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Postmenopausal osteoporosis (PMOP) is a prevalent condition among elderly women. After menopause, women exhibit decreased iron excretion, which is prone to osteoporosis. To design a specific titanium implant for PMOP, we first analyze miRNAs and DNA characteristics of postmenopausal patients with and without osteoporosis. The results indicate that iron overload disrupts iron homeostasis in the pathogenesis of PMOP. Further experiments confirm that iron overload can cause lipid peroxidation and ferroptosis of MSCs, thus breaking bone homeostasis. Based on the findings above, we have designed a novel Ti implant coated with nanospheres of caffeic acid (CA) and deferoxamine (DFO). CA can bind on the Ti surface through the two adjacent phenolic hydroxyls and polymerize into polycaffeic acid (PCA) dimer, as well as the PCA nanospheres with the repetitive 1,4-benzodioxan units. DFO was grafted with PCA through borate ester bonds. The experimental results showed that modified Ti can inhibit the ferroptosis of MSCs in the pathological environment of PMOP and promote osseointegration in two main ways. Firstly, DFO was released under high oxidative stress, chelating with excess iron and decreasing the labile iron pool in MSCs. Meanwhile, CA and DFO activated the KEAP1/NRF2/HMOX1 pathway in MSCs and reduced the level of intracellular lipid peroxidation. So, the ferroptosis of MSCs is inhibited by promoting the SLC7A11/GSH/GPX4 pathway. Furthermore, the remained CA coating on the Ti surface could reduce the extracellular oxidative stress and glutathione level. This study offers a novel inspiration for the specific design of Ti implants in the treatment of PMOP.
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Steel slag is the main by-product of the steel industry and can be used to produce steel slag fine aggregate (SSFA). SSFA can be used as a fine aggregate in mortar or concrete. However, SSFA contains f-CaO, which is the main reason for the expansion damage of mortar and concrete. In this study, the carbonation treatment of SSFA was adopted to reduce the f-CaO content; the influence of the carbonation time on the content of f-CaO in the SSFA was studied; and the effects of the carbonated SSFA replacement ratio on the expansion rate, mechanical properties and carbonation depth of mortar were investigated through tests. The results showed that as the carbonation time increased, the content of f-CaO in the SSFA gradually decreased. Compared to the mortar specimens with carbonated SSFA, the specimens with uncarbonated SSFA showed faster and more severe damage and a higher expansion rate. When the replacement ratio of carbonated SSFA was less than 45%, the carbonated SSFA had an inhibitory effect on the expansion development of the specimens. The compressive strengths of the specimens with a carbonated SSFA replacement ratio of 60% and 45% were 1.29% and 6.81% higher than those of the specimens with an uncarbonated SSFA replacement ratio of 60% and 45%, respectively. Carbonation treatment could improve the replacement ratio of SSFA while ensuring the compressive strength of specimens. Compared with mortar specimens with uncarbonated SSFA, the anti-carbonation performance of mortar specimens with carbonated SSFA was reduced.
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BACKGROUND: Steroid-induced osteonecrosis of femoral head (SONFH) is a severe health risk, and this study aims to identify immune-related biomarkers and pathways associated with the disease through bioinformatics analysis and animal experiments. METHOD: Using SONFH-related datasets obtained from the GEO database, we performed differential expression analysis and weighted gene co-expression network analysis (WGCNA) to extract SONFH-related genes. A protein-protein interaction (PPI) network was then constructed, and core sub-network genes were identified. Immune cell infiltration and clustering analysis of SONFH samples were performed to assess differences in immune cell populations. WGCNA analysis was used to identify module genes associated with immune cells, and hub genes were identified using machine learning. Internal and external validation along with animal experiments were conducted to confirm the differential expression of hub genes and infiltration of immune cells in SONFH. RESULTS: Differential expression analysis revealed 502 DEGs. WGCNA analysis identified a blue module closely related to SONFH, containing 1928 module genes. Intersection analysis between DEGs and blue module genes resulted in 453 intersecting genes. The PPI network and MCODE module identified 15 key targets enriched in various signaling pathways. Analysis of immune cell infiltration showed statistically significant differences in CD8 + t cells, monocytes, macrophages M2 and neutrophils between SONFH and control samples. Unsupervised clustering classified SONFH samples into two clusters (C1 and C2), which also exhibited significant differences in immune cell infiltration. The hub genes (ICAM1, NR3C1, and IKBKB) were further identified using WGCNA and machine learning analysis. Based on these hub genes, a clinical prediction model was constructed and validated internally and externally. Animal experiments confirmed the upregulation of hub genes in SONFH, with an associated increase in immune cell infiltration. CONCLUSION: This study identified ICAM1, NR3C1, and IKBKB as potential immune-related biomarkers involved in immune cell infiltration of CD8 + t cells, monocytes, macrophages M2, neutrophils and other immune cells in the pathogenesis of SONFH. These biomarkers act through modulation of the chemokine signaling pathway, Toll-like receptor signaling pathway, and other pathways. These findings provide valuable insights into the disease mechanism of SONFH and may aid in future drug development efforts.
