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Superconductivity in a highly correlated kagome system has been theoretically proposed for years (refs. 1-5), yet the experimental realization is hard to achieve6,7. The recently discovered vanadium-based kagome materials8, which exhibit both superconductivity9-11 and charge-density-wave orders12-14, are nonmagnetic8,9 and weakly correlated15,16. Thus these materials are unlikely to host the exotic superconductivity theoretically proposed. Here we report the discovery of a chromium-based kagome metal, CsCr3Sb5, which is contrastingly featured with strong electron correlations, frustrated magnetism and characteristic flat bands close to the Fermi level. Under ambient pressure, this kagome metal undergoes a concurrent structural and magnetic phase transition at 55 K, with a stripe-like 4a0 structural modulation. At high pressure, the phase transition evolves into two transitions, possibly associated with charge-density-wave and antiferromagnetic spin-density-wave orderings. These density-wave-like orders are gradually suppressed with pressure and, remarkably, a superconducting dome emerges at 3.65-8.0 GPa. The maximum of the superconducting transition temperature, Tcmax = 6.4 K, appears when the density-wave-like orders are completely suppressed at 4.2 GPa, and the normal state exhibits a non-Fermi-liquid behaviour, reminiscent of unconventional superconductivity and quantum criticality in iron-based superconductors17,18. Our work offers an unprecedented platform for investigating superconductivity in correlated kagome systems.
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Increasing evidence indicates a strong correlation between the deposition of cuticular waxes and drought tolerance. However, the precise regulatory mechanism remains elusive. Here, we conducted a comprehensive transcriptome analysis of two wheat (Triticum aestivum) near-isogenic lines, the glaucous line G-JM38 rich in cuticular waxes and the non-glaucous line NG-JM31. We identified 85,143 protein-coding mRNAs, 4,485 lncRNAs, and 1,130 miRNAs. Using the lncRNA-miRNA-mRNA network and endogenous target mimic (eTM) prediction, we discovered that lncRNA35557 acted as an eTM for the miRNA tae-miR6206, effectively preventing tae-miR6206 from cleaving the NAC transcription factor gene TaNAC018. This lncRNA-miRNA interaction led to higher transcript abundance for TaNAC018 and enhanced drought-stress tolerance. Additionally, treatment with mannitol and abscisic acid (ABA) each influenced the levels of tae-miR6206, lncRNA35557, and TaNAC018 transcript. The ectopic expression of TaNAC018 in Arabidopsis also improved tolerance toward mannitol and ABA treatment, whereas knocking down TaNAC018 transcript levels via virus-induced gene silencing in wheat rendered seedlings more sensitive to mannitol stress. Our results indicate that lncRNA35557 functions as a competing endogenous RNA to modulate TaNAC018 expression by acting as a decoy target for tae-miR6206 in glaucous wheat, suggesting that non-coding RNA has important roles in the regulatory mechanisms responsible for wheat stress tolerance.
