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As widely used antibiotics, tetracycline residues exist in food and environmental media, which pose certain hidden dangers and negative effects on public health. Therefore, the sensing and discrimination of tetracycline analogs (TCs) have great significance for improving food safety and preventing environmental pollution. Herein, a 7-hydroxycoumarin-3-carboxylic acid-embedded Eu-MOF (HC@Eu-MOF) material was constructed and then developed for the detection of TCs. Upon addition of TCs, the synthesized sensor displays opposite fluorescence changes at two different wavelengths due to the simultaneous presence of the inner filter effect (IFE) and the antenna effect (AE), and achieves a stable ratio signal response within 90 s. In addition, six important tetracycline analogs, including chlortetracycline (CTC), oxytetracycline (OTC), tetracycline (TC), metacycline (MC), doxycycline (DC) and demeclocycline (DMC) can be discriminated with 100 % accuracy through the principal component analysis even in extremely complicated mixtures. Further, a smartphone-assisted portable device was applied for visual sensing of TCs. The as-developed platform possessed the characteristics of simple synthesis, fast response, high sensitivity, and high stability, which further lays a further foundation for the on-site visual detection and discrimination of TCs in real samples.
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Cumarínicos , Estruturas Metalorgânicas , Tetraciclinas , Cumarínicos/química , Estruturas Metalorgânicas/química , Tetraciclinas/análise , Európio/química , Espectrometria de Fluorescência/métodos , Antibacterianos/análise , Fluorescência , Corantes Fluorescentes/química , Tetraciclina/análise , Limite de DetecçãoRESUMO
Various technologies and projects have been explored and developed for the synergetic control of environmental pollution and carbon emissions in aquatic ecosystems. Planting submerged vegetation in shallow waters was also expected to achieve this purpose. However, the magnitude and mechanism of carbon dioxide (CO2) emission affected by submerged vegetation is not clear enough in complex aquatic ecosystems. This study investigated the influences of submerged plants on CO2 emission, ecosystem metabolism features, and microbial community traits based on observations in river networks on the Changjiang River Delta. The results showed that CO2 emission from planted waters accounted for 73% of unplanted waters. Meanwhile, planted waters had higher dissolved organic carbon removal capacity in overlying water and higher potential of carbon sequestration in sediment at the same time. These distinctions between the two habitats were attributed to (1) improved CO2 and bicarbonate consumption in water columns via enhancing photosynthesis and (2) inhibited CO2 production by reconstructing the benthic microbial community. Additional eco-advantages were found in planted sediments, such as a high potential of methane oxidation and xenobiotics biodegradation and a low risk of becoming black and odorous. In brief, submerged vegetation is beneficial in promoting pollution removal and carbon retention synchronously. This study advances our understanding of the feedback between aquatic metabolism and CO2 emission.
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Dióxido de Carbono , Carbono , Rios , Rios/química , Dióxido de Carbono/análise , Carbono/análise , Ecossistema , Sequestro de Carbono , China , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Biodegradação AmbientalRESUMO
Near-infrared laser-pumped optical rectification (OR) using quasi-phase matching (QPM) in lithium niobate (LN) is widely employed to generate multi-cycle terahertz (THz) pulses, which, however, suffer from low efficiency. Here, we demonstrate that mid-infrared pumping is an effective approach to increase the efficiency of multi-cycle THz generation. By using a 2.3-µm laser to pump a QPM macro-crystal composed of ten x-cut lithium niobate wafers, with their ferroelectric Z axis alternately rotated by π, a laser-to-THz conversion efficiency up to â¼0.4% has been achieved at room temperature, more than twice the efficiencies attained with near-infrared pumping. Electro-optic sampling reveals the generation of five-cycle THz pulses at 0.15 THz for 350-µm-thick wafers and 0.22â THz for 250-µm-thick wafers. Such mid-infrared laser-pumped OR in QPM wafer stacks provides an efficient, controllable, and scalable method for generating intense multi-cycle THz pulses suitable for diverse narrow-bandwidth applications.
