a high frequency of 100 % in crayfish, with tripropyl phosphate (TPP) being the predominant pollutant found in edible portions while also exhibiting secondary contamination within the crayfish food chain. Monte Carlo modeling combined with @risk risk assessment software demonstrated that TPP present in crayfish muscles had the most substantial impact on health effects, however, overall OPFR exposure did not pose significant risks to human health. Furthermore, analysis of OPFRs bioenrichment ability indicated that crayfish predominantly accumulated these compounds within their edible parts from surrounding environmental water sources, particularly highlighting TPP's potential for bioaccumulation.
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Contaminantes Ambientales , Retardadores de Llama , Animales , Humanos , Organofosfatos/análisis , Retardadores de Llama/análisis , Astacoidea , Bioacumulación , Cromatografía Liquida , Ríos/química , Espectrometría de Masas en Tándem/métodos , Contaminantes Ambientales/análisis , Fosfatos/análisis , Agua/análisis , Medición de RiesgoRESUMEN
Quantum dots (QDs) are promising color conversion materials for efficient full-color micro light-emitting diode (micro-LED) displays owing to their high color purity and wide color gamut. However, achieving high-resolution QD patterns with enough thickness for efficient color conversion is challenging. Here, we demonstrate a facile and compatible approach by combining replicate molding, plasma etching and transfer printing to produce QD patterns with a sufficient thickness over ten micrometers in a wide range of resolutions. Our technique can remarkably simplify the preparation of QD inks and minimize optical damage to QD materials. The pixel resolution and thickness of QD patterns can be controlled by well-defining the microstructures of the molding template and the etching process. The transfer printing process allows QD patterns to be assembled sequentially onto a receiving substrate, which will further improve the original pixel resolution and avoid repetitive optical damage to QDs during the patterning process. Consequently, various QD patterns can be fabricated in this work, including perovskite quantum dot (PQD) patterns with a pixel resolution of up to 669 pixels per inch (ppi) and a maximum thickness of up to 19.74 µm, a wafer-scale high-resolution PQD pattern with sufficient thickness on a flexible substrate, and a dual-color pattern comprising green PQDs and red CdSe QDs. Furthermore, these fabricated QD films with a thickness of over 10 µm show improved color conversion when integrated onto a blue micro-LED, revealing the potential of our technique for full-color micro-LED displays.
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Background: Immune checkpoint inhibitors (ICIs) have become the standard second-line treatment for advanced non-small cell lung cancer (NSCLC). Recent findings indicating an intertwined regulation of vascular endothelial growth factor (VEGF) signaling and immunosuppression in the tumor microenvironment suggest that the combination of ICIs and angiogenesis inhibitors could have synergistic antitumor activity, along with favorable tolerability. However, ICIs plus anti-angiogenesis therapy has not been widely evaluated. The purpose of this pilot study was to evaluate the efficacy and safety of ICIs plus recombinant human (rh)-endostatin as second-line treatment in advanced NSCLC with negative driver gene. Method: Prospectively evaluated the efficacy and safety of ICIs plus rh-endostain as second-line treatment in advanced NSCLC with negative driver gene. The primary endpoints of the study were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR), disease control rate (ORR), and safety. Results: A total of 34 patients were recruited in this study. 18 patients received ICIs plus anti-angiogenesis therapy (ICIs combination therapy), and 16 patients received ICIs monotherapy. DCR was 88.9% vs 43.8% (P = 0.009). Median PFS (mPFS) was 8.3 months vs. 3.7 months (HR = 0.276, 95% CI 0.125-0.607, P = 0.001). Median OS (mOS) was 18.0 months vs 9.6 months (HR=0.364, 95% CI 0.147-0.902, P=0.009). In multivariate Cox regression analysis, ICI combination therapy prolonged PFS (HR = 0.069, 95% CI 0.019-0.185, P < 0.001) and OS (HR = 0.044, 95% CI 0.011-0.185, P < 0.001). We did not observe a significant difference in the incidence of adverse events (AEs) between the two groups (P > 0.05). Conclusions: Compared with ICIs monotherapy, ICIs combination therapy improves clinical response in patients with advanced NSCLC with negative driver gene, significantly prolongs PFS and OS, and does not significantly difference the incidence of AEs.
