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Reducing unnecessary blood loss in hemostasis is a major challenge for traditional hemostatic materials due to uncontrolled blood absorption. Tuning the hydrophilic and hydrophobic properties of hemostatic materials provides a road to reduce blood loss. Here, we developed a superhydrophobic aerogel that enabled remarkably reduced blood loss. The aerogel was fabricated with polydopamine-coated and fluoroalkyl chain-modified bacterial cellulose via a directional freeze-drying method. Primarily, the hydrophobic feature prevented blood from uncontrolled absorption by the material and overflowing laterally. Additionally, the aerogel had a dense network of channels that allowed it to absorb water from blood due to the capillary effect, and fluoroalkyl chains trapped the blood cells entering the channels to form a compact barrier via hydrophobic interaction at the bottom of the aerogel, causing quick fibrin generation and blood coagulation. The animal experiments reveal that the aerogel reduced the hemostatic time by 68% and blood loss by 87 wt % compared with QuikClot combat gauze. The study demonstrates the superiority of superhydrophobic aerogels for hemostasis and provides new insights into the development of hemostatic materials.
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Celulose , Hemostasia , Hemostáticos , Interações Hidrofóbicas e Hidrofílicas , Nanofibras , Celulose/química , Celulose/farmacologia , Animais , Nanofibras/química , Hemostáticos/química , Hemostáticos/farmacologia , Hemostasia/efeitos dos fármacos , Géis/química , Polímeros/química , Polímeros/farmacologia , Camundongos , Humanos , Coagulação Sanguínea/efeitos dos fármacos , Indóis/químicaRESUMO
Interactions among ecosystem services (ESs) involve tradeoffs and synergies. Quantitatively studying the trade-off and synergistic relationships between land use/land cover change (LULC) and ESs enables the precise identification of the quality status and driving factors of ESs within the region, which is crucial for rational resource allocation and environmental protection. In this study, the spatial and temporal change characteristics of the three ESs of carbon storage (CS), soil retention (SR) and habitat quality (HQ) are explored by using the InVEST model and GIS technology in the region around Taihu Lake, and the tradeoffs and synergies among the three are determined based on the difference comparison. The results indicate that: (1) The study area has a downward trajectory in CS and HQ from 1990 to 2020, while SR experiences some fluctuations. The spatial distribution of the three ESs exhibits high levels in the southwest and low levels in the northeast. (2) The most sensitive regions where tradeoffs and synergies are most pronounced occur primarily in the newly construction land regions and the southwestern mountainous and hilly areas. In newly construction land regions, there are often tradeoffs relationships observed between CS and SR, as well as between HQ and SR. Conversely, a predominantly negative synergy is mainly observed between CS and HQ. In the southwestern hilly terrain, due to changes in landscape patterns, HQ and SR exhibit higher levels of negative synergistic relationships. (3) LULC is a significant driver of spatial and temporal changes in ESs, as well as changes in tradeoffs and synergies in the study area, necessitating integrated research from economic, social and climate change perspectives.
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BACKGROUND: PD-1/PD-L1 blockade has become a powerful method to treat malignant tumors. However, a large proportion of patients still do not benefit from this treatment, due to low tumor immunogenicity and low tumor penetration of the agents. Recently, neutrophil elastase has been shown to induce robust tumor immunogenicity, while the insufficient enzyme activity at the tumor site restricted its anti-tumor application. Here, we designed polyethyleneimine-modified neutrophil elastase (PEI-elastase) loaded with PD-L1small interfering RNA (PD-L1 siRNA) for improving enzymatic activity and delivering siRNA to tumor, which was expected to solve the above-mentioned problems. RESULTS: We first demonstrated that PEI-elastase possessed high enzymatic activity, which was also identified as an excellent gene-delivery material. Then, we synthesized anti-tumor lipopolymer (P-E/S Lip) by encapsulating PEI-elastase and PD-L1siRNA with pH-responsive anionic liposomes. The P-E/S Lip could be rapidly cleaved in tumor acidic environment, leading to exposure of the PEI-elastase/PD-L1 siRNA. Consequently, PEI-elastase induced powerful tumor immunogenicity upon direct tumor killing with minimal toxicity to normal cells. In parallel, PEI-elastase delivered PD-L1siRNA into the tumor and reduced PD-L1 expression. Orthotopic tumor administration of P-E/S Lip not only attenuated primary tumor growth, but also produced systemic anti-tumor immune response to inhibit growth of distant tumors and metastasis. Moreover, intravenous administration of P-E/S Lip into mice bearing subcutaneous tumors leaded to an effective inhibition of established B16-F10 tumor and 4T1 tumor, with histological analyses indicating an absence of detectable toxicity. CONCLUSIONS: In our study, a protease-based nanoplatform was used to cooperatively provoke robust tumor immunogenicity and down-regulate PD-L1 expression, which exhibited great potential as a combination therapy for precisely treating solid tumors.
