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Anaerobic digestion (AD) is an important biological resource recovery process, where microorganisms play key roles for material transformation. There has been some knowledge about the prokaryotic community and antibiotic resistance genes (ARGs) in AD, but there has been very limited knowledge of phages. In this study, samples from a full-scale AD plant were collected over 13 months, sequenced, and analyzed for viral and prokaryotic metagenomes. Totally, 3015 viral operational taxonomic units (vOTUs) were detected, mostly assigned to Caudoviricetes. The phage community had faster temporal variation than the prokaryotic community. Warm seasons harbored a higher abundance of both temperate phages and broad host-range phages. Seven ARGs of 6 subtypes were carried by 20 vOTUs, a representative ermT gene was synthesized and expressed, and the resistance activity in the host was examined, confirming the real activity of virus-carried ARGs in the AD process. Some of the ARGs were horizontally transferred between the phage and prokaryotic genomes. However, phage infection was not found to contribute to ARG transfer. This study provided an insight into the ecological patterns of the phage community, confirmed the antibiotic resistance activity of virus-carried ARGs, evaluated the contribution of phages on the ARG prevalence, and laid the foundation for the control strategies of the community and antibiotic resistance in the AD process.
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Bacteriófagos , Esgotos , Bacteriófagos/genética , Antibacterianos/farmacologia , Anaerobiose , Prevalência , Resistência Microbiana a Medicamentos/genética , Genes BacterianosRESUMO
The plasmonic photothermal conversion efficiency can be enhanced by coupling among plasmonic atoms or plasmonic molecules due to the amplified local electric field and extinction cross-section. Recently, it has been theoretically proved that hybridization between dipolar modes and higher order modes can provide higher enhancement than that among dipolar modes in terms of both near- and far-field, which may lead to a higher photothermal conversion rate. In this work, we systematically investigated the photothermal conversion enhancement of plasmonic coupling between a dipolar mode of a titanium nitride nanoparticle (TiN NP) and a higher order mode of a gold nanorod (Au NR), which was compared to that of coupling among TiN NPs' dipolar modes. We evaluated the photothermal conversion efficiency of dipole-dipole coupling and dipole-multipole coupling in the nanocluster under the illumination of a monochromatic laser of 808 nm wavelength and simulated solar light, respectively. Both experimental tests and numerical simulations suggested that the plasmonic dipole-multipole coupling exhibited higher enhancement in photothermal conversion than dipole-dipole plasmonic coupling.
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BACKGROUND The objective of this investigation was to assess the effectiveness of using T-shaped steel plates through the anterior lateral approach and Gerdy's tubercle osteotomy for treating posterior lateral tibial plateau fractures. MATERIAL AND METHODS A retrospective analysis was conducted on clinical data from 20 patients, aged on average 53.9±10.36 years, who were admitted for tibial plateau fractures involving the posterior lateral condyle between January 2019 and October 2022. The fixation and reduction of the posterior lateral bone block were performed using the anterior lateral approach combined with Gerdy's tubercle osteotomy to address the posterior lateral tibial plateau fracture. Post-surgery assessment was conducted using the Hospital for Special Surgery (HSS) knee combined score. RESULTS During the 12-24 (14.2±1.7) month postoperative period, we conducted 20 surgeries. Within 9 to 12 weeks, fracture healing transpired without any complications such as incision infection, nerve injury, or fracture displacement being detected. Assessment of knee joint function at the final follow-up was conducted using the HSS knee combined score, with results indicating 16 cases rated as excellent, 3 cases as good, and 1 case as fair. CONCLUSIONS In tibial plateau fractures impacting the posterior lateral condyle, the anterior lateral approach, combined with Gerdy's tubercle osteotomy, allows for direct exposure and manipulation of the posterior lateral bone block fracture. Using a T-shaped support plate and a lateral locking plate provides a reliable method for fracture fixation, aiding in convenient surgical positioning and intraoperative fluoroscopy. The treatment approach effectively manages fractures located on the posterior lateral aspect of the tibial plateau.
