RESUMO
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The inflammatory cytokine storm causes systemic organ damage, especially acute lung injury in sepsis. In this study, we found that the expression of S-phase kinase-associated protein 2 (Skp2) was significantly decreased in sepsis-induced acute lung injury (ALI). Sepsis activated the MEK/ERK pathway and inhibited Skp2 expression in the pulmonary epithelium, resulting in a reduction of K48 ubiquitination of solute carrier family 3 member 2 (SLC3A2), thereby impairing its membrane localization and cystine/glutamate exchange function. Consequently, the dysregulated intracellular redox reactions induced ferroptosis in pulmonary epithelial cells, leading to lung injury. Finally, we demonstrated that intravenous administration of Skp2 mRNA-encapsulating lipid nanoparticles (LNPs) inhibited ferroptosis in the pulmonary epithelium and alleviated lung injury in septic mice. Taken together, these data provide an innovative understanding of the underlying mechanisms of sepsis-induced ALI and a promising therapeutic strategy for sepsis.
Assuntos
Lesão Pulmonar Aguda , Ferroptose , Camundongos Endogâmicos C57BL , Proteínas Quinases Associadas a Fase S , Sepse , Ubiquitinação , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/etiologia , Sepse/metabolismo , Sepse/complicações , Sepse/patologia , Animais , Camundongos , Humanos , Masculino , Proteínas Quinases Associadas a Fase S/metabolismo , Proteínas Quinases Associadas a Fase S/genética , Pulmão/patologia , Pulmão/metabolismo , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genéticaRESUMO
Quantum communication satellites have potential for applications in future quantum networks. Photonics integrated chips, due to their compact and lightweight nature, are well-suited for satellite deployment. However, the harsh radiation environment of space can cause permanent damage to these chips, resulting in degraded performance or complete loss of functionality. In this work, we conducted a series of radiation experiments to evaluate the effects of γ rays and high energy protons on quantum key distribution transmitter chips. The results suggest that the insertion loss of the chip is slightly reduced by about 1.5 dB after 100 krad (Si) γ ray irradiation, and further reduced by about 0.5 to 1 dB after 2.39 × 1011/cm2 proton radiation. The half-wave voltages, extinction ratios, and polarization angles are not changed significantly within the measurement error range. Our work proves the feasibility of deploying quantum constellations utilizing terminals based on photonics chips.
RESUMO
Sepsis is an acute life-threatening disorder associated with multiorgan dysfunction that remains the leading cause of death in intensive care units. As sepsis progresses, it causes prolonged immunosuppression, which results in sustained mortality, morbidity, and susceptibility to secondary infections. Using a mouse model of sepsis, we found that the long noncoding RNA HOTAIRM1 (HOXA transcript antisense RNA myeloid-specific 1) was highly expressed in mice during the late phase of sepsis. The upregulation of HOTAIRM1 was induced by Notch/Hes1 activation and, moreover, was critical for the formation of an immunosuppressive microenvironment. HOTAIRM1 induced T cell exhaustion by increasing the percentage of PD-1+ T cells and regulatory T cells, accompanied by elevated PD-L1. Blockade of either Notch/Hes1 signaling or HOTAIRM1 inhibited T cell exhaustion in late sepsis, having alleviated lung injury and improved survival of mice. Further mechanistic studies identified HOXA1 as a key transcription factor targeted by HOTAIRM1 to regulate PD-L1 expression in lung alveolar epithelial cells. These results implicated that the Notch/Hes1/HOTAIRM1/HOXA1/PD-L1 axis was critical for sepsis-induced immunosuppression and could be a potential target for sepsis therapies.