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Antígeno B7-H1 , Imunoterapia , Polietilenoimina , RNA Interferente Pequeno , Animais , Polietilenoimina/química , RNA Interferente Pequeno/química , Antígeno B7-H1/metabolismo , Camundongos , Imunoterapia/métodos , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos Endogâmicos BALB C , Lipossomos/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Neoplasias/imunologia , Camundongos Endogâmicos C57BL , Inativação GênicaRESUMO
Recent breakthroughs in cancer immunology have propelled immunotherapy to the forefront of cancer research as a promising treatment approach that harnesses the body's immune system to effectively identify and eliminate cancer cells. In this study, three novel cyclometalated Ir(III) complexes, Ir1, Ir2, and Ir3, were designed, synthesized, and assessed in vitro for cytotoxic activity against several tumor-derived cell lines. Among these, Ir1 exhibited the highest cytotoxic activity, with an IC50 value of 0.4 ± 0.1 µM showcasing its significant anticancer potential. Detailed mechanistic analysis revealed that co-incubation of Ir1 with 143B cells led to Ir1 accumulation within mitochondria and the endoplasmic reticulum (ER). Furthermore, Ir1 induced G0/G1 phase cell cycle arrest, while also diminishing mitochondrial membrane potential, disrupting mitochondrial function, and triggering ER stress. Intriguingly, in mice the Ir1-induced ER stress response disrupted calcium homeostasis to thereby trigger immunogenic cell death (ICD), which subsequently activated the host antitumor immune response while concurrently dampening the in vivo tumor-induced inflammatory response.
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Antineoplásicos , Complexos de Coordenação , Estresse do Retículo Endoplasmático , Retículo Endoplasmático , Morte Celular Imunogênica , Irídio , Mitocôndrias , Irídio/química , Irídio/farmacologia , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Morte Celular Imunogênica/efeitos dos fármacos , Animais , Camundongos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Linhagem Celular Tumoral , Potencial da Membrana Mitocondrial/efeitos dos fármacosRESUMO
The water quality in the drinking water reservoir directly affects people's quality of life and health. When external pollution input is effectively controlled, endogenous release is considered the main cause of water quality deterioration. As the major nitrogen (N) and phosphorus (P) sources in reservoirs, sediment plays a vital role in affecting the water quality. To understand the spatial and temporal variation of N and P in the sediment, this study analyzed the current characteristics and cumulative effects of a semi-humid reservoir, Yuqiao Reservoir, in North China. The N and P concentrations in the reservoir sediment were decreased along the flow direction, while the minimum values were recorded at the central sediment profile. External input and algal deposition were the main factors leading to higher sediment concentrations in the east (Re-E) and west (Re-W) areas of reservoir sediment profiles. According to the long-term datasets, the peaks of both sediment total nitrogen content and deposition rate were observed in the 2010s, which has increased about three times and six times than in the1990s, respectively. Therefore, the increase in phosphorus concentration may be the main reason for eutrophication in water in recent years. The mineralization of organic matter has a significant promoting effect on releasing N and P from sediments, which will intensify eutrophication in water dominated by P and bring huge challenges to water environment management. This study highlights that the current imbalance in N and P inputs into reservoirs and the endogenous P release from sediment will have a significant impact on water quality.