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Brucellosis, caused by several species of Brucella, continues to be a significant illness that poses a global threat to public health. China remains a persistent hotspot for brucellosis, despite the implementation of extensive control measures. This study aims to conduct a systematic review and meta-analysis of the seroprevalence of bovine brucellosis in different breeds and regions of China from 2014-2024, and to provide predictions on the future prevalence patterns of brucellosis in cattle and humans. The analysis comprised a total of 80 research studies, which consisted of 187 datasets and a combined sample size of 3,130,706. We estimated the overall pooled seroprevalence of bovine brucellosis in China to be 1.5% (95% CI: 0.6-2.6%). Subgroup analysis revealed that the seroprevalence in dairy cattle was 3.1%, surpassing the seroprevalence in beef cattle (1.3%) and yak (1.5%). Regions that had authorized vaccination programs exhibited higher seroprevalence (1.8%) compared to regions that did not have vaccination (0.5%). Notably, the study observed a simultaneous rise in both the prevalence of brucellosis in cattle and the number of human brucellosis cases. This suggests that high-quality routine surveillance of brucellosis in cattle will be essential for predicting and responding to cases in humans. Additionally, given the existing prevention and control measures, brucellosis will likely continue to be prevalent in both cattle and people. This systematic review will assist policymakers in adjusting animal surveillance and interregional livestock movement policies, ultimately contributing to the public safety goal of preventing brucellosis in humans by controlling it in animals.
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Adoptive cell therapy (ACT) has revolutionized the treatment of patients with cancer. The success of ACT depends largely on transferred T cell status, particularly their less-differentiated state with stem cell-like properties, which enhances ACT effectiveness. Stem cell-like memory T (TSCM) cells exhibit continuous self-renewal and multilineage differentiation similar to pluripotent stem cells. TSCM cells are promising candidates for cancer immunotherapies, whereas maintenance of a more stem-cell-like state before transfer is challenging. Here, we established a highly efficient protocol for generating CD8+ TSCM cells from peripheral blood mononuclear cells (PBMCs). The process involved activating PBMCs using anti-CD3 monoclonal antibody and RetroNectin, followed by a transient-resting culture period (24 h) and subsequent long-term expansion in vitro with interlukien-2. We report that this transient-resting culture after activation preserves CD8+ T cells in a stem memory phenotype (CD95+ CD45RA+ CCR7+) compared to the conventional culture method. Further, this approach reduces the expression of T cell immunoglobulin mucin-3, an exhaustion marker, and increases the expression of T cell factor-1, a master regulator of stemness even after long-term culture compared to the conventional culture method. In conclusion, our study presents a simplified and cost-effective method for generating and expanding CD8+ TSCM cells ex vivo. This approach streamlines the optimization of cancer immunotherapy using ACT.
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This study utilized meta-analysis and Mendelian randomization (MR) to identify risk factors for endocrine-related immune-related adverse events (EirAEs) and to ascertain whether EirAEs confer better prognosis of immunotherapy. The meta-analysis identified several risk factors for EirAEs, including elevated baseline TSH (OR = 1.30, 95% CI 1.10-1.53), positive TgAb (OR = 14.23, p < .001), positive TPOAb (OR = 3.75, p < .001), prior thyroid-related medical history (OR = 4.19), increased BMI (OR = 1.11), combination immune checkpoint inhibitors (ICIs) therapy with targeted treatment (OR = 2.71, 95% CI 2.11-3.47), and dual ICI therapy (OR = 3.26, 95% CI 2.22-4.79). MR analysis further supported causalities between extreme BMI, hypothyroidism, and irAEs from a genetic perspective. In addition, cancer patients who experienced EirAEs exhibited significantly prolonged PFS (HR = 0.84, 95% CI 0.73-0.97) and OS (HR = 0.59, 95% CI 0.45-0.76) compared to those without. These findings provide valuable insights for clinical decision-making among healthcare professionals and offer direction for future research in this field.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Análise da Randomização Mendeliana , Humanos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/imunologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/mortalidade , Prognóstico , Fatores de RiscoRESUMO
Nowadays, there are many types of flame retardants, whether halogenated or halogen-free, that can improve the flame retardancy of wood. However, they continue to pose a significant threat to our environment and cause a substantial increase in the weight gain rates after treatment. It is highly desirable yet challenging to develop an eco-friendly and efficient flame retardant with low weight gain rates. Here, we report a simple and fast process for making eco-friendly flame retardants (chitosan, gelatin, sodium phytate and clay) with weight gain rates of 3.7 %, which form excellent flame retardancy systems. This method can be used to create a 53.5 % reduction in peak heat release rate (pHRR) an 189 % increase in ignition time (cone colorimeter), and a 71.9 % reduction in peak temperature (alcohol spray lamps) compared to raw wood. The results displayed that the effect of flame retardancy (Decreased ratio for pHRR/Weight percent gain) was the best in the past three years. In addition, the flame retardancy mechanism is thoroughly analyzed using the techniques of Raman and so on. This study proposes a novel strategy featured by eco-friendly and simple preparation process for enhancing the flame retardancy of wood in important areas.
