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Bone adhesives, as alternatives to traditional bone fracture treatment methods, have great benefits in achieving effective fixation and healing of fractured bones. However, current available bone adhesives have limitations in terms of weak mechanical properties, low adhesion strength, and inappropriate degradability, hindering their clinical applications. The development of bone adhesives with strong mechanical properties, adhesion strength, and appropriate degradability remains a great challenge. In this study, polyacrylic acid was incorporated with tetracalcium phosphate and O-phospho-L-serine to form a new bone adhesive via coordination and ionic interactions to achieve exceptional mechanical properties, adhesion strength, and degradability. The bone adhesive could achieve an initial adhesion strength of approximately 3.26 MPa and 0.86 MPa on titanium alloys and bones after 15 min of curing, respectively, and it increased to 5.59 MPa and 2.73 MPa, after 24 h of incubation in water or simulated body fluid (SBF). The compressive strength of the adhesive increased from 10.06 MPa to 72.64 MPa over two weeks, which provided sufficient support for the fractured bone. Importantly, the adhesive started to degrade after 6 to 8 weeks of incubation in SBF, which is beneficial to cell ingrowth and the bone healing process. In addition, the bone adhesives exhibited favorable mineralization capability, biocompatibility, and osteogenic activity. In vivo experiments showed that it has a better bone-healing effect compared with the traditional polymethyl methacrylate bone cement. These results demonstrate that the bone adhesive has great potential in the treatment of bone fractures.
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Research on interactions between grazers and toxigenic algae is fundamental for understanding toxin dynamics within aquatic ecosystems and developing biotic approaches to mitigate harmful algal blooms. The dinoflagellate Alexandrium minutum is a well-known microalga responsible for paralytic shellfish toxins (PSTs) contamination in many coastal regions worldwide. This study investigated the impact of the ciliate Euplotes balteatus on cell density and PSTs transfer in simulated A. minutum blooms under controlled conditions. E. balteatus exhibited resistance to the PSTs produced by A. minutum with a density of up to 10,000 cells/mL, sustaining growth and reproduction while eliminating algal cells within a few days. The cellular PSTs content of A. minutum increased in response to the grazing pressure from E. balteatus. However, due to the substantial reduction in density, the overall toxicity of the algal population decreased to a negligible level. Most PSTs contained within algal cells were temporarily accumulated in E. balteatus before being released into the water column, suggesting unclear mechanisms for PSTs excretion in unicellular grazers. In principle, the grazing of E. balteatus on A. minutum promotes the transfer of the majority of intracellular PSTs into extracellular portions, thereby mitigating the risk of their accumulation and contamination through marine trophic pathways. However, this process also introduces an increase in the potential environmental hazards posed by extracellular PSTs to some extent.
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Mandarin fish (Siniperca chuatsi) represents a typical carnivorous freshwater economic fish in China. Recently, the study of their feeding behavior to acclimate formulated diets has become a research focus. This study evaluated the effects of various diets on the body composition, nutritional content, digestive enzyme activity, gene expression, and gut microbiota of mandarin fish. Firstly, no significant differences were found in the muscle's basic nutritional components (moisture, crude protein, crude fat, and crude ash), as well as in the fatty acid and amino acid content, between the live feed group (LFSC) and the compound feed group (CFSC). However, mandarin fish in the LFSC group exhibited significantly higher lipase activity in the liver and intestine compared to the CFSC group, while amylase activity in the intestine showed an opposite pattern. Additionally, intestinal transcriptome analysis revealed 6238 differentially expressed genes and identified several differentially expressed clock genes associated with diet type. Furthermore, gut microbiota analysis indicated that different feeding regimens influenced microbial composition, revealing correlations between bacterial genera and intestinal gene expression levels. These findings provided novel insights into the gut microbiota and transcriptomic responses of mandarin fish to different dietary types.
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Abalone is a popular mollusk in the marine aquaculture industry of China. However, existing challenges, like slow growth, individual miniaturization, and the absence of abundant abalone, have emerged as significant obstacles impeding its long-term progress in aquaculture. Studies have demonstrated that insulin-related peptide (IRP) is a crucial factor in the growth of marine organisms. However, limited studies have been conducted on IRP in abalone. This study indicated that the hdh-MIRP1 open reading frame (ORF) was composed of 456 base pairs, which encoded 151 amino acids. Based on the gene expression and immunofluorescence analyses, the cerebral ganglion of Haliotis discus hannai (H. discus hannai) was the primary site of hdh-MIRP1 mRNA expression. Moreover, hdh-MIRP1 expression was observed to be higher in the larger group than in the smaller group abalones. Only single nucleotide polymorphism (SNP) was related to their growth characteristics. However, approximately 82 proteins that may interact with hdh-MIRP1 were identified. The functional enrichment analysis of the 82 genes indicated that hdh-MIRP1 may be involved in the regulation of glucose metabolism and the process of growth. This study established a benchwork for further investigating the role of IRP in the growth of abalone.