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Arabidopsis , MicroRNAs , RNA Longo não Codificante , RNA Endógeno Competitivo , RNA Longo não Codificante/genética , Ácido Abscísico/farmacologia , Arabidopsis/genética , Manitol , MicroRNAs/genética , RNA Mensageiro , Triticum/genética , CerasRESUMO
BACKGROUND: Immunohistochemistry (IHC) is an essential technique in surgical and clinical pathology for detecting diagnostic, prognostic, and predictive biomarkers for personalized cancer therapy. However, the lack of standardization and reference controls results in poor reproducibility, and a reliable tool for IHC quantification is urgently required. The objective of this study was to describe a novel approach in which H3F3B (histone H3, family 3B) can be used as an internal reference standard to quantify protein expression levels using IHC. METHODS: The authors enrolled 89 patients who had human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). They used a novel IHC-based assay to measure protein expression using H3F3B as the internal reference standard. H3F3B was uniformly expressed at the protein level in all tumor regions in cancer tissues. HER2 expression levels were measured with the H-score using HALO software. RESULTS: Kaplan-Meier analysis indicated that, among patients who had HER2-positive BC in The Cancer Genome Atlas data set and the authors' data set, the subgroup with low HER2 expression had a significantly better prognosis than the subgroup with high HER2 expression. Furthermore, the authors observed that HER2 expression levels were precisely evaluated using the proposed method, which can classify patients who are at higher risk of HER2-positive BC to receive trastuzumab-based adjuvant therapy. Dual-color IHC with H3F3B is an excellent tool for internal and external quality control of HER2 expression assays. CONCLUSIONS: The proposed IHC-based quantification method accurately assesses HER2 expression levels and provides insights for predicting clinical prognosis in patients with HER2-positive BC who receive trastuzumab-based adjuvant therapy.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Histonas , Imuno-Histoquímica , Reprodutibilidade dos Testes , Receptor ErbB-2/genética , Trastuzumab/uso terapêutico , Padrões de Referência , Biomarcadores Tumorais/metabolismoRESUMO
We report on the efficient generation of intense terahertz radiation from the organic crystal N-benzyl-2-methyl-4-nitroaniline pumped by chirped Ti:sapphire femtosecond laser pulses. The THz energy and spectrum as a function of the pump fluence and duration of the chirped laser pulses are studied systematically. For the appropriate positively chirped pump pulses, a significant boost in the THz generation efficiency by a factor of around 2.5 is achieved, and the enhancement of high-frequency components (>1â THz) shortens the THz pulse duration. Via complete characterization of THz properties and transmitted laser spectra, this nonlinear behavior is attributed to the extended effective interaction length for phase matching as a result of the self-phase modulation of the intense pump laser pulses. Numerical calculations well reproduce the experimental observation. Our results demonstrate a robust, efficient, strong-field (up to several MV/cm) THz source using the common sub-10â mJ and sub-100â fs Ti:sapphire laser systems without optical parametric amplifiers.
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Increasing evidence points to the tight relationship between alternative splicing (AS) and the salt stress response in plants. However, the mechanisms linking these two phenomena remain unclear. In this study, we have found that Salt-Responsive Alternatively Spliced gene 1 (SRAS1), encoding a RING-Type E3 ligase, generates two splicing variants: SRAS1.1 and SRAS1.2, which exhibit opposing responses to salt stress. The salt stress-responsive AS event resulted in greater accumulation of SRAS1.1 and a lower level of SRAS1.2. Comprehensive phenotype analysis showed that overexpression of SRAS1.1 made the plants more tolerant to salt stress, whereas overexpression of SRAS1.2 made them more sensitive. In addition, we successfully identified the COP9 signalosome 5A (CSN5A) as the target of SRAS1. CSN5A is an essential player in the regulation of plant development and stress. The full-length SRAS1.1 promoted degradation of CSN5A by the 26S proteasome. By contrast, SRAS1.2 protected CSN5A by competing with SRAS1.1 on the same binding site. Thus, the salt stress-triggered AS controls the ratio of SRAS1.1/SRAS1.2 and switches on and off the degradation of CSN5A to balance the plant development and salt tolerance. Together, these results provide insights that salt-responsive AS acts as post-transcriptional regulation in mediating the function of E3 ligase.