Assuntos
Tolerância Imunológica/imunologia , MicroRNAs/genética , Sepse/imunologia , Linfócitos T Reguladores/imunologia , Animais , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Proteínas de Homeodomínio/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Sepse/microbiologia , Fatores de Transcrição HES-1/metabolismo , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: HSK3486 (ciprofol), a new candidate drug similar to propofol, exerts sedative and hypnotic effects through gamma-aminobutyric acid type A receptors; however, its potential role in colorectal cancer is currently unknown. AIMS: This study aimed to evaluate the effects of HSK3486 on colorectal cancer cell proliferation. METHODS: Imaging was performed to detect reactive oxygen species and mitochondrial membrane potential. Western blotting was used to determine the expression of target signals. The HSK3486 molecular mechanism was investigated through ATPase inhibitory factor 1 knockdown and xenograft model experiments to assess mitochondrial function in colorectal cancer cells. RESULTS: Cell Counting Kit-8 and Annexin V/propidium iodide double staining assays showed that HSK3486 inhibited colorectal cancer cell proliferation in a concentration-dependent manner. In addition, HSK3486 treatment increased the expression of B-cell lymphoma-2-associated X, cleaved caspase 3, and cleaved poly (ADP-ribose) polymerase, whereas myeloid cell leukemia-1 and B-cell lymphoma 2 expression decreased. HSK3486 promoted mitochondrial dysfunction by inducing ATPase inhibitor factor 1 expression. Furthermore, HSK3486 promoted oxidative stress, as shown by the increase in reactive oxygen species and lactate dehydrogenase levels, along with a decrease in mitochondrial membrane potential and ATP levels. ATPase inhibitor factor 1 small interfering RNA pretreatment dramatically increased the mitochondrial membrane potential and tumor size in a xenograft model following exposure to HSK3486. CONCLUSION: Collectively, our findings revealed that HSK3486 induces oxidative stress, resulting in colorectal cancer cell apoptosis, making it a potential candidate therapeutic strategy for colorectal cancer.
Assuntos
Apoptose , Neoplasias Colorretais , Humanos , Adenosina Trifosfatases/metabolismo , Adenosina Trifosfatases/farmacologia , Adenosina Trifosfatases/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Potencial da Membrana Mitocondrial , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proteína Inibidora de ATPase/efeitos dos fármacosRESUMO
BACKGROUND: Cryptococcus neoformans, an opportunistic fungal pathogen, seldom causes infection in immunocompetent people. Cryptococcal osteomyelitis is an uncommon condition in which Cryptococcus invades the bone. It usually occurs as part of a disseminated infection and rarely in isolation. The spine has been reported as the most common site of cryptococcal osteomyelitis; however, isolated case of sacrum involvement in immunocompetent patients has never been reported. CASE PRESENTATION: We report the case of a 37-year-old man without underlying disease who presented with progressive low back and sacrococcygeal pain. The patient was initially diagnosed with sacral tumour by a local doctor, and subsequently, after admission, was diagnosed with sacral tuberculosis. He was empirically treated with antitubercular drugs. The patient failed to respond to antitubercular drugs and complained of worsening low back pain. Additionally, he developed persistent radiating pain and numbness in his legs. For further diagnosis, we performed a computed tomography-guided puncture biopsy of the sacrum, which revealed granulomatous inflammation with massive macrophage infiltration and special staining revealed a fungal infection. We performed sacral debridement and drainage and obtained purulent specimens for pathological examination and microbial culture. Microbial identification and drug susceptibility tests revealed a Cryptococcus neoformans infection sensitive to fluconazole. Postoperatively, the persistent radiating pain and numbness in the legs resolved. After 12 consecutive weeks of antifungal therapy, all his symptoms resolved. The patient remained without any signs of recurrence at the 8-month follow-up. CONCLUSION: We reported a rare case of isolated sacrum cryptococcal osteomyelitis in an immunocompetent patient. Furthermore, we identified and reviewed 18 published cases of spine cryptococcal osteomyelitis. Immunocompetent individuals are also at risk for cryptococcal osteomyelitis. Clinical manifestation and imaging are insufficient to diagnose cryptococcal osteomyelitis of the spine, and invasive examinations, such as puncture biopsy and fungal examinations, are needed. Antifungal therapy yields satisfactory results for the treatment of cryptococcal osteomyelitis of the spine, however, if the infective lesion is large, especially when it compresses the spinal cord and nerves, a regimen combining aggressive surgery with antifungal therapy is indispensable.