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Fixação Interna de Fraturas , Osteotomia , Fraturas do Planalto Tibial , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placas Ósseas , Fixação Interna de Fraturas/métodos , Consolidação da Fratura , Articulação do Joelho/cirurgia , Osteotomia/métodos , Estudos Retrospectivos , Fraturas do Planalto Tibial/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVE: An emergency cesarean section (CS), which is extremely life-threatening to the mother or fetus, seems to be performed within an adequate time horizon to avoid negative fetal-maternal denouement. An effective and vigilant technique for anesthesia remains vital for emergency cesarean delivery. Therefore, this study aimed to validate the impact of various anesthesia tactics on maternal and neonatal outcomes. METHOD: This was a retrospective cohort study of parturient patients who were selected for emergency CS with the assistance of general or neuraxial anesthesia between January 2015 and July 2021 at our institution. The 5-min Apgar score was documented as the primary outcome. Secondary outcomes, including the 1 min Apgar score, decision-to-delivery interval (DDI), onset of anesthesia to incision interval (OAII), decision to incision interval (DII), duration of operation, length of hospitalization, height and weight of the newborn, use of vasopressors, blood loss, neonatal resuscitation rate, admission to neonatal intensive care unit (NICU), duration of NICU and complications, were also measured. RESULTS: Of the 539 patients included in the analysis, 337 CSs were performed under general anesthesia (GA), 137 under epidural anesthesia (EA) and 65 under combined spinal-epidural anesthesia (CSEA). The Apgar scores at 1 min and 5 min in newborns receiving GA were lower than those receiving intraspinal anesthesia, and no difference was found between those receiving EA and those receiving CSEA. The DDI of parturients under GA, EA, and CSE were 7[6,7], 6[6,7], and 14[11.5,20.5], respectively. The DDI and DII of GA and EA were shorter than those of CSE, and the DDI and DII were similar between GA and EA. Compared to that in the GA group, the OAII in the intraspinal anesthesia group was significantly greater. GA administration correlated with more frequent resuscitative interventions, increased admission rates to NICU, and a greater incidence of neonatal respiratory distress syndrome (NRDS). Nevertheless, the duration of NICU stay and the incidence rates of neonatal hypoxic ischemic encephalopathy (HIE) and pneumonia did not significantly differ based on the type of anesthesia performed. CONCLUSION: Compared with general anesthesia, epidural anesthesia may not be associated with a negative impact on neonatal or maternal outcomes and could be utilized as an alternative to general anesthesia in our selected patient population following emergency cesarean section; In addition, a comparably short DDI was achieved for emergency cesarean delivery under epidural anesthesia when compared to general anesthesia in our study. However, the possibility that selection bias related to the retrospective study design may have influenced the results cannot be excluded.
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Anestesia Epidural , Anestesia Obstétrica , Recém-Nascido , Humanos , Gravidez , Feminino , Cesárea/métodos , Estudos Retrospectivos , Ressuscitação , Anestesia Geral/efeitos adversosRESUMO
BACKGROUND: The surgical treatment and management of postoperative soft tissue complications in diabetic patients with displaced calcaneal fractures are still controversial. We aimed to evaluate the short-term efficacy of percutaneous minimally invasive screw fixation in treatment of diabetic patients with Sanders II and III calcaneal fractures under subtalar arthroscopy assisted by preoperative musculoskeletal ultrasonic locating lateral calcaneal branch (LCB) of the sural nerve and calcaneal-talar joint distraction device. METHODS: The clinical data of 52 diabetic patients diagnosed with Sanders II or III calcaneal fractures from March 2016 to August 2020 were followed up and analyzed. There were 23 patients of type II and 29 patients of type III, 34 males and 18 females, with a mean age of 61.7 ± 14.5 years (range: 45-72 years). Preoperative musculoskeletal ultrasonography was routinely examined to locate LCB of the sural nerve. During surgery, we performed arthroscopic percutaneous prying reduction screw fixation assisted by medial calcaneal-talar joint distraction. Incision healing, local skin paraesthesia and other conditions were observed regularly at 3 days, 6, 12 months, and the last follow-up after surgery. Also, we measured the length, width, height, Böhler angle, and Gissane angle of the calcaneus on lateral and axial x-rays. Visual analogue pain scale (VAS), American Orthopedic Foot and Ankle Society (AOFAS) score and Maryland score were used to evaluate the efficacy. RESULTS: 52 patients were followed up for 23.7 ± 3.2 months (range: 20-28 months) without incision-related complications. Calcaneal radiographic parameters (length, width, height, Böhler/Gissane angle) were improved after surgery, and the differences were all statistically significant (P<0.05). There was no difference between calcaneal radiographic parameters at 6,12 months and the last follow-up compared with 3 days after surgery without significant loss in overall morphology (P>0.05). Postoperative VAS, AOFAS scores, and Maryland scores were significantly improved compared with those before surgery (P<0.05). CONCLUSIONS: Preoperative ultrasonic locating LCB of the sural nerve and arthroscopic percutaneous minimally invasive screw fixation of Sanders II and III calcaneal fractures with the assistance of calcaneal-talar joint distraction have good short-term efficacy and clinical feasibility in diabetic patients.