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OBJECTIVES: To explore the role of endothelial-mesenchymal transition (EndMT) mediated by the TGF-ß/SMAD signalling pathway in the pathogenesis of ankylosing spondylitis (AS). METHODS: Serum levels of TGF-ß1 were measured by enzyme-linked immunosorbent assay (ELISA) in 48 patients with AS and 15 healthy subjects. The expression levels of TGF-ß1, SMAD7, CTGF, CD34 and EndMT-related markers (α-SMA, vimentin, FSP-1, VE-cadherin) in the sacroiliac joint (SIJ) of three AS patients were detected by immunohistochemistry, and three non-spondyloarthritis (SpA) autopsy samples were used as controls. RESULTS: Serum TGF-ß1 level of AS patients was significantly higher than that of healthy controls (22971 ± 7667 pg/ml vs. 14837±4653 pg/ml, p<0.01). Compared with the non-SpA control group, the microvascular density (MVD) at the pannus formation site of SIJ in AS patients was significantly increased, accompanied by respectively increased expressions of TGF-ß1, CTGF, α-SMA, vimentin, and FSP-1 (all p<0.05), whereas respectively decreased expressions of VE-cadherin and SMAD7 (p<0.01). The expression level of FSP-1 was positively correlated with levels of TGF-ß1 and MVD, and negatively correlated with SMAD7. CONCLUSIONS: Our findings show that EndMT is involved in the promotion of pannus formation by TGF-ß/SMAD signalling pathway activation in AS.
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Transdução de Sinais , Proteína Smad7 , Espondilite Anquilosante , Fator de Crescimento Transformador beta1 , Vimentina , Humanos , Espondilite Anquilosante/metabolismo , Espondilite Anquilosante/patologia , Masculino , Feminino , Adulto , Fator de Crescimento Transformador beta1/metabolismo , Proteína Smad7/metabolismo , Vimentina/metabolismo , Estudos de Casos e Controles , Antígenos CD/metabolismo , Caderinas/metabolismo , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Transição Epitelial-Mesenquimal , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo , Proteína A4 de Ligação a Cálcio da Família S100/genética , Actinas/metabolismo , Pessoa de Meia-Idade , Adulto Jovem , Biomarcadores/sangue , Proteína A7 Ligante de Cálcio S100/metabolismo , Proteína A7 Ligante de Cálcio S100/genética , Neovascularização Patológica , Transição Endotélio-MesênquimaRESUMO
Transition metal complexes with characteristics of unique packaging in nanoparticles and remarkable cancer cell cytotoxicity have emerged as potential alternatives to platinum-based antitumor drugs. Here we report the synthesis, characterization, and antitumor activities of three new Ruthenium complexes that introduce 5-fluorouracil-derived ligands. Notably, encapsulation of one such metal complex, Ru3, within pluronic® F-127 micelles (Ru3-M) significantly enhanced Ru3 cytotoxicity toward A549 cells by a factor of four. To determine the mechanisms underlying Ru3-M cytotoxicity, additional in vitro experiments were conducted that revealed A549 cell treatment with lysosome-targeting Ru3-M triggered oxidative stress, induced mitochondrial membrane potential depolarization, and drastically reduced intracellular ATP levels. Taken together, these results demonstrated that Ru3-M killed cells mainly via a non-apoptotic pathway known as oncosis, as evidenced by observed Ru3-M-induced cellular morphological changes including cytosolic flushing, cell swelling, and cytoplasmic vacuolation. In turn, these changes together caused cytoskeletal collapse and activation of porimin and calpain1 proteins with known oncotic functions that distinguished this oncotic process from other cell death processes. In summary, Ru3-M is a potential anticancer agent that kills A549 cells via a novel mechanism involving Ru(II) complex triggering of cell death via oncosis.
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Antineoplásicos , Complexos de Coordenação , Lisossomos , Poloxâmero , Rutênio , Humanos , Poloxâmero/química , Poloxâmero/farmacologia , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Células A549 , Antineoplásicos/farmacologia , Antineoplásicos/química , Rutênio/química , Rutênio/farmacologia , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Estresse Oxidativo/efeitos dos fármacosRESUMO
The circadian clock regulator Bmal1 modulates tumorigenesis, but its reported effects are inconsistent. Here, we show that Bmal1 has a context-dependent role in mouse melanoma tumor growth. Loss of Bmal1 in YUMM2.1 or B16-F10 melanoma cells eliminates clock function and diminishes hypoxic gene expression and tumorigenesis, which could be rescued by ectopic expression of HIF1α in YUMM2.1 cells. By contrast, over-expressed wild-type or a transcriptionally inactive mutant Bmal1 non-canonically sequester myosin heavy chain 9 (Myh9) to increase MRTF-SRF activity and AP-1 transcriptional signature, and shift YUMM2.1 cells from a Sox10high to a Sox9high immune resistant, mesenchymal cell state that is found in human melanomas. Our work describes a link between Bmal1, Myh9, mouse melanoma cell plasticity, and tumor immunity. This connection may underlie cancer therapeutic resistance and underpin the link between the circadian clock, MRTF-SRF and the cytoskeleton.