Assuntos
Criptococose , Cryptococcus neoformans , Osteomielite , Masculino , Humanos , Adulto , Antifúngicos/uso terapêutico , Sacro/patologia , Hipestesia/tratamento farmacológico , Criptococose/diagnóstico , Osteomielite/microbiologia , Antituberculosos/uso terapêuticoRESUMO
Colorectal cancer (CRC) is one of the leading causes of death worldwide, and hence, there is a need to elucidate the molecular mechanisms contributing to the progression of CRC. In this study, we aimed at assessing the role of long non-coding RNA NBPF4 on the tumorigenesis of CRC. Silencing or overexpression experiments were performed on HCT116 and SW260 in vitro models. BALB/c athymic female nude mice aged 5-6 weeks were used as in vivo models. To assess the relationship between NBPF4 and its regulatory RNA pull-down assay, RNA immunoprecipitation, luciferase activity, Western blotting and qRT-PCR were employed. Initially, we identified that NBPF4 was downregulated in CRC tissues and cell lines. Furthermore, we observed that NBPF4 decreased tumorigenesis in both in vitro and in vivo models. Additionally, we identified that ETFA was highly expressed in CRCs and was negatively associated with NBPF4. Subsequently, we identified that EZH2, a transcriptional factor, activated ETFA by enhancing the methylation of its promoter, and EZH2 was also highly regulated in CRCs. Using COAD and READ databases, we confirmed that EZH2 and ETFA were positively correlated. Furthermore, we identified NBPF4 and EZH2 were targets for ZFP36, which bound and positively regulated NBPF4. This prevented NBPF4 from binding to its negative regulator miR-17-3p. Our results demonstrated that NBPF4 downregulated EZH2 and stabilized itself by binding to ZFP36, thus escaping from inhibition by miR-17-3p, which allowed mitigation of CRC through inhibition of ETFA.
Assuntos
Neoplasias Colorretais/metabolismo , Flavoproteínas Transferidoras de Elétrons/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Proteínas de Neoplasias/metabolismo , Animais , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos NusRESUMO
Both the activation and attenuation of MAVS/IFN signaling are critical for host defensing against viral infection and thus lead to an elaborate regulation of MAVS-mediated signaling. However, the regulatory mechanisms concerning MAVS/IFN signaling in teleost fish are not well understood. RIPK3 has been identified as a key regulator of necroptosis, apoptosis, and inflammatory signaling in human and mammals. Here we report the identification of the RIPK3 homologue from black carp Mylopharyngodon piceus (bcRIPK3) and describe its role in regulating MAVS/IFN signaling. qPCR results demonstrated that bcRIPK3 was transcriptionally activated in response to poly (I:C) or LPS stimulation. Immunoblot assay and immunofluorescent staining assay showed that bcRIPK3 was a cytosolic protein with molecular weights of 47 kDa. Like its mammalian counterparts, bcRIPK3 exhibited a conserved function in inducing cell death. The reporter assay and plaque assay showed that overexpression of bcRIPK3 restricted bcMAVS-activated transcription of the interferon promoters of black carp and zebrafish, and suppressed bcMAVS-mediated antiviral activity. Notably, EPC cells co-expressing bcRIPK3, bcRIPK1 and bcMAVS presented much attenuated antiviral activity than the cells co-expressing bcRIPK3 and bcMAVS; and the subsequent co-IP assay identified the interaction between bcRIPK3 and bcRIPK1. Our findings collectively elucidate for the first time in teleost that black carp RIPK3 interacts with RIPK1 to inhibit MAVS-mediated antiviral signaling.