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Processamento Alternativo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Complexo do Signalossomo COP9/genética , Estresse Salino , Ubiquitina-Proteína Ligases/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Genes de Plantas , Isoformas de Proteínas/genética , Salinidade , Ubiquitina-Proteína Ligases/genéticaRESUMO
OBJECTIVE: The aim of this study was to investigate the dynamic expression of the SMAD family during guided bone regeneration for the reconstruction of cranio-maxillofacial bone defects. METHODS: A swine model of guided bone regeneration was established with one side of the rib as the trauma group and the contralateral as control group. Periosteal and regenerative tissue specimens were harvested at 9 time points in the early, middle, and late phases, and were subjected to gene sequencing and tissue staining. Expression data of each SMAD family were extracted for further analysis, in which the correlation of the expression of the respective members within and between groups and at different time points was analyzed. RESULTS: The expression of individual members of the SMAD family fluctuates greatly, especially during the first month. The SMAD3 and SMAD4 genes were the most highly expressed. The foldchange value of SMAD6 was the largest and remained above 1.5 throughout the process. The dynamic expression levels of SMAD2, SMAD4, SMAD5, SMAD6, and SMAD9 showed a significant positive correlation in both groups. The expression levels of each gene showed a positive correlation with other SMAD genes. Tissue staining showed that the overall contour of the regenerated bone tissue was basically formed within the first 1 month. CONCLUSION: The first month of guided bone regeneration is a critical period for bone regeneration and is an important period for the SMAD family to play a role. The SMAD6 may play an important role in the whole process of guided bone regeneration.
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JQ-1 is a typical BRD4 inhibitor with the ability to directly fight tumor cells and evoke antitumor immunity via reducing the expression of PD-L1. However, problems arise with the development of JQ-1 in clinical trials, such as marked lymphoid and hematopoietic toxicity, leading to the investigation of combination therapy. SZU-101 is a TLR7 agonist designed and synthesized by our group with potent immunostimulatory activity. Therefore, we hypothesized that combination therapy of SZU-101 and JQ-1 would target innate immunity and adaptive immunity simultaneously, to achieve a better antitumor efficacy than monotherapy. In this study, the repressive effects of the combination administration on tumor growth and metastasis were demonstrated in both murine breast cancer and melanoma models. In 4T1 tumor-bearing mice, i.t. treatment with SZU-101 in combination with i.p. treatment with JQ-1 suppressed the growth of tumors at both injected and uninjected sites. Combination therapy increased M1/M2 ratio in TAMs, decreased PD-L1 expression and promoted the recruitment of activated CD8+ T cells in the TME. In summary, the improved therapeutic efficacy of the novel combination therapy appears to be feasible for the treatment of a diversity of cancers.
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Adenina , Proteínas que Contêm Bromodomínio , Melanoma , Succinatos , Receptor 7 Toll-Like , Animais , Camundongos , Adenina/análogos & derivados , Adjuvantes Imunológicos , Antígeno B7-H1 , Linfócitos T CD8-Positivos , Proteínas Nucleares , Receptor 7 Toll-Like/agonistas , Fatores de Transcrição , Proteínas que Contêm Bromodomínio/antagonistas & inibidoresRESUMO
MicroRNAs (miRNAs) play crucial roles in regulating plant development and stress responses. However, the functions and mechanism of intronic miRNAs in plants are poorly understood. This study reports a stress-responsive RNA splicing mechanism for intronic miR400 production, whereby miR400 modulates reactive oxygen species (ROS) accumulation and improves plant tolerance by downregulating its target expression. To monitor the intron splicing events, we used an intronic miR400 splicing-dependent luciferase transgenic line. Luciferase activity was observed to decrease after high cadmium concentration treatment due to the retention of the miR400-containing intron, which inhibited the production of mature miR400. Furthermore, we demonstrated that under Cd treatments, Pentatricopeptide Repeat Protein 1 (PPR1), the target of miR400, acts as a positive regulator by inducing ROS accumulation. Ppr1 mutation affected the Complex III activity in the electron transport chain and RNA editing of the mitochondrial gene ccmB. This study illustrates intron splicing as a key step in intronic miR400 production and highlights the function of intronic miRNAs as a 'signal transducer' in enhancing plant stress tolerance.
