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Vissers-Bodmer Syndrome (VIBOS) is an autosomal dominant disorder caused by variants in the CNOT1 gene. It is characterized by systemic developmental and language-motor delay, intellectual disabilities, growth and behavioral abnormalities, hypotonia, and distal skeletal defects, such as deformities of the hands and feet. This syndrome becomes evident during infancy and can display a highly variable phenotype. Thirty-nine individuals with heterozygous de novo CNOT1 variants were first reported in 2019. Herein, we report a child with VIBOS who exhibited delayed motor development for over 4 years, along with hypotonia and atypical facial features. Notably, the patient developed short stature as the primary characteristic without any intellectual disability or organic nervous system lesions. Genetic testing revealed a de novo base duplication variant in exon 5 of the CNOT1 gene, NM_016284.5(CNOT1):c.316_317dup(p.Pro107Serfs*10). Importantly, the pathogenicity of this specific variant has not been reported in relevant literature. This study reports a new variant, thereby enriching the variant spectrum of CNOT1 associated with VIBOS, and contributes to the genetic counseling of affected families.
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Deficiência Intelectual , Transtornos do Desenvolvimento da Linguagem , Criança , Humanos , Deficiências do Desenvolvimento/genética , Hipotonia Muscular/genética , Mutação da Fase de Leitura/genética , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Síndrome , Fatores de Transcrição/genéticaRESUMO
PURPOSE: The goal is to identify risk factors associated with receiving a blood transfusion during the perioperative period in patients who undergo total laparoscopic hysterectomy (TLH) using a large-scale national database. METHODS: In this retrospective analysis, data from the Nationwide Inpatient Sample (NIS) was utilized to review the medical records of all patients who underwent TLH from 2010 to 2019. The researchers identified patients who had received a blood transfusion during the perioperative period and compared with those who had not. The subsequent factors associated with blood transfusion were examined: hospital characteristics (type of admission and payer, patient demographics (age and race), bed size, teaching status, location, and region of hospital), length of stay (LOS), total charges during hospitalization, in-hospital mortality, comorbidities, and perioperative complications. The data was analyzed using descriptive statistics. The independent risk factors of perioperative blood transfusion after TLH was identified by performing multivariate logistic regression. RESULTS: A total of 79,933 TLH were captured from the NIS database, among which 3433 (4.40%) patients received a perioperative blood transfusion. TLH patients affected by blood transfusion were 2 days longer hospital stays (P < 0.001), higher overall costs (P < 0.001), the patients who received a transfusion after a long-term hospitalization had a significantly higher rate of mortality (0.5% vs. 0.1%; P < 0.001). Perioperative blood transfusion after TLH was associated with chronic blood loss anemia, deficiency anemia, coagulopathy, congestive heart failure, fluid and electrolyte disorders, renal failure, metastatic cancer, sepsis, weight loss, deep vein thrombosis, gastrointestinal hemorrhage, shock, acute myocardial infarction, and pneumonia, stroke, hemorrhage, pulmonary embolism, and disease of the genitourinary system. CONCLUSION: Studying the risk factors of perioperative blood transfusion after TLH is advantageous in order to ensure proper management and optimize outcomes.
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Anemia , Laparoscopia , Feminino , Humanos , Estudos Retrospectivos , Histerectomia , Transfusão de SangueRESUMO
The aberrant activation of NLRP3 inflammasomes is intricately linked to various inflammatory diseases. In this study, we present the discovery and optimization of a series of NLRP3 inflammasome inhibitors based on the pterostilbene skeleton. All compounds underwent screening to evaluate their inhibitory effects on LPS/Nigericin-induced IL-1ß secretion and anti-cellular pyroptosis. Most compounds exhibit good biological activity and cellular safety, with compound D20 showing the most prominent activity. Preliminary mechanism studies suggest that compound D20 may affect the assembly of NLRP3 inflammasomes by targeting the NLRP3 protein, thereby inhibiting the activation of NLRP3 inflammasomes. The in vivo anti-inflammatory activity demonstrated significant therapeutic effect of compound D20 on DSS-induced acute colitis model in mice. This work has important reference significance for the development of drugs targeting NLRP3 inflammasomes.