Assuntos
Cyprinidae/genética , Cyprinidae/imunologia , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Sequência de Aminoácidos , Animais , Perfilação da Expressão Gênica/veterinária , Filogenia , Proteína Serina-Treonina Quinases de Interação com Receptores/química , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/imunologia , Rhabdoviridae/fisiologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/veterinária , Alinhamento de Sequência/veterináriaRESUMO
Tumor necrosis factor receptor 1 (TNFR1) associated death domain protein (TRADD) is a pivotal adaptor in TNF signaling pathway and up-regulates MAVS/IFN signaling pathway in human and mammal. However, the role of TRADD in teleost fish remains obscure. To reveal the function of teleost TRADD in the innate immune response, the TRADD homologue (bcTRADD) of black carp (Mylopharyngodon piceus) has been cloned and the function of bcTRADD is investigated in this study, which shares similar functional domain to its mammalian counterpart. bcTRADD mRNA expression level increased in response to different stimuli, including LPS, poly (I:C) and virus infection in host cells. bcTRADD activated the transcriptional activity of NF-κB promoter in the reporter assay; however, showed hardly any effect on the transcriptional activity of IFN promoter. It was interesting that black carp mitochondria antiviral signaling protein (bcMAVS)-activated IFN promoter transcription were dramatically depressed by bcTRADD and the C-terminal death domain of bcTRADD was indispensable for its regulation of bcMAVS. Accordingly, the plaque assay result showed that EPC cells co-expressing bcMAVS and bcTRADD presented much attenuated antiviral activity than EPC cells expressing bcMAVS alone. Knockdown of bcTRADD slightly promoted the antiviral ability of the host cells against SVCV. The current data support the conclusion that bcTRADD suppresses MAVS-mediated antiviral signaling, which is different to its mammalian counterpart.
Assuntos
Carpas/genética , Carpas/imunologia , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Proteína de Domínio de Morte Associada a Receptor de TNF/genética , Proteína de Domínio de Morte Associada a Receptor de TNF/imunologia , Sequência de Aminoácidos , Animais , Linhagem Celular , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Células HEK293 , Humanos , Lipopolissacarídeos/farmacologia , Filogenia , Poli I-C/farmacologia , Rhabdoviridae/fisiologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/veterinária , Alinhamento de Sequência/veterinária , Proteína de Domínio de Morte Associada a Receptor de TNF/químicaRESUMO
ADCs based on the natural product maytansine have been successfully employed clinically. In a previous report, ADCs based on hydrophilic non-cell permeable maytansinoids was presented. The authors in this report further explore the maytansine scaffold to develop tubulin inhibitors capable of cell permeation. The research resulted in amino-benzoyl-maytansinoid payloads that were further elaborated with linkers for conjugating to antibodies. This approach was applied to MUC16 tumor targeting antibodies for ovarian cancers. A positive control ADC was evaluated alongside the amino-benzoyl-maytansinoid ADC and the efficacy observed was equivalent while the isotype control ADCs had no effect.
Assuntos
Imunoconjugados/metabolismo , Maitansina/química , Moduladores de Tubulina/química , Animais , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Imunoconjugados/química , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Maitansina/metabolismo , Camundongos SCID , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Relação Estrutura-Atividade , Transplante Heterólogo , Moduladores de Tubulina/metabolismoRESUMO
Manganese contributes to anti-oxidative stress particularly in catalase-devoid bacteria, and DtxR family metalloregulators, through sensing cellular Mn2+ content, regulate its homeostasis. Here, we show that metalloregulator MntR (So-MntR) functions dually as Mn2+ and H2O2 sensors in mediating H2O2 resistance by an oral streptococcus. H2O2 disrupted So-MntR binding to Mn2+ transporter mntABC promoter and induced disulfide-linked dimerization of the protein. Mass spectrometry identified Cys-11/Cys-156 and Cys-11/Cys-11 disulfide-linked peptides in H2O2-treated So-MntR. Site mutagenesis of Cys-11 and Cys-156 and particularly Cys-11 abolished H2O2-induced disulfide-linked dimers and weakened H2O2 damage on So-MntR binding, indicating that H2O2 inactivates So-MntR via disulfide-linked dimerization. So-MntR C123S mutant was extremely sensitive to H2O2 oxidization in dimerization/oligomerization, probably because the mutagenesis caused a conformational change that facilitates Cys-11/Cys-156 disulfide linkage. Intermolecular Cys-11/Cys-11 disulfide was detected in C123S/C156S double mutant. Redox Western blot detected So-MntR oligomers in air-exposed cells but remarkably decreased upon H2O2 pulsing, suggesting a proteolysis of the disulfide-linked So-MntR oligomers. Remarkably, elevated C11S and C156S but much lower C123S proteins were detected in H2O2-pulsed cells, confirming Cys-11 and Cys-156 contributed to H2O2-induced oligomerization and degradation. Accordingly, in the C11S and C156S mutants, expression of mntABC and cellular Mn2+ decreased, but H2O2 susceptibility increased. In the C123S mutant, increased mntABC expression, cellular Mn2+ content, and manganese-mediated H2O2 survival were determined. Given the wide distribution of Cys-11 in streptococcal DtxR-like metalloregulators, the disclosed redox regulatory function and mechanism of So-MntR can be employed by the DtxR family proteins in bacterial resistance to oxidative stress.
