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Skin wound healing is a complex and multistage process, where any abnormalities at any stage can result in the accumulation of non-functional fibrotic tissue, leading to the formation of skin scars. Epigenetic modifications play a crucial role in regulating gene expression, inhibiting cell fate determination, and responding to environmental stimuli. m6A methylation is the most common post-transcriptional modification of eukaryotic mRNAs and long non-coding RNAs. However, it remains unclear how RNA methylation controls cell fate in different physiological environments. This review aims to discuss the current understanding of the regulatory pathways of RNA methylation in skin wound healing and their therapeutic implications with a focus on the specific mechanisms involved.
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Accurate source localization of the epileptogenic zone (EZ) is the primary condition of surgical removal of EZ. The traditional localization results based on three-dimensional ball model or standard head model may cause errors. This study intended to localize the EZ by using the patient-specific head model and multi-dipole algorithms using spikes during sleep. Then the current density distribution on the cortex was computed and used to construct the phase transfer entropy functional connectivity network between different brain areas to obtain the localization of EZ. The experiment result showed that our improved methods could reach the accuracy of 89.27% and the number of implanted electrodes could be reduced by (19.34 ± 7.15)%. This work can not only improve the accuracy of EZ localization, but also reduce the additional injury and potential risk caused by preoperative examination and surgical operation, and provide a more intuitive and effective reference for neurosurgeons to make surgical plans.
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Epilepsia , Couro Cabeludo , Humanos , Mapeamento Encefálico/métodos , Epilepsia/diagnóstico , Eletroencefalografia/métodos , EncéfaloRESUMO
BACKGROUND: Exercise preconditioning (EP) is essential for preventing ischemic stroke. Recent studies have shown that EP exerts neuroprotective effects in the cerebral ischemia-reperfusion injury model. Nonetheless, there have been few reports on the relationship between EP and the Th17/Treg balance. Moreover, it is unclear whether the JAK2/STAT3 pathway is responsible for the neuroprotective effect of EP. Therefore, we aimed to explore the impact of EP, other than the anti-inflammatory and antiapoptotic functions, on the Th17/Treg balance via the JAK2/STAT3 pathway in a middle cerebral artery occlusion (MCAO)-induced model. RESULTS: Fifty rats were randomly allocated into five groups, including the sham group (n = 10), EP+sham group (n = 10), MCAO group (n = 10), EP+MCAO group (n = 10), and EP+MCAO+JAK2/STAT3 pathway agonist (coumermycin A1, CA1) group (n = 10). The results indicated that EP alleviated neurological deficits, reduced infarct volume, and ameliorated neuronal apoptosis induced by MCAO. Additionally, the MCAO-induced Th17/Treg imbalance could be rectified by EP. The decreased levels of IL-10 and Foxp3 and increased IL-17 and RORα in the MCAO group were reversed by EP treatment. Regarding inflammation, EP reduced the concentrations of IL-6 and IL-17 and elevated those of IL-10 and TGF-ß. The neuroprotective effects of EP were accompanied by decreased phosphorylation of JAK2 and STAT3. Furthermore, CA1 pretreatment diminished all the beneficial effects of EP partially. CONCLUSION: Our findings suggest that EP contributes to attenuating neuronal apoptosis, Th17/Treg imbalance, and inflammation induced by MCAO via inhibiting the JAK2/STAT3 pathway, indicating its therapeutic potential in ischemic stroke.