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Clonagem Molecular , Gastrópodes , Animais , Gastrópodes/genética , Gastrópodes/metabolismo , Polimorfismo de Nucleotídeo Único , Sequência de Aminoácidos , Fases de Leitura Aberta/genética , FilogeniaRESUMO
Diquat (DQ) poisoning can cause multiple organ damage, and the kidney is considered to be the main target organ. Increasing evidence shows that alleviating oxidative stress and inflammatory response has promising application prospects. Epigallocatechin gallate (EGCG) has potent antioxidant and anti-inflammatory effects. In this study, red blood cell membrane (RBCm)-camouflaged polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) were synthesized to deliver EGCG (EGCG-RBCm/NPs) for renal injury induced by DQ. Human renal tubular epithelial cells (HK-2 cells) were stimulated with 600 µM DQ for 12 h and mice were intraperitoneally injected with 50 mg/kg b.w. DQ, followed by 20 mg/kg b.w./day EGCG or EGCG-RBCM/NPs for 3 days. The assessment of cellular vitality was carried out using the CCK-8 assay, while the quantification of reactive oxygen species (ROS) was performed through ROS specific probes. Apoptosis analysis was conducted by both flow cytometry and TUNEL staining methods. Pathological changes in renal tissue were observed. The expressions of NLRP3, IL-1ß, IL-18, NFκB and Caspase1 were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemistry, immunofluorescence, and Western blot. The results showed that the DQ group had increased ROS expression, increased the level of oxidative stress, and increased apoptosis rate compared with the control group. Histopathological analysis of mice in the DQ group showed renal tubular injury and elevated levels of blood urea nitrogen (BUN), serum creatinine (SCr), kidney injury molecule-1 (KIM-1), and cystatin C (Cys C). Furthermore, the DQ group exhibited heightened expression of NLRP3, p-NFκB p65, Caspase1 p20, IL-1ß, and IL-18. However, EGCG-RBCm/NPs treatment mitigated DQ-induced increases in ROS, apoptosis, and oxidative stress, as well as renal toxicity and decreases in renal biomarker levels. Meanwhile, the expression of the above proteins were significantly decreased, and the survival rate of mice was ultimately improved, with an effect better than that of the EGCG treatment group. In conclusion, EGCG-RBCm/NPs can improve oxidative stress, inflammation, and apoptosis induced by DQ. This effect is related to the NF-κB/NLRP3 inflammasome pathway. Overall, this study provides a new approach for treating renal injury induced by DQ.
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Purpose: Sepsis-induced cardiomyopathy (SICM) is a prevalent cardiac dysfunction caused by sepsis. Mitochondrial dysfunction is a crucial pathogenic factor associated with adverse cardiovascular adverse events; however, research on SICM remains insufficient. Methods: To investigate the factors contributing to the pathological progression of SICM, we performed a comprehensive analysis of transcriptomic data from the GEO database using bioinformatics and machine learning techniques. CRISPR-Cas9 S100A9 knockout mice and primary cardiomyocytes were exposed to lipopolysaccharide to simulate SICM. Transcriptome analysis and mass spectrometry of primary cardiomyocytes were used to determine the potential pathogenic mechanisms of S100A9. The mitochondrial ultrastructure and mitochondrial membrane potential (MMP) were detected using transmission electron microscopy and flow cytometry, respectively. Pink1/Parkin and Drp1 proteins were detected using Western blotting to evaluate mitochondrial autophagy and division. The mtDNA and mRNA levels of mitochondrial transcription factors and synthases were evaluated using real-time polymerase chain reaction. Results: Bioinformatics analysis identified 12 common differentially expressed genes, including SERPINA3N, LCN2, MS4A6D, LRG1, OSMR, SOCS3, FCGR2b, S100A9, S100A8, CASP4, ABCA8A, and NFKBIZ. Significant S100A9 upregulation was closely associated with myocardial injury exacerbation and cardiac function deterioration. GSEA revealed that myocardial contractile function, oxidative stress, and mitochondrial function were significantly affected by S100A9. Knocking out S100A9 alleviates the inflammatory response and mitochondrial dysfunction. The interaction of S100A9 with ATP5 enhanced mitochondrial division and autophagy, inhibited MMP and ATP synthesis, and induced oxidative stress, which are related to the Nlrp3-Nfkb-Caspase1 and Drp1-Pink1-Parkin signaling pathways. The expression of mitochondrial transcription factors (TFAM and TFBM) and ATP synthetases (ATP6 and ATP8, as well as COX1, COX2, and COX3) was further suppressed by S100A9 in SICM. Targeted S100A9 inhibition by paquinimod partially reversed myocardial mitochondrial dysfunction and oxidative stress. Conclusion: The interaction of S100A9 with ATP5 exacerbates myocardial damage in sepsis by inducing mitochondrial dysfunction and oxidative stress.