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Arabidopsis , MicroRNAs , MicroRNAs/genética , MicroRNAs/metabolismo , Arabidopsis/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Íntrons/genética , Splicing de RNA/genética , Regulação da Expressão Gênica de PlantasRESUMO
INTRODUCTION: Acute ischemic stroke (AIS) accounts for the majority of all stroke, globally the second leading cause of death. Due to its rapid development after onset, its early diagnosis is crucial. OBJECTIVES: We aim to identify potential highly reliable blood-based biomarkers for early diagnosis of AIS using quantitative plasma lipid profiling via a machine learning approach. METHODS: Lipidomics was used for quantitative plasma lipid profiling, based on ultra-performance liquid chromatography tandem mass spectrometry. Our samples were divided into a discovery and a validation set, each containing 30 AIS patients and 30 health controls (HC). Differentially expressed lipid metabolites were screened based on the criteria VIP > 1, p < 0.05, and fold change > 1.5 or < 0.67. The least absolute shrinkage and selection operator (LASSO) and random forest algorithms in machine learning were used to select differential lipid metabolites as potential biomarkers. RESULTS: Three key differential lipid metabolites, CarnitineC10:1, CarnitineC10:1-OH and Cer(d18:0/16:0), were identified as potential biomarkers for early diagnosis of AIS. The former two, associated with thermogenesis, were down-regulated, whereas the latter, associated with necroptosis and sphingolipd metabolism, was upregulated. Univariate and multivariate logistic regressions showed that these three lipid metabolites and the resulting diagnostic model exhibited a strong ability in discriminating between AIS patients and HCs in both the discovery and validation sets, with an area under the curve above 0.9. CONCLUSIONS: Our work provides valuable information on the pathophysiology of AIS and constitutes an important step toward clinical application of blood-based biomarkers for diagnosing AIS.
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AVC Isquêmico , Lipidômica , Humanos , Metabolômica , Biomarcadores , Diagnóstico Precoce , LipídeosRESUMO
BACKGROUND: Depressive and anxiety symptoms affect about one-fourth of Chinese secondary school students. However, the prevalence and correlates of mental distress among secondary school students from Western China remain largely unexplored. This study aimed to examine the prevalence and associations of depressive and anxiety symptoms with demographic, family, school, life, and behavior factors in a large, representative sample of secondary school students in Zigong, a city in Western China. METHODS: Secondary school students were recruited using cluster sampling. The 9-item Patient Health Questionnaire, the 7-item Generalized Anxiety Disorder Questionnaire, Multidimensional Peer-Victimization Scale, the Pittsburgh Sleep Quality Index, and Nine-Item Internet Gaming Disorder Scale-Short Form were used. Descriptive statistic was used to describe the sociodemographic characteristics of participants. The clustering effect was adjusted by the "survey" package of R to calculate weighted prevalence. Univariate and multivariate logistic regression were used to explore associated factors of depression and anxiety, respectively. RESULTS: A total of 63,205 participants were involved, in which the weighted prevalence of depression in all subjects was 23.0% (95% CI: 19.6- 27.0%), and the weighted prevalence of anxiety was 13.9% (95% CI: 11.2- 17.0%). Logistic regression results showed girls, being single-child, non-nuclear family, peer bullying, sleep disturbance, and internet gaming disorder symptoms were positively associated with depressive and anxiety symptoms. CONCLUSION: Depressive and anxiety symptoms were prevalent among secondary school students in Western China. Our results can guide policy strategies for the assessment, prevention, and intervention of psychological status among Chinese secondary school students.
