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Introduction: Bacterial urinary tract infections (UTI) are among the most common infectious diseases worldwide. The rise of multidrug-resistant (MDR) uropathogenic Escherichia coli (UPEC) UTI cases is a significant threat to healthcare systems. Several probiotic bacteria have been proposed as an alternative to combat MDR UTI. Lactic acid bacteria in the genus Limosilactobacillus are some of the most studied and used probiotics. However, strain-specific effects play a critical role in probiotic properties. L. reuteri KUB-AC5 (AC5), isolated from the chicken gut, confers antimicrobial and immunobiotic effects against some human pathogens. However, the antibacterial and immune modulatory effects of AC5 on UPEC have never been explored. Methods: Here, we investigated both the direct and indirect effects of AC5 against UPEC isolates (UTI89, CFT073, and clinical MDR UPEC AT31) in vitro. Using a spot-on lawn, agar-well diffusion, and competitive growth assays, we found that viable AC5 cells and cell-free components of this probiotic significantly reduced the UPEC growth of all strains tested. The human bladder epithelial cell line UM-UC-3 was used to assess the adhesion and pathogen-attachment inhibition properties of AC5 on UPEC. Results and discussion: Our data showed that AC5 can attach to UM-UC-3 and decrease UPEC attachment in a dose-dependent manner. Pretreatment of UPEC-infected murine macrophage RAW264.7 cells with viable AC5 (multiplicity of infection, MOI = 1) for 24 hours enhanced macrophage-killing activity and increased proinflammatory (Nos2, Il6, and Tnfa) and anti-inflammatory (Il10) gene expression. These findings indicate the gut-derived AC5 probiotic could be a potential urogenital probiotic against MDR UTI.
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Limosilactobacillus reuteri , Macrófagos , Probióticos , Escherichia coli Uropatogênica , Probióticos/farmacologia , Escherichia coli Uropatogênica/efeitos dos fármacos , Escherichia coli Uropatogênica/imunologia , Limosilactobacillus reuteri/fisiologia , Animais , Camundongos , Macrófagos/imunologia , Macrófagos/microbiologia , Humanos , Urotélio/microbiologia , Infecções Urinárias/microbiologia , Infecções Urinárias/prevenção & controle , Linhagem Celular , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/prevenção & controle , Células RAW 264.7 , Células Epiteliais/microbiologia , Galinhas , Aderência Bacteriana/efeitos dos fármacosRESUMO
Background: Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignant tumor. Currently, there is a lack of reliable prognostic markers in clinical practice. Extensive research has shown that long non-coding RNA (lncRNA) are critical factors in the initiation and progression of cancer, closely associated with early diagnosis and prognosis. Previous studies have identified that ZFHX4 antisense RNA 1 (ZFHX4-AS1) is aberrantly expressed in various cancers and is associated with poor outcomes. This study investigates whether ZFHX4-AS1 affects the prognosis of ACC patients and, if so, the potential mechanisms involved. Methods: In this study, utilizing four multi-center cohorts from The Cancer Genome Atlas (TCGA) program and Gene Expression Omnibus (GEO), we validated the prognostic capability of ZFHX4-AS1 in ACC patients through Kaplan-Meier survival analysis, cox regression models, and nomograms. Then, we explored the biological functions of ZFHX4-AS1 using gene set enrichment analysis (GSEA), competing endogenous RNA (ceRNA) networks, and analyses of somatic mutations and copy number variation (CNV). Finally, in vitro experiments were conducted to further validate the impact of ZFHX4-AS1 on proliferation and migration capabilities of ACC cell lines. Results: Survival analysis indicated that patients in the high ZFHX4-AS1 expression group of ACC had worse prognosis. Cox regression analyses suggested that ZFHX4-AS1 levels were independent risk factors for prognosis. Subsequently, we constructed nomograms based on clinical features and ZFHX4-AS1 levels, demonstrating good predictive performance under the time-dependent receiver operating characteristic (ROC) curve. Analysis based on somatic mutations and CNV revealed that CTNNB1 and 9p21.3-Del drove the expression of ZFHX4-AS1. Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays confirmed that knockdown of ZFHX4-AS1 inhibited proliferation and migration of ACC cells. Conclusions: This study demonstrates that ZFHX4-AS1 has a reliable predictive value for the prognosis of ACC patients and is a promising biomarker.