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The COMMD (Copper Metabolism gene MURR1 Domain) gene family consists of 10 members, which are involved in various biological processes such as copper and sodium transport, NF-κB activity and cell cycle progression. However, the study of COMMD gene family in large yellow croaker (Larimichthys crocea) is largely unknown. In this study, 10 COMMD gene family members (named LcCOMMDs) were successfully identified from large yellow croaker. The results showed that there were differences in the number of LcCOMMDs exons at the level of gene structure, which reflected that they had adjusted and changed accordingly in the process of evolution to adapt to the environment and achieved functional diversification. Through phylogenetic analysis, we found that the LcCOMMDs was highly conserved, indicating their important functions in organisms. It was worth noting that the expression levels of LcCOMMD1, LcCOMMD2, LcCOMMD3, LcCOMMD5 and LcCOMMD10 in the spleen changed significantly after bacterial stress, which suggested that these genes might be involved in the regulation of innate immune response. In addition, the expression levels of LcCOMMD1, LcCOMMD2, LcCOMMD3, LcCOMMD5, LcCOMMD7, LcCOMMD8, LcCOMMD9 and LcCOMMD10 changed significantly after hypoxia exposure, which further proved the role of LcCOMMDs in immune function. In summary, this study not only revealed the important role of COMMD genes in the innate immune response of large yellow croaker, but also provided valuable information for further understanding the regulatory mechanism of COMMD gene family under different conditions.
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Doenças dos Peixes , Proteínas de Peixes , Imunidade Inata , Perciformes , Filogenia , Infecções por Pseudomonas , Pseudomonas , Animais , Perciformes/imunologia , Perciformes/genética , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/química , Doenças dos Peixes/imunologia , Imunidade Inata/genética , Pseudomonas/fisiologia , Infecções por Pseudomonas/veterinária , Infecções por Pseudomonas/imunologia , Regulação da Expressão Gênica/imunologia , Perfilação da Expressão Gênica/veterinária , Alinhamento de Sequência/veterinária , Estresse Fisiológico/imunologia , Sequência de Aminoácidos , Hipóxia/imunologia , Hipóxia/veterinária , Hipóxia/genética , Família MultigênicaRESUMO
Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are central components of the machinery mediating cell membrane fusion and intracellular vesicular trafficking in eukaryotic cells, and have been well-documented to play critical roles in growth, development, and pathogenesis in the filamentous fungal plant pathogens. However, little is known about the contributions of SNAREs to the physiology and biocontrol potential in entomopathogenic filamentous fungi. Here, a genome-wide analysis of SNARE genes was performed taking advantage of the available whole genome sequence of Beauveria bassiana, a classical entomopathogenic fungus. Based on the compared genomic method, 22 genes encoding putative SNAREs were identified from the whole genome of B. bassiana, and were classified into four groups (7 Qa-, 4 Qb-, 6 Qc-, and 5 R-SNAREs) according to the conserved structural features of their encoding proteins. An R-SNARE encoding gene BbSEC22 was further functionally characterized by gene disruption and complementation. The BbSEC22 null mutant showed a fluffy appearance in mycelial growth and an obvious lag in conidial germination. The null mutant also exhibited significantly increased sensitivity to oxidative stress and cell wall perturbing agents and reduced the yield of conidia production by 43.1% compared with the wild-type strain. Moreover, disruption of BbSEC22 caused a significant decrease in conidial virulence to Spodoptera litura larvae. Overall, our results provide an overview of vesicle trafficking in B. bassiana and revealed that BbSec22 was a multifunctional protein associated with mycelial growth, sporulation, conidial germination, stress tolerance, and insecticidal virulence.