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BACKGROUND: Unsafe sex is recognized as an important risk factor for cervical cancer (CC). Understanding the global disease burden of CC attributable to unsafe sex can assist policymakers in allocating healthcare resources. METHODS: Data were obtained from the 2019 global burden of disease database (GBD). We examined global, regional, and national levels of CC mortality, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) caused by unsafe sex. ASRs were evaluated using estimated annual percentage changes (EAPCs). RESULTS: Attributable to unsafe sex, there were 280,479 CC-related deaths in 2019 and 8,955,013 CC-related DALYs. In the period 1990-2019, the global ASRs of CC due to unsafe sex decreased around the world; for age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR), the EAPCs were -0.93 and -0.95. The highest ASMRs and ASDRs were found in central sub-Saharan Africa and the lowest in Australasia. CONCLUSION: In the past few decades, the ASMR and ASDR of CC caused by unsafe sexual practices have decreased over time, with significant variations observed among different countries and regions. Increased focus is needed on spreading awareness about sexual health and promoting CC prevention and screening, particularly in low- and middle-income nations.
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Carga Global da Doença , Sexo sem Proteção , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/epidemiologia , Feminino , Adulto , Sexo sem Proteção/estatística & dados numéricos , Pessoa de Meia-Idade , Anos de Vida Ajustados por Deficiência , Fatores de Risco , IdosoRESUMO
Near-infrared region (NIR; 650-1700 nm) dyes offer many advantages over traditional dyes with absorption and emission in the visible region. However, developing new NIR dyes, especially organic dyes with long wavelengths, small molecular weight, and excellent stability and biocompatibility, is still quite challenging. Herein, we present a general method to enhance the absorption and emission wavelengths of traditional fluorophores by simply appending a charge separation structure, dihydropyridopyrazine. These novel NIR dyes not only exhibited greatly redshifted wavelengths compared to their parent dyes, but also displayed a small molecular weight increase together with retained stability and biocompatibility. Specifically, dye NIR-OX, a dihydropyridopyra-zine derivative of oxazine with a molecular mass of 386.2 Da, exhibited an absorption at 822 nm and an emission extending to 1200 nm, making it one of the smallest molecular-weight NIR-II emitting dyes. Thanks to its rapid metabolism and long wave-length, NIR-OX enabled high-contrast bioimaging and assessment of cholestatic liver injury in vivo and also facilitated the evalua-tion of the efficacy of liver protection medicines against cholestatic liver injury.
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Bacterial infections can easily occur when patients mishandle wounds or eat moldy food. The prompt diagnosis of a bacterial infection could effectively reduce the risk of possible anatomical damage. However, non-invasive early detection of bacterial infections is difficult to achieve due to the lack of favorable tools. Here, we designed two hNQO1 fluorescent probes (RX2 and RX3) to visualize bacterial infection after deep learning on the pathogenesis of bacterial infection. RX2 and RX3 enable early detection of bacterial infection and are verified to be, respectively, suitable for fluorescence imaging (FLI) and photoacoustic imaging (PAI) by comparing the signal-to-background ratio of both probes in a mouse model of myositis caused by Escherichia coli infection. In view of the difference in penetration depth between the two imaging modalities, we further applied RX2 for FLI of E. coli-infected wounds and RX3 for PAI of E. coli-infected inflammatory bowel disease, suggesting the great potential of both probes for early diagnosis of bacterial infections.