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OBJECTIVE: The aim of this study was to analyze the clinical significance and prognostic value of CD8+ T cell-related regulatory genes in hepatocellular carcinoma (HCC). METHODS: This was a retrospective study. We combined TCGA-LIHC and single-cell RNA sequencing data for Lasso-Cox regression analysis to screen for CD8+ T cell-associated genes to construct a novel signature. The expression of the signature genes was detected at cellular and tissue levels using qRT-PCR, immunohistochemistry, and tissue microarrays. The CIBERSORT algorithm was then used to assess the immune microenvironmental differences between the different risk groups and a drug sensitivity analysis was performed to screen for potential HCC therapeutic agents. RESULTS: An 8-gene CD8 + T cell-associated signature (FABP5, GZMH, ANXA2, KLRB1, CD7, IL7R, BATF, and RGS2) was constructed. Survival analysis showed that high-risk patients had a poorer prognosis in all cohorts. Tumor immune microenvironment analysis revealed 22 immune cell types that differed significantly between patients in different risk groups, with patients in the low-risk group having an immune system that was more active in terms of immune function. Patients in the high-risk group were more prone to immune escape and had a poorer response to immunotherapy, and AZD7762 was screened as the most sensitive drug in the high-risk group. Finally, preliminary experiments have shown that BATF has a promoting effect on the proliferation, migration and invasion of HuH-7 cells. CONCLUSIONS: The CD8+ T-cell-associated signature is expected to be a tool for optimizing individual patient decision-making and monitoring protocols, and to provide new ideas for treatment and prognostic assessment of HCC.
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Linfócitos T CD8-Positivos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Microambiente Tumoral , Humanos , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Prognóstico , Microambiente Tumoral/imunologia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: M2-like tumor-associated macrophages (M2-like TAMs) play key roles in tumor progression and the immune response. However, the clinical significance and prognostic value of M2-like TAMs-associated regulatory genes in gastric cancer (GC) have not been clarified. METHODS: Herein, we identified M2-like TAM-related genes by weighted gene coexpression network analysis of TCGA-STAD and GSE84437 cohort. Lasso-Cox regression analyses were then performed to screen for signature genes, and a novel signature was constructed to quantify the risk score for each patient. Tumor mutation burden (TMB), survival outcomes, immune cells, and immune function were analyzed in the risk groups to further reveal the immune status of GC patients. A gene-drug correlation analysis and sensitivity analysis of anticancer drugs were used to identify potential therapeutic agents. Finally, we verified the mRNA expression of signature genes in patient tissues by qRT-PCR, and analyzed the expression distribution of these genes by IHC. RESULTS: A 4-gene (SERPINE1, MATN3, CD36, and CNTN1) signature was developed and validated, and the risk score was shown to be an independent prognostic factor for GC patients. Further analyses revealed that GC patients in the high-risk group had a worse prognosis than those in the low-risk group, with significant differences in TMB, clinical features, enriched pathways, TIDE score, and tumor microenvironment features. Finally, we used qRT-PCR and IHC analysis to verify mRNA and protein level expression of signature genes. CONCLUSION: These findings highlight the importance of M2-like TAMs, provide a new perspective on individualized immunotherapy for GC patients.
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Mixed oxygen ion and electron-conducting materials are viable cathodes for solid oxide fuel cells due to their excellent oxygen transport kinetics and mixed electrical conductivity, which ensure highly efficient operation at low and medium temperatures. However, iron-based double perovskite oxides usually exhibit poor electrocatalytic activity due to low electron and oxygen ion conductivity. In this paper, Ca is doped in PrBaFe2O5+δ A-site to improve the electrochemical performance of PrBaFe2O5+δ. Results show that replacing Pr with Ca does not change the crystal structure, and the Ca doping effectively increases the adsorbed oxygen content and accelerates the migration and diffusion rate of O2- to the electrolyte|cathode interface. The polarization resistance of the symmetric cell PC0.15BF|CGO|PC0.15BF is 0.033 Ω·cm2 at 800 °C, which is about 56% lower than that of PBF, confirming the enhancement of the mixed conduction of oxygen ions and electrons. In addition, the anode-supported single cell has a peak power density of 512 mW·cm-2 at 800 °C.