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Decapod iridescent virus 1 (DIV1) stands as a significant pathogen affecting crustaceans, posing a grave threat to the shrimp industries in aquaculture dependent nations. Within the Iridoviridae family, the conserved envelope protein DIV1-168L plays a pivotal role in virion entry. Nonetheless, the host factors that interact with 168L remain unidentified. To address this gap, we established a cDNA library derived from Litopenaeus vannamei gill tissue and conducted yeast two-hybrid screening to identify host factors that interact with 168L. Additionally, we performed co-immunoprecipitation assays to verify the interaction between cuticle protein 8 (CP8) and 168L. Expression pattern analysis revealed the presence of CP8 transcripts in the gill and epidermis. Furthermore, immunohistochemistry results demonstrated the expression of CP8 in gill cells and its localization in the gill filament epithelium. Fluorescence analysis indicated that full-length CP8 colocalized with 168L in the cytoplasm of Sf9 cells. Removal of the signal peptide from the N-terminal of CP8 eliminated its concentration in the cytoplasm. Additionally, CP8 expression was significantly inhibited during DIV1 infection. Therefore, our research contributes to a better understanding of the entry mechanism of iridovirids. The GenBank accession number for the DIV1 sequence is MF197913.1.
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Asexual development is the main propagation and transmission mode of Beauveria bassiana and the basis of its pathogenicity. The regulation mechanism of conidiation and the key gene resources for utilization are key links to improving the conidia yield and quality of Beauveria bassiana. Their clarification may promote the industrialization of fungal pesticides. Here, we compared the regulation of morphology, resistance to external stress, virulence, and nutrient utilization capacity between the upstream developmental regulatory gene fluG and the key genes brlA, abaA, and wetA in the central growth and development pathway. The results showed that the ΔbrlA and ΔabaA mutants completely lost the capacity to conidiate and that the ΔwetA mutant had seriously reduced conidiation capacity. Although the deletion of fluG did not reduce the conidiation ability as much as deletions of brlA, abaA, and wetA, it significantly reduced the fungal response to external stress, virulence, and nutrient utilization, while the deletion of the three other genes had little effect. Via transcriptome analysis and screening the yeast nuclear system library, we found that the differentially expressed genes in the ΔfluG mutants were concentrated in the signaling pathways of ABC transporters, propionate metabolism, tryptophan metabolism, DNA replication, mismatch repair, and fatty acid metabolism. FluG directly acted on 40 proteins that were involved in various signaling pathways such as metabolism, oxidative stress, and cell homeostasis. The analysis indicated that the regulatory function of fluG was mainly involved in DNA replication, cell homeostasis, fungal growth and metabolism, and the response to external stress. Our results revealed the biological function of fluG in asexual development and the responses to several environmental stresses as well as its influence on the asexual development regulatory network in B. bassiana.
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Beauveria , Proteínas Fúngicas , Regulação Fúngica da Expressão Gênica , Reprodução Assexuada , Esporos Fúngicos , Beauveria/genética , Beauveria/crescimento & desenvolvimento , Beauveria/patogenicidade , Beauveria/fisiologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Reprodução Assexuada/genética , Esporos Fúngicos/crescimento & desenvolvimento , Esporos Fúngicos/genética , Virulência/genética , Perfilação da Expressão Gênica , Estresse Fisiológico , TranscriptomaRESUMO
The suppressor of cytokine signaling (SOCS) gene family is a group of genes involved in the negative regulation of cytokine signal transduction. The members of this family play a crucial role in regulating immune and inflammatory processes. However, comprehensive investigations of these genes have not yet been conducted in the economically significant fish large yellow croaker (Larimichthys crocea). In this study, a total of 13 SOCS genes (LcSOCS1a, LcSOCS1b, LcSOCS2, LcSOCS3a, LcSOCS3b, LcSOCS4, LcSOCS5a, LcSOCS5b, LcSOCS6, LcSOCS7a, LcSOCS7b, LcCISHa and LcCISHb) were identified and analyzed in L. crocea. The phylogenetic tree revealed a high conservation of SOCS genes in evolution, and the gene structure and motif analysis indicated a high similarity in the structure of LcSOCSs in the same subfamily. In addition, the expression patterns of LcSOCSs showed that LcSOCS1b was significantly down-regulated in all time under acute hypoxia stress, but it was markedly up-regulated throughout the entire process after P. plecoglossicida infection, revealing its different immune effects to two stresses. Besides, LcSOCS2a, LcSOCS6 and LcSOCS7a only participated in acute hypoxic stress, while LcSOCS5a was more sensitive to P. plecoglossicida infection. In summary, these results indicated that SOCS genes were involved in stress responses to both biological and non-biological stimuli, setting the foundation for deeper study on the functions of SOCS genes.