Assuntos
Proteínas de Bactérias/fisiologia , Peróxido de Hidrogênio/farmacologia , Estresse Oxidativo , Proteínas Repressoras/fisiologia , Streptococcus/química , Transportadores de Cassetes de Ligação de ATP , Dimerização , Homeostase/efeitos dos fármacos , Manganês/metabolismo , Mutagênese Sítio-Dirigida , Estresse Oxidativo/efeitos dos fármacos , Streptococcus/metabolismoRESUMO
Natural products have been used for many medicinal purposes for centuries. Antibody drug conjugates (ADCs) have utilized this rich source of small molecule therapeutics to produce several clinically useful treatments. ADCs based on the natural product maytansine have been successful clinically. The authors further the utility of the anti-cancer natural product maytansine by developing efficacious payloads and linker-payloads for conjugating to antibodies. The success of our approach was realized in the EGFRvIII targeting ADC EGFRvIII-16. The ADC was able to regress tumors in 2 tumor models (U251/EGFRvIII and MMT/EGFRvIII). When compared to a positive control ADC, the efficacy observed was similar or improved while the isotype control ADCs had no effect.
Assuntos
Antineoplásicos/farmacologia , Imunotoxinas/farmacologia , Maitansina/farmacologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/imunologia , Células CHO , Linhagem Celular Tumoral , Cricetulus , Receptores ErbB/imunologia , Feminino , Humanos , Interações Hidrofóbicas e Hidrofílicas , Imunotoxinas/química , Imunotoxinas/imunologia , Cinética , Masculino , Maitansina/síntese química , Maitansina/química , Camundongos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: To identify factors and indicators that affect chronic pain and pain relief, and to develop predictive models using machine learning. METHODS: We analyzed the data of 67,028 outpatient cases and 11,310 valid samples with pain from a large retrospective cohort. We used decision tree, random forest, AdaBoost, neural network, and logistic regression to discover significant indicators and to predict pain and treatment relief. FINDINGS: The random forest model had the highest accuracy, F1 value, precision, and recall rates for predicting pain relief. The main factors affecting pain and treatment relief included body mass index, blood pressure, age, body temperature, heart rate, pulse, and neutrophil/lymphocyte × platelet ratio. The logistic regression model had high sensitivity and specificity for predicting pain occurrence. IMPLICATIONS: Machine learning models can be used to analyze the risk factors and predictors of chronic pain and pain relief, and to provide personalized and evidence-based pain management.
Assuntos
Dor Crônica , Aprendizado de Máquina , Humanos , Estudos Retrospectivos , Dor Crônica/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Idoso , Manejo da Dor/métodos , Modelos Logísticos , Fatores de Risco , Árvores de DecisõesRESUMO
BACKGROUND: Sorafenib is an oral multikinase inhibitor with antiangiogenic and antitumor activity. In most cases, the commercially available 200 mg tablet is not suitable for administration to children. We studied the chemical and physical stability of extemporaneously prepared formulations and evaluated the pharmacokinetic profile of cut tablets and smaller-dosage capsules of sorafenib in children. PROCEDURE: Commercially available 200 mg tablets of sorafenib tosylate were used to prepare liquid suspensions of sorafenib in oil and Ora-Plus(®):Ora-Sweet(®) solution, and to prepare 5, 10, 20, 50, and 100 mg capsules. Plasma concentrations of sorafenib were measured in patients receiving capsules and cut tablets, using a validated HPLC-based method with tandem mass spectrometric detection. RESULTS: At room temperature and under refrigeration, sorafenib concentrations in Ora Plus(®):Ora Sweet(®) were highly variable (means ranging from 75% to 131% of the intended concentration of 50 mg/ml). In oil suspension, sorafenib concentrations were inconsistent during compounding. In contrast, all smaller-dosage capsules, except the 5 mg capsule, were within 91-99% of the intended content and were stable at room temperature for at least 8 months. Sorafenib pharmacokinetic parameters in patients receiving capsules or cut tablets were consistent with those reported previously in adults and children receiving intact tablets. CONCLUSIONS: Sorafenib is not stable in an oral suspension prepared from commercially available tablets, but compounded capsules in smaller-dosage forms that can be sprinkled on food or cut tablets are alternatives for administration to children who need smaller doses based on body surface area or cannot swallow tablets.
Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Neoplasias/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/farmacocinética , Administração Oral , Adolescente , Adulto , Antineoplásicos/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Niacinamida/farmacocinética , Compostos de Fenilureia/efeitos adversos , SorafenibeRESUMO
Biofilms are multicellular communities with a spatial structure. Different from single-cell scale diffusion in planktonic systems, the diffusion distance becomes the dimension of multicellular clusters in a biofilm. Such differences in diffusion behavior affect the tolerance and response to exogenous stress. Here, we found that at the same doses of exogenous hydrogen peroxide (H2O2), planktonic Escherichia coli were completely killed within two hours, whereas the biofilm resumed growth in six hours by building a catalase barrier to block H2O2 penetration, despite the growth burden. Unexpectedly, when we changed the carbon source from glucose to glycerol, H2O2 instantly counterintuitively boosted biofilm growth due to supplemental oxygen, which was the growth-limiting factor. We further demonstrated that the energy metabolism modes determined the growth-limiting factor, which then determined the two patterns of biofilms resistances to H2O2.
Assuntos
Biofilmes , Peróxido de Hidrogênio , Peróxido de Hidrogênio/farmacologia , Estresse Oxidativo , Difusão , Escherichia coli/fisiologia , PlânctonRESUMO
Urban economic competitiveness is a fundamental indicator for assessing the level of urban development and serves as an effective approach for understanding regional disparities. Traditional economic competitiveness research that relies solely on traditional regression models and assumes feature relationship theory tends to fall short in fully exploring the intricate interrelationships and nonlinear associations among features. As a result, the study of urban economic disparities remains limited to a narrow range of urban features, which is insufficient for comprehending cities as complex systems. The ability of deep learning neural networks to automatically construct models of nonlinear relationships among complex features provides a new approach to research in this issue. In this study, a complex urban feature dataset comprising 1008 features was constructed based on statistical data from 283 prefecture-level cities in China. Employing a machine learning approach based on convolutional neural network (CNN), a novel analytical model is constructed to capture the interrelationships among urban features, which is applied to achieve accurate classification of urban economic competitiveness. In addition, considering the limited number of samples in the dataset owing to the fixed number of cities, this study developed a data augmentation approach based on deep convolutional generative adversarial network (DCGAN) to further enhance the accuracy and generalization ability of the model. The performance of the CNN classification model was effectively improved by adding the generated samples to the original sample dataset. This study provides a precise and stable analytical model for investigating disparities in regional development. In the meantime, it offers a feasible solution to the limited sample size issue in the application of deep learning in urban research.
Assuntos
Aprendizado de Máquina , Redes Neurais de Computação , Cidades , ChinaRESUMO
BACKGROUND: In recent years, unilateral biportal endoscopic spinal surgery has been used for the treatment of lumbar spinal stenosis with good results. Some investigators counted the total incidence of complications in unilateral biportal endoscopic surgery for lumbar spinal stenosis, but none have analyzed the incidence of specific complications. The present study further counted the incidence of specific complications and gave the possible causes of the complications. METHODS: English databases including PubMed were searched to collect relevant literature on unilateral biportal endoscopic spinal surgery for lumbar spinal stenosis. The inquiry period is from January 1, 2015, to July 1, 2022. The literature was screened, information extracted, and risk of bias evaluated by the researchers, followed by Meta analysis using R4.2.1 and RStudio statistical software. RESULTS: In total, we included 14 studies involving 707 patients. The included studies were retrospective case series, The results of the single-arm rate meta-analysis showed that the total complication rate of unilateral biportal endoscopic surgery treatment of lumbar spinal stenosis was 8.1% (95% confidence interval [CI] [0.060; 0.103]); of which, the highest incidence of dural tear was 4.5% (95% CI [0.030; 0.064]), the incidence of symptomatic postoperative spinal epidural hematoma was approximately 1.1% (95% CI [0.001; 0.027]), the incidence of incomplete decompression was 2.0% (95% CI [0.007; 0.038]), the incidence of transient palsy was 2.6% (95% CI [0.005; 0.057]). CONCLUSIONS: The incidence of total complications of unilateral biportal endoscopic surgery for lumbar spinal stenosis was 8.1%, dural tear remained a major complication with an incidence of 4.5%, incomplete decompression was 2.0%, transient palsy was 2.6%, and, unexpectedly, symptomatic postoperative spinal epidural hematoma was only 1.1%.