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BACKGROUND: Owing to the heterogeneity of prostate cancer (PCa), the clinical indicators traditionally fall short of meeting the requirements for personalized medicine. The realm of RNA modification has emerged as an increasingly relevant domain, shedding light on its pivotal role in tumor heterogeneity. However, the specific contributions of RNA modification regulators within the context of PCa remain largely unexplored. METHODS: In this study, we undertook a literature review to summarize the common 8 types of RNA modifications (ac4c, AI, APA, m1A, m5c, m6A, m7G, Ψ) encompassing a total of 84 regulators. Moreover, we integrated multi-center cohorts with Ridge regression to develop the Regulators' Co-Expression Score (RMRCoeS). Then we assessed the role of RMRCoeS in several clinical aspects such as biochemical recurrence (BCR), responses to chemotherapy, androgen receptor signaling inhibitor (ARSI) therapy and immunotherapy in PCa. Finally, we validated the cancer-promoting performance of five hub genes through immunohistochemistry and in vitro assays. RESULTS: Within the mutation landscape of RNA modification regulators, we observed a relatively low overall mutation rate. Remarkably, RMRCoeS, comprising 81 RNA modification regulators, exhibited a notable capability for accurately predicting the prognosis and therapeutic responses in PCa patients subjected to BCR, chemotherapy, ARSI therapy, and immunotherapy. A high RMRCoeS was indicative of a poor prognosis and unfavorable therapy responses. Functional enrichment analysis unveiled that RMRCoeS may exert its influence on PCa progression through various metabolic pathways. Furthermore, a higher RMRCoeS showed a positive correlation with elevated CNV mutations. Lastly, we validated the oncogene effects of CPSF4, WBSCR22, RPUSD3, TRMT61A, and NSUN5-five hub regulators-within the context of PCa. CONCLUSION: The function of different RNA modifications is interconnected. Comprising eight distinct RNA modifications' regulators, RMRCoeS exhibits multifaceted roles in various aspects of PCa, including disease progression, prognosis, and responses to multiple therapies. Furthermore, we provide the initial validation of the oncogene effect associated with WBSCR22, RPUSD3, TRMT61A and NSUN5 in PCa. Our findings offer novel insights into the significance of RNA modifications in PCa personalized medicine.
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Regulação Neoplásica da Expressão Gênica , Recidiva Local de Neoplasia , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Recidiva Local de Neoplasia/genética , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , RNA/genética , RNA/metabolismo , Linhagem Celular Tumoral , Mutação , Imunoterapia/métodos , Medicina de Precisão , MultiômicaRESUMO
SrFe1-x Si x O3-δF y cathode materials (x = 0.05, 0.1, 0.15; y = 0, 0.1, 0.5) were prepared via a solid-state method. X-ray diffraction results show that the synthesized F doping samples were perovskite structure. X-ray photoelectron spectroscopy findings show that F- anions were doped into SrFe1-x Si x O3-δ. Transmission electron microscopy and energy-dispersive spectroscopy were performed to analyze the microstructure and element distribution in the materials, respectively. Double-layer composite cathode symmetric cells were prepared through a screen printing method. Scanning electron microscopy images revealed that the double-layer composite cathode adhered well to the electrolyte. The doping with F- can increase the coefficient of thermal expansion of SrFe1-x Si x O3-δ. The electrochemical impedance spectroscopy results indicate that the oxygen transport capacity of the SrFe0.95Si0.05O3-δ material can be improved by doping with F-, but such a method can decrease the oxygen transport capacity of SrFe0.9Si0.1O3-δ. At 800 °C, the peak power density of the single cell supported by an anode and SrFe0.9Si0.1O3-δF0.1 as the cathode reached 388.91 mW/cm2. Thus, the incorporation of F- into SrFe1-x Si x O3-δ cathode materials can improve their electrochemical performance and enable their application as cathode materials for solid-oxide fuel cells.