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Colite Ulcerativa , Infecção dos Ferimentos , Camundongos , Animais , Colite Ulcerativa/diagnóstico por imagem , Escherichia coli , Corantes Fluorescentes , Imagem ÓpticaRESUMO
Nonsmall cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Circular RNAs (circRNAs) have been the focus of numerous studies, and some circRNAs have been linked to the development of multiple malignant tumors, including NSCLC. Nevertheless, the functional role and mechanisms of circRNAs in NSCLC remain largely unknown. The primary objective of this study was to screen the associated circRNA in NSCLC and investigate its mechanism. CircRNA microarray was used to identify circRNAs that were abnormally expressed in NSCLC tissue samples. Expression of hsa_circRNA_0088036 was validated in NSCLC tissues and cell lines after the correlation between hsa_circRNA_0088036 and prognosis was determined. We then used a series of function gain-and-loss assays to determine the role of hsa_circ_0088036 in NSCLC progression. RNA-binding protein immunoprecipitation (RIP), RNA pull-down, and RNA interference assays were used to assess the interaction between hsa_circ_0088036 and miR-1343-3p/Bcl-3 axis. Moreover, mechanistic assays were applied to investigate the involved signaling pathway regulated by the hsa_circ_0088036/miR-1343-3p/Bcl-3 axis. Microarray analysis and reverse transcription polymerase chain reaction confirmed the presence of a circRNA termed hsa_circ 0088036 that was upregulated in NSCLC tissue samples and cell lines and indicated a positive association with patient prognosis. Functionally, hsa_circ_0088036 silencing inhibited proliferative, invasive, and migrative potential of NSCLC cells as well as epithelial-mesenchymal transition (EMT)-related proteins by sponging miR-1343-3p to inhibit Bcl-3. Furthermore, mechanistic experiments demonstrated that hsa_circ_0088036 promoted NSCLC progression by activating the TGFß/Smad3/EMT signaling pathway via miR-1343-3p/Bcl-3 axis. In conclusion, hsa_circ_0088036 functions as an oncogene by targeting the miR-1343-3p/Bcl-3 axis via TGFß/Smad3/EMT signaling pathway.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , Fator de Crescimento Transformador beta/genéticaRESUMO
Recent progress on the temporal response (TR) of lanthanide-doped upconversion luminescence (UCL) has enriched the means of UCL regulation, promoted advanced designs for customized applications such as biological diagnosis, high-capacity optical coding, and dynamic optical anti-counterfeiting, and pushed us to reacquaint the dynamic responses of sensitizer/activator ions in UCL systems. In particular, the lifetime of UCL should be revisited after discovery of novel experimental phenomena and luminescence mechanisms, i. e., it should be understood as the collective TR (in the decay edge) of all the involved ions rather than the reciprocal of the radiative rate of an individual ion. In this Concept, we retraced the latest understanding of the dynamics in UCL with special attention to the relationship between excitation and emission, means of TR regulation, and discussed existing challenges. It is expected to provide some fundamental insights to deepened understanding, further regulation, and frontier applications of TR features of UCL.