Assuntos
Hematoma Epidural Espinal , Estenose Espinal , Humanos , Descompressão Cirúrgica/efeitos adversos , Descompressão Cirúrgica/métodos , Endoscopia/efeitos adversos , Endoscopia/métodos , Hematoma Epidural Espinal/cirurgia , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Estenose Espinal/cirurgia , Estenose Espinal/complicações , Resultado do TratamentoRESUMO
Osteosarcoma (OS) is the most malignant bone tumor which mainly occurs in childhood or adolescence. The previous studies indicated that OS is difficult to treat. KIAA1429 is one of the components of m6A complex that regulating the process of m6A modification, which plays a crucial role in tumorigenesis. But the mechanism of KIAA1429 regulating OS cell identity was not entirely clear, which needs further investigate. RT-qPCR and western blotting were applied to determine KIAA1429 expression station in OS cells and tissues. To further detect the KIAA1429 function in OS cells, the ability of proliferation, migration and invasion were analyzed by Edu, wound-healing and transwell experiments respectively. Besides, RNA sequencing was also used to further find the downstream of KIAA1429 regulation and small molecule inhibitor was added to explore the specific role of signaling pathway. Our data found that KIAA1429 is up-regulated in human OS cell lines compared to the human osteoblast cells. Meanwhile, the deletion of KIAA1429 significantly decreased cell proliferation, migration, and invasion. Interestingly, the JAK2/STAT3 signal pathway was involved in KIAA1429 regulation on OS cell characters. The KIAA1429 eliminated OS cells exhibited a decreased activity of JAK2/STAT3 signal. And the addition of JAK2/STAT3 stimulator (colivelin) could distinctly rescue the decreased OS cells' proliferation, migration, and invasion upon KIAA1429 knockdown. In summary, these data demonstrated that KIAA1429/JAK2/STAT3 axis may a new target for OS therapy.
RESUMO
BACKGROUND: The aim of this study was to evaluate whether there is a superior clinical effect of unilateral biportal endoscopy compared with microscopic decompression in the treatment of lumbar spinal stenosis. METHODS: We searched CNKI, WANFANG, CQVIP, CBM, PubMed, and Web of Science up to January 2022, and selected studies that met our inclusion criteria. RESULTS: The results of this meta-analysis indicated that unilateral biportal endoscopy was demonstrated to be more beneficial for patients compared with microscopic decompression for the following outcomes: Operation time [standardized mean difference (SMD)â =â -0.943, 95% confidence interval (CI) (-1.856, -0.031), Pâ =â .043], hospital stays [SMDâ =â -2.652, 95% CI (-4.390, -0.914), Pâ =â .003], EuroQol 5-Dimension questionnaire [SMDâ =â 0.354, 95% CI (0.070, 0.638), Pâ =â .014], back pain visual analogue score [SMDâ =â -0.506, 95% CI (-0.861, -0.151), Pâ =â .005], leg pain visual analogue score [SMDâ =â -0.241, 95% CI (-0.371, -.0112), Pâ =â .000], the C-reactive protein level [SMDâ =â -1.492,95% CI (-2.432, -0.552), Pâ =â .002]. Other outcomes demonstrated no significant differences between the 2 groups. CONCLUSION: For patients with lumbar spinal stenosis, unilateral biportal endoscopy was found to be more superior than microscopic decompression in terms of operation time, hospital stays, EuroQol 5-Dimension questionnaire, back visual analogue score, leg visual analogue score and the C-reactive protein level. There was no significant difference between the 2 groups in other outcome indicators.