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Objective: The aim of this study is to explore the value of combined detection of ABO blood group and tumor markers in the diagnosis of gastric cancer. Methods: A total of 3650 gastric cancer patients treated in our center from January 2015 to December 2019, and 5822 controls were recruited, and divided into training set and validation set according to 7:3. The diagnostic and predictive model of gastric cancer was constructed by binary logistic regression method in the training set. The diagnostic value of the prediction model for gastric cancer was evaluated by calculating the prediction probability P value and drawing the Receiver operating characteristic (ROC) curve, and was verified in the validation set. Results: The Area under the curve (AUC) of the diagnosis and prediction model in the training set was 0.936 (95%CI: 0.926-0.941), the sensitivity was 81.66%, and the specificity was 98.61%. In the validation set, the AUC was 0.941 (95%CI: 0.932-0.950), the sensitivity was 82.33%, and the specificity was 99.02%. Furthermore, the diagnostic model obtained in this study had a high diagnostic value for early gastric cancer patients in the healthy population (AUC of training set, validation set and total population were 0.906, 0.920 and 0.908, respectively). Conclusions: We constructed a diagnostic model for gastric cancer including blood group and tumor markers, which has high reference value for the diagnosis of gastric cancer patients, and the model can better distinguish early gastric cancer from healthy people.
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Lactobacillus acidophilus is widely used as a food additive or medication in our daily lives. The objective of this study was to investigate the effects of L. acidophilus and L. reuteri on bone mass in OVX mice and their associated mechanisms. Fifty 6-week-old female C57BL/6J mice were subjected to five different treatments: sham surgery, OVX surgery, OVXandL. reuteri fed, OVXandL. acidophilus fed, OVXandboth L. reuteri and L. acidophilus co-fed, respectively. Serum samples were collected, and IL-1ß,IL-6,TNF-α, and OCN levels were determined. The bone volume fraction and trabecular number, trabecular thickness, trabecular separation, and cortical thickness of the mice were analyzed by micro-CT in both femurs. Mice feces were taken for Illumina high-throughput sequencing to analyze the microbial composition and characteristics. After probiotic feeding, the bone volume fraction, the trabecular number, and the trabecular thickness increased, and the trabecular separation decreased in OVX mice. IL-1ß, IL-6, and TNF-α in the blood significantly decreased. The observed Chao1 and ACE indexes increased significantly. Changes in intestinal microorganisms occurred in all groups of mice. The change of index in the gut microbes, may indicate that the bone mass of OVX mice is changing. L. acidophilus shares the same role as L. reuteri in preventing bone loss in OVX mice. The mechanism of action may be through inhibition of the activation of inflammatory factors in the osteoclast activation pathway in bone metabolism, modulation of gut microbial diversity, and alteration of the richness of specific microorganisms that lead to attenuation of bone loss.
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Microbioma Gastrointestinal , Limosilactobacillus reuteri , Probióticos , Camundongos , Feminino , Animais , Humanos , Lactobacillus acidophilus , Fator de Necrose Tumoral alfa , Interleucina-6 , Camundongos Endogâmicos C57BL , Probióticos/farmacologia , Probióticos/uso terapêutico , OvariectomiaRESUMO
This study aims to investigate the implications of transition-metal Zn doping at the B-site on the crystal structure, average thermal expansion coefficient (TEC), electrocatalytic activity, and electrochemical performance of LaBaFe2O5+δ by preparing LaBaFe2-xZnxO5+δ (x = 0, 0.05, 0.1, 0.15, 0.2, LBFZx). The X-ray diffraction (XRD) results show that Zn2+ doping does not change the crystal structure, the unit cell volume increases, and the lattice expands. The X-ray photoelectron spectroscopy (XPS) and mineral titration results show that the oxygen vacancy concentration and Fe4+ content gradually increase with the increase in doping amount. TEC decreases with the increase in Zn2+ doping amount, and the TEC of LBFZ0.2 is 11.4 × 10-6 K-1 at 30-750 °C. The conductivity has the best value of 103 S cm-1 at the doping amount of x = 0.1. The scanning electron microscopy (SEM) images demonstrate that the electrolyte CGO(Gd0.1Ce0.9O1.95) becomes denser after high-temperature calcination, and the cathode material is well attached to the electrolyte. The electrochemical impedance analysis shows that Zn2+ doping at the B-site can reduce the (Rp) polarization resistance, and the Rp value of the symmetric cell with LaBaFe1.8Zn0.2O5+δ as cathode at 800 °C is 0.014 Ω cm2. The peak power density (PPD) value of the anode-supported single cell is 453 mW cm-2, which shows excellent electrochemical performance.