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Necrose da Cabeça do Fêmur , Mapas de Interação de Proteínas , Animais , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/genética , Necrose da Cabeça do Fêmur/imunologia , Humanos , Biomarcadores/metabolismo , Perfilação da Expressão Gênica , Modelos Animais de Doenças , Biologia Computacional , Redes Reguladoras de Genes , Camundongos , Masculino , Esteroides , Aprendizado de Máquina , Transdução de Sinais/genéticaRESUMO
The neuroinflammatory response triggered by cerebral ischemia-reperfusion injury (CIRI) is characterized by the upsurge of pro-inflammatory cytokines, including TNF-α, IL-1ß, and IL-6, which promote leukocyte infiltration and subsequent accumulation in the ischemic zone. This accumulation further intensifies inflammation and aggravates ischemic damage. Certolizumab pegol (CZP), a monoclonal antibody targeting TNF-α, is widely used in treating various inflammatory diseases. This study explored the therapeutic potential of CZP in a mouse model of CIRI, induced by middle cerebral artery occlusion (MCAO), focusing on its influence on the microglial inflammatory response. In vitro analyses revealed that CZP markedly inhibits TNF-α-stimulated inflammation in primary microglia with an EC50 of 1.743 ng/mL. In vivo, MCAO mice treated with CZP (10 µg/mouse, i.p.) for 3 days showed reduced infarct volume, partially improved neurological function, and diminished blood-brain barrierdisruption. Additionally, CZP treatment curtailed microglial activation and the release of pro-inflammatory mediators in the early stages of stroke. It also favorably modulated microglial M1/M2 polarization, rebalanced Th17/Treg cells dynamics, and inhibited Caspase-8-mediated GSDMD cleavage, preventing microglial pyroptosis. Collectively, this study described that the treatment with CZP reversed damaging process caused by CIRI, offering a promising therapeutic strategy for the treatment of ischemic stroke.
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Certolizumab Pegol , Infarto da Artéria Cerebral Média , Camundongos Endogâmicos C57BL , Microglia , Traumatismo por Reperfusão , Fator de Necrose Tumoral alfa , Animais , Traumatismo por Reperfusão/tratamento farmacológico , Certolizumab Pegol/uso terapêutico , Certolizumab Pegol/farmacologia , Masculino , Camundongos , Microglia/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Modelos Animais de Doenças , Isquemia Encefálica/tratamento farmacológico , Células Cultivadas , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Humanos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/metabolismo , Citocinas/metabolismoRESUMO
BACKGROUND: Rapamycin has been extensively utilized for coating coronary artery stents to reduce the occurrence of restenosis, yet there has been limited research on the potential harms of rapamycin-eluting stents. Herein, We report a case of eosinophilia and interstitial pneumonia caused by a cobalt-based alloy stent eluted with rapamycin. CASE PRESENTATION: The patient was admitted due to fever, cough, and expectoration symptoms. Previously, the patient had undergone a procedure of percutaneous coronary stent implantation in our hospital's cardiology department, which led to a gradual rise in blood eosinophil count. This time, the eosinophil count was higher than the previous admission. A chest CT scan revealed multiple flocculent density increases in both lungs and bronchiectasis. The rapamycin-eluting stents may have caused eosinophilia and interstitial pneumonia, which improved after administering corticosteroids. A systematic review of relevant literature was conducted to summarize the characteristics of interstitial pneumonia caused by drug-eluting stents. CONCLUSION: Paclitaxel, everolimus, zotarolimus, and rapamycin are the types of drugs that can lead to drug-eluting stents, and because of the rarity of their onset, clinical doctors must be precise and prompt in diagnosing suspected cases to avoid misdiagnosis and delayed treatment.