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Artroscopia , Calcâneo , Fixação Interna de Fraturas , Procedimentos Cirúrgicos Minimamente Invasivos , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Calcâneo/cirurgia , Calcâneo/lesões , Calcâneo/diagnóstico por imagem , Idoso , Estudos Retrospectivos , Artroscopia/métodos , Resultado do Tratamento , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Fraturas Ósseas/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Parafusos Ósseos , Articulação Talocalcânea/cirurgia , Articulação Talocalcânea/diagnóstico por imagem , Articulação Talocalcânea/lesões , Seguimentos , Nervo Sural/lesões , Nervo Sural/cirurgiaRESUMO
5-Hydroxytryptamine receptors (5-HTRs) are strongly correlated with tumor progression in various types of cancer. Despite this, the underlying mechanisms responsible for the role of 5-HTRs in non-small cell lung cancer (NSCLC) remains unclear. This study aimed to investigate the relationship between 5-hydroxytryptamine receptor 3A (HTR3A) and NSCLC development. Our findings indicated a higher distribution of HTR3A expression in NSCLC tissues when compared with normal tissues, where patients with high HTR3A levels demonstrated shorter overall survival times. In vitro analyses revealed that overexpression of HTR3A facilitated the proliferation and migration of NSCLC cell lines (A549 and NCI-H3255). Similarly, a notable acceleration of tumor growth and enhanced pulmonary tumorigenic potential were observed in HTR3A-overexpressing tumor-bearing mice. Mechanistically, upregulation of Forkhead Box H1 (FOXH1) by HTR3A led to the activation of Wnt3A/ß-catenin signaling pathways, thereby promoting the development of NSCLC. Our report thus highlights the significance of the HTR3A/FOXH1 axis during tumor progression in NSCLC, proposing HTR3A as a possible diagnostic indicator and candidate target for clinical therapy.
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Mesotrione, topramezone, tembotrione, and sulcotrione are four types of 4-hydroxyphenylpyruvate dioxidase (HPPD) inhibitor herbicides that are extensively employed in agricultural practices, but their usage also leads to environmental pollution and poses risks to human health. A probe (E)-1-((2-(pyridin-2-yl) hydrazineylidene) methyl) naphthalen-2-ol (CHMN) based on chelation enhancement (CHEF) effect synthesized. CHMN was first chelated with Zn2+ to form a probe system with green, which can be further used to detect mesotrione, topramezone, tembotrione and sulcotrione in complicated environment. CHMN-Zn2+ detection of four pesticides was accurate, with an excellent linear relationship between 0 and 100⯵M. The detection limits were LODmesotrione = 7.79⯵M, LODtopramezone = 1.91⯵M, LODtembotrione = 1.38⯵M and LODsulcotrione = 2.43⯵M. The detection time is 1â¯min, and it is successfully applied in real water sample and bioimaging. This work can provide a novel method for studying the migration and behavior of environmental pollutants.