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The dosage of X-linked genes is accurately regulated with the development of fetal germ cells (FGCs)1,2. How aberrant dosage of X-linked genes impairs FGC development in humans remains poorly understood. FGCs of patients with Klinefelter syndrome (KS), who have an extra X chromosome, provide natural models for addressing this issue3. Here we demonstrate that most human FGCs in KS are arrested at an early stage, characterized by the upregulation of genes related to pluripotency, the WNT pathway and the TGF-ß pathway, along with the downregulation of genes involved in FGC differentiation. The limited KS FGCs that are capable of reaching the late stage remain relatively naive. X chromosomes are not inactivated and the dosage of X-linked genes is excessive in KS FGCs. X-linked genes dominate the differentially expressed genes and are enriched in critical biological processes associated with the developmental delay of KS FGCs. Moreover, aberrant interactions between Sertoli cells and FGCs disrupt the migration of late FGCs to the basement membrane in KS. Notably, inhibition of the TGF-ß pathway improves the differentiation of KS FGCs. Our findings elucidate how the extra X chromosome impairs the development of male FGCs and reveal the initial molecular events preceding germ cell loss in KS.
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Using magnetite-based nanocomposite adsorbents to remove and recycle phosphate from wastewater is crucial for controlling eutrophication and ensuring the sustainable use of phosphorus resources. However, the weak structural stability between magnetite and adsorptive nanoparticles often reduces phosphate removal efficiency in real-world applications. This instability primarily results from the loss of adsorptive nanoparticles from the magnetite surfaces, particularly when metal oxide nanoparticles are used for phosphate removal and recycling. In this study, we present a top-down approach that involves lattice locking magnesium iron oxide nanoparticles to the magnetite core, preventing magnesium loss from the magnetite surfaces. These nanocomposites exhibit exceptional performance in both phosphate recycling and removal, with a maximum adsorption capacity of 101.8 mg P·g-1. Excellent adsorption performance is also observed even in the presence of competing anions at phosphate-to-competing ion molar ratios of 1:5, 1:25, and 1:100, as well as dissolved organic matter, across a broad pH range of 4 to 10. The adsorbent also demonstrated minimal magnesium release during regeneration and in acidic conditions. Microscopic and spectroscopic analyses reveal that surface deposition is the primary mechanism of phosphate removal in the magnesium-containing shells. The findings of this study address the current limitations of magnetite nanocomposites in phosphate removal, paving the way for the development of highly stable and sustainable nanocomposites for various chemical removal and recycling applications in wastewater treatment.
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Human fetuses exhibit notable sex differences in growth rate and response to the intrauterine environment, yet their origins and underlying mechanisms remain uncertain. Here, we conduct a detailed investigation of sex differences in human pre-gastrulation embryos. The lower methylation and incomplete inactivation of the X chromosome in females, as well as the sex-specific cell-cell communication patterns, contribute to sex-differential transcription. Male trophectoderm is more inclined toward syncytiotrophoblast differentiation and exhibits a stronger hormone secretion capacity, while female trophectoderm tends to retain cytotrophoblast program with stronger mitochondrial function as well as higher vasculogenesis and immunotolerance signals. Male primitive endoderm initiates the anterior visceral endoderm transcriptional program earlier than females. The cell cycle activities of the epiblast and primitive endoderm are higher in males compared to females, while the situation is opposite in the trophectoderm. In conclusion, our study provides in-depth insights into the sex differences in human pre-gastrulation embryos and contributes to unraveling the origins of the sex differences in human fetal development.