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PURPOSE: To explore whether glycated albumin (GA) or fasting plasma glucose (FPG), both routinely monitored during patients' hospital stay, can be used to predict post-transplantation diabetes mellitus (PTDM). METHODS: All kidney transplantation recipients (KTRs) from January 2017 to December 2018 were followed-up for 1 year. PTDM was diagnosed from day 45 post-operation to 1 year. When the completeness was above 80%, FPG or GA data on the day was selected, analyzed, and presented as range parameters and standard deviation (SD) and compared between PTDM and non-PTDM groups in fluctuation and stable periods. The predictive cut-off values were determined via receiver operating characteristic (ROC) analysis. The PTDM combined predictive mode, formed by the independent risk factors derived from logistic regression analyses, was compared with each independent risk factor with the independent ROC curve test. RESULTS: Among 536 KTRs, 38 patients developed PTDM up to 1 year post-operatively. The family history diabetes mellitus (OR, 3.21; P = 0.035), the FPG SD in fluctuation period >2.09 mmol/L (OR, 3.06; P = 0.002), and the FPG maximum in stable period >5.08 mmol/L (OR, 6.85; P < 0.001) were the PTDM independent risk factors. The discrimination of the combined mode (area under the curve = 0.81, sensitivity = 73.68%, and specificity = 76.31%) was higher than each prediction (P < 0.05). CONCLUSIONS: The FPG standard deviation during the fluctuation period, FPG maximum during the stable period, and family history diabetes mellitus predicted PTDM with good discrimination and potential routine clinical use.
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BACKGROUND: Previous studies have suggested that a single dose of rifampin has protective effects against leprosy in close contacts of patients with the disease. Rifapentine was shown to have greater bactericidal activity against Mycobacterium leprae than rifampin in murine models of leprosy, but data regarding its effectiveness in preventing leprosy are lacking. METHODS: We conducted a cluster-randomized, controlled trial to investigate whether single-dose rifapentine is effective in preventing leprosy in household contacts of patients with leprosy. The clusters (counties or districts in Southwest China) were assigned to one of three trial groups: single-dose rifapentine, single-dose rifampin, or control (no intervention). The primary outcome was the 4-year cumulative incidence of leprosy among household contacts. RESULTS: A total of 207 clusters comprising 7450 household contacts underwent randomization; 68 clusters (2331 household contacts) were assigned to the rifapentine group, 71 (2760) to the rifampin group, and 68 (2359) to the control group. A total of 24 new cases of leprosy occurred over the 4-year follow-up, for a cumulative incidence of 0.09% (95% confidence interval [CI], 0.02 to 0.34) with rifapentine (2 cases), 0.33% (95% CI, 0.17 to 0.63) with rifampin (9 cases), and 0.55% (95% CI, 0.32 to 0.95) with no intervention (13 cases). In an intention-to-treat analysis, the cumulative incidence in the rifapentine group was 84% lower than that in the control group (cumulative incidence ratio, 0.16; multiplicity-adjusted 95% CI, 0.03 to 0.87; P = 0.02); the cumulative incidence did not differ significantly between the rifampin group and the control group (cumulative incidence ratio, 0.59; multiplicity-adjusted 95% CI, 0.22 to 1.57; P = 0.23). In a per-protocol analysis, the cumulative incidence was 0.05% with rifapentine, 0.19% with rifampin, and 0.63% with no intervention. No severe adverse events were observed. CONCLUSIONS: The incidence of leprosy among household contacts over 4 years was lower with single-dose rifapentine than with no intervention. (Funded by the Ministry of Health of China and the Chinese Academy of Medical Sciences; Chinese Clinical Trial Registry number, ChiCTR-IPR-15007075.).
