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Colorectal cancer (CRC) is a prevalent cancer with intraperitoneal free cancer cells (IFCCs) playing a significant role in prognosis, especially during surgeries. The identification of IFCCs is crucial for determining the stage and treatment of patients with CRC. Existing methods for IFCC detection, such as conventional cytology, immunocytochemistry (ICC), and polymerase chain reaction (PCR), have limitations in sensitivity and specificity. This study investigates the potential of long noncoding RNA (lncRNA) SNHG1 as a biomarker for detecting IFCCs in patients with CRC. Testing on a cohort of 91 patients with CRC and 26 patients with gastrointestinal benign disease showed that SNHG1 outperformed CEA in distinguishing CRC cells and detecting IFCCs across different disease stages. SNHG1 demonstrated higher sensitivity (76.1% vs. 43.1%) and specificity (68.4% vs. 52.3%) than CEA for IFCC detection in patients with CRC, suggesting its promising role as a clinical method for identifying IFCCs in CRC.
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BACKGROUND: Malaria transmission-blocking vaccines (TBVs) aim to inhibit malaria parasite development in mosquitoes and prevent further transmission to the human host. The putative-secreted ookinete protein 25 (PSOP25), highly conserved in Plasmodium spp., is a promising TBV target. Here, we investigated PvPSOP25 from P. vivax as a TBV candidate using transgenic murine parasite P. berghei and clinical P. vivax isolates. METHODS AND FINDINGS: A transgenic P. berghei line expressing PvPSOP25 (TrPvPSOP25Pb) was generated. Full-length PvPSOP25 was expressed in the yeast Pichia pastoris and used to immunize mice to obtain anti-rPvPSOP25 sera. The transmission-blocking activity of the anti-rPvPSOP25 sera was evaluated through in vitro assays and mosquito-feeding experiments. The antisera generated by immunization with rPvPSOP25 specifically recognized the native PvPSOP25 antigen expressed in TrPvPSOP25Pb ookinetes. In vitro assays showed that the immune sera significantly inhibited exflagellation and ookinete formation of the TrPvPSOP25Pb parasite. Mosquitoes feeding on mice infected with the transgenic parasite and passively transferred with the anti-rPvPSOP25 sera showed a 70.7% reduction in oocyst density compared to the control group. In a direct membrane feeding assay conducted with five clinical P. vivax isolates, the mouse anti-rPvPSOP25 antibodies significantly reduced the oocyst density while showing a negligible influence on mosquito infection prevalence. CONCLUSIONS: This study supported the feasibility of transgenic murine malaria parasites expressing P. vivax antigens as a useful tool for evaluating P. vivax TBV candidates. Meanwhile, the moderate transmission-reducing activity of the generated anti-rPvPSOP25 sera necessitates further research to optimize its efficacy.
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Vacinas Antimaláricas , Malária Vivax , Plasmodium berghei , Plasmodium vivax , Proteínas de Protozoários , Animais , Camundongos , Plasmodium vivax/genética , Plasmodium vivax/imunologia , Vacinas Antimaláricas/imunologia , Vacinas Antimaláricas/administração & dosagem , Plasmodium berghei/genética , Plasmodium berghei/imunologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Humanos , Malária Vivax/transmissão , Malária Vivax/parasitologia , Malária Vivax/prevenção & controle , Malária Vivax/imunologia , Feminino , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Malária/transmissão , Malária/prevenção & controle , Malária/parasitologia , Malária/imunologia , Camundongos Endogâmicos BALB CRESUMO
The successful completion of gamete fertilization is essential for malaria parasite transmission, and this process can be targeted by intervention strategies. In this study, we identified a conserved gene (PBANKA_0813300) in the rodent malaria parasite Plasmodium berghei, which encodes a protein of 54 kDa (designated as Pbs54). Localization studies indicated that Pbs54 is associated with the plasma membranes of gametes and ookinetes. Functional studies by gene disruption showed that the Δpbs54 parasites had no defect in asexual proliferation, gametocyte development, or gametogenesis. However, the interactions between male and female gametes were significantly decreased compared with wild-type parasites. The Δpbs54 lines did not show a further reduction in zygote and ookinete numbers during in vitro culture, indicating that the defects were probably restricted to gamete fertilization. Consistent with this finding, mosquitoes fed on Δpbs54-infected mice showed a 30.1% reduction in infection prevalence and a 74.7% reduction in oocyst intensity. Cross-fertilization assay indicated that both male and female gametes were impaired in the Δpbs54 parasites. To evaluate its transmission-blocking potential, we obtained polyclonal antibodies from mice immunized with the recombinant Pbs54 (rPbs54) protein. In vitro assays showed that anti-rPbs54 sera inhibited ookinete formation by 42.7%. Our experiments identified Pbs54 as a fertility factor required for mosquito transmission and a novel candidate for a malaria transmission-blocking vaccine.