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Pre-implantation genetic testing for aneuploidy (PGT-A) is used in approximately half of in vitro fertilization cycles. Given the limited understanding of the genetics of human embryos, the current use of PGT-A is based on biologically uncertain assumptions and unvalidated guidelines, leading to the possibility of disposing of embryos with pregnancy potential. We isolated and sequenced all single cells (1133) from in vitro cultured 20 human blastocysts. We found that all blastocysts exhibited mosaicism with mitotic-induced aneuploid cells and showed an ~25% aneuploidy rate per embryo. Moreover, 70% (14/20) of blastocysts contained 'chromosome-complementary' cells, suggesting genetic mosaicism is underestimated in routine PGT-A. Additionally, the analysis of 20,945 single cells from day 8-14 embryos (in vitro cultured) and embryonic/fetal organs showed that 97% of the analyzed embryos/organs were mosaic. Over 96% of their aneuploid cells harbored ≤ 2 chromosome errors. Our findings have revealed a high prevalence of mosaicism in human embryos.
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To assess the effects of a time-restricted feeding (TRF) regimen on meat quality of pigs exposed to high ambient temperature, a two-month feeding and heat treatment (HT) trial was conducted using a 2 × 2 factorial design. A total of 24 growing pigs (11.0 ± 1.9 kg) were randomly divided into four groups: thermal neutral group (NT, 24 ± 3 °C), HT group (exposed to a high temperature at 35 ± 2 °C from 11:00 to 15:00), TRF group and HT + TRF group (HT and TRF co-treatment group, n = 6 for each group). Pigs in TRF groups got access to feed within 5 h from 9:00 to14:00, while the others were fed at 6:00, 11:30, and 16:00. All pigs received the same diet during the trail. The results showed that HT increased the drip loss, shear force, lightness, and malondialdehyde production in Longissimus thoracis et lumborum (LTL) muscle. TRF reversely reduced the shear force and drip loss, accompanied by decreased intramuscular fat and increased moisture content. Enhanced fiber transformation from type 1 to type 2b and down-regulated expression of muscle growth-related genes were observed by HT, while TRF suppressed the fiber transformation and expression of muscle atrophy-related genes. Furthermore, TRF restored the diminished protein expressions of Nrf2 and HO-1 in LTL muscle by chronic HT. Accumulation of HSP70 in muscle of HT group was reduced by treatment of TRF. HT declined the expression of vital genes involved in fatty acids poly-desaturation and the proportion of (polyunsaturated fatty acids) PUFAs, mainly omega-6 in LTL muscle, while TRF group promoted the expression of poly-desaturation pathway and displayed the highest proportion of PUFAs. These results demonstrated that TRF relieved the chronic high temperature affected meat quality by the restored expression of Nrf2/HO-1 anti-oxidative cascade, modified muscle fiber composition, and enriched PUFAs in LTL muscle.
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Stable magnetic core-shell nanostructures are developed by lattice locking lanthanide-iron (La-Fe) oxide shells with magnetite cores to prevent the release of La from the surfaces of the magnetite nanostructures. The resulting core-shell nanostructures demonstrate excellent outstanding regeneration performance and high adsorption capacity for phosphate (115 mg P·g-1). These nanostructures release minimal La from the magnetite core surfaces after adsorbent regeneration, with a La loss of only 20% compared to the control sample, Mag@La(OH)3. La3+ ions were released at concentrations ranging from 1 to 2.3 µg·L-1 at pH levels of 4 to 8, which is within the metal content range found in natural aquatic environments. These results demonstrate the high stability of the nanostructures after regeneration. Furthermore, the adsorbent exhibits high extraction capacity across a wide pH range of 4 to 10 and performs well even in the presence of interfering anions at phosphate-to-anion molar ratios of 1:5, 1:25, and 1:100. Microscopic and spectroscopic analyses reveal that the primary extraction mechanism of phosphate in the La-containing shells is surface precipitation. This approach not only improves the use of magnetic core-shell nanostructures as adsorbents but also demonstrates the creation of a broad range of stable magnetic functional materials for diverse applications.