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BACKGROUND: Immune checkpoint inhibitors targeting PD-1 or CTLA-4 individually have shown substantial clinical benefits in the treatment of malignancies. We aimed to assess the safety and antitumour activity of cadonilimab monotherapy, a bispecific PD-1/CTLA-4 antibody, in patients with advanced solid tumours. METHODS: This multicentre, open-label, phase 1b/2 trial was conducted across 30 hospitals in China. Patients aged 18 years or older with histologically or cytologically confirmed, unresectable advanced solid tumours, unsuccessful completion of at least one previous systemic therapy, and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible for inclusion. Patients who had previously received anti-PD-1, anti-PD-L1, or anti-CTLA-4 treatment were not eligible for inclusion. In the dose escalation phase of phase 1b, patients received intravenous cadonilimab at 6 mg/kg and 10 mg/kg every 2 weeks. In the dose expansion phase of phase 1b, cadonilimab at 6 mg/kg and a fixed dose of 450âmg were given intravenously every 2 weeks. In phase 2, cadonilimab at 6 mg/kg was administered intravenously every 2 weeks in three cohorts: patients with cervical cancer, oesophageal squamous cell carcinoma, and hepatocellular carcinoma. The primary endpoints were the safety of cadonilimab in phase 1b and objective response rate in phase 2, based on the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The safety analysis was done in all patients who received at least one dose of cadonilimab. Antitumour activity was assessed in the full analysis set for the cervical cancer cohort, and in all patients with measurable disease at baseline and who received at least one dose of cadonilimab in the oesophageal squamous cell carcinoma and hepatocellular carcinoma cohorts. The study is registered on ClinicalTrial.gov, NCT03852251, and closed to new participants; follow-up has been completed. FINDINGS: Between Jan 18, 2019, and Jan 8, 2021, 240 patients (83 [43 male and 40 female] in phase 1b and 157 in phase 2) were enrolled. Phase 2 enrolled 111 female patients with cervical cancer, 22 patients with oesophageal squamous cell carcinoma (15 male and seven female), and 24 patients with hepatocellular carcinoma (17 male and seven female). During dose escalation, no dose-limiting toxicities occurred. Grade 3-4 treatment-related adverse events occurred in 67 (28%) of 240 patients; the most frequent grade 3 or worse treatment-related adverse events were anaemia (seven [3%]), increased lipase (four [2%]), decreased bodyweight (three [1%]), decreased appetite (four [2%]), decreased neutrophil count (three [1%]), and infusion-related reaction (two [1%]). 17 (7%) patients discontinued treatment due to treatment-related adverse events. 54 (23%) of 240 patients reported serious treatment-related adverse events, including five patients who died (one due to myocardial infarction; cause unknown for four). In phase 2, in the cervical cancer cohort, with a median follow-up of 14·6 months (IQR 13·1-17·5), the objective response rate was 32·3% (32 of 99; 95% CI 23·3-42·5). In the oesophageal squamous cell carcinoma cohort, with a median follow-up of 17·9 months (IQR 4·0-15·1), the objective response rate was 18·2% (four of 22; 95% CI 5·2-40·3). In the hepatocellular carcinoma cohort, with a median follow-up of 19·6 months (IQR 8·7-19·8), the objective response rate was 16·7% (four of 24; 95% CI 4·7-37·4). INTERPRETATION: Cadonilimab showed an encouraging tumour response rate, with a manageable safety profile, suggesting the potential of cadonilimab for the treatment of advanced solid tumours. FUNDING: Akeso Biopharma. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Antineoplásicos Inmunológicos , Carcinoma Hepatocelular , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Neoplasias Hepáticas , Neoplasias del Cuello Uterino , Humanos , Masculino , Femenino , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Antígeno CTLA-4 , Receptor de Muerte Celular Programada 1 , Empatía , Anticuerpos Monoclonales Humanizados , Antineoplásicos Inmunológicos/efectos adversos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/inducido químicamente , Neoplasias Hepáticas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Shot is one of the fundamental unit in the content structure of a film, which can provide insights into the film-director's ideas. By analyzing the properties and types of shots, we can gain a better understanding of a film's visual language. In this paper, we delve deeply into the task of shot type classification, proposing that utilizing multimodal video inputs can effectively improve the accuracy of the task, and that shot type classification is closely related to low-level spatiotemporal semantic features. To this end, we propose a Lightweight Weak Semantic Relevance Framework (LWSRNet) for classifying cinematographic shot types. Our framework comprises two modules: a Linear Modalities Fusion module (LMF Module) capable of fusing an arbitrary number of video modalities, and a Weak Semantic 3D-CNN based Feature Extraction Backbone (WSFE Module) for classifying shot movement and scale, respectively. Moreover, to support practical cinematographic analysis, we collect FullShots, a large film shot dataset containing 27K shots from 19 movies with professionally annotations for movement and scale information. Following experimental results validate the correctness of our proposed hypotheses, while our framework also outperforms previous methods in terms of accuracy with fewer parameters and computations, on both FullShots and MovieShots datasets. Our code is available at ( https://github.com/litchiar/ShotClassification ).