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Relógios Circadianos , Melanoma , Animais , Humanos , Camundongos , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Carcinogênese/genética , Relógios Circadianos/genética , Ritmo Circadiano/genética , Melanoma/genéticaRESUMO
Food packaging films play a vital role in preserving and protecting food. However, due to their non-biodegradability, conventional packaging materials have led to significant environmental pollution. To overcome this hurdle, we have developed safe, innovative, sustainable and biodegradable packaging materials that can effectively extend the shelf life of food. In this study, two types of cellulose materials cellulose nanofibers (CNF) and carboxymethyl cellulose (CMC) with complementary roles were combined to prepare nanocellulose composite films with high transparency (90.3 %) of a certain thickness (30 ± 0.019 µm) by solution casting method, and their mechanical properties were further optimized by the addition of plasticizer-glycerol (Gly) and cross-linking agent-glutaraldehyde (GA), so as to maintain the strong tensile strength (≈112.60 MPa) and better malleability (4.12 %). In addition, we loaded the natural active agent tea polyphenols (TPs) with different concentrations to study the inhibition effect on E.coli and S.aureus and to simulate food packaging. Finally, we also found that the synthesized nanocellulose composite films can also achieve rapid degradation in a short time through soil burial, water flushing and immersion. The excellent performance demonstrated in this study provides reference value for further replacing petroleum-based materials with biomass materials in the field of food packaging.
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Antibacterianos , Embalagem de Alimentos , Embalagem de Alimentos/métodos , Antibacterianos/farmacologia , Água , Glutaral , CeluloseRESUMO
OBJECTIVES: Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) and transumbilical laparoendoscopic single-site surgery (LESS) have shown the prospection as minimally invasive procedures. Here we aimed to compare ovarian cystectomy assisted by vNOTES and by LESS for ovarian mature cystic teratoma (OMCT). MATERIAL AND METHODS: A total of 81 premenopausal women with OMCT were randomized to undergo ovarian cystectomy assisted by either vNOTES (n = 41) or LESS (n = 40). The main outcome was the operative time. Secondary outcomes included the length of hospital stay, visual analog scale (VAS) pain scores, abdominal contamination by teratoma contents, and intraoperative and postoperative complications. RESULTS: There were no intergroup differences in age, body mass index, tumor size, or bilaterality of tumor. The operative time for the vNOTES group was significantly shorter than that for the LESS group (68.41 ± 20.92 min vs 85.05 ± 32.94 min, p = 0.008). The highest VAS pain score 24 hours postoperatively was 1.21 ± 0.48 in the vNOTES group and 2.43 ± 0.57 in the LESS group (p < 0.001). Twenty-four of the 40 patients in the LESS group experienced teratoma rupture intraoperatively, leading to abdominal contamination by the teratoma content, while 5 abdominal contamination was observed in the vNOTES group ï¼p = 0.005. No significant differences between the two groups were observed in the other outcomes. CONCLUSIONS: vNOTES assisted ovarian cystectomy has short operative time, fast recovery, no scarring, less pain, and low rate of abdominal contamination. Consequently, vNOTES might be superior to LESS for treating OMCTs.