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4-Hidroxifenilpiruvato Dioxigenase , Cicloexanonas , Herbicidas , Mesilatos , Sulfonas , Humanos , Fluorescência , Herbicidas/farmacologia , Zinco , Inibidores Enzimáticos/farmacologiaRESUMO
Phospholipid phosphatase related 4 (PLPPR4), a neuron-specific membrane protein located at the postsynaptic density of glutamatergic synapses, is a putative regulator of neuronal plasticity. However, PLPPR4 dysfunction has not been linked to genetic disorders. In this study, we report three unrelated patients with intellectual disability (ID) or autism spectrum disorder (ASD) who harbour a de novo heterozygous copy number loss of PLPPR4 in 1p21.2p21.3, a heterozygous nonsense mutation in PLPPR4 (NM_014839, c.4C > T, p.Gln2*) and a homozygous splice mutation in PLPPR4 (NM_014839: c.408 + 2 T > C), respectively. Bionano single-molecule optical mapping confirmed PLPPR4 deletion contains no additional pathogenic genes. Our results suggested that the loss of function of PLPPR4 is associated with neurodevelopmental disorders. To test the pathogenesis of PLPPR4, peripheral blood mononuclear cells obtained from the patient with heterozygous deletion of PLPPR4 were induced to specific iPSCs (CHWi001-A) and then differentiated into neurons. The neurons carrying the deletion of PLPPR4 displayed the reduced density of dendritic protrusions, shorter neurites and reduced axon length, suggesting the causal role of PLPPR4 in neurodevelopmental disorders. As the mTOR signalling pathway was essential for regulating the axon maturation and function, we found that mTOR signalling was inhibited with a higher level of p-AKT, p-mTOR and p-ERK1/2, decreased p-PI3K in PLPPR4-iPSCs neurons. Additionally, we found silencing PLPPR4 disturbed the mTOR signalling pathway. Our results suggested PLPPR4 modulates neurodevelopment by affecting the plasticity of neurons via the mTOR signalling pathway.
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Transtorno do Espectro Autista , Transtornos do Neurodesenvolvimento , Humanos , Transtorno do Espectro Autista/genética , Haploinsuficiência/genética , Leucócitos Mononucleares/patologia , Transtornos do Neurodesenvolvimento/genética , Plasticidade Neuronal/genética , Serina-Treonina Quinases TOR/genéticaRESUMO
BACKGROUND: Cryotherapy is a prevalent percutaneous ablative therapy for solid tumors. Here, we report a novel device using liquid nitrogen for endoscopic cryotherapy of bladder cancer. METHODS: In this multicenter, randomized, parallel controlled, Phase 2 trial, we compared endoscopic balloon cryoablation (EBCA) with a single instillation (SI) of pirarubicin after transurethral resection (TUR). Eligible participants were randomly assigned (1:1) to the TUR-EBCA or TUR-SI group. Repeat TUR or tissue biopsies were performed to evaluate residual tumor at 4 to 6 weeks after primary treatment. The primary end point was the local control rate. The secondary end points included the tumor upgrading/upstaging, catheter indwelling duration, and adverse events. RESULTS: In total, 205 patients received EBCA or SI after TUR between November 2017 and September 2020, of whom 163 completed all the required interventions. In the per-protocol set, the local control rate was 91.5% (75/82) in TUR-EBCA group compared with 76.5% (61/81) in TUR-SI group (risk difference, 15%; 95% CI, 0.03-0.27, p < .001), meeting the criteria for noninferiority. Similar results were found in the modified intention-to-treat analysis. Tumor upgrading/upstaging was found in five patients from the TUR-SI group. There was no significant difference in the catheter indwelling duration (5.1 vs. 5.2 days, p = .76) or serious adverse event rate (3.0% vs. 3.9%, p = .52). The median follow-up time of post hoc analysis was 31 (range, 15-50) months. Patients in the TUR-EBCA group had a better recurrence-free survival and progression-free survival. CONCLUSION: EBCA is a safe and effective adjuvant therapy with TUR for non-muscle-invasive bladder cancer. PLAIN LANGUAGE SUMMARY: This is the first randomized trial that evaluated endoscopic cryotherapy after transurethral resection (TUR) of bladder tumors. The efficacy and safety analysis shows endoscopic balloon cryoablation (EBCA) is a promising alternative. Results report that EBCA is not inferior to a single instillation of intravesical chemotherapy in eliminating residual bladder tumor. Further analysis with â¼3 years' median follow-up suggested a better prognosis in patients who received EBCA after TUR.
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Carcinoma de Células de Transição , Criocirurgia , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/patologia , Procedimentos Cirúrgicos Urológicos , Prognóstico , Administração Intravesical , Recidiva Local de Neoplasia/tratamento farmacológicoRESUMO
The therapeutic effects of existing drug regimens against pancreatic neuroendocrine neoplasms (pNENs) remain limited, and identifying ideal therapeutic targets is warranted. PDZ binding kinase (PBK) may play an oncogenic role in most solid tumors. However, its function in pNEN remains unclear. In this study, pNEN samples and International Cancer Genome Consortium data were used to determine the clinical significance of PBK. Cell counting and CCK8 assays were used to assess cell proliferation. Flow cytometry was used to assess drug-induced apoptosis and cell cycle arrest. An in vivo PBK-targeting experiment was performed in mice bearing pNENs. Western blotting, quantitative PCR, and immunohistochemistry were performed to assess the molecular mechanisms. PBK was significantly upregulated in pNEN tissues compared with paracancerous tissues. Additionally, PBK was a poor prognostic factor for pNEN patients. PBK was found to promote the proliferation of pNEN cells by activating the AKT/mTOR pathway. Furthermore, PBK inhibition combined with everolimus treatment had enhanced antitumour effects on pNEN via inhibiting AKT/mTOR pathway and inducing G0/G1 phase cell cycle arrest. This study highlights that PBK plays an oncogenic role in and is a promising therapeutic target for pNEN.