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Culicidae , Vacinas Antimaláricas , Malária , Animais , Feminino , Masculino , Camundongos , Anticorpos Antiprotozoários , Fertilização , Células Germinativas , Malária/prevenção & controle , Proteínas de Membrana/genética , Plasmodium berghei/genética , Plasmodium berghei/metabolismo , Proteínas de Protozoários/metabolismo , Proteínas RecombinantesRESUMO
Leaf margin morphology is an important quality trait affecting the commodity and environmental adaptability of crops. Brassica rapa is an ideal research material for exploring the molecular mechanisms underlying leaf lobe development. Here, we identified BrrA02.LMI1 to be a promising gene underlying the QTL qBrrLLA02 controlling leaf lobe formation in B. rapa, which was detected in our previous study. Sequence comparison analysis showed that the promoter divergences were the most obvious variations of BrrA02.LMI1 between parental lines. The higher expression level and promoter activity of BrrA02.LMI1 in the lobe-leafed parent indicated that promoter variations of BrrA02.LMI1 were responsible for elevating expression and ultimately causing different allele effects. Histochemical GUS staining indicated that BrrA02.LMI1 is mainly expressed at the leaf margin, with the highest expression at the tip of each lobe. Subcellular localization results showed that BrrA02.LMI1 was in the nucleus. The ectopic expression of BrrA02.LMI1 in A. thaliana resulted in a deep leaf lobe in the wild-type plants, and lobed leaf formation was disturbed in BrrA02.LMI11-downregulated plants. Our findings revealed that BrrA02.LMI1 plays a vital role in regulating the formation of lobed leaves, providing a theoretical basis for the selection and breeding of leaf-shape-diverse varieties of B. rapa.
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Brassica rapa , Alelos , Brassica rapa/genética , Proteínas de Homeodomínio , Melhoramento Vegetal , Folhas de Planta/genéticaRESUMO
Key message BrLMI1 is a positive regulatory factor of leaf lobe formation in non-heading Chinese cabbage, and cis-regulatory variations lead to the phenotype of lobed or entire leaf margins.Abstract Leaves are the main consumed organ in leafy non-heading Chinese cabbage (Brassica rapa L. ssp. chinensis Makino), and the shape of the leaves is an important economic trait. However, the molecular regulatory mechanism underlying the lobed-leaf trait in non-heading Chinese cabbage remains unclear. Here, we identified a stable incompletely dominant major locus, qLLA10, for lobed leaf formation in non-heading Chinese cabbage. Based on map-based cloning strategies, BrLMI1, a LATE MERISTEM IDENTITY1 (LMI1)-like gene, was predicted as the candidate gene for qLLA10. Genotyping analysis showed that promoter variations of BrLMI1 in the two parents are responsible for elevating the expression in the lobed-leaf parent and ultimately causing the difference in leaf shape between the two parents, and the promoter activity of BrLMI1 was significantly affected by the promoter variations. BrLMI1 was exclusively localized in the nucleus and expressed mainly at the tip of each lobe. Leaf lobe development was perturbed in BrLMI1-silenced plants produced by virus-induced gene silencing assays, and ectopic overexpression of BrLMI1 in Arabidopsis led to deeply lobed leaves never seen in the wild type, which indicates that BrLMI1 is required for leaf lobe formation in non-heading Chinese cabbage. These findings suggested that BrLMI1 is a positive regulatory factor of leaf lobe formation in non-heading Chinese cabbage and that cis-regulatory variations lead to the phenotype of lobed or entire leaf margins, thus providing a theoretical basis for unraveling the molecular mechanism underlying the lobed leaf phenotype in Brassica crops.