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Stents Farmacológicos , Eosinofilia , Doenças Pulmonares Intersticiais , Sirolimo , Humanos , Stents Farmacológicos/efeitos adversos , Sirolimo/efeitos adversos , Masculino , Tomografia Computadorizada por Raios X , Intervenção Coronária Percutânea/efeitos adversos , IdosoRESUMO
Endophytes have been shown to promote plant growth and health. In the present study, a Bacillus velezensis CH1 (CH1) strain was isolated and identified from high-quality oats, which was capable of producing indole-3-acetic acid (IAA) and strong biofilms, and capabilities in the nitrogen-fixing and iron carriers. CH1 has a 3920 kb chromosome with 47.3% GC content and 3776 code genes. Compared genome analysis showed that the largest proportion of the COG database was metabolism-related (44.79%), and 1135 out of 1508 genes were associated with the function "biosynthesis, transport, and catabolism of secondary metabolites." Furthermore, thirteen gene clusters had been identified in CH1, which were responsible for the synthesis of fifteen secondary metabolites that exhibit antifungal and antibacterial properties. Additionally, the strain harbors genes involved in plant growth promotion, such as seven putative genes for IAA production, spermidine and polyamine synthase genes, along with multiple membrane-associated genes. The enrichment of these functions was strong evidence of the antimicrobial properties of strain CH1, which has the potential to be a biofertilizer for promoting oat growth and disease resistance.
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Avena , Bacillus , Ácidos Indolacéticos , Bacillus/genética , Bacillus/metabolismo , Bacillus/isolamento & purificação , Avena/microbiologia , Avena/crescimento & desenvolvimento , Ácidos Indolacéticos/metabolismo , Biofilmes/crescimento & desenvolvimento , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Fixação de Nitrogênio , Filogenia , Endófitos/isolamento & purificação , Endófitos/metabolismo , Endófitos/genética , Genoma BacterianoRESUMO
To increase the efficiency of deep-hole blasting driving in mine rock tunnels, an innovative pattern of wedge cutting blasting with hole-inner delay was proposed. First, the blasting mechanisms of conventional and innovative wedge cutting patterns were theoretically investigated. The results showed that the resistance from large upper rock blocks and the clamping action from the surrounding rock were the major challenges of conventional cutting methods. For the innovative cutting pattern, under the conversion of the spatial distribution and release sequence of blasting energy, the first blasting of the upper charge can strengthen the breaking of the upper rock mass and create a new free surface, which provides favorable conditions for the delayed blasting of the bottom charge. Second, finite element models of two cutting patterns were established and solved, and the simulation results visually revealed the propagation of a stress wave. Critically, the stress strength in the upper cavity increased by 66-83% under the action of the upper charge, which was conducive to the breaking of the upper rock mass and the generation of a new free surface. Therefore, the rock mass in the bottom cavity can be readily broken and discharged. Ultimately, field applications were executed in a rock tunnel. Compared with a conventional cutting pattern, the proposed innovative cutting pattern can prominently increase the cycle advance and hole utilization and greatly reduce the unit consumption of explosives and detonators. This research confirms the usability of the innovative wedge cutting pattern with hole-inner delay in deep-hole blasting driving of rock tunnels.