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Quinases de Proteína Quinase Ativadas por Mitógeno , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Animais , Camundongos , Linhagem Celular Tumoral , MAP Quinases Reguladas por Sinal Extracelular , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
Head neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors which ranks the sixth incidence in the world. Although treatments for HNSCC have improved significantly in recent years, its recurrence rate and mortality rate remain high. Myosin genes have been studied in a variety of tumors, however its role in HNSCC has not been elucidated. GSE58911 and GSE30784 gene expression profile analysis were performed to detect significantly dys-regulated myosin genes in HNSCC. The Cancer Genome Atlas (TCGA) HNSCC database was used to verify the dys-regulated myosin genes and study the relationship between these genes and prognosis in HNSCC. The results showed that MYL1, MYL2, MYL3, MYH2, and MYH7 were down-regulated, while MYH10 was up-regulated in patients with HNSCC. Interestingly, MYL1, MYL2, MYH1, MYH2, and MYH7 were shown to be unfavorable prognostic markers in HNSCC. It is also worth noting that MYL1 was a specific unfavorable prognostic biomarker in HNSCC. MYL1, MYL2, MYL3, MYH2, MYH7, and MYH10 promoted CD4 + T cells activation in HNSCC. MYL1 was proved to be down-regulated in HNSCC tissues compared to normal tissues at protein levels. MYL1 overexpression had no effect on proliferation, but significantly promoted migration of Fadu cells. MYL1 increased EGF and EGFR protein expression levels. Moreover, there is a positive correlation between MYL1 expression and Tcm CD8 cells, Tcm CD4 + cells, NK cells, Mast cells, NKT cells, Tfh cells and Treg cells in HNSCC. Overall, MYL1 facilitates tumor metastasis and correlates with tumor immune infiltration in HNSCC and these effects may be associated with the EGF/EGFR pathway.
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Neoplasias de Cabeça e Pescoço , Segunda Neoplasia Primária , Humanos , Biomarcadores , Fator de Crescimento Epidérmico , Receptores ErbB , Neoplasias de Cabeça e Pescoço/genética , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
BACKGROUND: We aimed to develop an autophagy-related prognostic model with single-cell RNA sequencing (ScRNA-Seq) data for hepatocellular carcinoma (HCC) patients. METHODS: ScRNA-Seq datasets of HCC patients were analyzed by Seurat. The expression of genes involved in canonical and noncanonical autophagy pathways in scRNA-seq data was also compared. Cox regression was applied to construct an AutRG risk prediction model. Subsequently, we examined the characteristics of AutRG high-risk and low-risk group patients. RESULTS: Six major cell types (hepatocytes, myeloid cells, T/NK cells, B cells, fibroblast cells, and endothelial cells) were identified in the scRNA-Seq dataset. The results showed that most of the canonical and noncanonical autophagy genes were highly expressed in hepatocytes, with the exception of MAP 1LC3B, SQSTM1, MAP 1LC3A, CYBB, and ATG3. Six AutRG risk prediction models originating from different cell types were constructed and compared. The AutRG prognostic signature (GAPDH, HSP90AA1, and TUBA1C) in endothelial cells had the best overall performance for predicting the overall survival of HCC patients, with 1-year, 3-year, and 5-year AUCs equal to 0.758, 0.68, and 0.651 in the training cohort and 0.760, 0.796, and 0.840 in the validation cohort, respectively. The different tumor mutation burden, immune infiltration, and gene set enrichment characteristics of the AutRG high-risk and low-risk group patients were identified. CONCLUSION: We constructed an endothelial cell-related and autophagy-related prognostic model of HCC patients using the ScRNA-Seq dataset for the first time. This model demonstrated the good calibration ability of HCC patients and provided a new understanding of the evaluation of prognosis.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Células Endoteliais , Prognóstico , Neoplasias Hepáticas/genética , Autofagia/genéticaRESUMO