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Laparoscopia , Cirurgia Endoscópica por Orifício Natural , Neoplasias Ovarianas , Teratoma , Humanos , Feminino , Cirurgia Endoscópica por Orifício Natural/métodos , Adulto , Teratoma/cirurgia , Neoplasias Ovarianas/cirurgia , Laparoscopia/métodos , Resultado do Tratamento , Duração da Cirurgia , Umbigo/cirurgia , Pessoa de Meia-Idade , Adulto Jovem , Tempo de Internação/estatística & dados numéricosRESUMO
BACKGROUND: Hemoglobin (Hb) Chile [ß28(B10) Leu > Met; HBB: c.85 C > A] is a rare hemoglobin variant caused by a missense mutation in the HBB gene. Only one case of Hb Chile has been reported worldwide so far. It is an unstable hemoglobin, characterized by cyanosis associated with chronic methemoglobinemia and hemolytic anemia induced by sulfonamides or methylene blue. CASE PRESENTATION: A 9-year-3-month-old girl had mild anemia of unknown etiology for more than 6 years. She had a slight pallor without other symptoms or signs. The complete blood count revealed normocytic normochromic anemia with a sometimes-elevated reticulocyte count, and the bone marrow cytology showed marked erythroid hyperplasia, but the tests related to hemolysis were normal. Therefore, the whole exome sequencing was performed and showed a heterozygous mutation for HBB: c.85 C > A. With asymptomatic methemoglobinemia confirmed later, she was eventually diagnosed with Hb Chile. CONCLUSIONS: This is the first report of Hb Chile in China and the second worldwide. This case shows that Hb Chile is clinically heterogeneous and difficult to diagnose and expands our understanding on the clinical and hematological traits of the disease.
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Anemia Hemolítica , Hemoglobinas Anormais , Metemoglobinemia , Feminino , Humanos , Lactente , Metemoglobinemia/diagnóstico , Metemoglobinemia/genética , Hemoglobinas Anormais/genética , Anemia Hemolítica/diagnóstico , Anemia Hemolítica/genética , ChinaRESUMO
RNA In situ imaging through DNA self-assembly is advantaged in illustrating its structures and functions with high-resolution, while the limited reaction efficiency and time-consuming operation hinder its clinical application. Here, we first proposed a new strand displacement reaction (SDR) model (Cas12a thrusting SDR, CtSDR), in which Cas12a could overcome the inherent reaction limitation and dramatically enhance efficiency through energy replenishment and by-product consumption. The target-initiated CtSDR amplification was established for RNA analysis, with order of magnitude lower limit of detection (LOD) than the Cas13a system. The CtSDR-based RNA in situ imaging strategy was developed to monitor intra-cellular microRNA expression change and delineate the landscape of oncogenic RNA in 66 clinic tissue samples, possessing a clear advantage over classic in situ hybridization (ISH) in terms of operation time (1 h versus 14 h) while showing comparable sensitivity and specificity. This work presents a promising approach to developing advanced molecular diagnostic tools.
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Técnicas Biossensoriais , RNA , RNA/genética , Sistemas CRISPR-Cas , DNA/genética , DNA/química , Sensibilidade e Especificidade , Hibridização In Situ , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas Biossensoriais/métodosRESUMO
Immunotherapy has been shown to provide superior antitumor efficacy by activating the innate immune system to recognize, attack and eliminate tumor cells without seriously harming normal cells. Herein, we designed and synthesized three new cyclometalated iridium(III) complexes (Ir1, Ir2, Ir3) then evaluated their antitumor activity. When co-incubated with HepG2 cells, the complex Ir1 localized in the lysosome, where it induced paraptosis and endoplasmic reticulum stress (ER stress). Notably, Ir1 also induced immunogenic cell death (ICD), promoted dendritic cell maturation that enhanced effector T cell chemotaxis to tumor tissues, down-regulated proportions of immunosuppressive regulatory T cells within tumor tissues and triggered activation of antitumor immunity throughout the body. To date, Ir1 is the first reported iridium(III) complex-based paraptosis inducer to successfully induce tumor cell ICD. Furthermore, Ir1 induced ICD of HepG2 cells without affecting cell cycle or reactive oxygen species levels.
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Morte Celular Imunogênica , Irídio , Humanos , Células Hep G2 , Irídio/farmacologia , Ciclo Celular , Diferenciação CelularRESUMO
Ruthenium complexes are one of the most promising anticancer drugs triggered extensive research. Here, the synthesis and characterization of two ruthenium(II) polypyridine complexes containing 8-hydroxylquinoline as ligand, [Ru(dip)2(8HQ)]PF6 (Ru1), [Ru(dpq)2(8HQ)]PF6 (Ru2) (8HQ = 8-hydroxylquinoline; dip = 4,7-diphenyl-1,10-phenanthroline; dpq = pyrazino[2,3-f][1,10]phenanthroline) were reported. On the basis of cytotoxicity tests, Ru1 (IC50 = 1.98 ± 0.02 µM) and Ru2 (IC50 = 10.02 ± 0.19 µM) both showed good anticancer activity in a panel of cell lines, especially in HeLa cells. Researches on mechanism indicated that Ru1 and Ru2 acted on mitochondria and nuclei and induced reactive oxygen species (ROS) accumulation, while the morphology of nuclei and cell cycle had no significant change. Western blot assay further proved that GPX4 and Ferritin were down-regulated, which eventually triggered ferroptosis in HeLa cells. In addition, the toxicity test of zebrafish embryos showed that the concentrations of Ru1 and Ru2 below 120 µM and 60 µM were safe and did not have obvious effect on the normal development of zebrafish embryos.