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Hansenostáticos , Hanseníase , Mycobacterium leprae , Rifampina , Humanos , Incidência , Hanseníase/epidemiologia , Hanseníase/prevenção & controle , Hanseníase/transmissão , Rifampina/administração & dosagem , Rifampina/análogos & derivados , Hansenostáticos/administração & dosagem , Hansenostáticos/uso terapêutico , Características da FamíliaRESUMO
BACKGROUND: The brain is a common metastatic site in patients with non-small cell lung cancer (NSCLC), resulting in a relatively poor prognosis. Systemic therapy with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is recommended as the first-line treatment for EGFR-mutated, advanced NSCLC patients. However, intracranial activity varies in different drugs. Thus, brain metastasis (BM) should be considered when choosing the treatment regimens. We conducted this network meta-analysis to explore the optimal first-line therapeutic schedule for advanced EGFR-mutated NSCLC patients with different BM statuses. METHODS: Randomized controlled trials focusing on EGFR-TKIs (alone or in combination) in advanced and EGFR-mutant NSCLC patients, who have not received systematic treatment, were systematically searched up to December 2021. We extracted and analyzed progression-free survival (PFS) and overall survival (OS). A network meta-analysis was performed with the Bayesian statistical model to determine the survival outcomes of all included therapy regimens using the R software. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to compare intervention measures, and overall rankings of therapies were estimated under the Bayesian framework. RESULTS: This analysis included 17 RCTs with 5077 patients and 12 therapies, including osimertinib + bevacizumab, aumolertinib, osimertinib, afatinib, dacomitinib, standards of care (SoC, including gefitinib, erlotinib, or icotinib), SoC + apatinib, SoC + bevacizumab, SoC + ramucirumab, SoC + pemetrexed based chemotherapy (PbCT), PbCT, and pemetrexed free chemotherapy (PfCT). For patients with BM, SoC + PbCT improved PFS compared with SoC (HR = 0.40, 95% CI: 0.17-0.95), and osimertinib + bevacizumab was most likely to rank first in PFS, with a cumulative probability of 34.5%, followed by aumolertinib, with a cumulative probability of 28.3%. For patients without BM, osimertinib + bevacizumab, osimertinib, aumolertinib, SoC + PbCT, dacomitinib, SoC + ramucirumab, SoC + bevacizumab, and afatinib showed superior efficacy compared with SoC (HR = 0.43, 95% CI: 0.20-0.90; HR = 0.46, 95% CI: 0.31-0.68; HR = 0.51, 95% CI: 0.34-0.77; HR = 0.50, 95% CI: 0.38-0.66; HR = 0.62, 95% CI: 0.43-0.89; HR = 0.64, 95% CI: 0.44-0.94; HR = 0.61, 95% CI: 0.48-0.76; HR = 0.71, 95% CI: 0.50-1.00), PbCT (HR = 0.29, 95% CI: 0.11-0.74; HR = 0.31, 95% CI: 0.15-0.62; HR = 0.34, 95% CI: 0.17-0.69; HR = 0.34, 95% CI: 0.18-0.64; HR = 0.42, 95% CI: 0.21-0.82; HR = 0.43, 95% CI: 0.22-0.87; HR = 0.41, 95% CI: 0.22-0.74; HR = 0.48, 95% CI: 0.31-0.75), and PfCT (HR = 0.14, 95% CI: 0.06-0.32; HR = 0.15, 95% CI: 0.09-0.26; HR = 0.17, 95% CI: 0.09-0.29; HR = 0.16, 95% CI: 0.10-0.26; HR = 0.21, 95% CI: 0.12-0.35; HR = 0.21, 95% CI: 0.12-0.39; HR = 0.20, 95% CI: 0.12-0.31; HR = 0.23, 95% CI: 0.16-0.34) in terms of PFS. And, SoC + apatinib showed relatively superior PFS when compared with PbCT (HR = 0.44, 95% CI: 0.22-0.92) and PfCT (HR = 0.21, 95% CI: 0.12-0.39), but similar PFS to SoC (HR = 0.65, 95% CI: 0.42-1.03). No statistical differences were observed for PFS in patients without BM between PbCT and SoC (HR = 1.49, 95% CI: 0.84-2.64), but both showed favorable PFS when compared with PfCT (PfCT vs. SoC, HR = 3.09, 95% CI: 2.06-4.55; PbCT vs. PfCT, HR = 0.14, 95% CI: 0.06-0.32). For OS, SoC + PbCT was most likely to rank first in patients with and without BM, with cumulative probabilities of 46.8%, and 37.3%, respectively. CONCLUSION: Osimertinib + bevacizumab is most likely to rank first in PFS in advanced EGFR-mutated NSCLC patients with or without BM, and SoC + PbCT is most likely to rank first in OS.