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BACKGROUND: Mitofusin 2 (MFN2) plays an important role in many tumors, but how its role in renal clear cell carcinoma needs further research. METHODS: In this study, we analyzed the expression of MFN2 in renal clear cell carcinoma tissues and normal kidney tissues through the Cancer Genome Atlas (TCGA) database and our clinical samples.Enrichment analysis was performed to determine MFN2-related pathways and biological functions. The correlation of MFN2 expression with immune cells was analyzed.The correlation of the expression of methylation and the methylation sites of MFN2 were analyzed by UALCAN and TCGA databases. Univariate / multivariate COX risk regression and Kaplan-Meier methods were used to determine the prognostic value of MFN2.Nomograms were drawn to predict overall survival (OS) at 1,3, and 5 years. We investigated the role of MFN2 in renal cancer cells using CCK 8, clone formation, wound healing assay, and methylase qPCR experiments. RESULTS: MFN2 is poorly expressed in renal clear cell carcinoma compared to normal kidney tissue,and is significantly negatively associated with TNM stage, histological grade and pathological stage.MFN2 was directly associated with OS after multivariate Cox regression analysis.MFN2 shows a hypomethylation state and shows a positive correlation with multiple methylation sites.Signaling pathways through functional enrichment to B-cell receptors and oxidative stress-induced senescence.Moreover, the low expression of MFN2 was positively correlated with the degree of immune cell infiltration in a variety of immune cells.In vitro experiments showed that overexpression of MFN2 significantly inhibited the proliferation and migration of renal clear cells and promoted methylation. CONCLUSIONS: In conclusion, MFN2 can be used as a novel prognostic marker for renal clear cell carcinoma and requires further investigation of its role in tumor development.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Proteínas Mitocondriais/genética , Carcinoma de Células Renais/genética , Prognóstico , Dinâmica Mitocondrial , Neoplasias Renais/genética , Hidrolases , GTP Fosfo-Hidrolases/genéticaRESUMO
BACKGROUND: Common air pollutants such as ozone (O3), sulfur dioxide (SO2), nitrogen dioxide (NO2), and particulate matter play significant roles as influential factors in influenza-like illness (ILI). However, evidence regarding the impact of O3 on influenza transmissibility in multi-subtropical regions is limited, and our understanding of the effects of O3 on influenza transmissibility in temperate regions remain unknown. METHODS: We studied the transmissibility of influenza in eight provinces across both temperate and subtropical regions in China based on 2013 to 2018 provincial-level surveillance data on influenza-like illness (ILI) incidence and viral activity. We estimated influenza transmissibility by using the instantaneous reproduction number ([Formula: see text]) and examined the relationships between transmissibility and daily O3 concentrations, air temperature, humidity, and school holidays. We developed a multivariable regression model for [Formula: see text] to quantify the contribution of O3 to variations in transmissibility. RESULTS: Our findings revealed a significant association between O3 and influenza transmissibility. In Beijing, Tianjin, Shanghai and Jiangsu, the association exhibited a U-shaped trend. In Liaoning, Gansu, Hunan, and Guangdong, the association was L-shaped. When aggregating data across all eight provinces, a U-shaped association was emerged. O3 was able to accounted for up to 13% of the variance in [Formula: see text]. O3 plus other environmental drivers including mean daily temperature, relative humidity, absolute humidity, and school holidays explained up to 20% of the variance in [Formula: see text]. CONCLUSIONS: O3 was a significant driver of influenza transmissibility, and the association between O3 and influenza transmissibility tended to display a U-shaped pattern.
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Poluentes Atmosféricos , Poluição do Ar , Influenza Humana , Ozônio , Humanos , Ozônio/análise , Poluição do Ar/análise , China/epidemiologia , Influenza Humana/epidemiologia , Poluentes Atmosféricos/análiseRESUMO
Hydrogels are 3D network structures composed of physically or chemically crosslinked, hydrophilic molecules. Compared with conventional hydrogels with static and permanent network structures, injectable and responsive hydrogels generated from dynamic networks, have attracted increasing attention from various disciplines due to their wide-ranging applications in tissue engineering, drug delivery, soft robotics, etc. Herein, an injectable self-healing and multiple-responsive hyaluronic acid (HA)- histamine (His)/metal hydrogel is developed by modifying His onto HA and the subsequent, dynamic coordination between imidazole and metal ions. The pH-responsive and mechanical behaviors exhibited by the HA-His/metal hydrogels are tunable with the kinds and the concentrations of metal ions. The HA-His/Zr4+ hydrogels demonstrate a moldable capability at a neutral pH and a multi-stimulus-responsive capability when exposed to a weak alkaline environment and hyaluronidase, which inhibits bacterial growth and biofilm formation. Biocompatibilities and accelerated wound healing are demonstrated in vitro and in vivo and are thoroughly investigated and well characterized. The HA-His/Zr4+ hydrogel has great potential in various biomedical applications, such as pH- and hyaluronidase-responsive sustained release, antibacterial, and implantable materials for tissue engineering.