In addition to higher-order executive functions, underlying sensory processing ability is also thought to play an important role in Attention-Deficit/Hyperactivity Disorder (AD/HD). An event-related potential feature, the mismatch negativity, reflects the ability of automatic sensory change processing and may be correlated with AD/HD symptoms and executive functions. This study aims to investigate the characteristics of visual mismatch negativity (vMMN) in adults with AD/HD. Twenty eight adults with AD/HD and 31 healthy controls were included in this study. These two groups were matched in age, IQ and sex. In addition, both groups completed psychiatric evaluations, a visual ERP task used to elicit vMMN, and psychological measures about AD/HD symptoms and day-to-day executive functions. Compared to trols, the late vMMN (230-330 ms) was significantly reduced in the AD/HD group. Correlation analyses showed that late vMMN was correlated with executive functions but not AD/HD symptoms. However, further mediation analyses showed that different executive functions had mediated the relationships between late vMMN and AD/HD symptoms. Our findings indicate that the late vMMN, reflecting automatic sensory change processing ability, was impaired in adults with AD/HD. This impairment could have negative impact on AD/HD symptoms via affecting day-to-day executive functions.
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Circular RNAs (circRNAs) play critical roles in different diseases. Exosomes are important intermediates of intercellular communication. While both have been widely reported in cancers, exosome-derived circRNAs are rarely studied. In this work, we identified the differently expressed circRNAs in bladder cancer (BCa) tissue and exosomes through high-throughput sequencing. RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays were used to investigate the interactions between specific circRNAs, microRNAs (miRNAs), and mRNAs. Wound-healing, Transwell, Cell Counting Kit-8 (CCK8), and colony-formation assays were used to study the biological roles in vitro. Metabolomics were used to explore the mechanism of how specific circRNAs influenced BCa cell behavior. Flow cytometry was used to study how specific circRNAs affected the function of CD8+ T cells in tumor microenvironments. We identified that exosome-derived hsa_circ_0085361 (circTRPS1) was correlated with aggressive phenotypes of BCa cells via sponging miR-141-3p. Metabolomics and RNA sequencing (RNA-seq) identified GLS1-mediated glutamine metabolism was involved in circTRPS1-mediated alterations. Exosomes derived from circTRPS1 knocked down BCa cells, prevented CD8+ T cells from exhaustion, and repressed the malignant phenotype of BCa cells. In conclusion, exosome-derived circTRPS1 from BCa cells can modulate the intracellular reactive oxygen species (ROS) balance and CD8+ T cell exhaustion via the circTRPS1/miR141-3p/GLS1 axis. Our work may provide a potential biomarker and therapeutic target for BCa.
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Exossomos , MicroRNAs , Neoplasias , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Exossomos/genética , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética , Fenótipo , RNA Circular/genética , Microambiente Tumoral/genética , Bexiga Urinária/metabolismoRESUMO
BACKGROUND: This study aimed to investigate the effect of the pathological staging of acute histological chorioamnionitis (HCA) on laboratory indicators and to conduct further studies to reassess the threshold values used by clinicians to identify acute HCA in febrile parturients undergoing epidural analgesia. METHODS: A retrospective study of febrile mothers receiving epidural analgesia at Nanjing Maternal and Child Health Care Hospital from January 1, 2018 to December 31, 2018. The participants were grouped by the progression of acute HCA, and the laboratory parameters were compared between groups. The ability of C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and monocyte-leukocyte ratio (M%), alone or in combination, to identify acute HCA in febrile parturients undergoing epidural analgesia was assessed using logistic regression and ROC curves. RESULTS: The area under the curve (AUC) of the best logistic regression model predicting HCA climbed to 0.706 (CRP + MLR). Maternal CRP, NLR, and MLR significantly and progressively increased with the progression of acute HCA (p < 0.0001). Based on the ROC curves, the following thresholds were selected to define increased laboratory indicators for identifying acute HCA: CRP ≥ 6.90 mg/L, NLR ≥ 11.93, and MLR ≥ 0.57. In addition, the AUC of the best logistic regression model predicting HCA ≥ stage 2 was 0.710, so these inflammatory markers were more precise in predicting HCA ≥ stage 2. CONCLUSION: Increased CRP (≥ 6.90 mg/L), NLR (≥ 11.93), and MLR (≥ 0.57) may help clinicians to identify early potential acute HCA in febrile parturients receiving epidural analgesia and to monitor progression to optimize clinical treatment options. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry on November 24, 2021 ( http://www.chictr.org.cn , ChiCTR2100053554).