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Nd0.6Sr0.4Co1-xCuxO3-δ (x = 0, 0.05, 0.1, 0.15, 0.2) (NSCCx) was prepared by replacing Co with Cu. Its chemical compatibility, electrical conductivity, and electrochemical properties were studied by X-ray powder diffractometry, scanning electron microscopy, and X-ray photoelectron spectroscopy. The conductivity, AC impedance spectra, and output power of the single cell were tested in an electrochemical workstation. Results showed that the thermal expansion coefficient (TEC) and electrical conductivity of the sample decreased with the increase in Cu content. The TEC of NSCC0.1 decreased by 16.28% in the temperature range of 35 °C-800 °C, and its conductivity was 541 S cm-1 at 800 °C. Furthermore, a single cell was constructed with NSCCx as the cathode, NiO-GDC as the anode, and GDC as the electrolyte. The peak power of the cell at 800 °C was 444.87 mW·cm-2, which was similar to that of the undoped sample. Compared with the undoped NSCC, NSCC0.1 showed lower TEC while maintaining its output power. Therefore, this material can be used as a cathode for solid oxide fuel cells.
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Ln2-x Y x CuO4+δ (Ln = Pr, Nd, Sm; x = 0, 0.025, 0.05, 0.1) cathode materials were synthesized using a sol-gel method and calcination at 1000 °C for 24 h. The phase structure, coefficient of thermal expansion (CTE), electrical conductivity, and electrochemical impedance of cathode materials were characterized. X-ray diffraction (XRD) patterns show that the cell volume of each cathode material decreases with the increase in the Y3+ doping amount and has good chemical compatibility with the Sm0.2Ce0.8O1.9 electrolyte. The thermal expansion test shows that the increase in Y3+ doping reduces the average CTE of Ln2CuO4+δ. The conductivity test shows that Y3+ doping increases the conductivity of Ln2CuO4+δ, and Pr1.975Y0.025CuO4+δ has the highest conductivity of 256 S·cm-1 at 800 °C. The AC impedance test shows that Y3+ doping reduces the polarization impedance of Ln2CuO4+δ, and Pr1.9Y0.1CuO4+δ has a minimum area-specific resistance (ASR) of 0.204 Ω·cm2 at 800 °C. In conclusion, Pr1.975Y0.025CuO4+δ has the best performance and is more suitable as a cathode material for a solid oxide fuel cell (SOFC).
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Poor carrier transport capacity and numerous surface defects of charge transporting layers (CTLs), coupled with misalignment of energy levels between perovskites and CTLs, impact photoelectric conversion efficiency (PCE) of inverted perovskite solar cells (PSCs) profoundly. Herein, a collaborative passivation strategy is proposed based on 4-(chloromethyl) benzonitrile (CBN) as a solution additive for fabrication of both [6,6]-phenyl-C61-butyric acid methylester (PCBM) and poly(triarylamine) (PTAA) CTLs. This additive can improve wettability of PTAA and reduce the agglomeration of PCBM particles, which enhance the PCE and device stability of the PSCs. As a result, a PCE exceeding 20% with a remarkable short circuit current of 23.9 mA cm-2 , and an improved fill factor of 81% is obtained for the CBN- modified inverted PSCs. Devices maintain 80% and 70% of the initial PCE after storage under 30% and 85% humidity ambient conditions for 1000 h without encapsulation, as well as negligible light state PCE loss. This strategy demonstrates feasibility of the additive engineering to improve interfacial contact between the CTLs and perovskites for fabrication of efficient and stable inverted PSCs.
