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Sulfonated hierarchical H-ZSM-5 monoliths were synthesized via ice-templating as solid acid catalysts for biodiesel production. Characterization confirmed successful -SO3 group grafting, increasing acid density. The catalysts achieved over 90% conversion of oleic acid in esterification, with easy recovery and reuse, and the relationship between porosity and acid density was explored.
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Treatment of lung cancer leptomeningeal carcinomatosis (LM) remains challenging partly due to the biological nature of the blood-brain barrier (BBB). Cisplatin has limited effects on LM, and it is notorious for neurotoxicity. Aptamers are small oligonucleotides considered as antibody surrogates. Here we report a DNA therapeutics, AptBCis1. AptBCis1 is a cisplatin-conjugated, BBB-penetrating, and cancer-targeting DNA aptamer. Its backbone, AptB1, was identified via in vivo SELEX using lung cancer LM orthotopic mouse models. The AptB1 binds to EAAT2, Nucleolin, and YB-1 proteins. Treatment with AptBCis1 1 mg/kg (equivalent to cisplatin 0.35 mg/kg) showed superior tumor suppressive effects compared to cisplatin 2 mg/kg in mice with lung cancer LM diseases. The cerebrospinal fluid platinum concentration in the AptBCis1 group was 10% of that in the cisplatin group. The data suggested the translational potential of AptBCis1 in lung cancer with LM and in cancers in which platinum-based chemotherapy remains as the standard of care.
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Antineoplásicos , Aptámeros de Nucleótidos , Cisplatino , Neoplasias Pulmonares , Carcinomatosis Meníngea , Aptámeros de Nucleótidos/química , Cisplatino/farmacología , Cisplatino/química , Animales , Carcinomatosis Meníngea/tratamiento farmacológico , Carcinomatosis Meníngea/secundario , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Ratones , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Línea Celular Tumoral , FemeninoRESUMEN
Due to the seamless interfaces between solid polymer electrolytes (SPEs) and electrode materials, SPEs-based all-solid-state sodium-ion batteries (ASSSIBs) are considered promising energy storage systems. However, the sluggish Na+ transport and uncontrollable Na dendrite propagation still hinder the practical application of SPEs-based ASSSIBs. Herein, Ca-doped CeO2 (Ca-CeO2) nanotube framework is synthesized and integrated with poly (ethylene oxide) methyl ether acrylate-perfluoropolyether copolymer (PEOA-PFPE), resulting in multifunctional solid nanocomposite electrolytes (namely SNEs, i.e., PEOA-PFPE/Ca-CeO2). Our investigations demonstrate that the fluorous effect incurred by the fluorine-containing PEOA-PFPE and the oxygen vacancy effect induced by the Ca-CeO2 framework could synergistically promote the dissociation of sodium salt, ultimately enhancing the Na+ mobility in SNEs. Besides, the resultant SNEs construct rapid Na+ transport channels and homogenize the Na deposition in SNEs/Na interface, which effectively prevents the Na dendrite growth. Furthermore, the assembled carbon-coated sodium vanadium phosphate (NVP@C)||PEOA-PFPE/Ca-CeO2||Na coin cell delivers impressive rate capability of 97.9 mA h g-1 at 2 C and outstanding cycling stability with capacity retention of 84.3% after 300 cycles at 1 C. This work illustrates that constructing multifunctional SNEs via incorporating functional inorganic frameworks into fluorine-containing SPEs could be a promising strategy for the commercialization of robust and high-performance ASSSIBs.
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Gastrochilusbalangshanensis, a new orchid species from the Balang Mountain, Sichuan Province, Southwest China, is described and illustrated. It morphologically resembles G.affinis, but differs in having shorter stems, a reniform epichile and a sub-hemispherical hypochile (spur), obtuse-rounded at the apex. The results of molecular phylogenetic analyses based on nuclear ribosome internal transcribed spacer (nrITS) and four chloroplast DNA markers (matK, psbA-trnH, psbM-trnD and trnL-F) from 50 Gastrochilus species indicate that G.balangshanensis is closely related to G.heminii and G.bernhardtianus, also endemic to the Hengduan Mountains. The novelty is a branch and trunk epiphyte in mixed coniferous forest.