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Ácido Hialurônico , Hidrogéis , Hidrogéis/química , Ácido Hialurônico/química , Histamina , Engenharia Tecidual , Hialuronoglucosaminidase , Antibacterianos/químicaRESUMO
The pterostilbene skeleton is a promising chemical scaffold that exerts anti-inflammatory, anti-depressant, and anti-tumor effects. In this study, we aim to reduce in vivo and in vitro toxicity of compound 32 (preliminary work) and maintain its biological activity. A series of novel pterostilbene derivatives (D1-D43) were designed and synthesized, and their anti-inflammatory activities were screened. All compounds were screened to evaluate their inhibitory effect on LPS/Nigericin-induced IL-1ß production and pyroptosis. The structure-activity relationships was deduced, and finally 1-((E)-4-(2-ethoxyethoxy)styryl)-3,5-dimethoxy-2-((E)-2-nitrovinyl)benzene (D22) was found to be a low-toxic compound with most potent inhibitory efficacy (against IL-1ß: IC50 = 2.41 µM). Preliminary mechanism studies showed that compound D22 may affect the assembly of NLRP3 inflammasome by targeting NLRP3 protein, thereby inhibiting the activation of NLRP3 inflammasome. The in vivo anti-inflammatory activity indicated that compound D22 had significant therapeutic effects on DSS-induced mouse acute colitis models.
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Colite , Inflamassomos , Estilbenos , Animais , Camundongos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Inflamassomos/antagonistas & inibidores , Inflamassomos/metabolismo , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estilbenos/química , Estilbenos/farmacologiaRESUMO
Change of hydrodynamic conditions is a key factor inducing sedimentation, water eutrophication and algal blooms in the Three Gorges Reservoir (TGR). How to mitigate sedimentation and phosphorus (P) retention by improving hydrodynamic conditions in the Three Gorges Reservoir area (TGRA) is an urgent issue in the study of sediment and water environment. In this study, a Hydrodynamic-Sediment-Water quality model for the whole TGRA is proposed considering sediment and P inputs from numerous tributaries, and a new reservoir operation method namely the tide-type operation method (TTOM) is used to investigate the large-scale sediment and P transport in the TGR based on the model. Results indicate that the TTOM can reduce sedimentation and total phosphorus (TP) retention in the TGR. Compared with the actual operation method (AOM), sediment outflow and sediment export ratio (Eratio) of the TGR increased about 17.13% and 1%-3% in 2015-2017, and sedimentation decreased about 3% under the TTOM. TP retention flux and retention rate (RE) decreased about 13.77% and 2%-4%. The flow velocity (V) and sediment carrying capacity (S*) increased about 40% in the local reach. Larger daily water level fluctuation at dam site is more conducive to reducing sedimentation and TP retention in the TGR. Sediment inputs from the Yangtze River, Jialing River, Wu River and other tributaries account for 59.27%, 11.21%, 3.81% and 25.70% of the total sediment inflow during 2015-2017, and TP inputs were 65.96%, 10.01%, 17.40% and 6.63%. In the paper, an innovative method is proposed to reduce sedimentation and P retention in the TGR under the given hydrodynamic conditions and related quantitative contribution driven by the proposed method is analyzed. The work is favorable for expanding the understanding of the hydrodynamic and nutrition flux changes in the TGR, and provides a new perspective for water environment protection and reasonable operation of large reservoirs.