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Doenças dos Peixes , Proteínas de Peixes , Regulação da Expressão Gênica , Imunidade Inata , Perciformes , Filogenia , Infecções por Pseudomonas , Pseudomonas , Proteínas Supressoras da Sinalização de Citocina , Animais , Perciformes/imunologia , Perciformes/genética , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/química , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/imunologia , Proteínas Supressoras da Sinalização de Citocina/química , Imunidade Inata/genética , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/veterinária , Infecções por Pseudomonas/genética , Pseudomonas/fisiologia , Regulação da Expressão Gênica/imunologia , Perfilação da Expressão Gênica/veterinária , Estresse Fisiológico/imunologia , Estresse Fisiológico/genética , Alinhamento de Sequência/veterinária , Hipóxia/genética , Hipóxia/imunologia , Hipóxia/veterináriaRESUMO
BACKGROUND: To analyze the perioperative bleeding and hidden blood loss (HBL) of sacroiliac screw minimally invasive treatment of pelvic posterior ring injury and explore the influential factors of HBL after operation for providing reference for clinical treatment. METHOD: A retrospective analysis was conducted on data from 369 patients with posterior pelvic ring injuries treated with sacroiliac screws internal fixation at our hospital from January 2015 to January 2022. The research was registered in the Chinese Clinical Trial Registry in July 2022 (ChiCTR2200061866). The total blood loss (TBL) and HBL of patients were counted, and the factors such as gender, age, and surgical duration were statistically analyzed. The influential factors of HBL were analyzed by multiple linear regression. RESULTS: The TBL was 417.96 ± 98.05 ml, of which the visible blood loss (VBL) was 37.00 ± 9.0 ml and the HBL was 380.96 ± 68.8 ml. The HBL accounted for 91.14 ± 7.36% of the TBL. Gender, surgical duration, fixed position, and fixed depth had significant effects on the HBL (P < 0.05). CONCLUSIONS: The HBL was the main cause of anemia after minimally invasive treatment of posterior pelvic ring injury with a sacroiliac screw. Gender, surgical duration, fixed position, and fixed depth were closely related to the occurrence of HBL. In clinical treatment, we should consider these influential factors and take effective measures to reduce the impact of HBL on patients.
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Perda Sanguínea Cirúrgica , Parafusos Ósseos , Fixação Interna de Fraturas , Ossos Pélvicos , Humanos , Masculino , Feminino , Estudos Retrospectivos , Ossos Pélvicos/lesões , Ossos Pélvicos/cirurgia , Adulto , Pessoa de Meia-Idade , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Resultado do Tratamento , Fatores de Risco , Adulto Jovem , Fraturas Ósseas/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Fatores de Tempo , China , Idoso , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Anemia/etiologiaRESUMO
Secondary lignification of the root exodermis of Kandelia obovata is crucial for its response to adversity such as high salinity and anaerobic environment, and this lignification is also effective in blocking cadmium transport to the roots. However, how the differences in lignification of root exodermis at different developmental stages respond to Cd stress and its regulatory mechanisms have not been revealed. In this study, after analyzing the root structure and cell wall thickness using a Phenom scanning electron microscope as well as measuring cadmium content in the root cell wall, we found that the exodermis of young and mature roots of K. obovata responded to Cd stress through the polymerization of different lignin monomers, forming two different mechanisms: chelation and blocking. Through small RNA sequencing, RLM-5'-RACE and dual luciferase transient expression system, we found that miR397 targets and regulates KoLAC4/17/7 expression. The expression of KoLAC4/17 promoted the accumulation of guaiacyl lignin during lignification and enhanced the binding of cadmium to the cell wall. Meanwhile, KoLAC7 expression promotes the accumulation of syringyl lignin during lignification, which enhances the obstruction of cadmium and improves the tolerance to cadmium. These findings enhance our understanding of the molecular mechanisms underlying the differential lignification of the root exodermis of K. obovata in response to cadmium stress, and provide scientific guidance for the conservation of mangrove forests under heavy metal pollution.