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Ferroptose , Rutênio , Humanos , Animais , Células HeLa , Ferritinas , Peixe-Zebra , OxiquinolinaRESUMO
OBJECTIVES: In this study, we aimed to examine the prevalence of alcohol consumption among methadone maintenance treatment (MMT) clients in Shanghai and to determine whether a brief intervention (BI) affects drinking among them. METHODS: A total of 837 clients from 14 local MMT clinics were invited to complete the Alcohol Use Disorders Identification Test (AUDIT). One hundred one were included in the study and randomly assigned to the BI group or the control group. Clients in the BI group received a BI and general health education, whereas clients in the control group received the general health education only. Baseline and postintervention assessments were conducted by using the AUDIT, the Drinking Attitude Questionnaire, the Depression Module of the Patient Health Questionnaire, the Generalized Anxiety Disorder Scale, and the General Well-Being Schedule. RESULTS: Two hundred fifty-nine (30.9%) reported drinking during the last year, and 103 (12.3%) met the criteria for harmful use. At the 3-month follow-up, the AUDIT scores of the 2 groups were significantly decreased, and the time effect was statistically significant ( F = 6.224, P = 0.018), but there was no group difference in AUDIT scores ( F = 1.953, P = 0.172). Both groups had a main time effect of time on the improvement of depression ( F = 8.044, P = 0.008), anxiety ( F = 9.650, P = 0.004), and general well-being ( F = 5.056, P = 0.033). However, there was no statistical difference between the 2 groups ( P > 0.05), and no statistical difference in the time ( F = 1.738, P = 0.198) and group ( F = 0.658, P = 0.424) effect of drinking attitude. CONCLUSIONS: Alcohol consumption is common among MMT clients in China. Brief intervention, in its current form, could not effectively help them reduce their alcohol consumption.
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Alcoolismo , Humanos , Alcoolismo/epidemiologia , Alcoolismo/terapia , Intervenção em Crise , Estudos de Viabilidade , China/epidemiologia , Metadona/uso terapêutico , Consumo de Bebidas Alcoólicas/epidemiologiaRESUMO
An isothermal, one-pot toolbox (called OPT-Cas) based on CRISPR-Cas12a collateral cleavage capability is proposed for highly sensitive and selective determination of terminal deoxynucleotidyl transferase (TdT) activity. Oligonucleotide primers with 3'-hydroxyl (OH) terminal were randomly introduced for TdT-induced elongation. In the presence of TdT, dTTP nucleotides polymerized at the 3' terminals of the primers to generate abundant polyT-tails, which function as triggers for the synchronous activation of Cas12a proteins. Finally, the activated Cas12a trans-cleaved FAM and BHQ1 dual-labeled single-stranded DNA (ssDNA-FQ) reporters, producing significantly amplified fluorescence signals. This one-pot assay, that is primer, crRNA, Cas12a protein and ssDNA-FQ reporter are all in one tube, allows simple but high-sensitive quantification of TdT activity with a low detection limit of 6.16 × 10-5 U µL-1 in the concentration scope from 1 × 10-4 U µL-1 to 1 × 10-1 U µL-1, and achieves extraordinary selectivity with other interfering proteins. Furthermore, the OPT-Cas was successfully used to detect TdT in complex matrices and accurate determination of TdT activity in acute lymphoblastic leukemia cells, which might be a reliable technique platform for the diagnosis of TdT-related diseases and biomedical research applications.