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Assessing the emissions of heavy-duty diesel trucks (HDDTs) is crucial for managing air quality in megacities, especially concerning nitrogen oxides (NOX) and black carbon (BC). This study employed mobile plume chasing to monitor the real-world emissions of over 7778 HDDTs in Shenzhen. The findings indicate that the real-world NOX emission factors (EF) of China IV trucks did not differ significantly from those of China III, whereas China V and VI vehicles demonstrated fleet-averaged reductions of 27% and 85%, respectively. For China V, a significant decrease in the NOX EF for HDDTs registered after 2017 was attributed to the installation of advanced aftertreatment systems, including diesel oxidation catalysts (DOC) and Diesel Particle Filters (DPF), along with selective catalytic reduction (SCR). These technologies led to an average reduction of 42% in NOX and 61% in BC emissions. Seasonal variations were pronounced, with winter (â¼20 °C) NOX EF 40% higher than summer (â¼35 °C) levels. Conversely, BC EF decreased by 26% in winter, indicating significant impacts of ambient temperature on emissions. Spatial analysis revealed that the average NOX EF of HDDTs on east freeways was 1.4 times higher than that on urban expressways, influenced by variations in the proportion of vehicle types segmented by usage. These findings offer a comprehensive perspective on HDDTs emissions, highlighting the importance of large-scale emission monitoring through plume chasing for precise and effective control of real-world HDDTs emissions.
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Contaminantes Atmosféricos , Contaminación del Aire , Monitoreo del Ambiente , Óxidos de Nitrógeno , Emisiones de Vehículos , Emisiones de Vehículos/análisis , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Óxidos de Nitrógeno/análisis , China , Contaminación del Aire/estadística & datos numéricos , Vehículos a Motor , Ciudades , Hollín/análisis , Estaciones del AñoAsunto(s)
Detección Precoz del Cáncer , Neoplasias Pulmonares , Tomografía Computarizada por Rayos X , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Detección Precoz del Cáncer/métodosRESUMEN
INTRODUCTION: This study aimed to evaluate the midpalatal suture (MPS) maturation stages using the cone-beam computed tomography classification method in Chinese children aged 5-10 years, adolescents aged 11-15 years, and postadolescents aged 16-20 years and identify a correlation between maturation stage and age and sex. METHODS: Axial sections of tomographic images from 717 participants (369 female and 348 male participants) aged 5-20 years were used to classify the maturation stage of the MPS (stages A, B, C, D, and E). Kappa statistics were used to evaluate the measurement error. The chi-square test was applied to analyze the differences in the distribution of MPS stages by age group and by sex among all participants, as well as the adolescent group. The Fisher exact test was employed to assess the differences in MPS stage distribution by sex among children aged 5-10 years and among the postadolescent group. The Mann-Whitney U test was used to assess the potential variance in age distribution between stages C and D. RESULTS: The most prevalent maturation stage was stage C (40.3%). Of the total population, 69.4% had MPS in stages A, B, or C. A significant difference in age distribution was observed between stage C and stage D (P <0.001). The distribution of the MPS maturation stage significantly varied by age group (P <0.001) and sex (P <0.001). CONCLUSIONS: The distribution of participants in advanced maturation stages increases with age. Female patients generally experience earlier MPS maturation than male patients, particularly between the ages of 11-20 years.
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Colostrum from yaks and buffaloes possesses substantial nutritional value, yet the complete array of metabolites within remains insufficiently elucidated. This study scrutinizes the metabolite profiles of yak, buffalo, and cow colostrum utilizing targeted metabolomics paired with ultra-performance liquid chromatography-tandem triple quadrupole linear ion trap mass spectrometry (UPLC-QTRAP-MS). The analysis detected 362 metabolites across all samples. Furthermore, 63, 77, and 46 differential metabolites were selected between yak and buffalo colostrum, yak and cow colostrum, and buffalo and cow colostrum, respectively. Yak colostrum notably contained higher concentrations of inositol, glycine, and carnitine, whereas buffalo colostrum was distinguished by a substantial presence of primary bile acids, which facilitate fat digestion. These findings offer profound insights into yak and buffalo colostrum, providing critical data to propel advancements in the dairy industry.