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Fósforo , Poluentes Químicos da Água , Fósforo/análise , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Eutrofização , Qualidade da Água , Rios , ChinaRESUMO
Full-scale anaerobic ammonium oxidation (anammox) engineering applications are vastly limited by the sensitivity of anammox bacteria to the complex mainstream ambience factors. Therefore, it is of great necessity to comprehensively summarize and overcome performance-related challenges in mainstream anammox process at the macro/micro level, including the macroscopic process variable regulation and microscopic biological metabolic enhancement. This article systematically reviewed the recent important advances in the enrichment and retention of anammox bacteria and main factors affecting metabolic regulation under mainstream conditions, and proposed key strategies for the related performance optimization. The characteristics and behavior mechanism of anammox consortia in response to mainstream environment were then discussed in details, and we revealed that the synergistic nitrogen metabolism of multi-functional bacterial genera based on anammox microbiome was conducive to mainstream anammox nitrogen removal processes. Finally, the critical outcomes of anammox extracellular electron transfer (EET) at the micro level were well presented, carbon-based conductive materials or exogenous electron shuttles can stimulate and mediate anammox EET in mainstream environments to optimize system performance from a micro perspective. Overall, this review advances the extensive implementation of mainstream anammox practice in future as well as shedding new light on the related EET and microbial mechanisms.
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Compostos de Amônio , Águas Residuárias , Desnitrificação , Compostos de Amônio/metabolismo , Oxidação Anaeróbia da Amônia , Oxirredução , Reatores Biológicos/microbiologia , Bactérias/metabolismo , Anaerobiose , Nitrogênio/metabolismo , Esgotos/microbiologiaRESUMO
OBJECTIVES: Comparing the long-term tumor control results of partial cystectomy(PC)and radical cystectomy(RC)in the treatment of muscle-invasive bladder cancer, and to explore the feasible method of bladder preservation therapy (BPT)in patients with MIBC. METHODS: We retrospectively analyzed the clinical data of 102 patients with muscle-invasive bladder cancer in our hospital between January 2012 and December 2018, of whom 32 cases in the partial cystectomy group and 70 cases in the radical cystectomy group. We performed a comparative analysis of patient general information, perioperative-related indicators and postoperative follow-up data, comparing OS, PFS, and DSS at 1, 2, 3, 4, and 5 years in both groups, and comparing tumour recurrence and metastasis in postoperative patients. RESULTS: All the 102 cases in this study were successfully completed. Partial cystectomy group and Radical cystectomy group median operating time (169.50(130.00 ~ 225.25) min and 420.00(343.75 ~ 483.75) min, p < 0.001), median intraoperative blood loss was (100(50 ~ 100)ml and 400(200 ~ 1000)ml, p < 0.001), median perioperative blood transfusion volume (0(0 ~ 0)ml and 600(150.00 ~ 906.25)ml, p < 0.001), median total hospital stay (18(14.25 ~ 20.00) and 24.5(20.00 ~ 34.25) days, p < 0.001), median preoperative preparation time (7(4.25 ~ 8.00) and 10(8.00 ~ 13.00) days, p < 0.001), median postoperative hospital stay (9(8.00 ~ 13.50) and 14(11.00 ~ 21.25) days, p < 0.001), the incidence of perioperative blood transfusion was (15.6% and 75.7%, p < 0.001), the incidence of surgical complications was(28.1%(9/32) and 50.0%(35/70), p = 0.033), average hospitalization cost ((26435.76 ± 9877.82) yuan and (58464.36 ± 19753.13) yuan, p < 0.001), the differences were statistically significant (p < 0.05). Perioperative mortality (0 vs. 2.9%(2/70), p = 1), and OS at 1, 2, 3, 4, and 5 years after surgery were (80.0%, 59.8%, 56.1%, 51.0%, 44.6% vs. 76.5%, 67.4%, 64.9%, 57.9%, 52.6%, p = 0.524), PFS (68.2%, 64.6%, 60.3%, 54.8%, 54.8% vs. 82.7%, 78.3%, 75.4%, 67.3%, 62.1%, p = 0.259). DSS (89.9%, 72.4%, 68.6%, 68.6%, 62.4% vs. 87.3%, 83.4%, 80.9%, 73.6%, 68.0%, p = 0.424), and the incidence of tumor recurrence or metastasis was (40.0%(12/30) vs. 25.4%(16/63), p = 0.151), the differences were not statistically significant (p > 0.05). CONCLUSION: In patients with limited solitary T2N0M0 and T3N0M0 muscle-invasive bladder cancer, partial cystectomy plus bladder instillations treatment can achieve comparable tumour control to radical cystectomy. However, patients in the PC group have significant advantages in terms of operative time, intraoperative bleeding, intraoperative and postoperative blood transfusion, preoperative preparation time, total hospital stay, postoperative recovery time, operative costs and operative complications. This option may be considered for such patients with a need for bladder preservation.