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Arabidopsis , Brassica rapa , Brassica , Brassica rapa/genética , Genes Homeobox , Genes de Plantas , Brassica/genética , Folhas de Planta/genética , Arabidopsis/genética , Regulação da Expressão Gênica de PlantasRESUMO
Freshwater microorganisms are an essential component of the global biogeochemical cycle and a significant contributory factor in water quality. Unraveling the mechanisms controlling microbial community spatial distribution is crucial for the assessment of water quality and health of aquatic ecosystems. This research provided a comprehensive analysis of microbial communities in Florida freshwater springs. The 16S rRNA gene sequencing and bioinformatics analyses revealed the bacterial compositional heterogeneity as well as numerous unique ASVs and biomarkers in different springs. Statistical analysis showed both geographic distance and environmental variables contributed to regional bacterial community variation, while nitrate was the dominant environmental stressor that shaped the bacterial communities. The phylogenetic bin-based null model characterized both deterministic and stochastic factors contributing to community assembly in Florida springs, with the majority of bins dominated by ecological drift. Mapping of predicted pathways to the MetaCyc database revealed the inconsistency between microbial taxonomic and functional profiles, implying the functional redundancy pattern. Collectively, our work sheds insights into the microbial spatial distribution, community assembly, and function traits in one of the world's most productive aquifers. Therefore, this work provides a unique view of the health of Florida's artesian springs and offers new perspectives for freshwater quality assessment and sustainable management.
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Ecossistema , Microbiota , Filogenia , Florida , RNA Ribossômico 16S/genética , Bactérias/genética , Água DoceRESUMO
We report a high-energy, picosecond, mid-infrared (MIR) optical parametric oscillator (OPO), in which a length of hollow-core-fiber (HCF) is employed to enable operation at 1-MHz repetition rate in a compact cavity format. The OPO is synchronously pumped by an ytterbium-doped-fiber (YDF) master-oscillator-power-amplifier (MOPA) system, seeded by a 1040-nm gain-switched laser diode (GSLD). Using periodically poled lithium niobate (PPLN) as the nonlinear crystal, the OPO generates signal and idler beams with tunable wavelengths in the range of 1329-1641â nm and 2841-4790â nm, respectively. The OPO provides 137-ps pulses with a maximum signal energy of 10.05 µJ at 1600â nm and a maximum idler energy of 5.13 µJ at 2967â nm. This, to the best of our knowledge, represents the highest energy MIR pulses, as well as the highest total converted pulse energy (15.18 µJ), ever achieved from a fiber laser pumped picosecond OPO.
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Colorectal cancer is one of the top-ranked human malignancies. The development and progression of colorectal cancer are associated with aberrant expression of multiple coding and non-coding genes. Long non-coding RNAs (lncRNAs) have an important role in regulating gene stability as well as gene expression. Numerous current studies have shown that lncRNAs are promising biomarkers and therapeutic targets for colorectal cancer. In this review, we have searched the available literature to list lncRNAs involved in the pathogenesis and regulation of colorectal cancer. We focus on the role of lncRNAs in cancer promotion or suppression, their value in tumor diagnosis, and their role in treatment response and prognosis prediction. In addition, we will discuss the signaling pathways that these lncRNAs are mainly associated with in colorectal cancer. We also summarize the role of lncRNAs in colorectal precancerous lesions and colorectal cancer consensus molecular subgroups. We hope this review article will bring you the latest research progress and outlook on lncRNAs in colorectal cancer.
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Programmed death ligand 1 (PD-L1) is widely expressed in human tumors. It is widely known for its immunosuppressive function as it can help tumor cells evade T cell immune killing through the PD-1/PD-L1 signal. A number of clinical trials have proved that the destruction of the combination of PD-1 and PD-L1 by antibodies could significantly affect patients with advanced cancer. However, a number of patients with cancer still cannot benefit from PD-1/PD-L1 blocking therapy. The main reason is that PD-L1 also has some intrinsic regulatory functions to promote the progression of tumors. PD-L1 Protein contains an intrinsic domain that could link to other signal pathways, but the mechanism has not yet been fully revealed. The present review mainly discussed the non-immune checkpoint functions of PD-L1, such as its role in regulating cell proliferation, cell metabolism, drug resistance and maintaining epithelial-mesenchymal transition and stemness.