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Depressão , População do Leste Asiático , Feminino , Humanos , Depressão/epidemiologia , Depressão/psicologia , Prevalência , Ansiedade/epidemiologia , Ansiedade/psicologia , Estudantes/psicologia , Instituições Acadêmicas , China/epidemiologiaRESUMO
INTRODUCTION: Tumor necrosis factor (TNF)-α released after follicular injury such as that caused by plucking plays a role in the activation of hair regeneration. Microneedle (MN) treatment is applied to the scalp to increase permeability and facilitate the delivery of any number of compounds. Because the MN treatment causes injury to the epidermis, albeit minor, we reasoned that this treatment would lead to a temporary TNF-α surge and thereby promote hair regeneration. METHODS: To investigate the effects of MN-treatment-induced microinjury and TNF-α on hair growth, we used C57BL/6N mice which were divided into six experimental groups: three groups of 1) negative control (NC), 2) plucking positive control (PK), and 3) MN therapy system (MTS) mice; and three groups identical to above were treated with a TNF-α blocker for 3 weeks: 4) NCB, 5) PKB, and 6) MTSB group. RESULTS: After injury, TNF-α surge occurred on day 3 in the PK group and on day 6 in the MTS group. Wnt proteins and VEGF expression were markedly increased in the PK group on day 3 and on day 6 in the MTS group compared to the NC group. Following wound healing, only MTS and PK groups displayed thickened epidermis and longer HF length. Within the 2 weeks following treatment, the rate of hair growth was much slower in the injured mice treated with the TNF-α blocker. CONCLUSION: Our findings indicate that microinjury stimulates the wound-healing mechanism via TNF-α/Wnt/VEGF surge to induce hair growth, and that blocking TNF-α inhibits this growth process.
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Fator de Necrose Tumoral alfa , Fator A de Crescimento do Endotélio Vascular , Camundongos , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Camundongos Endogâmicos C57BL , Cicatrização , Cabelo/metabolismo , RegeneraçãoRESUMO
The flexible arm easily vibrates due to its thin structural characteristics, which affect the operation accuracy, so reducing the vibration of the flexible arm is a significant issue. Smart materials are very widely used in the research topic of vibration suppression. Considering the hysteresis characteristic of the smart materials, based on previous simulation research, this paper proposes an experimental system design of nonlinear vibration control by using the interactive actuation from shape memory alloy (SMA) for a flexible arm. The experiment system was an interactive actuator-sensor-controller combination. The vibration suppression strategy was integrated with an operator-based vibration controller, a designed integral compensator and the designed n-times feedback loop. In detail, a nonlinear vibration controller based on operator theory was designed to guarantee the robust stability of the flexible arm. An integral compensator based on an estimation mechanism was designed to optimally reduce the displacement of the flexible arm. Obtaining the desired tracking performance of the flexible arm was a further step, by increasing the n-times feedback loop. From the three experimental cases, when the vibration controller was integrated with the designed integral compensator, the vibration displacement of the flexible arm was much reduced compared to that without the integral compensator. Increasing the number of n-times feedback loops improves the tracking performance. The desired vibration control performance can be satisfied when n tends to infinity. The conventional PD controller stabilizes the vibration displacement after the 7th vibration waveform, while the vibration displacement approaches zero after the 4th vibration waveform using the proposed vibration control method, which is proved to be faster and more effective in controlling the flexible arm's vibration. The experimental cases verify the effectiveness of the proposed interactive actuation vibration control approach. It is observed from the experimental results that the vibration displacement of the flexible arm becomes almost zero within less time and with lower input power, compared with a traditional controller.
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INTRODUCTION: The last systematic review on this topic was published in 2008. With advances in surgical techniques, patients with mangled extremities may now be potentially salvageable with comparable outcomes. This review aims to evaluate the outcomes of limb salvage compared to primary amputation in patients with severe open tibial fractures. MATERIALS AND METHODS: A comprehensive search on PubMed, MEDLINE, Embase, Web of Science, Scopus, CENTRAL and CINAHL was performed from inception to 19 January 2022. The primary outcome was to evaluate clinical and functional outcomes. Secondary outcomes were to evaluate pain, patient preference, quality of life, and patient preferences. Methodological quality was evaluated using the MINORS criteria. Pooled estimates of relative risk (RR) and mean difference (MD) with 95% confidence interval (CI) were used as a summary statistic for dichotomous variables and continuous variables, respectively. RESULTS: Sixteen studies with 645 patients met inclusion criteria. The methodological quality was moderate based on the MINORS score. The majority were male. Mean age was 36.3 years. There was no significant differences in the length of hospitalization (n = 8), return to work rates (n = 9), return to sport rates (n = 4) and quality of life scores (n = 4). Patients with primary amputation had a significantly lower risk of total complications (RR 0.21, 95% CI 0.08-0.53, p = 0.001) (n = 10), infections (RR 0.46, 95% CI 0.25-0.85, p = 0.01) (n = 9), and number of surgeries (MD - 4.17, 95% CI - 6.49 to - 1.85, p = 0.0004) (n = 6). Patients with primary amputation were able to ambulate significantly earlier (MD - 4.06, 95% CI - 7.65 to - 0.46, p = 0.03) (n = 3). Three studies found a significantly higher cost of hospitalization in limb salvage patients. Functional outcomes were similar in both groups. CONCLUSION: While patients with primary amputation had better clinical outcomes in the short-term, functional outcomes were not significantly different in both groups. Despite the heterogenicity of the results in this review, surgeons need to contextualize the decision making for their patients and incorporate these findings. LEVEL OF EVIDENCE: III. TRIAL REGISTRATION: PROSPERO CRD42022303357.