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Analgesia Epidural , Corioamnionite , Gravidez , Feminino , Criança , Humanos , Estudos Retrospectivos , Corioamnionite/diagnóstico , Biomarcadores , Linfócitos , Neutrófilos , Proteína C-Reativa/análiseRESUMO
BACKGROUND The aim of the study was to explore the clinical implications of median approach combined with radial auxiliary plate in the treatment of C-type distal radius fractures. MATERIAL AND METHODS From January 2017 to January 2022, a total of 20 cases were collected, including 6 male and 14 female patients with closed fresh distal radius fractures. All patients received volar medium approach T-shaped locking plate treatment, as well as radial auxiliary plate open reduction and internal fixation. We recorded the incidence of median nerve injury, incidence of radial artery and vein or their branches injury, postoperative X-ray measurement of radial styloid process height, ulnar declination, palmar inclination, and Gartland-Werley score. RESULTS All surgical procedures were successful, and all patients were monitored for 3 to 12 months after the procedure. In the postoperative follow-up, there was no obvious loss of reduction. At the last follow-up, all patients' articular surface flatness was less than 2 mm, and the mean values for palmar inclination and ulnar declination were (14.36°±3.55°) and (19.79°±2.57°), respectively. The average height of a radial styloid was 117±2.42 mm; functional evaluation: excellent in 12 (60%), good in 6 (30%), and fair in 2 cases (10%) cases. Five patients showed slight nerve injury, but all recovered quickly within 6 months. CONCLUSIONS The volar median approach, which combines a T-locking plate with a radial auxiliary plate for open reduction and internal fixation, is an effective treatment for unstable distal radius fractures.
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Fraturas do Rádio , Fraturas do Punho , Humanos , Masculino , Feminino , Fraturas do Rádio/diagnóstico por imagem , Fraturas do Rádio/cirurgia , Amplitude de Movimento Articular , Radiografia , Resultado do Tratamento , Fixação Interna de Fraturas/métodos , Placas ÓsseasRESUMO
Minimally invasive testing for early detection of lung cancer to improve patient survival is a major unmet clinical need. This study aimed to develop and validate a serum multi-microRNA (multimiR) panel as a minimally invasive test for early detection of nonsmall cell lung cancer (NSCLC) regardless of smoking status, gender, and ethnicity. Our study included 744 NSCLC cases and 944 matched controls, including smokers and nonsmokers, male and female, with Asian and Caucasian subjects. Using RT-qPCR and a tightly controlled workflow, we quantified the absolute expression of 520 circulating microRNAs (miRNAs) in a Chinese cohort of 180 early stage NSCLC cases and 216 healthy controls (male smokers). Candidate biomarkers were verified in two case-control cohorts of 432 Chinese and 218 Caucasians, respectively (including females and nonsmokers). A multimiR panel for NSCLC detection was developed using a twofold cross-validation and validated in three additional Asian cohorts comprising 642 subjects. We discovered 35 candidate miRNA biomarkers, verified 22 of them, and developed a five-miR panel that detected NSCLC with area under curve (AUC) of 0.936-0.984 in the discovery and verification cohorts. The panel was validated in three independent cohorts with AUCs of 0.973, 0.916, and 0.917. The sensitivity of five-miR test was 81.3% for all stages, 82.9% for stages I and II, and 83.0% for stage I NSCLC, when the specificity is at 90.7%. We developed a minimally invasive five-miR serum test for detecting early stage NSCLC and validated its performance in multiple patient cohorts independent of smoking status, gender, and ethnicity.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Detecção Precoce de Câncer , MicroRNAs/sangue , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-IdadeRESUMO
Cu2+ is an essential trace element for the organism, but its excess can also cause irreversible damage to the organism. As such, a "Turn-Off" fluorescent probe DPAP for the specific detection of Cu2+ was successfully constructed. DPAP exhibits large Stokes shift (120 nm), fast reaction speed (1 min), low detection limit (15.2 nM), low toxicity, and good cell permeability. Cu2+ quenches the fluorescence of DPAP by blocking its intramolecular charge transfer process to achieve the detection of Cu2+ and has been confirmed by HRMS, 1H NMR and DFT calculations. Excitingly, the five-cycle detection of Cu2+ and the successful recovery of trace Cu2+ in environmental water samples fully demonstrate the potential of DPAP for practical applications. In particular, DPAP can observe the distribution and translocation patterns of exogenous Cu2+ in HeLa cells and zebrafish in real-time. This research concept has offered important theoretical support for the study of the environmental behavior of heavy metal ions.