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PFAS (per- and polyfluoroalkyl substances) have been extensively used across numerous industries and consumer goods. Due to their high persistence and mobility, they are ubiquitous in the environment. Exposure to PFAS occurs in people via multiple pathways such as dermal contact, water supply, air inhalation, and dietary intake. Even if some PFAS are being phased out because of their persistent presence in the environment and harmful impacts on human health, mixes of replacement and legacy PFAS will continue to pollute the ecosystem. Numerous toxicological investigations have revealed harmful effects of PFAS exposure on female reproductive health, e.g., polycystic ovaries syndrome, premature ovarian failure, endometriosis, reproductive system tumors, pregnancy complications, and adverse pregnancy outcomes. Despite extensive epidemiological studies on the reproductive toxicity of PFAS, research findings remain inconsistent, and the underlying mechanisms are not well understood. In this review, we give an in-depth description of the sources and pathways of PFAS, and then review the reproductive toxicity of PFAS and its possible mechanisms.
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Sustainable Cr(VI) reduction by microbial fuel cell (MFC) is a major challenge due to the electrode passivation and available electron donors. In this study, the chromate removal across a period of more than three months in a membrane-less TPBC-MFC with solid watermelon rind (SWMR) as electron donors was investigated. The TPBC benefited the Cr(VI) reduction and voltage output owing to the enhanced mass transfer. The average Cr(VI) removal efficiency (RE) of 97%, effluent COD of 80 mg/L and voltage output of 130 mV were achieved during the long-term operation on the TPBC-MFC. The SEM-EDS analysis showed that all biofilms were predominated by rod- and coccus-shaped bacteria and the Cr(VI) reduction was mainly carried out by the S-cathode. The XPS, XRD and FT-IR analysis revealed that the major product of cathodic Cr(VI) reduction was a Cr(III) precipitate in the form of Cr(OH)3. Microbial community structure disclosed that fermentation microorganisms (e.g. Anaeroarcus) and electroactive bacteria (e.g. Porphyromonadaceae) jointly responsible for SWMR degradation and electricity generation were dominant at the anode, while the chromate-associated microorganisms (e.g. Comamonadaceae and Cloacibacterium) dominated at the cathode. The biofilms adsorbing Cr(OH)3 precipitates fell off from the cathode periodically to avoid the passivation. Overall, our study suggests a really sustainable approach with which a goal of simultaneously reusing watermelon rind, reducing Cr(VI) and producing electricity was attained perfectly.
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BACKGROUND: Vegetative insecticidal proteins (Vip3) from Bacillus thuringiensis (Bt) have been utilized for control of lepidopteran insect pests. The majority of known Vip3 proteins possess exceptional high toxicity against Noctuid insects such as the fall armyworm (FAW, Spodoptera frugiperda), beet armyworm (BAW, Spodoptera exigua) and cotton bollworm (CBW, Helicoverpa armigera), but generally have relatively low or even no activity against some very important pest insects, such as Asian corn borer (ACB, Ostrinia furnacalis), European corn borer (ECB, Ostrinia nubilalis), rice stem borer (RSB, Chilo suppressalis) and oriental armyworm (OAW, Mythimna separata). RESULTS: Here, we report mutant Vip3Af with a single amino acid mutation, Vip3Af-T686R, which gains significantly higher insecticidal activity against ACB, OAW and BAW, while retaining high activity against FAW, CBW and RSB. Protein proteolytic activation in vitro showed that the proteolytic activation efficiency of the mutant protein was greater than the wild-type protein in the midgut juice of ACB, OAW and BAW. Transgenic corn expressing this mutant Vip3Af showed high levels of resistance to ACB, OAW, FAW, BAW and CBW. CONCLUSION: Our results suggest that Vip3Af may be a superior Vip3A mutant for the development of transgenic crops with resistance to a broad range of lepidopteran pest species. © 2024 Society of Chemical Industry.