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We report a high-power single-mode mid-infrared (MIR) pulse delivery system via anti-resonant hollow-core fiber (HCF) with a record delivery distance of 108 m. Near-diffraction-limited MIR light was transmitted by HCFs at wavelengths of 3.12-3.58 µm using a tunable optical parametric oscillator (OPO) as the light source. The HCFs were purged beforehand with argon in order to remove or reduce loss due to parasitic gas absorption (HCl, CO2, etc.). The minimum fiber loss values were 0.05 and 0.24â dB/m at 3.4-3.6 µm and 4.5-4.6 µm, respectively, with the 4.5-4.6 µm loss figure representing, to the best of our knowledge, a new low loss record for a HCF in this spectral region. At a coupling efficiency of â¼70%, average powers of 592â mW and 133â mW were delivered through 5 m and 108 m of HCF, respectively. Assuming the 120-ps duration of the MIR pulses remained constant over the low-dispersion HCF (theoretical maximum: 0.4 ps/nm/km), the corresponding calculated peak powers were 4.9â kW and 1.1â kW.
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Background and aims: Little data exist on exploring the subgroups and characteristics of problematic pornography use (PPU) in help-seeking adolescents. The aims of the study were to classify the subgroups among help-seeking male adolescents, explore their similarities and differences, and uncover their core symptoms. Methods: A total of 3,468 Chinese male adolescents (Mage = 16.64 years, SD = 1.24) who were distressed about their pornography use were recruited. The Problematic Pornography Consumption Scale, the Brief Pornography Screen Scale, and Moral Disapproval of Pornography Use were used to classify them. The General Health Questionnaire, the Pornography Craving Questionnaire, and the Sexual Compulsivity Scale were used to investigate participants' negative consequence related to their pornography use; and the Online Sexual Activity Questionnaire (OSAs) and time spent on pornography use every week were considered as quantitative indicators. Results: Help-seeking male adolescents could be divided into 3 profiles, namely, self-perceived problematic (SP, n = 755), impaired control (IC, n = 1,656), and problematic use groups (PPU, n = 1,057). Frequency of OSAs was important for the identification of SP individuals, while negative consequences were more effective in identifying individuals with objective dysregulated behavior. Salience and mood modification were shared by all groups; however, in addition to this, the SP and PPU groups also showed withdrawal symptoms. Discussion and conclusion: This study's results provide support for the presence of different profiles of help-seeking individuals and information on potential intervention targets among adolescents which is lacking in the literature.
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Literatura Erótica , Comportamento Sexual , Adolescente , Masculino , Humanos , Inquéritos e Questionários , Princípios Morais , EmoçõesRESUMO
BACKGROUND Previous studies have shown that primary repair (PR) and anterior cruciate ligament reconstruction (ACLR) can effectively treat ACL injuries. Our study aimed to compare different treatments of ACL tears, including autograft, allograft, hybrid graft ACLR, and PR, by assessing clinical outcomes and adverse events. MATERIAL AND METHODS PubMed, Cochrane Library, Embase, and CNKI databases were searched and a frequentist-framework network meta-analysis was used. RESULTS Overall, PR with augmentation was superior to ACLR only for activity recovery (WMD 0.28 95%CI [0.07 to 0.49]), and there was no significant difference shown between PR without augmentation and ACLR. ACLR with irradiated allograft was a poor option for the treatment of ACL rupture, showing the weakest subjective evaluations and functional outcomes and worst safety profile. PR with or without augmentation provided fairly good postoperative efficacy results and produced less postoperative knee laxity than irradiated allograft ACLR (PR: standardized mean difference [SMD] -1.27 [-1.80 to -0.74]; ACLR: SMD -1.36 [-1.88 to -0.83]). However, PR without augmentation showed a high failure rate compared with autograft ACLR (autograft vs PR without augmentation: risk ratio 0.29 [0.10 to 0.85]). CONCLUSIONS For surgical treatment of ACL rupture, irradiated allograft ACLR had the worst efficacy and safety and is not recommended. PR may be an ideal treatment method in terms of efficacy but it is related to a significantly higher revision risk if without augmentation. Autograft ACLR may be the preferred method currently available for most patients requiring surgical treatment of ACL rupture.