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BACKGROUND: Whether there are differences among the new-generation transcatheter aortic valve implantation (TAVI) devices for patients with aortic stenosis (AS) remains unclear. The aim of the study was to compare the efficiency and safety of different new-generation TAVI devices for patients with AS. MATERIALS AND METHODS: A comprehensive search of PubMed, Embase and Web of Science from their inception to February 1, 2022. Randomized clinical trials (RCT) and observational studies that compared two or more different TAVI devices were enrolled. Pairwise meta-analysis and frequentist network meta-analysis were conducted to pool the outcome estimates of interest. RESULTS: A total of 79 studies were finally included. According to the surface under the cumulative ranking, the top two ranked valves for lower rates of events were as follows: DFM (4.6%) and Lotus (48.8%) for lower rate of device success; Sapien 3 (16.8%) and DFM (19.7%) for lower mortality; DFM (8.6%) and Sapien 3 (25.5%) for lower rates of stroke; Evolut (27.6%) and DFM (35.8%) for lower rates of major and life-threatening bleeding (MLTB); Portico (22.6%) and Sapien 3 (41.9%) for lower rates of acute kidney injury (AKI); Acurate (8.6%) and DFM (13.2%) for lower rates of permanent pacemaker implantation (PPI); Lotus (0.3%) and Sapien 3 (22.7%) for lower rates of paravalvular leak (PVL); Evolut (1.4%) and Portico (29.1%) for lower rates of mean aortic valve gradients (MAVG). CONCLUSION: The findings of the present study suggested that the device success rates were comparable among these new-generation valves except for DFM. After excluding DFM, Sapien 3 might be the best effective for decreased mortality and stroke; Lotus might be the best effective for decreased PVL; Evolut might be the best effective for decreased MLTB and MAVG; Acurate and Portico might be the best effective for decreased PPI and AKI respectively.
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Defects are of significant importance to determine and improve the distinct properties of 2D materials, such as electronic, optical, and catalytic performance. In this report, we observe four types of point defects in atomically thin flakes of 1T-PtTe2 by using low-temperature scanning tunnelling microscopy and spectroscopy (STM/S). Through the combination of STM imaging and simulations, such defects are identified as a single tellurium vacancy from each side of the top PtTe2 layer and a single platinum vacancy from the topmost and next layer. The density functional theory (DFT) calculations reveal that the platinum vacancies from both the monolayer and bilayer exhibit a local magnetic moment. In bilayer PtTe2, the interlayer coulomb screening effect reduces the local magnetic momentum of the single platinum vacancy. Our research provides meaningful guidance for further experiments about the effects of intrinsic defects on potential functions of thin 1T-PtTe2, such as catalysis and spintronic applications.
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OBJECTIVES: The aim of this study is to make a diagnosis and a classification for congenital central slip hypoplasia. The surgical treatment was determined according to the classification. METHODS: A retrospective study of 25 treated digits in 13 patients with congenital central slip hypoplasia was carried out. The central slip was classified into two types. Type I: The distance between the insertion of central slip and the proximal interphalangeal joint was shorter than or equal to 5 mm. Type II: The distance between the insertion of central slip and the proximal interphalangeal joint was longer than 5 mm. Tendon advancement or tendon graft was used for type I or II, respectively. RESULTS: The preoperative mean extension lag was 91° (range, 80°-100°), and the mean follow-up duration was 18 months (range, 9-24 months). The postoperative mean extension lag was 19° (range, 0°-50°). No matter whether in type I or II, the postoperative ranges of proximal interphalangeal joint extension had significant improvement compared with the preoperative ones. There was no statistical difference of proximal interphalangeal joint extension lag changes before and after surgery between the two types. CONCLUSION: Congenital central slip hypoplasia could be classified into two types. Either tendon advancement or tendon graft might be effective, which depended on the classification.