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PURPOSE: To investigate the value of 2-deoxy-18f-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and circulating tumor cells (CTCs) for the differential diagnosis of patients with benign lung diseases and those with NSCLC. To explore the phenotypic heterogeneity of CTCs and their correlation with FDG uptake in patients with Stage I-IV NSCLC. METHODS: Blood specimens from patients with benign lung diseases and patients with primary NSCLC were collected for the detection of CTCs and their subtypes (epithelial, mixed, and mesenchymal) and analyzed for 18F-FDG PET/CT tumor metabolic parameters, including the maximum standardized uptake value (SUVmax), standard uptake value (SUL), metabolic tumor volume of primary lesion (MTV), total lesion glycolysis of primary lesion (TLG). Clinical data including age, gender, smoking history, tumor size, TNM stage and pathology type were also collected. The value of the two method alone and in combination for the differential diagnosis of benign and malignant was comparatively analyzed. Finally, the differences in CTC and its subtypes in different stages of NSCLC were compared, and FDG metabolic parameters were correlated with CTC subtypes. RESULTS: There were a total of 65 patients with pulmonary diseases, including 12 patients with benign pulmonary diseases and 53 patients with NSCLC. The mean age was 67 ± 10 (38-89 years), 27 were females and 38 were males. 31 (22 males and 9 females) had a long history of smoking. The mean size of the largest diameter of all single lesions was 36 ± 22 mm with a range of 10-108 mm. Seven out of 12 benign diseases were inflammatory granulomatous lesions and 5 were inflammatory pseudotumours. Twenty-four out of 53 NSCLC were adenocarcinomas and 29 were squamous carcinomas. Twelve out of 53 patients with NSCLC were in Stage I, 10 were in Stage II, 17 were in Stage III and 14 were in Stage IV. SUVmax, SUL, MTV, TLG, total CTCs, epithelial CTCs, and mixed CTCs were all valuable in the differential diagnosis of benign and malignant. TLG combined with mixed CTCs was statistically different from all other diagnostic methods (p < 0.05) and higher than any other diagnostic criteria. In the differential diagnosis of benign and Stage I NSCLC, only total CTC (Z = -2.188 p = 0.039) and mixed CTCs (Z = -3.020 p = 0.014) had certain diagnostic efficacy, and there was no statistical difference between them (p = 0.480). Only mesenchymal CTCs differed in Stage I-IV NSCLC, with a higher number of those who developed distant metastases than those who had non-distant metastases. Epithelial CTCs correlated with SUVmax (r = 0.333, p = 0.015) and SUL (r = 0.374, p = 0.006). Mmesenchymal CTCs correlated with MTV (r = 0.342, p = 0.018) and TLG (r = 0.319, p = 0.02). Further subgroup analyses revealed epithelial CTCs were correlated with SUVmax (r = 0.543, p = 0.009) and SUL (r = 0.552, p = 0.008), and the total CTCs was correlated with SUVmax (r = 0.622, p = 0.003), SUL (r = 0.652, p = 0.003), MTV (r = 0.460, p = 0.031), and TLG (r = 0.472, p = 0.027) in the early group (Stage I-II). Only mesenchymal CTCs was associated with MTV (r = 0.369, p = 0.041), and TLG (r = 0.415, p = 0.02) in the intermediate-late group (Stage III-IV). CONCLUSION: Both FDG PET metabolic parameters and CTCs demonstrated diagnostic value for NSCLC, and combining TLG with mixed CTCs could enhance their diagnostic efficacy. The total CTCs and mixed CTCs showed greater diagnostic value than FDG PET in distinguishing benign lesions from Stage I NSCLC. In NSCLC patients, the epithelial CTCs exhibited a positive correlation with SUVmax and SUL, while mesenchymal CTCs correlated with MTV, and TLG. Besides, epithelial CTCs showed stronger correlations with SUVmax and SUL, and total CTCs showed stronger correlations with SUVmax, SUL, MTV, and TLG in Stage I-II NSCLC. Only mesenchymal CTCs in Stage III-IV NSCLC showed correlations with MTV and TLG. Stage IV NSCLC cases displayed a higher number of mesenchymal CTCs.
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Carcinoma de Pulmón de Células no Pequeñas , Fluorodesoxiglucosa F18 , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Masculino , Femenino , Células Neoplásicas Circulantes/patología , Células Neoplásicas Circulantes/metabolismo , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico , Persona de Mediana Edad , Anciano , Diagnóstico Diferencial , Estadificación de Neoplasias , Adulto , Anciano de 80 o más Años , RadiofármacosRESUMEN
DNA polymerases are important drug targets, and many structural studies have captured them in distinct conformations. However, a detailed understanding of the impact of polymerase conformational dynamics on drug resistance is lacking. We determined cryoelectron microscopy (cryo-EM) structures of DNA-bound herpes simplex virus polymerase holoenzyme in multiple conformations and interacting with antivirals in clinical use. These structures reveal how the catalytic subunit Pol and the processivity factor UL42 bind DNA to promote processive DNA synthesis. Unexpectedly, in the absence of an incoming nucleotide, we observed Pol in multiple conformations with the closed state sampled by the fingers domain. Drug-bound structures reveal how antivirals may selectively bind enzymes that more readily adopt the closed conformation. Molecular dynamics simulations and the cryo-EM structure of a drug-resistant mutant indicate that some resistance mutations modulate conformational dynamics rather than directly impacting drug binding, thus clarifying mechanisms that drive drug selectivity.