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Ample studies attribute cognitive decline in Alzheimer's disease to amyloid-ß deposition 1-6 . However, brain amyloid-ß accumulation that saturates years before the manifestation of clinical symptoms is dissociated with cognitive decline of the disease 7 . It is unknown how these two processes are mechanistically linked. In this and our accompanied study, we report that thiamine pyrophosphokinase-1 (TPK) deficiency plays essential roles in both processes via distinct mechanisms. Here we describe that diminished microglia Tpk controls the propagation of amyloid-ß plaques. In APP/PS1 transgenic mice, microglia showed elevated Tpk expression at 2-month-old, but reduction in a plaque-centric manner at 8-month-old. Interestingly, lipopolysaccharide, but not amyloid-ß, induceed Tpk reduction in cultured microglia. Tpk reduction led to microglia dysfunction, showing volatile motility but reduced phagocytosis and weak response to focal tissue injury, with accumulation of intracellular lipid droplets and abnormal mitochrondria. In Alzheimer's disease mice, microglia-specific knockout of Tpk caused diminished plaque coverage, exacerbated plaque burden and synaptic loss. However, increased plaques were not accompanied by the development of neurofibrillary tangles or brain atrophy, in contrast to the phenotype described in our accompanied paper with neuronal Tpk deletion. In conclusion, plaque-induced inflammation reduces Tpk in microglia, selectively exacerbating the spread of amyloid pathology.
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Copper nanoclusters (Cu NCs) characterized by their well-defined electronic and optical properties are an ideal platform for organic photocatalysis and exploring atomic-level behaviors. However, their potential as greener, efficient catalysts for challenging reactions like decarboxylative oxygenation under mild conditions remains unexplored. Herein, we present Cu13(Nap)3(PPh3)7H10 (hereafter Cu13Nap), protected by 1-naphthalene thiolate (Nap), which performs well in decarboxylative oxidation (90% yield) under photochemical conditions. In comparison, the isostructural Cu13(DCBT)3(PPh3)7H10 (hereafter Cu13DCBT), stabilized by 2,4-dichlorobenzenethiolate (DCBT), yields only 28%, and other previously reported Cu NCs (Cu28, Cu29, Cu45, Cu57, and Cu61) yield in the range of 6-18%. The introduction of naphthalene thiolate to the surface of Cu13 NCs influences their electronic structure and charge transfer in the ligand shell, enhancing visible light absorption and catalytic performance. Density functional theory (DFT) and experimental evidence suggest that the reaction proceeds primarily through an energy transfer mechanism. The energy transfer pathway is uncommon in the context of previous reports for decarboxylative oxidation reactions. Our findings suggest that strategically manipulating ligands holds significant potential for creating composite active sites on atomically precise copper NCs, resulting in enhanced catalytic efficacy and selectivity across various challenging reactions.
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Gram-negative bacteria produce chaperone-usher pathway pili, which are extracellular protein fibers tipped with an adhesive protein that binds to a receptor with stereochemical specificity to determine host and tissue tropism. The outer-membrane usher protein, together with a periplasmic chaperone, assembles thousands of pilin subunits into a highly ordered pilus fiber. The tip adhesin in complex with its cognate chaperone activates the usher to allow extrusion across the outer membrane. The structural requirements to translocate the adhesin through the usher pore from the periplasm to the extracellular space remains incompletely understood. Here, we present a cryoelectron microscopy structure of a quaternary tip complex in the type 1 pilus system from Escherichia coli, which consists of the usher FimD, chaperone FimC, adhesin FimH, and the tip adapter FimF. In this structure, the usher FimD is caught in the act of secreting its cognate adhesin FimH. Comparison with previous structures depicting the adhesin either first entering or having completely exited the usher pore reveals remarkable structural plasticity of the two-domain adhesin during translocation. Moreover, a piliation assay demonstrated that the structural plasticity, enabled by a flexible linker between the two domains, is a prerequisite for adhesin translocation through the usher pore and thus pilus biogenesis. Overall, this study provides molecular details of adhesin translocation across the outer membrane and elucidates a unique conformational state adopted by the adhesin during stepwise secretion through the usher pore. This study elucidates fundamental aspects of FimH and usher dynamics critical in urinary tract infections and is leading to antibiotic-sparing therapeutics.