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Salvamento de Membro , Fraturas da Tíbia , Humanos , Masculino , Feminino , Adulto , Salvamento de Membro/métodos , Qualidade de Vida , Fraturas da Tíbia/complicações , Fraturas da Tíbia/cirurgia , Extremidades/cirurgia , Amputação CirúrgicaRESUMO
Phosphoglycerate mutase (PGAM) is a critical enzyme in glycolysis. PGAM2 is abundant in several types of tissues and malignant tumours. However, there is limited information regarding their clinicopathological significance in dysplastic nodules and hepatocellular carcinoma (HCC). This study aims to investigate the prognostic value of PGAM2 as a new biomarker for HCC. The PGAM2 expression level was evaluated by immunohistochemistry in liver cirrhosis (n = 10), low-grade dysplastic nodules (n = 15), high-grade dysplastic nodules (n = 15) and HCCs (n = 20) and 178 pairs of HCC and adjacent peritumoral liver tissues. We selected X-tile software for counting cut-point based on the outcomes for prognosis analysis, and used Kaplan-Meier analysis and Cox regression analysis can assess the prognosis of clinicopathologic parameters. Nuclear PGAM2 was significantly overexpressed in peritumoral liver tissues compared with HCC tissues (P = 0.0010). Kaplan-Meier analyses of 178 HCC samples revealed that nuclear PGAM2's high expression level, but not cytoplasmic PGAM2, was significantly related to good overall survival rate (OS). In addition, univariate and multivariate Cox analyses indicated nuclear PGAM2 expression could be regarded as valuable predictors for OS in HCC. PGAM2 was highly expressed in HCC tissues than liver cirrhosis tissues, and nuclear PGAM2's high expression might demonstrate HCC patients have poor postoperative results. Thus, nuclear PGAM2 can be regarded as valuable predictors for OS in HCC patients after surgery.
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Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fosfoglicerato Mutase/biossíntese , Biomarcadores Tumorais , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/patologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de RegressãoRESUMO
INTRODUCTION AND OBJECTIVES: Posthepatectomy liver failure (PHLF) is a serious complication after hepatectomy, and its effective methods for preoperative prediction are lacking. Here, we aim to identify predictive factors and build a nomogram to evaluate patients' risk of developing PHLF. PATIENTS AND METHODS: A retrospective review of a training cohort, including 199 patients who underwent hepatectomy at the Shanghai Eastern Hepatobiliary Surgery Hospital, was conducted. Independent risk variables for PHLF were identified using multivariate analysis of perioperative variables, and a nomogram was used to build a predictive model. To test the predictive power, a prospective study in which a validation cohort of 71 patients was evaluated using the nomogram. The prognostic value of this nomogram was evaluated by the C-index. RESULTS: Independent risk variables for PHLF were identified from perioperative variables. In multivariate analysis of the training cohort, tumor number, Pringle maneuver, blood loss, preoperative platelet count, postoperative ascites and use of anticoagulant medications were determined to be key risk factors for the development of PHLF, and they were selected for inclusion in our nomogram. The nomogram showed a 0.911 C-index for the training cohort. In the validation cohort, the nomogram also showed good prognostic value for predicting PHLF. The validation cohort was used with similarly successful results to evaluate risk in two previously published study models with calculated C-indexes of 0.718 and 0.711. CONCLUSION: Our study establishes for the first time a novel nomogram that can be used to identify patients at risk of developing PHLF.