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The suitability of human settlements is critical for quality of life and regional development. As comprehensive evaluations and research on the suitability of human settlements are lacking, a comprehensive evaluation of human settlements in the Yangtze River Delta (YRD) was carried out in 2020 by combining natural and human environmental elements based on multi-source data such as digital elevation models, Landsat remote sensing images, meteorological station data, and points of interest, other multi-source data, and constructions of the human settlements' suitability indexes. The results showed the following: (1) The spatial suitability of the natural environment in the YRD is significantly affected by the topographic conditions and distance from the sea, showing an increasing spatial differentiation from southwest to northeast, with Shanghai and Yancheng having the best natural environment suitability. (2) The suitability of the human environment in urban areas is better than that in non-urban areas and shows a decreasing trend from the south to the north circle. Shanghai, Zhoushan, and Huaibei have the best human environment suitability. (3) The comprehensive suitability of human settlements includes both the spatial differentiation characteristics of the suitability of natural and human environments. Shanghai and Zhoushan have the mosy comprehensive suitability for human settlements, while Huaibei and Xuzhou have the worst. (4) Land with a comprehensive suitability for human settlements of greater than 0.580 accounts for 23.60% of the total and contains 30.08% of the population and 32.31% of the economy, indicating that areas with a high suitability index have been fully utilized, and the populations and economies with human settlements suitability have a high degree of matching.
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Qualidade de Vida , Rios , Humanos , China/epidemiologia , CidadesRESUMO
Background: m6A modification plays a key role in the development of hepatocellular carcinoma (HCC). Angiogenesis-related genes (ARGs) are increasingly being used to define signatures predicting patient prognosis. The correlations between m6A-related ARGs (mARGs), clinical outcomes, and the immune and oxidative stress landscape are unclear. Methods: Univariate Cox regression analysis of 24 mARGs yielded 13 prognostic genes, which were then analyzed for their enriched functions and pathways. After LASSO regression analysis, a prognostic signature was constructed and its reliability validated. Patients were grouped by risk using the signature score, and then the clinical prognosis, the immune landscape, and the oxidative stress landscape between the two groups were analyzed. Drug sensitivity analysis was performed to identify potentially efficient therapeutic agents. Results: Thirteen prognosis-related mARGs consistently clustered patients with HCC into four groups with significantly different prognosis. Four mARGs (EGF, ITGA5, ITGAV, and PLG) were used to construct a prognostic signature and define risk groups. Among them, EGF, ITGA5, and ITGAV, were defined as prognostic risk factors, while PLG was defined as a prognostic protective factor. Compared to low-risk patients, HCC patients in the high-risk group had a poorer prognosis and showed significant differences in clinical characteristics, enriched pathways, tumor stemness, and tumor microenvironment. The drug sensitivity of oxaliplatin and LDK-378 negatively correlated with ITGAV expression. Ten drugs had lower IC50s in the high-risk group, indicating better antitumor efficacy than in the low-risk group, with epothilone B having the lowest IC50 value. Conclusions: A prognostic model consisting of mARGs can be used to predict the prognosis of HCC patients. The risk grouping of our model can be used to reveal differences in the tumor immune microenvironment of patients with HCC. Further in-depth study may provide new targets for future treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Fator de Crescimento Epidérmico/genética , Fator de Crescimento Epidérmico/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Oxaliplatina , Estresse Oxidativo/genética , Prognóstico , Reprodutibilidade dos Testes , Microambiente Tumoral/genéticaRESUMO