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Nodular roundworms (Oesophagostomum spp.) are frequent parasites of the large intestine in several mammal species including humans and pigs, and their study often requires the use of infective larvae produced using several coproculture techniques. However, there is no published comparison of techniques to determine which yields the highest number of larvae. This study compares the number of larvae recovered from coprocultures made with charcoal, sawdust, vermiculite, and water in an experiment repeated twice using feces from a sow naturally infected with Oesophagostomum spp. at an organic farm. A higher number of larvae were recovered from coprocultures using sawdust relative to other types of media used, and this was consistent across the two trials. The use of sawdust to culture Oesophagostomum spp. larvae is rarely reported and our study suggests it can yield higher numbers relative to other media.
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Nematodos , Esofagostomiasis , Enfermedades de los Porcinos , Humanos , Animales , Porcinos , Femenino , Oesophagostomum/genética , Esofagostomiasis/parasitología , Larva , Recuento de Huevos de Parásitos , Heces/parasitología , Enfermedades de los Porcinos/parasitología , MamíferosRESUMEN
Background: Cervical cancer is one of the most common types of carcinoma in women and has high morbidity and mortality rates worldwide. Recurrent and metastatic disease remains difficult to treat. Receptor interacting protein kinase 1 (RIPK1) is a key molecule in mediating apoptosis, necroptosis, and inflammatory pathways downstream of death receptors and pattern recognition receptors. This study sought to explore the clinicopathological and prognosis significance of RIPK1 expression in cervical squamous cell carcinoma (CSCC). Methods: The data of 100 CSCC patients who underwent curative surgery from 2019 to 2020 were retrospectively included in this study. We collected the clinicopathological information of the patients and detected RIPK1 protein expression using immunohistochemistry. The Chi-square test and a 1-way analysis of variance were used to make comparisons between groups stratified by RIPK1 expression. A Pearson linear correlation analysis was used to evaluate the association between RIPK1 expression and the clinicopathological characteristics of the patients. A Cox regression analysis and Kaplan-Meier curves were used to analyze overall survival (OS) and progression-free survival (PFS). A multivariable regression analysis was conducted to identify the risk factors for an impaired prognosis in CSCC. Results: RIPK1 was found to be overexpressed in the CSCC tissues. RIPK1 expression was significantly associated with age, the preoperative serum squamous cell carcinoma antigen (SCC-Ag) level, lymph node metastasis, invasion depth, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, PFS, and OS (P<0.05). The PFS and OS differed significantly among patients with RIPK1 expression (P<0.05). The multivariate analysis showed that RIPK1 was not independent risk factors for PFS and OS in CSCC patients (P>0.05). Conclusions: The expression of RIPK1 was significantly upregulated in CSCC and was associated with the clinicopathological features of CSCC. RIPK1 might serve as a novel marker that can be used to predict the prognosis of CSCC patients and as a biological target for the treatment of CSCC.