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Traumatismos dos Dedos , Tendões , Humanos , Tendões/cirurgia , Estudos Retrospectivos , Amplitude de Movimento Articular , Transferência Tendinosa , Extremidades , Articulações dos Dedos/cirurgia , Traumatismos dos Dedos/cirurgiaRESUMO
To address the problem of multiple solutions and improve the calculating speed, we construct a tandem architecture consisting of a forward modeling network and an inverse design network. Using this combined network, we inversely design the circular polarization converter and analyze the effect of different design parameters on the prediction accuracy of the polarization conversion rate. The average mean square error of the circular polarization converter is 0.00121 at an average prediction time of 1.56×10-2 s. If only the forward modeling process is considered, it takes 6.15×10-4 s, which is 2.1×105 times faster than that using the traditional numerical full-wave simulation method. By slightly resizing the network input and output layers, the network is adaptable to the design of both the linear cross-polarization and linear-to-circular polarization converters.
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As a unique 2D magnetic material with self-intercalated structure, Cr5Te8 exhibits many intriguing magnetic properties. While its ferromagnetism of Cr5Te8 has been previously reported, the research on its magnetic domain remains unexplored. Herein, we have successfully fabricated 2D Cr5Te8 nanosheets with controlled thickness and lateral size by chemical vapor deposition (CVD). Then magnetic property measurement system revealed Cr5Te8 nanosheets exhibiting intense out-of-plane ferromagnetism with a Curie temperature (TC) of 176 K. Significantly, we reported for the first time two magnetic domains: magnetic bubbles and thickness-dependent maze-like magnetic domains in our Cr5Te8 nanosheets by cryogenic magnetic force microscopy (MFM). The domain width of the maze-like magnetic domains increases rapidly with decreasing sample thickness; meanwhile, the domain contrast decreases. This indicates the dominant role of ferromagnetism shifts from dipolar interactions to magnetic anisotropy. Our research not only establishes a pathway for the controllable growth of 2D magnetic materials but also points toward novel avenues for regulating magnetic phases and methodically tuning domain characteristics.
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Background: Febrile seizures (FS) are a common cause of paediatric emergencies, but research on their aetiology and epidemiology are limited. The aim of this study was to investigate the prevalence of central nervous system (CNS) pathogenic infections in patients with FS-associated hospitalization. Methods: A prospective observational study was conducted in children under 16 years of age with FS-associated hospitalization. Demographic, clinical and laboratory data were recorded. Multiplex-PCR was performed on cerebrospinal fluid (CSF) samples for nine viruses, nine bacteria and one fungus. Results: A total of 119 children were enrolled between June 2021 and June 2022. Of these, 83.2% had a final diagnosis of FS (69.7%) or FS plus (13.4%). In addition, epilepsy and encephalitis/meningitis were also found in 16.8% (20/119). Seven pathogens were identified from 9 CSF samples (7.6%), including viruses (EV, EBV, HHV-6) and bacteria (H. influenzae, S. pneumoniae, M. tuberculosis, S. putrefaciens). There were no significant clinical or laboratory differences between children who tested positive or negative for pathogens in the CSF, except for the presentation of herpes pharyngitis. Children with encephalitis/meningitis had longer hospital stays compared with those diagnosed with FS at discharge; abnormal EEG findings were significantly more common in patients with epilepsy. Conclusion: FS-associated hospitalized children may have viral or bacterial intracranial infections. Pathogen testing of CSF is an important basis for timely antibiotic or antiviral therapy when clinical and laboratory findings make FS indistinguishable from other CNS disorders.