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Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Autoenxertos , Humanos , Articulação do Joelho/cirurgia , Metanálise em Rede , Ruptura/cirurgiaRESUMO
A compact, mid-infrared (MIR), synchronously pumped, fiber-feedback optical parametric oscillator (OPO) based on periodically poled lithium niobate (PPLN) is developed with tunable signal and idler wavelength ranges of 1472.0-1758.2â nm and 2559.1-3562.7â nm, respectively. A solid-core SMF-28 fiber and a hollow-core fiber (HCF) were used as the feedback fibers in order to compare the effect of their substantially different levels of nonlinearity. The OPO generates 1-MHz, 120-ps, MIR pulses with up to 1.50-µJ pulse energy and 11.7-kW peak power.
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PURPOSE: It has been found that childhood obesity (CO) may play an important role in the onset and progression of osteoarthritis (OA). Thus we conducted this mendelian randomisation analysis (MR) to evaluate the causal association between childhood obesity and osteoarthritis. METHODS: Instrumental variables (IVs) were obtained from publicly available genome-wide association study datasets. The leave-one-out sensitivity test, MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO), and Cochran's Q test were used to confirm the heterogeneity and pleiotropy of identified IVs, then five different models, including the inverse variance weighted model (IVW), weighted median estimator model (WME), weighted model-based method (WM), MR-Egger regression model (MER), and MR-Robust Adjusted Profile Score (MRAPS) were applied in this MR analysis. RESULTS: After excluding all outliers identified by the MR-PRESSO test, no evident directional pleiotropy was found. Significant heterogeneity was found in the secondary MR and as a result, the multiplicative random-effect model was used. Significant causal association between CO and OA (OR 1.0075, 95% CI [1.0054, 1.0010], p = 8.12 × 10-13). The secondary MR also revealed that CO was causally associated with knee OA (OR 1.1067, 95% CI [1.0769, 1.1373], p = 3.30 × 10-13) and hip OA (OR 1.1272, 95% CI [1.0610, 1.1976], p = 1.07 × 10-4). The accuracy and robustness of these findings were confirmed by sensitivity tests. CONCLUSION: There appears to be a causal relationship between childhood obesity and OA. Our results indicate that individuals with a history of childhood obesity require specific clinical attention to prevent the development of knee and hip OA.
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Osteoartrite do Quadril , Obesidade Infantil , Criança , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Osteoartrite do Quadril/etiologia , Osteoartrite do Quadril/genética , Obesidade Infantil/complicações , Obesidade Infantil/epidemiologia , Obesidade Infantil/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Perfluorocarboxylic acids (PFCAs) are one of the most widely detected classes of PFAS in the global environment after decades of intensive use. This study investigated the impact of perfluorinated carbon chain length on the transport behavior of PFCAs by testing and modeling two short-chain (PFPeA and PFHxA) and two long-chain PFCAs (PFOA and PFDA) in laboratory water-saturated columns. Moreover, their transport behavior was examined under different solution chemistry conditions, including pH, ionic strength, and cationic type. The experimental and simulation results indicated that the chain length had a limited impact on transport behaviors of PFPeA, PFHxA, and PFOA under various pH and ionic strengths, evidenced by their tracer-like breakthrough curves. In contrast, the mobility of PFDA was significantly affected by pH and ionic strengths. Additionally, the transport of all four PFCAs was inhabited in the presence of the divalent cation Ca2+. This study could help predict migration behavior and assess the potential risk of PFCAs in the subsurface system.