Background: M2-like tumor-associated macrophages (M2-like TAMs) have important roles in the progression and therapeutics of cancers. We aimed to detect novel M2-like TAM-related biomarkers in hepatocellular carcinoma (HCC) via integrative analysis of single-cell RNA-seq (scRNA-seq) and bulk RNA-seq data to construct a novel prognostic signature, reveal the "immune landscape", and screen drugs in HCC. Methods: M2-like TAM-related genes were obtained by overlapping the marker genes of TAM identified from scRNA-seq data and M2 macrophage modular genes identified by weighted gene co-expression network analysis (WGCNA) using bulk RNA-seq data. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were carried out to screen prognostic genes from M2-like TAM-related genes, followed by a construction of a prognostic signature, delineation of risk groups, and external validation of the prognostic signature. Analyses of immune cells, immune function, immune evasion scores, and immune-checkpoint genes between high- and low-risk groups were done to further reveal the immune landscape of HCC patients. To screen potential HCC therapeutic agents, analyses of gene-drug correlation and sensitivity to anti-cancer drugs were conducted. Results: A total of 127 M2-like TAM-related genes were identified by integrative analysis of scRNA-seq and bulk-seq data. PDLIM3, PAM, PDLIM7, FSCN1, DPYSL2, ARID5B, LGALS3, and KLF2 were screened as prognostic genes in HCC by univariate Cox regression and LASSO regression analyses. Then, a prognostic signature was constructed and validated based on those genes for predicting the survival of HCC patients. In terms of drug screening, expression of PAM and LGALS3 was correlated positively with sensitivity to simvastatin and ARRY-162, respectively. Based on risk grouping, we predicted 10 anticancer drugs with high sensitivity in the high-risk group, with epothilone B having the lowest half-maximal inhibitory concentration among all drugs tested. Conclusions: Our findings enhance understanding of the M2-like TAM-related molecular mechanisms involved in HCC, reveal the immune landscape of HCC, and provide potential targets for HCC treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proteínas de Transporte/metabolismo , Galectina 3/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteínas dos Microfilamentos/metabolismo , Prognóstico , Sinvastatina , Macrófagos Associados a TumorRESUMO
Respiratory muscle paralysis caused by acute cervical spinal cord injury usually leads to pulmonary ventilation dysfunction and even death from respiratory failure. In addition to invasive treatments such as mechanical ventilation, the utilization of noninvasive respiratory support equipment plays an important role in long-term assisted breathing. In this study, we describes a wearable, noninvasive vest with adjustable pressure that enables assisted breathing and with an automatic alarm, and we aims to explore its safety and effectiveness on healthy adult participants. The vest monitors the human heart rate and the blood oxygen index data in real time, the alarm is automatically activated when the data is abnormal. Eight healthy participants had no obvious discomfort during the test while wearing the vest. Lung volumes, antero-posterior diameters, and left-right diameters at the second, fourth, and sixth ribs levels were acquired before and after inflation of the vest airbag, the data acquired by the imaging analysis using chest computed tomography showed significant differences before and after the inflation (p < 0.05). Thus, The vest designed for this study can achieve uniform and effective compression of the thorax, significantly changed the size of the thorax and lungs. It is expected to be applied as noninvasive support for patients with respiratory dysfunction.
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Tórax , Dispositivos Eletrônicos Vestíveis , Adulto , Humanos , Pulmão , Pressão , Tórax/fisiologia , Tomografia Computadorizada por Raios XRESUMO
Laminectomy can cause the dura mater to adhere to the surrounding scar tissue, leading to soft spinal stenosis after surgery. Although artificial laminae are considered ideal substitutes, they present challenges such as insecure fixation and insufficient bionics. In this study, we fabricated a bionic titanium alloy artificial lamina using three-dimensional (3D)-printing technology and evaluated its adhesion prevention and stability after laminectomy in pigs. An in vitro biomechanical pull-out resistance test indicated that the pull-out strength of the artificial lamina was close to that of a single pedicle screw and was significantly higher than that of a cortical screw. In vivo animal implantation results indicated precise laminectomy and artificial lamina implantation, as well as a safe operation process with the assistance of guide plates. X-ray and computed tomography results indicated the well fixation of bionic titanium alloy artificial lamina and screws 10 weeks after laminectomy. The artificial lamina was not loosened after being removed from pigs (postoperative week 12), exhibiting good stability. Additionally, no adhesion was observed in the artificial lamina group, whereas a large amount of scar tissue in the spinal canal covered the dural surface in the control group. Thus, 3D-printed bionic titanium alloy artificial lamina can prevent epidural adhesion after laminectomy, while restoring the structural stability of the posterior complex, suggesting the potential of lamina substitutes for adhesion prevention after laminectomy.