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Charge density waves (CDWs) in 1T-TaS2 maintain 2D ordering by forming periodic in-plane star-of-David (SOD) patterns, while they also intertwined with orbital order in the c axis. Recent theoretical calculations and surface measurements have explored 3D CDW configurations, but interlayer intertwining of a 2D CDW order remains elusive. Here, we investigate the in- and out-of-plane ordering of the commensurate CDW superstructure in a 1T-TaS2 thin flake in real space, using aberration-corrected cryogenic transmission electronic microscopy (cryo-TEM) in low-dose mode, far below the threshold dose for an electron-induced CDW phase transition. By scrutinizing the phase intensity variation of modulated Ta atoms, we visualize the penetrative 3D CDW stacking structure, revealing an intertwining multidomain structure with three types of vertical CDW stacking configurations. Our results provide microstructural evidence for the coexistence of local Mott insulation and metal phases and offer a paradigm for studying the CDW structure and correlation order in condensed-matter physics using cryo-TEM.
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Renal cell carcinoma (RCC) is the most common malignancy of the urinary system, accounting for 3.7% of all new malignancies. The prognosis of RCC patients is still poor, especially patients in advanced stage. Limited studies have fully clarified the role of immune cell infiltration profiles in the prognosis and immunotherapy of RCC. In current study, we evaluated the abundance of the 22 tumor-infiltrating immune cells (TIICs) with CIBERSORT methods. The correlation between TIICs and clinicopathological parameters, tumor immune dysfunction and exclusion (TIDE) score and immunophenoscore (IPS) of RCC patients were also explored. Significant correlations were obtained between TIICs subpopulation and specific clinicopathologic parameters of RCC, including age, gender, tumor grade, clinical stage, T stage and distant metastasis. Moreover, RCC patients with high level of memory activated CD4 T cells, follicular helper T cells and regulatory T cells had a worse overall survival (OS) rate. RCC patients with high level of CD 8â +â T cells and M1 macrophages had a lower TIDE score and higher anti-CTLA IPS, higher anti-PD1 IPS as well as higher anti-PD1/CTLA4 IPS. Our results clarified the immune cell infiltration profiles of RCC. RCC patients with high level of CD 8â +â T cell and M1 macrophages had a lower TIDE score and higher IPS, suggesting that RCC patients with high level of CD 8â +â T cell and M1 macrophages may benefit from immunotherapy.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Relevância Clínica , Prognóstico , MacrófagosRESUMO
BACKGROUND: Helicobacter pylori infection and irritable bowel syndrome (IBS) negatively affect the quality of life. Some previous studies found that H. pylori infection should be positively associated with the risk of IBS, but others did not. The present study aims to clarify this association, and to further analyse whether H. pylori treatment can improve IBS symptoms. MATERIALS AND METHODS: The PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure, China Science and Technology Journal and Wanfang databases were searched. Meta-analysis was performed using a random-effect model. The pooled odds ratios (ORs)/risk ratios (RRs) and their 95% CIs were calculated. Heterogeneity was evaluated using the Cochran's Q test and I2 statistics. Meta-regression analysis was used to explore the sources of heterogeneity. RESULTS: Thirty-one studies with 21 867 individuals were included. Meta-analysis of 27 studies found that patients with IBS had a significantly higher risk of H. pylori infection than those without (OR = 1.68, 95% CI 1.29 to 2.18; p < 0.001). The heterogeneity was statistically significant (I² = 85%; p < 0.001). Meta-regression analyses indicated that study design and diagnostic criteria of IBS might be the potential sources of heterogeneity. Meta-analysis of eight studies demonstrated that H. pylori eradication treatment had a higher improvement rate of IBS symptoms (RR = 1.24, 95% CI 1.10 to 1.39; p < 0.001). The heterogeneity was not significant (I² = 32%; p = 0.170). Meta-analysis of four studies also demonstrated that successful H. pylori eradication had a higher improvement rate of IBS symptoms (RR = 1.25, 95% CI 1.01 to 1.53; p = 0.040). The heterogeneity was not significant (I² = 1%; p = 0.390). CONCLUSION: H. pylori infection is associated with an increased risk of IBS. H. pylori eradication treatment can improve IBS symptoms.