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Neoplasias da Bexiga Urinária , Bexiga Urinária , Humanos , Bexiga Urinária/cirurgia , Cistectomia/métodos , Administração Intravesical , Estudos Retrospectivos , Recidiva Local de Neoplasia/cirurgia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Músculos/patologia , Resultado do TratamentoRESUMO
The effect of Transgelin 2 (TAGLN2) on clear cell renal cell carcinoma (ccRCC) is unknown. This study explored the potential role and mechanism of ccRCC. The expression of TAGLN2 in Pan-cancers was analyzed using the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases. TCGA-KIRC database was used to analyze subsequent prognostic survival, pathway enrichment, and immune infiltration. Relevant experimental methods could explain the effect of TAGLN2 expression on tumor cell proliferation, migration, invasion, and apoptosis. Apoptosis, proliferation, Epithelial-to-Mesenchymal Transition (EMT), and PI3K/AKT signaling pathway-related protein expression were determined through western blotting. In the TCGA + GTEx database, mRNA-TAGLN2 expression was clearly increased in pan-cancer tissues, and the same result was found in ccRCC patients based on KIRC analysis results. In addition, TAGLN2 was associated with poor clinical stage, pathological grade, and survival prognosis. TAGLN2 is highly expressed in ccRCC tissues and in vitro TAGLN2 silencing of cells inhibits the proliferation, migration, invasion, and EMT of ccRCC cancer cells. Furthermore, TAGLN2-related differential genes enriched in the PI3K/AKT signaling pathway were negatively regulated after TAGLN2 silencing. Moreover, TAGLN2 may promote tumor immune escape and increase the risk of distant metastasis in immune infiltration-related analyses. TAGLN2 can be used as a single indicator to explain the survival probability of patients with ccRCC. In vitro TAGLN2 silencing inhibited the malignant properties of ccRCC by blocking the PI3K/AKT signaling pathway. In addition, TAGLN2 contributes to tumor immune escape and may be a potential therapeutic target for ccRCC.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais , Proliferação de Células/genéticaRESUMO
BACKGROUND: In megacities, there is an urgent need to establish more sensitive forecasting and early warning methods for acute respiratory infectious diseases. Existing prediction and early warning models for influenza and other acute respiratory infectious diseases have limitations and therefore there is room for improvement. OBJECTIVE: The aim of this study was to explore a new and better-performing deep-learning model to predict influenza trends from multisource heterogeneous data in a megacity. METHODS: We collected multisource heterogeneous data from the 26th week of 2012 to the 25th week of 2019, including influenza-like illness (ILI) cases and virological surveillance, data of climate and demography, and search engines data. To avoid collinearity, we selected the best predictor according to the weight and correlation of each factor. We established a new multiattention-long short-term memory (LSTM) deep-learning model (MAL model), which was used to predict the percentage of ILI (ILI%) cases and the product of ILI% and the influenza-positive rate (ILI%×positive%), respectively. We also combined the data in different forms and added several machine-learning and deep-learning models commonly used in the past to predict influenza trends for comparison. The R2 value, explained variance scores, mean absolute error, and mean square error were used to evaluate the quality of the models. RESULTS: The highest correlation coefficients were found for the Baidu search data for ILI% and for air quality for ILI%×positive%. We first used the MAL model to calculate the ILI%, and then combined ILI% with climate, demographic, and Baidu data in different forms. The ILI%+climate+demography+Baidu model had the best prediction effect, with the explained variance score reaching 0.78, R2 reaching 0.76, mean absolute error of 0.08, and mean squared error of 0.01. Similarly, we used the MAL model to calculate the ILI%×positive% and combined this prediction with different data forms. The ILI%×positive%+climate+demography+Baidu model had the best prediction effect, with an explained variance score reaching 0.74, R2 reaching 0.70, mean absolute error of 0.02, and mean squared error of 0.02. Comparisons with random forest, extreme gradient boosting, LSTM, and gated current unit models showed that the MAL model had the best prediction effect. CONCLUSIONS: The newly established MAL model outperformed existing models. Natural factors and search engine query data were more helpful in forecasting ILI patterns in megacities. With more timely and effective prediction of influenza and other respiratory infectious diseases and the epidemic intensity, early and better preparedness can be achieved to reduce the health damage to the population.