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Adesinas de Escherichia coli , Microscopia Crioeletrônica , Proteínas de Escherichia coli , Escherichia coli , Proteínas de Fímbrias , Fímbrias Bacterianas , Proteínas de Fímbrias/metabolismo , Proteínas de Fímbrias/química , Fímbrias Bacterianas/metabolismo , Adesinas de Escherichia coli/metabolismo , Adesinas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Escherichia coli/metabolismo , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/química , Modelos Moleculares , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas da Membrana Bacteriana Externa/químicaRESUMO
BACKGROUND: From 2004 onwards, the Chinese government has freely offered complimentary Chinese herbal medicine (CHM) to Chinese HIV/AIDS patients, alongside the prescribed first line therapy of highly active antiretroviral therapy (HAART). Thus, we aimed to explore the effectiveness and safety of CHM for patients with HIV/AIDS. METHODS: The data from the Guangxi pilot database and antiviral treatment sites database have been respectively developed into two datasets in this prospective cohort real-world study, the CHM combined HAART group (the integrated group) and the HAART group. A 1:1 propensity score matching (PSM) was performed and the longitudinal data were analyzed using a generalized estimating equation (GEE) model with an autocorrelation matrix and log link function attached to the Gamma distribution. RESULTS: A final sample of 629 patients, 455 and 174 in the integrated group and HAART group respectively, were obtained from the full dataset. As covariates for PSM, gender, age, baseline CD4+ and CD4+/ CD8+ were assessed based on the results of the logistic regression analyses. Following PSM, 166 pairs from the full dataset were matched successfully, with 98 pairs in the baseline CD4+ > 200 subgroup, and 55 pairs in the baseline CD4+ ≤ 200 subgroup. In the full dataset, HAART group achieved higher CD4+ count (OR = 1.119, 95%CI [1.018, 1.230]) and CD4+/CD8+ ratio (OR = 1.168, 95%CI [1.045, 1.305]) than the integrated group, so did in the CD4+ > 200 subgroup. For the CD4+ ≤ 200 subgroup, the CD4+ (OR = 0.825, 95%CI [0.694, 0.980]) and CD4+/CD8+ (OR = 0.826, 95%CI [0.684, 0.997]) of the integrated group were higher than those of the HAART group. The safety outcomes showed that there were no significant differences in BUN, ALT and AST levels between the groups but Cr showed significantly higher levels in HAART groups of all three datasets. CONCLUSIONS: Compared to HAART alone, CHMs combined with HAART had better effects in improving the immune function of HIV/AIDS in patients with baseline CD4+ count ≤ 200. The results of the two subgroups are in opposite directions, and chance does not explain the apparent subgroup effect. A study with larger sample size and longer follow-up period is warranted in order to increase study credibility.
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Terapia Antirretroviral de Alta Atividade , Medicamentos de Ervas Chinesas , Infecções por HIV , Pontuação de Propensão , Humanos , Masculino , Feminino , Medicamentos de Ervas Chinesas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adulto , China/epidemiologia , Pessoa de Meia-Idade , Contagem de Linfócito CD4 , Estudos ProspectivosRESUMO
OBJECTIVE: CDK4/6 inhibitors (CDK4/6is) in combination with endocrine therapy have secured a central role in the treatment of hormone receptor (HR)-positive advanced breast cancer (ABC) and have transformed the therapeutic landscape. Cross-line CDK4/6i therapy in which another CDK4/6i is continued after progression on a prior CDK4/6i may still offer advantageous therapeutic effects. Cross-line CDK4/6i therapy is an area of active investigation in the ongoing pursuit to improve outcomes for patients with HR+/human epidermal growth factor receptor 2 (HER2)- ABC. METHODS: This retrospective study enrolled 82 patients with HR+/HER2- ABC who were treated with cross-line CDK4/6is (abemaciclib, palbociclib, ribociclib, and dalpiciclib) after progression with another CDK4/6i. The primary endpoint was progression-free survival (PFS) according to version 1.1 of the Response Evaluation Criteria in Solid Tumors. Secondary endpoints included toxicity, objective response rate, disease control rate, and overall survival. Adverse events (AEs) were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events, as promulgated by the U.S. Department of Health and Human Services. RESULTS: Eighty-two HR+/HER2- ABC patients who received cross-line CDK4/6i therapy from January 2022 to February 2024 were enrolled. The median age of the patients was 60 years. The median PFS of all patients was 7.6 months (95% CI, 5.9-9.2). Cox regression analysis identified lung metastasis and a switch to endocrine therapy following prior CDK4/6i therapy as independent predictive factors for PFS. Notably, patients who previously received abemaciclib and switched to palbociclib upon disease progression had a median PFS of 10.7 months. The strategy of transitioning to chemotherapy after progression on a prior CDK4/6i, then to a subsequent CDK4/6i merits further investigation. Hematologic toxicity was the most common grade ≥ 3 AEs. No instances of fatal safety events were observed. CONCLUSIONS: Cross-line CDK4/6i therapy is associated with significant clinical benefits and manageable safety profiles in patients with HR+/HER2- ABC, which underscores cross-line CDK4/6i therapy potential as an effective treatment strategy.