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Infecções por Helicobacter , Síndrome do Intestino Irritável , Humanos , Infecções por Helicobacter/complicações , Helicobacter pylori , Síndrome do Intestino Irritável/complicaçõesRESUMO
Functional constipation (FC) is a high morbidity gastrointestinal disease for which dysfunction in the enteric nervous system is a major pathogenesis mechanism. To enhance our understanding of the involvement of intestinal microbiota and its metabolites in the pathogenesis of FC, we conducted a shotgun metagenomic sequencing analysis of gut microbiota and serum short-chain fatty acids (SCFAs) analysis in 460 Chinese women with different defecation frequencies. We observed that the abundance ofFusobacterium_varium, a butyric acid-producing bacterium, was positively correlated (P = 0.0096) with the frequency of defecation; however, the concentrations of serum butyric acid was negatively correlated (P = 3.51E-05) with defecation frequency. These results were verified in an independent cohort (6 patients with FC and 6 controls). To further study the effects of butyric acid on intestinal nerve cells, we treated mouse intestinal neurons in vitro with various concentrations of butyrate (0.1, 0.5, 1, and 2.5 mM). We found that intestinal neurons treated with 0.5 mM butyrate proliferated better than those in the other treatment groups, with significant differences in cell cycle and oxidative phosphorylation signal pathways. We suggest that the decreased butyrate production resulting from the reduced abundance of Fusobacterium in gut microbiota affects the proliferation of intestinal neurons and the energy supply of intestinal cells. However, with FC disease advancing, the consumption and excretion of butyric acid reduce, leading to its accumulation in the intestine. Moreover, the accumulation of an excessively high amount of butyric acid inhibits the proliferation of nerve cells and subsequently exacerbates the disease.
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In this paper, we propose a multiple images simultaneous encryption scheme by encrypting the orbital angular momentum (OAM) holography with ghost imaging. By controlling the topological charge of the incident OAM light beam on the OAM-multiplexing hologram, different images can be selectively obtained for ghost imaging (GI). Followed by the random speckles illumination, the bucket detector values in GI are obtained and then considered as the ciphertext transmitted to the receiver. The authorized user can distill the correct relationship between the bucket detections and the illuminating speckle patterns with the key and the additional topological charges, so that each holographic image can be successfully recovered, while the eavesdropper can not obtain any information about the holographic image without the key. The eavesdropper even can not get clear holographic image when all the key is eavesdropped but without topological charges. The experimental results show that the proposed encryption scheme has a higher capacity for multiple images because there is no theoretical topological charge limit for the selectivity of OAM holography, and the results also show that the proposed encryption scheme is more secure and has a stronger robustness. Our method may provide a promising avenue for multi-image encryption and has the potential for more applications.
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Lung adenocarcinoma (LUAD) is the main cause of death globally. The present study investigated the prognostic value and functional verification of nucleophosmin (NPM1) in LUAD. LUAD and normal samples from The Cancer Genome Atlas were analyzed to identify whether NPM1 is associated with LUAD prognosis. NPM1 protein expression level was verified by western blotting. Cell proliferation, migration and invasion were detected by Cell Counting Kit8, wound healing and Transwell assays, respectively. EGFR/MAPK pathwayrelated proteins [phosphorylated (p)EGFR/EGFR, pMEK/MEK, and pERK/ERK] expression was measured through western blotting. A xenograft tumor mice model was constructed to perform the in vivo verification. NPM1 was upregulated in LUAD cells, and highlevel NPM1 indicated poor prognosis in patients with LUAD. In vitro experiments revealed that NPM1 knockdown inhibited LUAD cell proliferation, migration and invasion. Moreover, protein expression of pEGFR/EGFR, pMEK/MEK and pERK/ERK was reduced with the NPM1 silencing. Furthermore, EGF, an activator of the EGFR/MAPK pathway, reversed the effects of NPM1. In vivo experiments showed that NPM1 knockdown inhibited tumor growth and protein levels of pEGFR/EGFR, pMEK/MEK and pERK/ERK. NPM1 is related to the poor prognosis of LUAD and promotes the malignant progression of LUAD by activating the EGFR/MAPK pathway. This discovery provides a new potential therapeutic target for the diagnosis and treatment of LUAD.