1,359 research outputs found

    Apatinib combined with camrelizumab in the treatment of recurrent/metastatic nasopharyngeal carcinoma: a prospective multicenter phase II study

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    BackgroundPreclinical studies demonstrated that immune checkpoint inhibitors combined with antiangiogenic drugs have a synergistic anti-tumor effect. This present phase II trial aimed to evaluate the efficacy and safety of apatinib combined with camrelizumab in patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC).MethodsPatients with RM-NPC were administered with apatinib at 250 mg orally once every day and with camrelizumab at 200 mg via intravenous infusion every 2 weeks until the disease progressed or toxicity became unacceptable. The objective response rate (ORR) was the primary endpoint, assessed using RECIST version 1.1. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety were the key secondary endpoints. This study was registered with ClinicalTrials.gov, NCT04350190.ResultsThis study enrolled 26 patients with RM-NPC between January 14, 2021 and September 15, 2021. At data cutoff (March 31, 2023), the median duration of follow-up was 16 months (ranging from 1 to 26 months). The ORR was 38.5% (10/26), the disease control rate (DCR) was 61.5% (16/26), and the median PFS was 6 months (IQR 3.0-20.0). The median OS was 14 months (IQR 6.0-21.25). Treatment-related grade 3 or 4 adverse events occurred in seven (26.9%) patients, and comprised anemia (7.7%), stomatitis (3.8%), headache (3.8%), pneumonia (7.7%), and myocarditis (3.8%). There were no serious treatment-related adverse events or treatment-related deaths.ConclusionIn patients with RM-NPC, apatinib plus camrelizumab showed promising antitumor activity and manageable toxicities

    Genetic characteristics and potential pathogenic agents in Campylobacter upsaliensis based on genomic analysis

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    ABSTRACTCampylobacter upsaliensis was the most common Campylobacter species in pets’ gastrointestinal tracts and has been isolated from patients with bacteremia, hemolytic-uremic syndrome, spontaneous abortion, and Guillain-Barré syndrome. However, the genetic characteristics and the full extent of its significance as a human pathogen remain to be fully understood. This study involved an investigation for genomic analysis of 154 strains from different sources and additional antimicrobial resistance profiles of 26 strains for this species. The genomes contained 1,558–1,971 CDS and the genome sizes were estimated to vary from 1.53 Mb to 1.86 Mb, with an average GC content of  34.71%. The entire analyzed genomes could be divided into three clades (A, B, and C) based on ANI and phylogenomic analysis. Significantly, nearly all strains in Clade B were isolated from patient samples, and the virulence-related sequences FlgD, GmhA, and CdtC might serve as determining factors for the classification of Clade B. Half of the tested isolates had MIC values over 64 μg mL−1 for nalidixic acid, gentamicin, and streptomycin. Isolates from pets in China carried more resistant elements in the genomes. This study both provided a comprehensive profile of C. upsaliensis for its genomic features and suggested some pathogenic agents for human infection with this species

    In situ electrolyte design: understanding the prospects and limitations of a high capacity Ca(BH4)2 anode for all solid state batteries

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    All-solid-state batteries have gained considerable attention due to their high safety and energy density. However, solid state electrolytes which contribute to the ionic conductivity component of a composite electrode, are not utilized during the electrode reaction and cannot directly contribute to capacity. This study focuses on decreasing the amount of electrolyte in the electrode by utilizing Ca(BH4)2 as an active electrode material. In this work, the charge-discharge properties of Ca(BH4)2 as an electrode material were determined for the first time. The lithiation of the Ca(BH4)2 anode creates LiBH4 within the electrode mixture, providing new Li-ion conduction pathways within the composite electrode in situ. An electrode fabricated only from Ca(BH4)2 and acetylene black (AB) showed an initial capacity of 473 mAh g-1 at 120 °C, which is comparable to the performance obtained from a composite electrode additionally containing electrolyte. Evidently, Ca(BH4)2 is a promising candidate negative electrode for increased energy density all-solid-state Li-ion batteries

    Drug repurposing screens identify Tubercidin as a potent antiviral agent against porcine nidovirus infections