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Cádmio , Lignina , MicroRNAs , Raízes de Plantas , Lignina/química , Cádmio/toxicidade , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , MicroRNAs/metabolismo , MicroRNAs/genética , Estresse Fisiológico/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Polimerização/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Araceae/efeitos dos fármacos , Araceae/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genéticaRESUMO
Background: The occurrence and development of sepsis are related to the excessive production of oxygen free radicals and the weakened natural clearance mechanism. Further dependable evidence is required to clarify the effectiveness of antioxidant therapy, especially its impact on short-term mortality. Objectives: The purpose of this systematic review and meta-analysis was to evaluate the effect of common antioxidant therapy on short-term mortality in patients with sepsis. Methods: According to PRISMA guidelines, a systematic literature search on antioxidants in adults sepsis patients was performed on PubMed/Medline, Embase, and the Cochrane Library from the establishment of the database to November 2023. Antioxidant supplements can be a single-drug or multi-drug combination: HAT (hydrocortisone, ascorbic acid, and thiamine), ascorbic acid, thiamine, N-acetylcysteine and selenium. The primary outcome was the effect of antioxidant treatment on short-term mortality, which included 28-day mortality, in-hospital mortality, intensive care unit mortality, and 30-day mortality. Subgroup analyses of short-term mortality were used to reduce statistical heterogeneity and publication bias. Results: Sixty studies of 130,986 sepsis patients fulfilled the predefined criteria and were quantified and meta-analyzed. Antioxidant therapy reduces the risk of short-term death in sepsis patients by multivariate meta-analysis of current data, including a reduction of in-hospital mortality (OR = 0.81, 95% CI 0.67 to 0.99; P = 0.040) and 28-day mortality (OR = 0.81, 95% CI 0.69 to 0.95]; P = 0.008). Particularly in subgroup analyses, ascorbic acid treatment can reduce in-hospital mortality (OR = 0.66, 95% CI 0.90 to 0.98; P = 0.006) and 28-day mortality (OR = 0.43, 95% CI 0.24 to 0.75; P = 0.003). However, the meta-analysis of RCTs found that antioxidant therapy drugs, especially ascorbic acid, did substantially reduce short-term mortality(OR = 0.78, 95% CI 0.62 to 0.98; P = 0.030; OR = 0.57, 95% CI 0.36 to 0.91; P = 0.020). Conclusions: According to current data of RCTs, antioxidant therapy, especially ascorbic acid, has a trend of improving short-term mortality in patients with sepsis, but the evidence remains to be further demonstrated.
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As a rising star among metal oxide nanomaterials, titanium dioxide (TiO2) has been widely investigated and employed in optical applications because of its excellent optical properties. In this work, we demonstrate the efficient and broadband nonlinear photonic properties of methylene blue (MB)-loaded reduced TiO2 (TiO2-x-MB) and explore the performance of a TiO2-x-MB-microfiber photonic device in broadband ultrafast photonics. Within an erbium-doped fiber laser (EDFL) system, utilizing the TiO2-x-MB-microfiber photonic device as a saturable absorber (SA), steady mode-locked pulses together with chaotic pulses were successfully achieved at the wavelength of 1.55 µm. Furthermore, by incorporating the TiO2-x-MB SA into a thulium-doped fiber laser (TDFL) system, an ultrashort single pulse and multiple pulses were obtained at 2.0 µm. These results indicate that TiO2-x-MB is an excellent nanomaterial for use in mode-locked lasers, being an alternative candidate for ultrafast fiber lasers via exploiting the chemical and physical properties of oxide nanomaterials.