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Neoplasias Pulmonares/patologia , Nucleofosmina , Linhagem Celular Tumoral , Movimento Celular/genética , Adenocarcinoma de Pulmão/patologia , Proliferação de Células/genética , Transdução de Sinais , Receptores ErbB/genética , Receptores ErbB/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND AND OBJECTIVE: There are a substantial proportion of elderly patients with ST-segment elevation myocardial infarction (STEMI) miss the optimal time window (12 h from symptom onset) of primary percutaneous coronary intervention (PCI). For these patients, the ideal timing of delayed PCI remains undetermined. Therefore, this study compared the clinical outcomes of early versus late delayed PCI in elderly patients with STEMI. METHODS: From January 2014 to September 2019, 512 patients aged ≥ 65 years with STEMI who underwent delayed PCI after 12 h from symptom onset were included and then categorized into the early PCI group (12-48 h, n = 111) and late PCI group (48 h-28 days, n = 401) according to the timing of delayed PCI. Propensity score matching (PSM) was conducted to adjust the confounding factors between groups. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, cardiac death, recurrent myocardial infarction (MI), stroke, and ischemia-driven revascularization. RESULTS: During a mean follow-up of 77 months, 163 (31.8%) patients developed MACCE and 93 (18.2%) died. Early or late delayed PCI did not make a significant difference in clinical outcomes of MACCE (Before PSM: HR 0.773, 95% CI 0.520-1.149, P = 0.203; After PSM: HR 0.869, 95% CI 0.498-1.517, P = 0.622), all-cause death, cardiac death, recurrent MI, stroke, and ischemia-driven revascularization in both overall patients and the PSM cohorts. CONCLUSION: Early delayed PCI (12-48 h from symptom onset), for elderly patients with STEMI who present > 12 h after symptom onset is not associated with better long-term clinical outcomes compared with late delayed PCI (48 h-28 days).
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Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Acidente Vascular Cerebral , Idoso , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento , Acidente Vascular Cerebral/etiologia , MorteRESUMO
Scutellaria baicalensis Georgi (SBG) has been widely used as medical plant in East Asia with remarkable anti-cancer activity. However, the underlying mechanisms are still confused. In this study, an integrated analysis was conducted to screen topoisomerase I (topo I) inhibitors from flavonoids of SBG and investigate the anti-cancer mechanisms, containing bioaffinity ultrafiltration UPLC-ESI-TripleTOF-MS/MS, molecular docking, and multiple complex networks. The SBG extract exhibited notable cytotoxic activity on Hela cells. Five flavonoids were identified as potential topo I inhibitors, including skullcapflavone II, wogonin, chrysin, oroxylin A, and tenaxin I. Their ESI-MS/MS spectra showed that RDA reaction and neutral molecule loss were the main fragment patterns. Docking results demonstrated that π-π interaction and the formation of hydrogen bond contributed most to their binding with topo I. The selected compounds, related target proteins and pathways were integrated into target-based multiple complex networks, which consisted of three subnetworks. Statistical and topological analysis of these networks revealed a series of characteristics, including scale-free property with power-law degree distribution, Poisson degree distribution, and small-world property. Chrysin, wogonin, and oroxylin A exhibited as main active components with much higher degree values. Chemical carcinogenesis-receptor activation (hsa05207) was considered as critical pathway due to remarkable centrality indexes. Additionally, potential synergistic effect of wogonin and chrysin was observed on the conversion of supercoiled DNA to relaxed forms. These results improved current understanding of flavonoid-rich plants on the treatment of cancer. Moreover, the multi-disciplinary approach provided a new strategy for the research of natural products from medical plants.