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Investigating oat tissue microflora during its different developmental stages is necessary for understanding its growth and anti-disease mechanism. In this study, 16S rDNA and ITS (Internally Transcribed Spacer) high-throughput sequencing technology were used to explore the microflora diversity of oat tissue. Twenty-seven samples of leaves, stems, and roots from three developmental stages, namely the seedling stage (SS), jointing stage (JS), and maturity stage (MS), underwent sequencing analysis. The analysis showed that 6480 operational taxonomic units (OTUs) were identified in the examined samples, of which 1698 were fungal and 4782 were bacterial. Furthermore, 126 OTUs were shared by fungi, mainly Ascomycota, Basidiomycota, and Mucoromycota at the phylum level, and 39 OTUs were shared by bacteria, mainly Actinobacteriota and Proteobacteria at the phylum level. The microbial diversity of oat tissue in the three developmental stages showed differences, and the α-diversity of the bacteria and ß-diversity of the bacteria and fungi in the roots were higher than those of the stems and leaves. Among the bacteria species, Thiiopseudomonas, Rikenellaceae RC9 gut group, and Brevibacterium were predominant in the leaves, MND1 was predominant in the roots, and Lactobacillus was predominant in the stems. Moreover, Brevibacterium maintained a stable state at all growth stages. In the fungal species, Phomatospora was dominant in the leaves, Kondoa was dominant in the roots, and Pyrenophora was dominant in the stems. All species with a high abundance were related to the growth process of oats and antagonistic bacteria. Furthermore, connection modules were denser in bacterial than in fungal populations. The samples were treated with superoxide dismutase and peroxidase. There were 42 strains associated with SOD (Superoxide dismutase), 60 strains associated with POD (Peroxidase), and 38 strains in total, which much higher than fungi. The network analysis showed that bacteria might have more dense connection modules than fungi, The number of bacterial connections to enzymes were much higher than that of fungi. Furthermore, these results provide a basis for further mechanistic research.
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Neuronal ferroptosis and autophagy are crucial in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). Mastoparan M (Mast-M), extracted from the crude venom of Vespa magnifica (Smith), comprises 14 amino acid residues. Previous studies suggested that Mast-M reduces neuronal damage following global CIRI, but its protective mechanisms remain unclear. The present study examined the effect of Mast-M on middle cerebral artery occlusion/reperfusion (MCAO/R) induced neurological deficits using Grip, Rotarod, Longa test, and TTC staining, followed by treating the mice for three days with Mast-M (20, 40, and 80⯵g/kg, subcutaneously). The results demonstrate that Mast-M promotes functional recovery in mice post-ischemic stroke, evidenced by improved neurological impairment, reduced infarct volume and neuronal damage. Meanwhile, the level of iron (Fe2+) and malonyldialdehyde was decreased in the ischemic hemisphere of MCAO/R mice at 24â¯hours or 48â¯hours by Mast-M (80⯵g/kg) treatment, while the expression of NRF2, x-CT, GPX4, and LC3B protein was increased. Furthermore, these findings were validated in three models-oxygen-glucose deprivation/ reoxygenation, H2O2-induced peroxidation, and erastin-induced ferroptosis-in hippocampal neuron HT22 cells or primary neurons. These data suggested that Mast-M activates autophagy as well as inhibits ferroptosis. Finally, autophagy inhibitors were introduced to determine the relationship between the autophagy and ferroptosis, indicating that Mast-M alleviates ferroptosis by activating autophagy. Taken together, this study described that Mast-M alleviates cerebral infarction, neurologic impairment, and neuronal damage by activating autophagy and inhibiting ferroptosis, presenting a potential therapeutic approach for CIRI.
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Autofagia , Ferroptose , Infarto da Artéria Cerebral Média , Recuperação de Função Fisiológica , Animais , Autofagia/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Masculino , Camundongos , Recuperação de Função Fisiológica/efeitos dos fármacos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/metabolismo , Camundongos Endogâmicos C57BL , Venenos de Vespas/farmacologia , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Modelos Animais de Doenças , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologiaRESUMO
Clarifying the relationship between the man-machine environment and its impact on the tunnel wall drilling task performance (TWDTP) is crucial for enhancing the task performance. Based on a questionnaire survey, indicators of the man-machine environment that affect the TWDTP were proposed in this study, and exploratory factor analysis and a structural equation model were employed to examine the potential factors influencing the task performance and their degrees of influence. By comparing the discrepancy between the perceived performance and importance, the satisfaction of potential factors was evaluated, and the priority order for optimizing these factors was determined by considering the degree of influence and dissatisfaction. The results of survey data analysis based on actual tunnel drilling operation scenarios indicated that tools had the greatest impact on the TWDTP, followed by the quality of the physical environment, while human factors had the least influence on the task performance. Convenient functional maintenance is the key to improving the TWDTP, along with enhancing the quality of the working environment. Once these main aspects are optimized, it is important to consider additional factors such as availability of spare tools, efficient personnel organization, man-tool matching, and safety and health assurance. This research approach provides significant guidance in understanding the relationships between the man-machine environmental factors affecting the performance of complex engineering tasks and identifying key influencing factors, thus providing essential insights for optimizing the TWDTP.