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Carcinoma Hepatocelular , Falência Hepática , Neoplasias Hepáticas , Humanos , Hepatectomia/efeitos adversos , Nomogramas , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Estudos Prospectivos , Anticoagulantes/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , China/epidemiologia , Falência Hepática/diagnóstico , Falência Hepática/etiologia , Falência Hepática/prevenção & controle , Fatores de Risco , Estudos RetrospectivosRESUMO
Sepsis-associated encephalopathy(SAE) caused by infections outside the central nervous system always presents extensive brain damage.It is common in clinical practice and associated with a poor prognosis.There are problems in the assessing and diagnosing of SAE.Many factors,such as sedation and mechanical ventilation,make it difficult to assess SAE,while electrophysiological examination may play a role in the assessment.We reviewed the studies of electrophysiological techniques such as electroencephalography and somatosensory evoked potentials for monitoring SAE,hoping to provide certain evidence for the clinical evaluation and diagnosis of SAE.
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Encefalopatia Associada a Sepse , Sepse , Humanos , Encefalopatia Associada a Sepse/diagnóstico , Encefalopatia Associada a Sepse/complicações , Sepse/complicações , Sepse/diagnóstico , EletroencefalografiaRESUMO
Glycogen metabolism commonly altered in cancer is just beginning to be understood. Phosphoglucomutase 1 (PGM1), the first enzyme in glycogenesis that catalyzes the reversible conversion between glucose 1-phosphate (G-1-P) and glucose 6-phosphate (G-6-P), participates in both the breakdown and synthesis of glycogen. Here, we show that PGM1 is down-regulated in hepatocellular carcinoma (HCC), which is associated with the malignancy and poor prognosis of HCC. Decreased PGM1 expression obstructed glycogenesis pathway, which leads to the increased flow of glucose into glycolysis, thereby promoting tumor cell proliferation and HCC development. The loss of forkhead box protein J2 (FOXJ2), at least partly due to low genomic copy number in HCC, releases cellular nucleic acid-binding protein (CNBP), a nucleic acid chaperon, to bind to and promote G-quadruplex formation in PGM1 promoter and therefore decreases PGM1 expression. In addition, integrated analyses of PGM1 and FOXJ2 expression provide a better prediction for the malignance and prognosis of HCC. This study establishes a tumor-suppressive role of PGM1 by regulating glucose trafficking and uncovers a novel regulatory mechanism of PGM1 expression.
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Carcinoma Hepatocelular/metabolismo , Glucose/metabolismo , Neoplasias Hepáticas/metabolismo , Fosfoglucomutase/metabolismo , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Regulação para Baixo , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glicólise , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Fosfoglucomutase/deficiência , Fosfoglucomutase/genética , Prognóstico , Regiões Promotoras Genéticas , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
Toxoplasma gondii (T. gondii) is a neurotropic protozoan parasite, which can cause mental and behavioural disorders. The present study aimed to elucidate the effects and underlying molecular mechanisms of sertraline (SERT) on T. gondii-induced depression-like behaviours. In the present study, a mouse model and a microglial cell line (BV2 cells) model were established by infecting with the T. gondii RH strain. In in vivo and in vitro experiments, the underlying molecular mechanisms of SERT in inhibiting depression-like behaviours and cellular perturbations caused by T. gondii infection were investigated in the mouse brain and BV2 cells. The administration of SERT significantly ameliorated depression-like behaviours in T. gondii-infected mice. Furthermore, SERT inhibited T. gondii proliferation. Treatment with SERT significantly inhibited the activation of microglia and decreased levels of pro-inflammatory cytokines such as tumour necrosis factor-alpha, and interferon-gamma, by down-regulating tumour necrosis factor receptor 1/nuclear factor-kappa B signalling pathway, thereby ameliorating the depression-like behaviours induced by T. gondii infection. Our study provides insight into the underlying molecular mechanisms of the newly discovered role of SERT against T. gondii-induced depression-like behaviours.