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Fluorocarbonos , Poluentes Químicos da Água , Carbono , Ácidos Carboxílicos , Fluorocarbonos/análise , Porosidade , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: The Plasmodium zygote-to-ookinete developmental transition is an essential step for establishing an infection in the mosquito vector, and antigens expressed during this stage are potential targets for transmission-blocking vaccines (TBVs). The secreted ookinete protein 26 (PSOP26) is a newly identified ookinete surface protein. The anti-PSOP26 serum has moderate transmission-blocking activity, indicating the benefit of further investigating this protein as a target for TBVs. METHODS: The function of psop26 was analyzed by targeted gene disruption. A chimeric PSOP25-PSOP26 protein was expressed in the Escherichia coli system. The PSOP25-PSOP26 fusion protein, along with mixed (PSOP25 + PSOP26) or single proteins (PSOP26 or PSOP25), were used for the immunization of mice. The antibody titers and immunogenicity of individual sera were analyzed by enzyme-linked immunoassay (ELISA), indirect immunofluorescence assay (IFA), and Western blot. The transmission-blocking activity of sera from different immunization schemes was assessed using in vitro and in vivo assays. RESULTS: PSOP26 is a surface protein expressed in Plasmodium gametes and ookinetes. The protein is dispensable for asexual blood-stage development, gametogenesis, and zygote formation, but is essential for the zygote-to-ookinete developmental transition. Specifically, both the prevalence of infections and oocyst densities were decreased in mosquitoes fed on psop26-null mutants. Mixtures of individual PSOP25 and PSOP26 fragments (PSOP25 + PSOP26), as well as chimeras (PSOP25-PSOP26), elicited high antibody levels in mice, with no immunological interference. Antisera against the mixed and fusion proteins elicited higher transmission-reducing activity (TRA) than antisera against the single PSOP26 antigen, but comparable to antisera against PSOP25 antigen alone. CONCLUSIONS: PSOP26 plays a critical role in the zygote-to-ookinete developmental transition. PSOP25 is a promising TBV candidate that could be used alone to target the ookinete stage.
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Vacinas Antimaláricas , Malária , Animais , Antígenos de Superfície , Soros Imunes , Malária/prevenção & controle , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Plasmodium berghei , Proteínas de Protozoários/metabolismoRESUMO
Phytoremediation is an effective remediation process for heavy metal contamination. The primary zone of phytoremediation is the rhizosphere where the plants uptake the heavy metals from the soil matrix. The bioavailability of the contaminants in the rhizosphere is affected by the physical, chemical, and biological conditions of the rhizosphere. In the study area of the Apalachicola National Forest, the concentrations of As, Pb and Cr in the bulk soil (n = 20) were 515.81, 220.77, and 2.02 mg/kg soil, respectively. Using a sequential extraction method, the bioavailability of heavy metals in the bulk soil (S-NR) and rhizosphere soil (S-R) was characterized. The results showed that the bioavailability of the three heavy metals had the order of Cr > Pb > As for S-NR and Pb > As > Cr for S-R. The bioavailability of these metals was affected by the nature of the heavy metals and the soil physicochemical properties. Native plant Eriocaulon decangulare could uptake a large number of heavy metals from the natural soil, demonstrating great phytoremediation potential for metal contamination. Energy Dispersive Spectroscopy (EDS) mapping successfully located the dominant accumulation of heavy metals in aerial parts of E. decangulare. E. decangulare was also found to be highly selective and Pb and As were both extensively accumulated in the shoots and roots. Cr was significantly immobilized in the rhizosphere soil, and also accumulated in the root of E. decangulare. This study not only correlated the phytoremediation potential with heavy metal bioavailability and soil physicochemical properties, but also demonstrated the important role of the nature of heavy metals played during the phytoremediation.
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Metais Pesados , Poluentes do Solo , Biodegradação Ambiental , Florestas , Chumbo , Metais Pesados/análise , Plantas , Solo/química , Poluentes do Solo/análiseRESUMO
Nanosilver (AgNP) has a large surface area that contributes to enhanced interactions with bacteria, as well as silver ion release. The actual AgNP antimicrobial effect is determined by the AgNP size. AgNPs with smaller diameters showed better antimicrobial effects because smaller AgNPs had larger surface areas, which led to greater silver ion release and stronger attachment to bacteria. The attachment of AgNPs to bacterial surfaces is attributed to the attractive interactions between the AgNPs and bacteria, which is also a function of the size of AgNPs. Although the antimicrobial activity of AgNPs has been extensively studied, there is a gap between antimicrobial effects of AgNPs on bacteria and their subsequent attachment. To fully understand the antimicrobial effectiveness of different-sized AgNPs, this study investigated the dynamic process of AgNP-bacteria interactions in aqueous media, including AgNP aggregation, AgNP attachment, and antimicrobial effects. AgNP-AgNP and AgNP-bacteria interactions were quantified based on DLVO and surface chemistry theories, which were used to interpret subsequent AgNP aggregation, AgNP-bacteria attachment and AgNP antimicrobial observations.