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Postpartum depression (PPD) has a significant impact on the physical and mental health of mothers, potentially leading to symptoms such as low mood, fatigue, and decreased appetite. It may also affect the healthy growth of the infant. The onset of PPD is closely related to abnormalities in inflammation and the immune system. PPD patients exhibit abnormalities in the proportion of peripheral blood immune cells, along with an increase in pro-inflammatory cytokines. Excessive pro-inflammatory cytokines in peripheral blood can disrupt the blood-brain barrier (BBB) by activating astrocytes and reducing transendothelial electrical resistance (TEER), allowing peripheral immune cells or cytokines to enter the brain and trigger inflammation, ultimately leading to the onset of depression. In addition, PPD lacks safe and effective treatment medications. In this study, we collected peripheral blood from both healthy postpartum women and those with PPD, conducted single cell RNA sequencing (scRNA-seq), and used an in-house analytical tool scSTAR to reveal that PPD patients exhibit elevated proportions of peripheral blood cDC2 and Proliferation B cells, which are significantly correlated with IL-1ß. Additionally, animal experiments were designed to validate that 919 granules can improve PPD by modulating the levels of peripheral blood IL-1ß, providing a potential therapeutic mechanism for PPD treatment.
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Depressão Pós-Parto , Interleucina-1beta , Animais , Feminino , Humanos , Masculino , Camundongos , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Depressão Pós-Parto/sangue , Depressão Pós-Parto/tratamento farmacológico , Interleucina-1beta/sangue , Adulto Jovem , AdultoRESUMO
Macrothelidae is a family of mygalomorph spiders containing the extant genera Macrothele and Vacrothele. China is an important center of diversity for Macrothele with 65â¯% of the known species occurring there. Previous work on Macrothele was able to uncover several important toxin compounds including Raventoxin which may have applications in biomedicine and agricultural chemistry. Despite the importance of Macrothele spiders, high-quality reference genomes are still lacking, which hinders our understanding and application of the toxin compounds. In this study, we assembled the genome of the Macrothele yani to help fill gaps in our understanding of toxin biology in this lineage of spiders to encourage the future study and applications of these compounds. The final assembled genome was 6.79 Gb in total length, had a contig N50 of 21.44â¯Mb, and scaffold N50 of 156.16â¯Mb. Hi-C scaffolding assigned 98.19â¯% of the genome to 46 pseudo-chromosomes with a BUSCO score of 95.7â¯% for the core eukaryotic gene set. The assembled genome was found to contain 75.62â¯% repetitive DNA and a total of 39,687 protein-coding genes were annotated making it the spider genome with highest number of genes. Through integrated analysis of venom gland transcriptomics and venom proteomics, a total of 194 venom toxins were identified, including 38 disulfide-rich peptide neurotoxins, among which 12 were ICK knottin peptides. In summary, we present the first high-quality genome assembly at the chromosomal level for any Macrothelidae spider, filling an important gap in our knowledge of these spiders. Such high-quality genomic data will be invaluable as a reference in resolving Araneae spider phylogenies and in screening different spider species for novel compounds applicable to numerous medical and agricultural applications.
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Genoma , Proteoma , Venenos de Aranha , Aranhas , Animais , Anotação de Sequência Molecular , Filogenia , Venenos de Aranha/genética , Venenos de Aranha/química , Aranhas/genética , Aranhas/classificaçãoRESUMO
Subsurface karst caves provide unique opportunities to study the deep biosphere, shedding light on microbial contribution to elemental cycling. Although ammonia oxidation driven by both ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) is well explored in soil and marine environments, our understanding in the subsurface biosphere still remained limited to date. To address this gap, weathered rock and sediment samples were collected from the Xincuntun Cave in Guilin City, an alkaline karst cave, and subjected to high-throughput sequencing and quantification of bacterial and archaeal amoA, along with determination of the potential nitrification rates (PNR). Results revealed that AOA dominated in ammonia oxidation, contributing 48-100% to the PNR, and AOA amoA gene copies outnumbered AOB by 2 to 6 orders. Nitrososphaera dominated in AOA communities, while Nitrosopira dominated AOB communities. AOA demonstrated significantly larger niche breadth than AOB. The development of AOA communities was influenced by deterministic processes (50.71%), while AOB communities were predominantly influenced by stochastic processes. TOC, NH4+, and Cl- played crucial roles in shaping the compositions of ammonia oxidizers at the OTU level. Cross-domain co-occurrence networks highlighted the dominance of AOA nodes in the networks and positive associations between AOA and AOB, especially in the inner zone, suggesting collaborative effort to thrive in extreme environments. Their high gene copies, dominance in the interaction with ammonia oxidizing bacteria, expansive niche breadth and substantial contribution to PNR collectively confirmed that AOA better adapted to alkaline, oligotrophic karst caves environments, and thus play a fundamental role in nitrogen cycling in subsurface biosphere.