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Neoplasias da Mama , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Inibidores de Proteínas Quinases , Receptor ErbB-2 , Receptores de Estrogênio , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Idoso , Receptor ErbB-2/metabolismo , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Adulto , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Intervalo Livre de Progressão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Idoso de 80 Anos ou mais , Aminopiridinas/uso terapêutico , Aminopiridinas/efeitos adversos , Piperazinas/uso terapêutico , Piperazinas/efeitos adversos , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Purinas/uso terapêuticoRESUMO
The extensive use of the antibiotic oxytetracycline (OTC) has led to considerable environmental contamination and other negative impacts, prompting an urgent need for a green, effective, and innovative OTC adsorption material. In this study, diatom-allophane bio-nanocomposites were synthesized using a simple and eco-friendly method, yielding a homogeneous coating of allophane nanoparticles on diatom surfaces. The resultant bio-nanocomposites were found to have hierarchically porous structures and abundant active sites derived from successful allophane loading and dispersion on diatom surfaces. The OTC adsorption capacity of this novel adsorbent is remarkable (219.112 mg·g-1), surpassing the capacities of raw allophane and diatoms by >5 and 10 times, respectively. Mechanistically, OTC adsorption by the bio-nanocomposites was found to be driven primarily by chemisorption through a process involving complexation between the amide and amino groups on OTC and the aluminum hydroxyl and carboxyl groups on the adsorbent surface. Electrostatic interactions and hydrogen bonding also contribute significantly to OTC capture. Furthermore, the diatom-allophane bio-nanocomposites exhibit excellent performance over a wide pH range (4-7), in the presence of various cations (Na+, K+, Ca2+, Mg2+) and anions (Cl-, NO3-, SO42-), and in real water bodies. These findings demonstrate the potential of the diatom-allophane bio-nanocomposite as a green, efficient, and promising biological-mineral adsorbent for environmental remediation, leveraging the combined utilization of biological and mineral resources.
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Diatomáceas , Nanocompostos , Oxitetraciclina , Poluentes Químicos da Água , Oxitetraciclina/química , Adsorção , Poluentes Químicos da Água/química , Nanocompostos/química , Antibacterianos/química , Química VerdeRESUMO
OBJECTIVE: Due to low prevalence and few studies, the morphologic risk factors for hip osteoarthritis (HOA) in Chinese population remain unknown. The purpose of this study was to investigate the relationship between 10 radiographic parameters measured via anteroposterior pelvic X-ray radiography and HOA in Chinese population. METHODS: Thirty-three patients who required total hip arthroplasty for unilateral HOA (2017-2022) and 132 healthy individuals were selected for this case-control study. We measured 10 radiological parameters via anteroposterior pelvic X-ray radiography, which were sharp angle, center edge angle, sourcil angle, neck shaft angle, α angle, pelvic height, pelvic width, femoral head diameter, femoral neck width, and ratio of the femoral head diameter to the femoral neck width. After measurements were obtained, logistic regression analysis was utilized to calculate the adjusted odds ratios (ORs) for confounding variables such as age, sex, and body mass index (BMI). Receiver operating characteristic (ROC) curves were utilized to determine the proportional risk contribution (PRC) of each radiographic factor. RESULTS: After adjustment for confounding factors, individuals with a larger sourcil angle (SA) (OR = 4.89, 95% CI 1.66-14.42, p = 0.004), larger α angle (OR = 4.14, 95% CI 1.53-11.23, p = 0.005), and wider femoral neck (OR = 5.27, 95% CI 1.50-18.51, p = 0.01) were found to have a greater risk of developing HOA. Among all radiographic parameters, the SA demonstrated the greatest risk contribution (PRC = 13.695%). CONCLUSIONS: Radiographic parameters correlate with the incidence of HOA. The SA is probably the most powerful of all the parameters related to HOA.