RESUMO
BACKGROUND: Although methylphenidate (MPH) and atomoxetine (ATX) can improve clinical symptoms and functional impairments in attention deficit/hyperactive disorder (ADHD), the underlying psychopharmacological mechanisms have not been clearly elucidated. Therefore, we aimed to explore the shared and unique neurologic basis of these 2 medications in alleviating the clinical symptoms and functional impairments observed in ADHD. METHODS: Sixty-seven ADHD and 44 age-matched children with typical development were included and underwent resting-state functional magnetic resonance imaging scans at baseline. Then patients were assigned to MPH, ATX, or untreated subgroups, based on the patients' and their parents' choice, for a 12-week follow-up and underwent a second functional magnetic resonance imaging scan. The treatment effect on degree centrality (DC) was identified and correlated with clinical symptoms and functional impairments in the ADHD group. RESULTS: Both MPH and ATX normalized the DC value in extensive brain regions mainly involving fronto-cingulo-parieto-cerebellum circuits. However, ATX showed limited significant effects on the cerebellum compared with ADHD at baseline. The improvements in clinical symptoms were correlated with increased DC in the right inferior temporal gyrus in both MPH and ATX subgroups but showed opposite effects. The alleviation of functional impairments in the school/learning domain negatively correlated with decreased DC in the bilateral cerebellum after MPH treatment, and the family functional domain positively correlated with decreased DC in the cerebellum and negatively correlated with decreased DC in the postcentral gyrus after ATX treatment. CONCLUSIONS: Both MPH and ATX can normalize abnormal brain functions that mainly involve the fronto-cingulo-parieto-cerebellum circuit in ADHD. Furthermore, the 2 medications showed shared and unique effects on brain functions to alleviate clinical symptoms and functional impairment.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Inibidores da Captação Adrenérgica/uso terapêutico , Cloridrato de Atomoxetina/farmacologia , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Encéfalo , Estimulantes do Sistema Nervoso Central/farmacologia , Criança , Humanos , Metilfenidato/farmacologiaRESUMO
Puccinellia tenuiflora is a forage grass with high nutritional value that is an extreme alkali-tolerant halophyte: it can survive at pH 10-11. Root secretion is perceived as a major plant alkali tolerance mechanism. In the present study, we applied a widely targeted metabolomic approach to identify and quantify the root exudates of P. tenuiflora under alkali stress. We also surveyed the transcriptional and metabolic profiling of P. tenuiflora roots under salt (96-mM Na+ , pH 6.8) and alkali (96-mM Na+ , pH 9.6) stresses to reveal the biological processes mediating root secretion. In P. tenuiflora plants, 493 root exudates were detected under control conditions, 544 root exudates under salt stress conditions, and 607 root exudates under alkali stress conditions. Salt-stressed plants and alkali-stressed plants shared 64 root exudates, and 60 root exudates were unique to alkali-stressed plants. The secretion rate of 56 phenolic acids, 43 fatty acids, and 9 organic acids was faster in alkali-stressed roots than in control and salt-stressed roots. In P. tenuiflora roots, alkali stress enhanced the accumulation of 23 phenolic acids, five organic acids, and only one fatty acid. In addition, transcriptomic analysis revealed that alkali stress upregulated glycolysis and phenylpropanoid biosynthesis pathways in P. tenuiflora roots. Taken together, extensive secretion of phenolic acids and fatty acids promotes rhizosphere pH regulation of P. tenuiflora under alkali stress, which contributes to its strong alkali tolerance. The root secretion of P. tenuiflora upon alkali stress is highly organized. Enhanced glycolysis, phenylpropanoid biosynthesis, and organic acid synthesis in the roots provide more reducing power and carbon source for the root secretion process of alkali-stressed P. tenuiflora.