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BACKGROUND: The use of immune checkpoint inhibitors has led to an increase in randomized controlled trials exploring various first-line combination treatment regimens. With the introduction of new PD-1/PD-L1 inhibitors, there are now more clinical options available. For the first time, the AK105 monoclonal antibody Penpulimab, developed in China, was included. The AK105-302 Phase III trial studied the efficacy and safety of Penpulimab combined with chemotherapy in patients with advanced or metastatic squamous NSCLC. To determine the optimal treatment options, we conducted an updated network meta-analysis to compare the effectiveness and safety of these regimens. METHODS: The system retrieves data from Chinese and English electronic databases, Clinical Trials, and the gov Clinical Trial Registration website up to September 6, 2023. The study indirectly compared the efficacy and safety of PD-1/PD-L1 combination regimens, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), all-grade adverse events, and above-grade III adverse events. Subgroup analyses were conducted based on programmed death ligand 1 (PD-L1) level, histological type, ECOG score, sex, and smoking history. RESULTS: Nineteen RCTS were included, with a total of ten thousand eight hundred patients. Penpulimab plus chemotherapy (Pen + CT) provided the best OS (HR = 0.55, 95% CI 0.38-0.81) for PD-L1 patients with non-selective advanced NSCLC. Except Nivolumab plus Ipilimumab (Niv + Ipi), other PD-1/PD-L1 combination therapies significantly extended PFS compared with CT, and Nivolumab plus Bevacizumab combined with chemotherapy (Niv + Bev + CT) (HR = 0.43, 95% CI 0.26-0.74) provided the best PFS benefit and was comparable to Pen + CT (HR = 1.0) for PFS prolongation. For ORR, except Niv + Ipi, all the other regimens significantly improved ORR compared with CT. In terms of safety, except Tor + CT, the incidence of any-grade AEs or grade ≥ 3 adverse events may be higher than those of chemotherapy. The subgroup analysis revealed that for patients with PD-L1 levels below 1%, treatment with Tor + CT resulted in the best progression-free survival (HR = 0.47, 95% CI 0.25-0.86). For patients with PD-L1 levels of 1% or higher, Sintilimab plus chemotherapy (Sin + CT) (HR = 0.56, 95% CI 0.31-0.99) and Camrelizumab plus chemotherapy (Cam + CT) (HR = 0.43, 95% CI 0.28-0.64) were associated with the best overall survival and progression-free survival, respectively. For patients with SqNSCLC, combined immunotherapy may provide greater survival benefits. For patients with Non-sqNSCLC, Niv + Bev + CT and Tor + CT were associated with optimal PFS and OS, respectively. Cam + CT provided the best PFS in male patients with a history of smoking and an ECOG score of 0. In both female and non-smoking patient subgroups, Pem + CT was associated with the best PFS and OS benefits. CONCLUSION: For patients with advanced non-selective PD-L1 NSCLC, two effective regimens are Pen + CT and Niv + Bev + CT, which rank first in OS and PFS among all patients. Cam + CT and Tor + CT have advantages for OS in patients with SqNSCLC and Non-sqNSCLC, respectively. Niv + Ipi + CT provided the best OS benefit for patients with an ECOG score of 0, while Pem + CT may be the most effective treatment for patients with an ECOG score of 1. Pem + CT has a better effect on female patients and non-smokers. Sin + CT was found to be the most effective treatment for male patients and the smoking subgroup, while Cam + CT was found to be the most effective for PFS. In addition, Tor + CT was associated with the best PFS for patients with negative PD-L1 expression. Pem + CT was found to significantly improve both PFS and OS compared to CT alone. For patients with positive PD-L1 expression, Sin + CT and Cam + CT were found to be optimal for OS and PFS, respectively. It is important to note that, with the exception of Tor + CT, the toxicity of the other combinations was higher than that of CT alone.