Assuntos
Estenose Espinal , Humanos , Estenose Espinal/cirurgia , Descompressão Cirúrgica/métodos , Proteína C-Reativa , Vértebras Lombares/cirurgia , Endoscopia/métodos , Endoscopia Gastrointestinal , Resultado do Tratamento , Estudos RetrospectivosRESUMO
BACKGROUND: As a newly discovered lncRNA, lncRNA High expression in hepatocellular carcinoma (HEIH) has been reported to correlate with poor clinical outcomes in several different cancers, In addition, studies have shown that HEIH is overexpressed in a variety of cancers and plays an oncogenic role. The present meta-analysis aims to elucidate the relationship between HEIH expression and prognosis and clinicopathological features among cancer patients. METHODS: PubMed, Web of Science, Cochrane Library, and EMBASE database were comprehensively and systematically searched. pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence interval (CI) were employed to assess the relationship between HEIH expression and clinical outcomes and clinicopathological features in cancer patients. CONCLUSION: The present study finally enrolled 11 studies which included 1227 cancer patients. The combined results indicated that HEIH overexpression was significantly associated with shorter overall survival (OS) (pooled HRâ =â 2.03, 95% CI 1.74-2.38, Pâ <â .00001).Meanwhile, regarding clinicopathology of cancer patients, upregulated HEIH expression was closely related to larger tumor size (ORâ =â 2.65, 95% CI: 1.52-4.65, Pâ =â .0006), advanced tumor T stage (ORâ =â 2.41, 95 % CI: 1.54-3.77, Pâ =â .0001), advanced TNM stage (ORâ =â 4.76, 95% CI: 2.73-8.29, Pâ <â .00001), distant metastasis (ORâ =â 2.94, 95% CI: 1.75-4.96, Pâ <â .0001) and lymph node metastasis (ORâ =â 2.07, 95% CI: 1.05-4.07, Pâ =â .04), respectively. CONCLUSIONS: High expression of HEIH in some cancers predicts shorter overall survival and higher clinical stage as well as larger tumor size. HEIH has great potential to become a prognostic marker for cancer patients.
Assuntos
Neoplasias Hepáticas , Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias/patologia , Prognóstico , Metástase LinfáticaRESUMO
BACKGROUND: Bone grafting is necessary in spinal tuberculosis surgery. Structural bone grafting is considered the gold standard treatment for spinal tuberculosis bone defects; however, nonstructural bone grafting via the posterior approach has recently gained attention. In this meta-analysis, we evaluated the clinical efficacy of structural versus nonstructural bone grafting via the posterior approach in the treatment of thoracic and lumbar tuberculosis. METHODS: Studies comparing the clinical efficacy of structural and nonstructural bone grafting via the posterior approach in spinal tuberculosis surgery were identified from 8 databases from inception to August 2022. Study selection, data extraction, and evaluation of the risk of bias were performed, and meta-analysis was conducted. RESULTS: Ten studies including 528 patients with spinal tuberculosis were enrolled. Meta-analysis revealed no between-group differences in fusion rate (P = 0.29), complications (P = 0.21), postoperative Cobb angle (P = 0.7), visual analog scale score (P = 0.66), erythrocyte sedimentation rate (P = 0.74), or C-reactive protein level (P = 0.14) at the final follow-up. Nonstructural bone grafting was associated with less intraoperative blood loss (P < 0.00001), shorter operation time (P < 0.0001), shorter fusion time (P < 0.01), and shorter hospital stay (P < 0.00001), while structural bone grafting was associated with lower Cobb angle loss (P = 0.002). CONCLUSIONS: Both techniques can achieve a satisfactory bony fusion rate for spinal tuberculosis. Nonstructural bone grafting has the advantages of less operative trauma, shorter fusion time, and shorter hospital stay, making it an attractive option for short-segment spinal tuberculosis. Nevertheless, structural bone grafting is superior for maintaining corrected kyphotic deformities.