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Toxoplasma , Toxoplasmose , Animais , Depressão/tratamento farmacológico , Camundongos , Microglia/metabolismo , Microglia/parasitologia , Sertralina/metabolismo , Sertralina/farmacologia , Toxoplasma/fisiologia , Toxoplasmose/tratamento farmacológico , Toxoplasmose/metabolismoRESUMO
Among many factors of controlling stem cell differentiation, the key transcription factor upregulation via physical force is a good strategy on the lineage-specific differentiation of stem cells. The study aimed to compare growth and myogenic potentials between the parental cells (PCs) and the 1-day-old C2C12 spheroid-derived cells (SDCs) in two-dimensional (2D) and three-dimensional (3D) culture conditions through examination of the cell proliferation and the expression of myogenic genes. The data showed that 1-day-old spheroids had more intense expression of MyoD gene with respect to the PCs. The proliferation of the SDCs is significantly higher than the PCs in a time-dependent manner. The SDCs had also significantly higher myogenic potential than the PCs in 2D and 3D culture conditions. The results suggest that MyoD gene upregulation through cell-cell contacts is the good approach for preparation of seed cells in muscle tissue engineering.
Assuntos
Técnicas de Cultura de Células , Células Musculares/metabolismo , Desenvolvimento Muscular/genética , Proteína MyoD/genética , Mioblastos/metabolismo , Esferoides Celulares/metabolismo , Actinina/genética , Actinina/metabolismo , Animais , Diferenciação Celular , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Colágeno/química , Colágeno/farmacologia , Regulação da Expressão Gênica , Camundongos , Células Musculares/citologia , Células Musculares/efeitos dos fármacos , Desenvolvimento Muscular/efeitos dos fármacos , Proteína MyoD/antagonistas & inibidores , Proteína MyoD/metabolismo , Mioblastos/citologia , Mioblastos/efeitos dos fármacos , Miogenina/genética , Miogenina/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Esferoides Celulares/citologia , Esferoides Celulares/efeitos dos fármacos , Engenharia Tecidual/métodosRESUMO
The increase in network applications diversity and different service quality requirements lead to service differentiation, making it more important than ever. In Wide Area Network (WAN), the non-responsive Long-Term Fast (LTF) flows are the main contributors to network congestion. Therefore, detecting and suppressing non-responsive LTF flows represent one of the key points for providing data transmission with controllable delay and service differentiation. However, the existing single-queue management algorithms are designed to serve only a small number of applications with similar requirements (low latency, high throughput, etc.). The lack of mechanisms to distinguish different traffic makes it difficult to implement differentiated services. This paper proposes an active queue management scheme, namely, SQM-LRU, which realizes service differentiation based on Shadow Queue (SQ) and improved Least-Recently-Used (LRU) strategy. The algorithm consists of three essential components: First, the flow detection module is based on the SQ and improved LRU. This module is used to detect non-responsive LTF flows. Second, different flows will be put into corresponding high or low priority sub-queues depending on the flow detection results. Third, the dual-queue adopts CoDel and RED, respectively, to manage packets. SQM-LRU intends to satisfy the stringent delay requirements of responsive flow while maximizing the throughput of non-responsive LTF flow. Our simulation results show that SQM-LRU outperforms traditional solutions with significant improvement in flow detection and reduces the delay, jitter, and Flow Completion Time (FCT) of responsive flow. As a result, it reduced the FCT by up to 50% and attained 95% of the link utilization. Additionally, the low overhead and the operations incur O(1) cost per packet, making it practical for the real network.