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    The emergence of new coronaviruses poses a significant threat to animal husbandry and human health. Porcine epidemic diarrhea virus (PEDV) is considered a re-emerging porcine enteric coronavirus, which causes fatal watery diarrhea in piglets. Currently, there are no effective drugs to combat PEDV. Drug repurposing screens have emerged as an attractive strategy to accelerate antiviral drug discovery and development. Here, we screened 206 natural products for antiviral activity using live PEDV infection in Vero cells and identified ten candidate antiviral agents. Among them, Tubercidin, a nucleoside analog derived from Streptomyces tubercidicus, showed promising antiviral activity against PEDV infection. Furthermore, we demonstrated that Tubercidin exhibited significant antiviral activity against both classical and variant PEDV. Time of addition assay showed that Tubercidin displayed a significant inhibitory effect on viral post-entry events but not during other periods. Molecular docking analysis indicated that Tubercidin had better docking efficiency and formed hydrophobic interactions with the active pocket of RNA-dependent RNA polymerase (RdRp) of PEDV and other nidoviruses. Additionally, Tubercidin can effectively suppress other porcine nidoviruses, such as SADS-CoV and PRRSV, demonstrating its broad-spectrum antiviral properties. In summary, our findings provide valuable evidence for the antiviral activity of Tubercidin and offer insights into the development of new strategies for the prevention and treatment of coronavirus infections

    Genetic characteristics and potential pathogenic agents in <i>Campylobacter upsaliensis</i> based on genomic analysis

    No full text
    Campylobacter upsaliensis was the most common Campylobacter species in pets’ gastrointestinal tracts and has been isolated from patients with bacteremia, hemolytic-uremic syndrome, spontaneous abortion, and Guillain-Barré syndrome. However, the genetic characteristics and the full extent of its significance as a human pathogen remain to be fully understood. This study involved an investigation for genomic analysis of 154 strains from different sources and additional antimicrobial resistance profiles of 26 strains for this species. The genomes contained 1,558–1,971 CDS and the genome sizes were estimated to vary from 1.53 Mb to 1.86 Mb, with an average GC content of  34.71%. The entire analyzed genomes could be divided into three clades (A, B, and C) based on ANI and phylogenomic analysis. Significantly, nearly all strains in Clade B were isolated from patient samples, and the virulence-related sequences FlgD, GmhA, and CdtC might serve as determining factors for the classification of Clade B. Half of the tested isolates had MIC values over 64 μg mL−1 for nalidixic acid, gentamicin, and streptomycin. Isolates from pets in China carried more resistant elements in the genomes. This study both provided a comprehensive profile of C. upsaliensis for its genomic features and suggested some pathogenic agents for human infection with this species.</p

    Neonatal per- and polyfluoroalkyl substance exposure in relation to retinoblastoma

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    BackgroundNeonatal per- and polyfluoroalkyl substance (PFAS) exposure can disrupt hormonal homeostasis and induce neuro- and immunotoxicity in children. In this exploratory study, we investigated associations between PFAS levels in neonatal dried blood spots and retinoblastoma risk.Materials and methodsThis study included 501 retinoblastoma cases born from 1983 to 2011 and 899 controls frequency-matched by birth year (20:1 matching ratio), born to 755 US-born and 366 Mexico-born mothers in California. Perfluorooctanesulfonic acid (PFOS), perflurooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) feature intensities were identified from neonatal blood spots from California newborn Genetic Disease Screening Program. Using logistic regression, we assessed whether an interquartile range (IQR) increase of PFAS levels or having above-mean levels of PFAS in blood affects retinoblastoma risk overall or its subtypes (i.e., unilateral, bilateral). We assessed children of US-born and Mexico-born mothers, separately.Results and discussionAmong all children, above-mean PFOS levels at birth increased the odds of retinoblastoma overall by 29% (95% Confidence Interval (CI): 1.00, 1.67) and unilateral retinoblastoma by 42% (95% CI: 1.03, 1.97). For children of Mexico-born mothers, we estimated the highest odds of retinoblastoma overall (adjusted odds ratio (aOR): 1.67; 95% CI: 1.06, 2.66) and bilateral retinoblastoma (aOR: 2.06; 95% CI: 1.12, 3.92) with above-mean PFOS levels. Among children of US-born mothers, higher PFOS levels increased the odds of unilateral retinoblastoma by 15% (95% CI: 0.99, 1.35) for each IQR increase and by 71% among children with above-mean PFOS levels (95% CI: 1.04, 2.90). In addition, for children of US-born mothers, PFOA increased the odds of retinoblastoma overall (aOR: 1.41; 95% CI: 1.00, 2.02 for above-mean levels, aOR: 1.06; 95% CI: 0.98, 1.16 per IQR increase). PFNA was not associated with retinoblastoma risk.ConclusionsOur results suggested that PFOS and PFOA might contribute to retinoblastoma risk in children born in California