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Antivirales , Microscopía por Crioelectrón , ADN Polimerasa Dirigida por ADN , Farmacorresistencia Viral , Simulación de Dinámica Molecular , Proteínas Virales , Antivirales/farmacología , Antivirales/química , Antivirales/metabolismo , ADN Polimerasa Dirigida por ADN/metabolismo , ADN Polimerasa Dirigida por ADN/química , Proteínas Virales/metabolismo , Proteínas Virales/química , Humanos , ADN Viral/metabolismo , ExodesoxirribonucleasasRESUMEN
Background: Currently, chemotherapy plus immunotherapy followed by maintenance therapy with immune monotherapy is the preferred first-line treatment option for extensive-stage small cell lung cancer (ES-SCLC), but with limited overall survival (OS) and progression-free survival (PFS) benefits. The combination of anti-angiogenic drugs with immunotherapy has shown encouraging anti-tumor activity and tolerability, with some degree of overcoming immune resistance. This study aimed to evaluate the effectiveness and safety of anlotinib plus anti-programmed cell death 1/ligand 1 (anti-PD-1/PD-L1) antibodies as maintenance therapy after first-line chemotherapy combined with immunotherapy in ES-SCLC. Methods: Between June 2020 and December 2021, 12 patients with newly diagnosed ES-SCLC in the First Affiliated Hospital of Army Medical University were retrospectively analyzed. All patients without disease progression after 4-6 cycles of first-line platinum-containing chemotherapy plus anti-PD-1/PD-L1 antibodies received anlotinib (12 mg oral/day, days 1-14, followed by 1 week off, every 3 weeks per cycle) plus anti-PD-1/PD-L1 antibodies as maintenance therapy. Several patients underwent chest radiotherapy (intensity-modulated radiotherapy using a 6 MV X-ray) without disease progression before maintenance therapy. The effectiveness and safety of anlotinib plus anti-PD-1/PD-L1 antibodies as maintenance therapy after first-line chemotherapy combined with immunotherapy in ES-SCLC were evaluated. Results: The median follow-up time was 31.1 months. During first-line treatment (including maintenance therapy), one patient achieved a complete response, eight patients achieved a partial response (PR), and three patients had stable disease, with an objective response rate of 75.0% and a disease control rate of 100.0%. During maintenance therapy with anlotinib plus anti-PD-1/PD-L1 antibodies, 50.0% of patients achieved further lesion remission on the basis of the prior initial treatment, of which one patient achieved a PR. The median PFS was 13.6 [95% confidence interval (CI): 11.2-15.6] months, and the median OS was 19.5 (95% CI: 14.5-24.5) months. Treatment-related any grade and grade 3-4 adverse events (AEs) were reported in 100.0% and 58.3% of patients, respectively. No life-threatening AEs were observed. Grade 3-4 AEs included leukocytopenia (58.3%, 7/12), thrombocytopenia (33.3%, 4/12), nausea (33.3%, 4/12), anemia (16.7%, 2/12), and fatigue (8.3%, 1/12). All AEs during maintenance therapy were tolerated and were regarded as grade 1-2, with the majority being fatigue, nausea, rash, and hemoptysis. Conclusions: The combination of anlotinib with anti-PD-1/PD-L1 antibodies demonstrated encouraging effectiveness and safety in treating patients with ES-SCLC, suggesting that it may be a preferred option for maintenance therapy after first-line chemotherapy combined with immunotherapy.
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Eastern equine encephalitis virus (EEEV) is the most virulent alphavirus that infects humans, and many survivors develop neurological sequelae, including paralysis and intellectual disability. Alphavirus spike proteins comprise trimers of heterodimers of glycoproteins E2 and E1 that mediate binding to cellular receptors and fusion of virus and host cell membranes during entry. We recently identified very-low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as cellular receptors for EEEV and a distantly related alphavirus, Semliki Forest virus (SFV). Here, we use single-particle cryo-electron microscopy (cryo-EM) to determine structures of the EEEV and SFV spike glycoproteins bound to the VLDLR ligand-binding domain and found that EEEV and SFV interact with the same cellular receptor through divergent binding modes. Our studies suggest that the ability of LDLR-related proteins to interact with viral spike proteins through very small footprints with flexible binding modes results in a low evolutionary barrier to the acquisition of LDLR-related proteins as cellular receptors for diverse sets of viruses.