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INTRODUCTION: Postoperative nausea and vomiting (PONV) is one of the most common adverse events following orthognathic surgery. It's a distressing feeling for patients and continues to be the cause of postoperative complications such as bleeding, delayed healing, and wound infection. This scoping review aims to identify effective PONV prophylaxis strategies during orthognathic surgery that have emerged in the past 15 years. METHODS: We searched Pubmed, Cochrane Controlled Register of Trials, and Embase from 2008 to May 2023. Studies meeting the following criteria were eligible for inclusion: (1) recruited patients undergo any orthognathic surgery; (2) evaluated any pharmacologic or non-pharmacologic method to prevent PONV. Studies meeting the following criteria were excluded: (1) case series, review papers, or retrospective studies; (2) did not report our prespecified outcomes. RESULTS: Twenty-one studies were included in this review. Pharmacological methods for PONV prevention include ondansetron and dexamethasone (3 studies), peripheral nerve block technique (4 studies), dexmedetomidine (1 study), pregabalin (2 studies), nefopam (2 studies), remifentanil (1 study), propofol (2 studies), and penehyclidine (1 study). Non-pharmacologic methods include capsicum plaster (1 study), throat packs (2 studies) and gastric aspiration (2 studies). CONCLUSIONS: Based on current evidence, we conclude that prophylactic antiemetics like dexamethasone, ondansetron, and penehyclidine are the first defense against PONV. Multimodal analgesia with nerve block techniques and non-opioid analgesics should be considered due to their notable opioid-sparing and PONV preventive effect. For the non-pharmacological methods, throat packs are not recommended for routine use because of their poor effect and serious complications. More prospective RCTs are required to confirm whether gastric aspiration can prevent PONV effectively for patients undergoing orthognathic surgery.
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Antieméticos , Cirurgia Ortognática , Humanos , Náusea e Vômito Pós-Operatórios/prevenção & controle , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Ondansetron/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , Antieméticos/uso terapêutico , Dexametasona/uso terapêuticoRESUMO
Temperature and humidity, along with concentrations of ammonia and hydrogen sulfide, are critical environmental factors that significantly influence the growth and health of pigs within porcine habitats. The ability to accurately predict these environmental variables in pig houses is pivotal, as it provides crucial decision-making support for the precise and targeted regulation of the internal environmental conditions. This approach ensures an optimal living environment, essential for the well-being and healthy development of the pigs. The existing methodologies for forecasting environmental factors in pig houses are currently hampered by issues of low predictive accuracy and significant fluctuations in environmental conditions. To address these challenges in this study, a hybrid model incorporating the improved dung beetle algorithm (DBO), temporal convolutional networks (TCNs), and gated recurrent units (GRUs) is proposed for the prediction and optimization of environmental factors in pig barns. The model enhances the global search capability of DBO by introducing the Osprey Eagle optimization algorithm (OOA). The hybrid model uses the optimization capability of DBO to initially fit the time-series data of environmental factors, and subsequently combines the long-term dependence capture capability of TCNs and the non-linear sequence processing capability of GRUs to accurately predict the residuals of the DBO fit. In the prediction of ammonia concentration, the OTDBO-TCN-GRU model shows excellent performance with mean absolute error (MAE), mean square error (MSE), and coefficient of determination (R2) of 0.0474, 0.0039, and 0.9871, respectively. Compared with the DBO-TCN-GRU model, OTDBO-TCN-GRU achieves significant reductions of 37.2% and 66.7% in MAE and MSE, respectively, while the R2 value is improved by 2.5%. Compared with the OOA model, the OTDBO-TCN-GRU achieved 48.7% and 74.2% reductions in the MAE and MSE metrics, respectively, while the R2 value improved by 3.6%. In addition, the improved OTDBO-TCN-GRU model has a prediction error of less than 0.3 mg/m3 for environmental gases compared with other algorithms, and has less influence on sudden environmental changes, which shows the robustness and adaptability of the model for environmental prediction. Therefore, the OTDBO-TCN-GRU model, as proposed in this study, optimizes the predictive performance of environmental factor time series and offers substantial decision support for environmental control in pig houses.