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BACKGROUND: Sepsis-induced acute lung injury (ALI) is associated with considerable morbidity and mortality in critically ill patients. S100A9, a key endothelial injury factor, is markedly upregulated in sepsis-induced ALI; however, its specific mechanism of action has not been fully elucidated. METHODS: The Gene Expression Omnibus database transcriptome data for sepsis-induced ALI were used to screen for key differentially expressed genes (DEGs). Using bioinformatics analysis methods such as Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network analyses, the pathogenesis of sepsis-induced ALI was revealed. Intratracheal infusion of lipopolysaccharide (LPS, 10 mg/kg) induced ALI in wild-type (WT) and S100A9 knockout mice. Multiomics analyses (transcriptomics and proteomics) were performed to investigate the potential mechanisms by which S100A9 exacerbates acute lung damage. Hematoxylin-eosin, Giemsa, and TUNEL staining were used to evaluate lung injury and cell apoptosis. LPS (10 µg/mL)-induced murine lung epithelial MLE-12 cells were utilized to mimic ALI and were modulated by S100A9 lentiviral transfection. The impact of S100A9 on cell apoptosis and inflammatory responses were identified using flow cytometry and PCR. The expression of interleukin (IL)-17-nuclear factor kappa B (NFκB)-caspase-3 signaling components was identified using western blotting. RESULTS: Six common DEGs (S100A9, S100A8, IFITM6, SAA3, CD177, and MMP9) were identified in the six datasets related to ALI in sepsis. Compared to WT sepsis mice, S100A9 knockout significantly alleviated LPS-induced ALI in mice, with reduced lung structural damage and inflammatory exudation, decreased exfoliated cell and protein content in the lung lavage fluid, and reduced apoptosis and necrosis of pulmonary epithelial cells. Transcriptomic analysis revealed that knocking out S100A9 significantly affected 123 DEGs, which were enriched in immune responses, defense responses against bacteria or lipopolysaccharides, cytokine-cytokine receptor interactions, and the IL-17 signaling pathway. Proteomic analysis revealed that S100A9 knockout alleviated muscle contraction dysfunction and structural remodeling in sepsis-induced ALI. Multiomics analysis revealed that S100A9 may be closely related to interferon-induced proteins with tetratricopeptide repeats and oligoadenylate synthase-like proteins. LPS decreased MLE12 cell activity, accompanied by high expression of S100A9. The expression of IL-17RA, pNFκB, and cleaved-caspase-3 were increased by S100A9 overexpression and reduced by S100A9 knockdown in LPS-stimulated MLE12 cells. S100A9 knockdown decreases transcription of apoptosis-related markers Bax, Bcl and caspase-3, alleviating LPS-induced apoptosis. CONCLUSIONS: S100A9 as a key biomarker of sepsis-induced acute lung injury, and exacerbates lung damage and epithelial cell apoptosis induced by LPS via the IL-17-NFκB-caspase-3 signaling pathway.
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Lesão Pulmonar Aguda , Sepse , Humanos , Camundongos , Animais , NF-kappa B/metabolismo , Interleucina-17/metabolismo , Caspase 3/metabolismo , Lipopolissacarídeos/farmacologia , Proteômica , Lesão Pulmonar Aguda/induzido quimicamente , Pulmão/patologia , Transdução de Sinais , Camundongos Knockout , Sepse/patologia , Calgranulina B/genética , Calgranulina B/metabolismoRESUMO
OBJECTIVE: To investigate the effectiveness of real-time tracking and virtual reality technologyï¼RTVIï¼ used to assist the intraoperative alignment of the trauma orthopaedic surgery robot for the treatment of femoral neck fractures and its impact on the treatment outcome. METHODS: A retrospective analysis was conducted on 60 patients with femoral neck fractures treated with trauma orthopedic robotic surgery from September 2020 to September 2022. Patients were divided into two groups according to whether RTVI technology was used during surgery to assist robotic surgery. There were 28 patients in the RTVI group ï¼12 males and 16 femalesï¼, with an average age of ï¼46.2±9.3ï¼ years old ranging from 28 to 60 years old. There were 32 patients in the simple Tianji surgical robot group, including 15 males and 17 females, aged ï¼48.2±7.8ï¼ years old ranging from 32 to 58. The number of registered fluoroscopy, operation time, total number of intraoperative fluoroscopy, intraoperative blood loss, and hospitalization time of the two groups of patients were observed and recorded. All patients received regular follow-up after surgery, and hip X-rays were routinely reviewed to record Garden alignment index, fracture healing time, postoperative complications, and Harris score. RESULTS: All 60 patients were followed up. The RTVI group was followed up for 9 to 16 months with an average of ï¼13.0±1.2ï¼ months, and the Tianji surgical robot group alone was followed up for 10 to 14 months with an average of ï¼12.0±1.3ï¼ months. During the follow-up period, the femoral neck fractures of both groups of patients healed well, and no complications such as internal fixation loosening and incision infection occurred. The number of registered fluoroscopy, operation time, and number of intraoperative fluoroscopy of patients in the RTVI group were significantly better than those in the simple Tianji surgical robot groupï¼P<0.01ï¼. There was no statistically significant difference in intraoperative blood loss, hospital stay, Garden alignment index, fracture healing time, and hip Harris score between two groupsï¼P>0.05ï¼. CONCLUSION: Although RTVI technology assisted by the surgical robot for femoral neck fracture surgery has little impact on its postoperative outcome, it can effectively reduce the operating time, the number of intraoperative X-ray projections, and the risk of intraoperative radiation exposure to patients. It also shortened the learning curve of the operator and better reflected the precision and efficiency of the trauma orthopaedic surgery robot.