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Anti-Infecciosos , Nanopartículas Metálicas , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Prata/farmacologia , TermodinâmicaRESUMO
BACKGROUND: Transmission-blocking vaccine (TBV) is a promising strategy for malaria elimination. It is hypothesized that mixing or fusing two antigens targeting different stages of sexual development may provide higher transmission-blocking activity than these antigens used individually. METHODS: A chimeric protein composed of fragments of Pbg37 and PSOP25 was designed and expressed the recombinant protein in Escherichia coli Rosetta-gami B (DE3). After immunizing mice with individual recombinant proteins Pbg37 and PSOP25, mixed proteins (Pbg37+PSOP25), or the fusion protein (Pbg37-PSOP25), the antibody titers of individual sera were analyzed by ELISA. IFA and Western blot were performed to test the reactivity of the antisera with the native proteins in the parasite. The transmission-blocking activity of the different immunization schemes was assessed using in vitro and in vivo assays. RESULTS: When Pbg37 and PSOP25 were co-administered in a mixture or as a fusion protein, they elicited similar antibody responses in mice as single antigens without causing immunological interference with each other. Antibodies against the mixed or fused antigens recognized the target proteins in the gametocyte, gamete, zygote, and ookinete stages. The mixed proteins or the fusion protein induced antibodies with significantly stronger transmission-reducing activities in vitro and in vivo than individual antigens. CONCLUSIONS: There was no immunological interference between Pbg37 and PSOP25. The bivalent vaccines, which expand the portion of the sexual development during which the transmission-blocking antibodies act, produced significantly stronger transmission-reducing activities than single antigens. Altogether, these data provide the theoretical basis for the development of combination TBVs targeting different sexual stages.
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Vacinas Antimaláricas/administração & dosagem , Malária/prevenção & controle , Plasmodium berghei/crescimento & desenvolvimento , Plasmodium berghei/imunologia , Proteínas de Protozoários/administração & dosagem , Vacinas Combinadas/administração & dosagem , Animais , Anticorpos Antiprotozoários/sangue , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Imunização , Malária/sangue , Malária/parasitologia , Malária/transmissão , Vacinas Antimaláricas/genética , Vacinas Antimaláricas/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Plasmodium berghei/genética , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Vacinas Combinadas/genética , Vacinas Combinadas/imunologiaRESUMO
Colorectal cancer (CRC) is one of the most common malignancies and most of the patients diagnosed with advanced CRC have unsatisfactory treatment effect and poor prognosis. The purpose of this study was to investigate the effect of CCNI2 on the development of CRC. In this sutdy, immunohistochemical staining was used to detect CCNI2 expression levels in clinical samples, meanwhile, the Kaplan-Meier survival analysis was conducted. Celigo cell counting assay was used for screening shCCNI2s. QPCR and WB were performed to verify knockdown efficiency of CCNI2. Cell proliferation, colony formation, cell cycle, apoptosis, and mechanism investigation of CCNI2 knockdown were investigated by MTT assay, colony formation assay, fluorescence-activated cell sorting, and human apoptosis antibody array, respectively. Otherwise, the mouse model of CCNI2 knockdown was also constructed. The results of immunohistochemical staining and qPCR indicated that CCNI2 had a high expression level in the CRC tissues and cell lines. Kaplan-Meier survival analysis manifested that the high expression of CCNI2 suggested poor prognosis. The expression of CCNI2 was significantly reduced by CCNI2-siRNAs, and the downregulated expression level of CCNI2 inhibited CRC cell proliferation and colony formation, arrested cell cycle in G2 phase, as well as promoted cell apoptosis. The various indexes of solid tumor in mice models indicated that CCNI2 knockdown could suppress the growth of CRC tumor. Based on the comprehensive analysis of the above results, CCNI2 was contributed to the progression of CRC and could serve as a prognostic marker for CRC.