    A cross-sectional study on knowledge and behavior regarding medication usage among guardians of left-behind children: evidence from China

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    Abstract Purpose The primary objective of this study was to evaluate knowledge and behavior of medication use among guardians of left-behind children (LBC) and non-left-behind children (NLBC). Methods A cross-sectional study was conducted in Chengdu, the major city of southwestern China from May 2020 to August 2020. A logistic regression model was conducted to assess medication-related knowledge and behavior of guardians between the LBC group and NLBC group, adjusted for confounders. Stratified analysis was further performed. Results The overall mean scores for knowledge and for behavior were 20.22 (standard deviation = 4.472) and 15.77 (standard deviation = 3.604), respectively. No significant difference was found in medication-related knowledge and behavior scores between LBC and NLBC guardians (P > 0.05). A significant difference was only observed after adjusting for past medical history and history of present illness (HPI). Conclusion There was no significant difference in the awareness and behavior of medication use between guardians of LBC and NLBC in this study, having more contact with the doctor was an effective method of health education that could possibly improve their health literacy

    Inactivation of photosynthetic cyclic electron transports upregulates photorespiration for compensation of efficient photosynthesis in Arabidopsis

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    Plants have multiple mechanisms to maintain efficient photosynthesis. Photosynthetic cyclic electron transports around photosystem I (CET), which includes the PGR5/PGRL1 and NDH pathways, and photorespiration play a crucial role in photosynthetic efficiency. However, how these two mechanisms are functionally linked is not clear. In this study, we revealed that photorespiration could compensate for the function of CET in efficient photosynthesis by comparison of the growth phenotypes, photosynthetic properties monitored with chlorophyll fluorescence parameters and photosynthetic oxygen evolution in leaves and photorespiratory activity monitored with the difference of photosynthetic oxygen evolution rate under high and low concentration of oxygen conditions between the deleted mutant PGR5 or PGRL1 under NDH defective background (pgr5 crr2 or pgrl1a1b crr2). Both CET mutants pgr5 crr2 and pgrl1a1b crr2 displayed similar suppression effects on photosynthetic capacities of light reaction and growth phenotypes under low light conditions. However, the total CET activity and photosynthetic oxygen evolution of pgr5 crr2 were evidently lower than those of pgrl1a1b crr2, accompanied by the upregulation of photorespiratory activity under low light conditions, resulting in severe suppression of photosynthetic capacities of light reaction and finally photodamaged phenotype under high light or fluctuating light conditions. Based on these findings, we suggest that photorespiration compensates for the loss of CET functions in the regulation of photosynthesis and that coordination of both mechanisms is essential for maintaining the efficient operation of photosynthesis, especially under stressed conditions

    Overexpressed PKM2 promotes macrophage phagocytosis and atherosclerosis

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    Abstract Background The expression of pyruvate kinase muscle 2 (PKM2) is augmented in macrophages of patients with atherosclerotic coronary artery disease. The role of PKM2 in atherosclerosis is to be determined. Methods Global and myeloid cell‐specific PKM2 knock‐in mice with ApoE−/− background (ApoE−/−, PKM2KI/KI and Lyz2‐cre, ApoE−/−, and PKM2flox/flox) were produced to evaluate the clinical significance of PKM2 in atherosclerosis development. Wild‐type and PKM2 knock‐in macrophages were isolated to assess the function of PKM2 in macrophage phagocytosis. Atherosclerotic mice were treated with PKM2 inhibitor shikonin (SKN) to evaluate the therapeutic potential of PKM2 suppression in atherosclerosis. Results Oxidized low‐density lipoprotein (oxLDL) upregulated PKM2 in macrophages. PKM2 in return promoted the uptake of oxLDL by macrophages. Overexpressed PKM2 accelerated atherosclerosis in mice. SKN blocked the progress of mouse atherosclerosis. Conclusions PKM2 accelerates macrophage phagocytosis and atherosclerosis. Targeting PKM2 is a potential therapy for atherosclerosis
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