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Microscopía por Crioelectrón , Virus de la Encefalitis Equina del Este , Receptores de LDL , Receptores de LDL/metabolismo , Receptores de LDL/química , Virus de la Encefalitis Equina del Este/metabolismo , Virus de la Encefalitis Equina del Este/ultraestructura , Humanos , Animales , Virus de los Bosques Semliki/metabolismo , Unión Proteica , Receptores Virales/metabolismo , Receptores Virales/química , Proteínas del Envoltorio Viral/metabolismo , Proteínas del Envoltorio Viral/química , Proteínas del Envoltorio Viral/ultraestructura , Modelos MolecularesRESUMEN
Perfluoroalkyl and polyfluoroalkyl substances (PFASs), widely utilized in various industries, may pose potential reproductive well-being risks. However, the research on the impact of PFAS exposures on pregnancy and live birth rates remains scarce. To address this gap, we conducted a cross-sectional study using the data from the United States National Health and Nutrition Examination Survey (NHANES) collected between 2013 and 2018. We focused on six PFAS compounds measured in the serum of women aged 20 to 50 years, employing the Poisson regression, Quantile G-composition (Qgcomp), and Weighted Quantile Sum (WQS) regression models. Adjusting for age, racial/ethnic origin, educational level, marital status, family income, body mass index (BMI), menarche age, birth control pill use, and other female hormone consumption, the Poisson regression identified significant negative associations between the individual PFAS exposures and pregnancy and live birth numbers (p < 0.05 for all 24 null hypotheses for which the slope of the trend line is zero). The Qgcomp analysis indicated that a one-quartile increase in the mixed PFAS exposures was associated with reductions of 0.09 (95% CI: -0.15, -0.03) in the pregnancy numbers and 0.12 (95% CI: -0.19, -0.05) in the live birth numbers. Similarly, the WQS analysis revealed that a unit increase in the WQS index corresponded to decreases of 0.14 (95% CI: -0.20, -0.07) in the pregnancy numbers and 0.14 (95% CI: -0.21, -0.06) in the live birth numbers. Among the six specific PFAS compounds we studied, perfluorononanoic acid (PFNA) had the most negative association with the pregnancy and live birth numbers. In conclusion, our findings suggest that PFAS exposures are associated with lower pregnancy and live birth numbers among women of reproductive age.
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Endocrine-disrupting chemicals (EDCs) exhibited the detriment in female reproductive health. Our objective was to investigate the individual and mixture effects of EDCs present in follicular fluid, the environment in which oocytes grow and develop, on early reproductive outcomes. We recruited 188 women seeking reproduction examination from the Study of Exposure and Reproductive Health (SEARCH) cohort between December 2020 and November 2021. We assessed the concentrations of 7 categories of 64 EDCs in follicular fluid, and measured early reproductive outcomes, including retrieved oocytes, mature oocytes, normal fertilized oocytes, and high-quality embryos. In this study Monomethyl phthalate (MMP) (2.17 ng/ml) were the compounds found in the highest median concentrations in follicular fluid. After adjusting for multiple testing, multivariate regression showed that multiple EDCs were significantly negatively associated with early assisted reproduction outcomes. For example, MMP showed a significant negative correlation with the number of high quality embryos (ß: -0.1, 95 % CI: -0.15, -0.04). Specifically, eight types of EDCs were significantly negatively associated with four early assisted reproductive outcomes (ß range: -0.2 â¼ -0.03). In the mixed exposure model, we found that mixtures of EDC were significantly negatively correlated with all four outcomes. In the quantile g-computation (QGCOMP) model, for each interquartile range increase in the concentration of EDC mixtures, the number of oocytes retrieved, mature oocytes, normally fertilized oocytes, and high-quality embryos decreased by 0.46, 0.52, 0.77, and 1.2, respectively. Moreover, we identified that phthalates (PAEs) predominantly contributed to the negative effects. Future research should validate our findings.