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Pesquisa Biomédica , Técnicas Biossensoriais , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Sistemas CRISPR-Cas , DNA Nucleotidilexotransferase , Bioensaio , DNA de Cadeia Simples/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMO
OBJECTIVE: The aim of this study was to review the levels of vitamin A and selenium in children with echinococcosis in Ganzi and Aba. METHODS: Twenty-six children with cystic echinococcosis and 104 apparently healthy controls from the Aba and Garze Tibetan Autonomous Prefecture of Sichuan province in China were recruited. The serum levels of selenium and vitamin A of the cases and controls were detected and stratified by sex and age. RESULTS: The results showed that the ratio of boys to girls was 1:1.36. Compared with the healthy controls, the vitamin A serum levels of the cases significantly declined. The rate of selenium deficiency was high in the cases, but there was no significant difference compared with the control group. Additionally, the lower the vitamin A serum level, the higher the risk for developing echinococcosis. CONCLUSIONS: To improve management strategies in children with cystic echinococcosis, or possibly to prevent the disease, children living in high-risk areas for cystic echinococcosis should be given supplemental vitamin A and encouraged to consume a vitamin A-rich diet containing paw-paw, carrot, palm oil, or fish. Children with vitamin A deficiency in high-risk areas should be screened for cystic echinococcosis.
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Equinococose , Selênio , Animais , Vitamina A , Tibet , Prevalência , China/epidemiologiaRESUMO
PURPOSE: To evaluate the accuracy of static guided implant placement with intraoral scanning technology and to analyze the influencing factors of guided surgery. METHODS: Totally 27 cases were included in this retrospective study. The implant designs were made in 3Shape Implant Studio and then guided implant surgeries were performed with CAD-CAM templates. Postoperative implant positions were detected with an intraoral scanner (3Shape TRIOS) and deviation of implantation was evaluated using established CAD/CAM based evaluation method. SAS 9.4 software package was used for data analysis. RESULTS: The mean deviation of entrance point and apical point was (1.182±0.609) mm and (1.658±0.741) mm, respectively. Angular deviation was (5.712±3.347)°. Implant quadrant, location of the implant site, guidance degree, supporting type and implant size influenced direction deviation, while angular deviation was mainly affected by guidance degree and number of missing teeth. CONCLUSIONS: Accuracy of static guided implant placement can be influenced by many factors. More research is needed to improve the accuracy of static guided implantation.
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Implantes Dentários , Cirurgia Assistida por Computador , Implantação Dentária Endóssea/métodos , Estudos Retrospectivos , Tomografia Computadorizada de Feixe Cônico , Cirurgia Assistida por Computador/métodos , Desenho Assistido por Computador , Imageamento Tridimensional/métodosRESUMO
Background: Endothelial-mesenchymal transition (EndMT) is an important process of angiogenesis, which plays a significant role in in tumor invasion and metastasis, while its regulatory mechanisms in breast cancer remain to be fully elucidated. We previously demonstrated that tumor-associated macrophages (TAMs) can induce EndMT in endothelial cells by secreting CCL18 through the activation of the TGF-ß and Notch signaling pathways in breast cancer. This study was designed to study the role of EndMT in breast cancer angiogenesis and progression in order to explore the underlying mechanism. Methods: Immunohistochemistry (IHC) was used to evaluate the expression of microvascular density (MVD) and EndMT markers in breast cancer. TGF-ß1 was used to induce EndMT models of differentiated-endothelial breast cancer stem-like cells (BCSLCs). In vitro cell migration, proliferation and matrigel tube-formation assays, as well as in vivo nude mouse tumor-bearing model and nude mouse dorsal skinfold window chamber (DSWC) model, were utilized to investigate the effects in order to explore the mechanism of EndMT induced by TGF-ß1 on breast cancer progression. Results: In this study, we demonstrated that the EndMT markers were positively associated with MVD indicating unfavorable prognosis of invasive ductal carcinoma (IDC) patients. Functionally, TGF-ß1 promoted migration, proliferation and angiogenesis of differentiated-endothelial BCSLCs by inducing EndMT in vitro and promoted tumor growth and angiogenesis in vivo. Mechanically, we revealed TGF-ß1 induced EndMT by activation of TGF-ß and Notch signaling pathways with increase of p-Smad2/3 and Notch1 expression. Moreover, we found Snail and Slug were key factors of TGF-ß and Notch signaling pathways. Conclusion: Our findings elucidated the mechanism of TGF-ß1 in the promotion of angiogenesis and progression by EndMT in breast cancer.