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Aprendizado Profundo , Epidemias , Influenza Humana , Humanos , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Previsões , ClimaRESUMO
Damage-free transfer of large-area two-dimensional (2D) materials is indispensable to unleash their full potentials in a wide range of electronic, photonic, and biochemical applications. However, the all-surface nature of 2D materials renders many of them vulnerable to surrounding environments, especially etchants and water involved during wet transfer process. Up to now, a scalable and damage-free transfer method for sensitive 2D materials is still lacking. Here, we report a general damage-free transfer method for sensitive 2D materials. The as-transferred 2D materials exhibit well-preserved structural integrity and unaltered physical properties. We further develop a facile TEM sample preparation technique that allows direct recycling of materials on TEM grids with high fidelity. This recycling technique provides an unprecedented opportunity to precisely relate structural characterization with physical/chemical/electrical probing for the same samples. This method can be readily generalized to diverse nanomaterials for large-area damage-free transfer and enables in-depth investigation of structure-property relationship.
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Nanoestruturas , Eletrônica/métodos , Nanoestruturas/químicaRESUMO
Two new inorganic-organic hybrid crystals based on PbI2 were assembled through the solvent evaporation method, namely, {[L1]·[Pb2I6]}n (1) and {[L2]2·[Pb3I10]}n (2). L1-L2 are a series of multivalent nitrogen-containing cationic ligands. Compounds 1-2 were characterized by single-crystal X-ray diffraction, elemental analysis, FT-IR, powder X-ray diffraction, and thermogravimetric microanalysis. The results showed that the adsorption rate of 80 mg compound 1 to iodine reached 96.59%, indicating a high iodine capture performance in cyclohexane solution. In the meantime, the adsorption kinetics is most suitable for a pseudo-second-order model, and the adsorption process is mainly chemisorption. Adsorption thermodynamics is most suitable for the Langmuir model, indicating that adsorption occurs on the surface of the monolayer. According to the adsorption mechanism, it can be inferred that the structure of compound 1 contains amino, benzene, N heterocyclic, and other active groups, that is, indirectly increases the adsorption site with iodine, and the chemical reaction with iodine improves the removal rate of iodine in cyclohexane solution. In addition, compound 1 was found to have good iodine adsorption and recyclability by cyclic experiments. Therefore, the synthesized compound 1 can be used as a potential and excellent iodide capture adsorbent, which may have a good application prospects in the future.
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In this paper, two benzimidazole derivative ligands were obtained using o-phenylenediamine and n-pyridine formaldehyde (n = 3, 4) by amine-aldol condensation reactions, which were reacted with selected inorganic metal salts by ambient temperature volatilization method to give compounds 1-4: {[(L1)6]·[Cu8I8]} (1), {[L1]·[CuBr]·H2O} (2), {[L2]·[CuBr]}n(3), and {[(L2)4]·[Cu4I4]} (4). They were characterized by IR, UV-Vis absorption spectroscopy, thermogravimetric analysis, and single crystal X-ray analysis. Simultaneously, compounds 1-4 were found to possess photocatalytic degradation of ciprofloxacin (CIP) by preliminary experimental investigations.