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Fraturas do Colo Femoral , Robótica , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Perda Sanguínea Cirúrgica , Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas , Resultado do TratamentoRESUMO
In response to increasing antibiotic resistance and the pressing demand for safer infected wound care, probiotics have emerged as promising bioactive agents. To address the challenges associated with the safe and efficient application of probiotics, this study successfully loaded metabolites from Lacticaseibacillus rhamnosus GG (LGG) into a gelatin cross-linked macromolecular network by an in situ blending and photopolymerization method. The obtained LM-GelMA possesses injectability and autonomous healing capabilities. Importantly, the incorporation of LGG metabolites endows LM-GelMA with excellent antibacterial properties against Staphylococcus aureus and Escherichia coli, while maintaining good biocompatibility. In vivo assessments revealed that LM-GelMA can accelerate wound healing by mitigating infections induced by pathogenic bacteria. This is accompanied by a reduction in the expression of key proinflammatory cytokines such as TNF-α, IL-6, VEGFR2, and TGF-ß, leading to increased re-epithelialization and collagen formation. Moreover, microbiological analysis confirmed that LM-GelMA can modulate the abundance of beneficial wound microbiota at family and genus levels. This study provides a facile strategy and insights into the functional design of hydrogels from the perspective of wound microenvironment regulation.
Assuntos
Lacticaseibacillus rhamnosus , Cicatrização , Antibacterianos/farmacologia , Citocinas , Escherichia coli , Hidrogéis/farmacologiaRESUMO
The emergence of nanotechnology has opened up a new way for tumor therapy. Among them, self-assembled nanotechnology has received extensive attention in medicine due to its simple preparation process, high drug-loading capacity, low toxicity, and low cost. This review mainly summarizes the preparation methods of self-assembled nano-delivery systems, as well as the self-assembled mechanism of carrier-free nanomedicine, polymer-carried nanomedicine, polypeptide, and metal drugs, and their applications in tumor therapy. In addition, we discuss the advantages and disadvantages, future challenges, and opportunities of these self-assembled nanomedicines, which provide important references for the development and application of self-assembled nanotechnology in the field of medical therapy.
Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias , Humanos , Nanotecnologia , Nanomedicina , Peptídeos/uso terapêutico , Neoplasias/tratamento farmacológicoRESUMO
OBJECTIVE: Traditional internal fixation of calcaneus fractures, involving lateral L-shaped incisions and plate fixation, has disadvantages such as increased operative exposure, eccentric plate fixation, and complications. The aim of this study was to design a Spatial Weaving Intra-calcaneal Fixator System (SWIFS) for the treatment of complex calcaneal fractures and to compare its biomechanical properties with those of traditional calcaneal plates. METHODS: The computed tomography (CT) data of the normal adult calcaneus was used for modeling, and the largest trapezoidal column structure was cut and separated from the model and related parameters were measured. The SWIFS was designed within the target trapezoid, according to the characteristics of the fracture of the calcaneus. The Sanders model classification type IV calcaneal fracture was established in finite element software, and fixation with calcaneal plate and the SWIFS examined. Overall structural strength distribution and displacement in the two groups were compared. RESULTS: The maximum 3D trapezoidal column in the calcaneus was constructed, and the dimensions were measured. The SWIFS and the corresponding guide device were successfully designed. In the one-legged erect position state, the SWIFS group exhibited a peak von Mises equivalent stress of 96.00 MPa, a maximum displacement of 0.31 mm, and a structural stiffness of 2258.06 N/mm. The conventional calcaneal plate showed a peak von Mises equivalent stress of 228.66 Mpa, a maximum displacement of 1.26 mm, and a structural stiffness of 555.56 N/mm. The SWIFS group exhibited a 75.40% decrease in displacement and a 306.45% increase in stiffness. CONCLUSION: Compared with fixation by conventional calcaneal plate, the SWIFS provides better structural stability and effective stress distribution.