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Disruptores Endocrinos , Líquido Folicular , Oocitos , Líquido Folicular/química , Líquido Folicular/metabolismo , Femenino , Oocitos/efectos de los fármacos , Humanos , Adulto , Fertilización/efectos de los fármacos , Ácidos FtálicosRESUMEN
Purpose: To evaluate the utility of supine roll test (SRT) and alternative positional tests, such as head-shaking test (HST), seated supine positioning test (SSPT), bow and lean test (BLT), and rapid axial roll test (RART) in determining the affected semicircular canal of horizontal semicircular canal benign paroxysmal positional vertigo (HSC-BPPV). Methods: In an observational cohort study, 553 patients diagnosed with HSC-BPPV were divided into five groups in terms of different positional tests received: SRT group (n = 110), HST+ SRT (n = 112), BLT + SRT (n = 114), SSPT+SRT (n = 108) and RART+SRT (n = 109). The same method was used for the last four groups: The patients were first subjected to different alternative positional tests and then to SRT, and the nystagmus was observed separately to determine the affected side. The primary outcomes compared included the accuracy and sensitivity of these tests in the determination of the affected semicircular canal in HSC-BPPV. Results: Patients with nystagmus elicited by positional tests accounted for 84.99% (470/553). The elicitation rate of nystagmus of SRT was lowest, being 77.27% (85/110). The elicitation rate of nystagmus were higher in the test groups than in the control group, and RART+SRT group yielded the highest elicitation rate of nystagmus (95.41%, 104/109). Among the alternative positional tests, RART attained the highest elicitation rate of nystagmus (101/109, 92.66%). Comparison between alternative positional tests and SRT, RART and SRT showed obviously better agreement in determining the affected semicircular canal (85.45%, 96/109) and eliciting nystagmus (95.41%, Kappa = 0.642), but no difference was found in curative effect when the affected side was accurately determined (χ2 = 1.618, p = 0.655). Conclusion: All alternative positional tests are helpful for eliciting nystagmus in patients with HSC-BPPV, and the significant advantages of RART include high-sensitivity in eliciting nystagmus and high accuracy in determining the affected semicircular canal, which provided objective support for the correct diagnosis of HSC-BPPV and the successful reduction of otolith.
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Cystatin C (CysC) has been proven to be used to diagnose acute kidney injury (AKI) rapidly and sensitively early. Therefore, it is urgent to develop a sensitive, novel, and rapid method for detecting CysC. In this work, a novel photoelectrochemical (PEC) biosensor was designed for ultrasensitive CysC detection. Ti-MOF@DM-LZU1@Au as a photosensitive material was first modified on the ITO electrode surface. Then, Ab1 and CysC were assembled on the electrode via the specific immunoresponse of an antigen and antibody. Lastly, the conjugate Ab2/l-Cys bilayer/l-Cys-hemin/G-quadruplex with self-catalytic enzyme performance, as a signal amplification approach, could further react with CysC and Ab1, which resulted in a stronger photocurrent. As expected, the constructed PEC sensor realized the ultrasensitive detection of CysC, with a detection range of 10 pg/mL to 16 µg/mL and a lower limit of 8.023 pg/mL. The biosensor had excellent repeatability, selectivity, and stability. Moreover, it can provide a new method for the sensitive and rapid detection of other protein molecules in clinical practice.
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AIM: This study aimed to explore the association between patient-reported items at different time points after hematopoietic stem cell transplantation (HSCT) and long-term survival. METHODS: We conducted a study with 144 allogeneic HSCT patients, following them for 5 years post-transplantation. Data from the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) questionnaire were collected before transplantation and at 1, 3, 6, 12, 18, 36, and 60 months after transplantation. Demographic characteristics and survival status were also assessed. RESULTS: Among the 144 cases, the 5-year overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM), and graft-versus-host disease-free (GRFS) rates were 65%, 48%, 17%, and 36% respectively. Health-related quality of life (HRQOL) showed a fluctuating pattern over 5 years. Using a latent class mixed model, patients were classified into two groups based on their physical well-being (PWB) scores during the 60-month follow-up. Class 1 had initially lower PWB scores, which gradually increased over time. In contrast, Class 2 maintained higher PWB scores with slight increases over time. Kaplan-Meier survival analysis revealed that Class 1 had better OS (70.9% vs. 52.9%, p = 0.021), PFS (60.5% vs. 41.2%, p = 0.039), and GRFS (35.1% vs. 29.3%, p = 0.035) compared to Class 2. CONCLUSIONS: Patients who had higher initial PWB scores after HSCT demonstrated improved long-term survival outcomes. The PWB score could serve as a valuable predictor for the prognosis of HSCT.