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The rheumatoid arthritis (RA) microenvironment is often followed by a vicious circle of high inflammation, endogenous gas levels imbalance, and poor treatment. To break the circle, we develop a dual-gas-mediated injectable hydrogel for modulating the immune microenvironment of RA and simultaneously releasing therapeutic drugs. The hydrogel (DNRS gel) could be broken down on-demand by consuming excessive nitric oxide (NO) and releasing therapeutic hydrogen sulfide (H2S), resulting in endogenous gas restoration, inflammation alleviation, and macrophage polarization to M2 type. Additionally, the hydrogel could suppress osteoclastogenesis and enhance osteogenesis. Furthermore, the intra-articularly injected hydrogel with methotrexate (MTX/DNRS gel) significantly alleviated inflammation and clinical symptoms and promoted the repair of bone erosion in the collagen-induced arthritis rat model. As a result, in vivo results demonstrated that MTX/DNRS gel restored the microenvironment and improved the therapeutic effect of MTX. This study provides a novel understanding of developing versatile smart delivery platforms for RA treatment.
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Type 2 diabetes mellitus (T2DM) is a progressive disease. We utilized bioinformatics analysis and experimental research to identify biomarkers indicative of the progression of T2DM, aiming for early detection of the disease and timely clinical intervention. Integrating Mfuzz analysis with differential expression analysis, we identified 76 genes associated with the progression of T2DM, which were primarily enriched in signaling pathways such as apoptosis, p53 signaling, and necroptosis. Subsequently, using various analytical methods, including machine learning, we further narrowed down the hub genes to STK17A and CCT5. Based on the hub genes, we calculated the risk score for samples and interestingly found that the score correlated with multiple programmed cell death (PCD) pathways. Animal experiments revealed that the diabetes model exhibited higher levels of MDA and LDH, with lower expression of SOD, accompanied by islet cell apoptosis. In conclusion, our study suggests that during the progression of diabetes, STK17A and CCT5 may contribute to the advancement of the disease by regulating oxidative stress, programmed cell death pathways, and critical signaling pathways such as p53 and MAPK, thereby promoting the death of islet cells. This provides substantial evidence in support of further disease prevention and treatment strategies.
Assuntos
Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Animais , Diabetes Mellitus Tipo 2/metabolismo , Intolerância à Glucose/metabolismo , Proteína Supressora de Tumor p53/genética , Biomarcadores , Biologia ComputacionalRESUMO
Cell-cell communication is essential to many key biological processes. Intercellular communication is generally mediated by ligand-receptor interactions (LRIs). Thus, building a comprehensive and high-quality LRI resource can significantly improve intercellular communication analysis. Meantime, due to lack of a "gold standard" dataset, it remains a challenge to evaluate LRI-mediated intercellular communication results. Here, we introduce CellGiQ, a high-confident LRI prediction framework for intercellular communication analysis. Highly confident LRIs are first inferred by LRI feature extraction with BioTriangle, LRI selection using LightGBM, and LRI classification based on ensemble of gradient boosted neural network and interpretable boosting machine. Subsequently, known and identified high-confident LRIs are filtered by combining single-cell RNA sequencing (scRNA-seq) data and further applied to intercellular communication inference through a quartile scoring strategy. To validation the predictions, CellGiQ exploited several evaluation strategies: using AUC and AUPR, it surpassed six competing LRI prediction models on four LRI datasets; through Venn diagrams and molecular docking, its predicted LRIs were validated by five other popular intercellular communication inference methods; based on the overlapping LRIs, it computed high Jaccard index with six other state-of-the-art intercellular communication prediction tools within human HNSCC tissues; by comparing with classical models and literature retrieve, its inferred HNSCC-related intercellular communication results was further validated. The novelty of this study is to identify high-confident LRIs based on machine learning as well as design several LRI validation ways, providing reference for computational LRI prediction. CellGiQ provides an open-source and useful tool to decompose LRI-mediated intercellular communication at single cell resolution. CellGiQ is freely available at https://github.com/plhhnu/CellGiQ.