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Different organic compounds can have varying degrees of impact on the activity of Lactobacillus paracasei. The study focused on the impact and action mechanism of different organic selenium products on the bioactivity of two strains of L. paracasei. The growth, antioxidant activity, extracellular polysaccharide secretion, quorum sensing (QS), and biofilm formation of the strains before and after the addition of organic selenium crude products and three organic selenium standard were evaluated. The results showed that the addition of crude organic selenium promoted the various activities of the strain. l-selenocysteine had the strongest regulatory effect, with maximum GIM1.80 biofilm formation when it reached a critical concentration of 0.4 µg/mL; l-selenomethionine resulted in the highest activity of the signal molecule Auto inducer-2 of GDMCC1.155, when it reached a critical concentration of 0.4 µg/mL. The results of scanning electron microscopy demonstrated that the addition of organic selenium effectively improved the morphological structure of the two bacterial cells. Molecular docking revealed that the mechanism by which organic selenium regulates QS in Lactobacillus was achieved by binding two crucial receptor proteins (histidine protein kinase HKP and periplasmic binding protein LuxP) from specific sites. Furthermore, organic selenium products have a beneficial regulatory effect on the biological activity of L. paracasei. Overall, these findings provide a new alternative (organic selenium) for regulating the viability and beneficial activity of L. paracasei.
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Lacticaseibacillus paracasei , Selênio , Percepção de Quorum , Antioxidantes/farmacologia , Selênio/farmacologia , Simulação de Acoplamento Molecular , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , BiofilmesRESUMO
Exploiting clean energy is essential for sustainable development and sunlight-driven photocatalytic water splitting represents one of the most promising approaches toward this goal. Metal-organic frameworks (MOFs) are competent photocatalysts owing to their tailorable functionality, well-defined structure, and high porosity. Yet, the introduction of the unambiguous metal-centered active site into MOFs is still challenging since framework motifs capable of anchoring metal ions firmly are lacking. Herein, the assembly using 1,4-dicarboxylbenzene-2,3-dithiol (H2 dcbdt) and Zr-Oxo clusters to give a thiol-functionalized UiO-66 type framework, UiO-66-dcbdt, is reported. The thiocatechols on the struts are allowed to capture transition metal (TM) ions to generate UiO-66-dcbdt-M (M = Fe, Ni, Cu) with unambiguous metal-thiocatecholate moieties for photocatalytic hydrogen evolution reaction (HER). UiO-66-dcbdt-Cu is found the best catalyst exhibiting an HER rate of 4.18 mmol g-1 h-1 upon irradiation with photosensitizing Ru-polypyridyl complex. To skip the use of the external sensitizer, UiO-66-dcbdt-Cu is heterojunctioned with titanium dioxide (TiO2 ) and achieves an HER rate of 12.63 mmol g-1 h-1 (32.3 times that of primitive TiO2 ). This work represents the first example of MOF assembly employing H2 dcbdt as the mere linker followed by chelation with TM ions and undoubtedly fuels the rational design of MOF photocatalysts bearing well-defined active sites.
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The unclear molecular mechanism by which peanuts adapt to chilling stress limits progress in molecular breeding for peanut chilling tolerance. Here, the physiological and transcriptional differences between two genotypes with contrasting tolerance under chilling stress were compared. The inhibition of photosynthesis mainly caused by stomatal factors was a common response of peanut seedlings to chilling stress. Chilling-tolerant genotypes could inhibit the accumulation of ROS to adapt to chilling stress, and enhanced activities of CAT and APX were major causes of lower H2O2 content. The results of a conjoint analysis of physiological indices and the RNA-Seq database by WGCNA indicated that the genes in key modules were significantly enriched in pathways related to the oxidation-reduction process. Hub genes encoding RLK, CAT, MYC4, AOS, GST, PP2C, UPL5 and ZFP8 were likely to positively regulate peanut chilling tolerance, but hub genes encoding PAO, NAC2 and NAC72 were likely to negatively regulate peanut chilling tolerance.
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Arachis , Transcriptoma , Arachis/genética , Arachis/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio/metabolismo , Plântula/genética , Plântula/metabolismo , Estresse Fisiológico/genéticaRESUMO
China is the largest producer and consumer of rice, and the classification of filled/unfilled rice grains is of great significance for rice breeding and genetic analysis. The traditional method for filled/unfilled rice grain identification was generally manual, which had the disadvantages of low efficiency, poor repeatability, and low precision. In this study, we have proposed a novel method for filled/unfilled grain classification based on structured light imaging and Improved PointNet++. Firstly, the 3D point cloud data of rice grains were obtained by structured light imaging. And then the specified processing algorithms were developed for the single grain segmentation, and data enhancement with normal vector. Finally, the PointNet++ network was improved by adding an additional Set Abstraction layer and combining the maximum pooling of normal vectors to realize filled/unfilled rice grain point cloud classification. To verify the model performance, the Improved PointNet++ was compared with six machine learning methods, PointNet and PointConv. The results showed that the optimal machine learning model is XGboost, with a classification accuracy of 91.99%, while the classification accuracy of Improved PointNet++ was 98.50% outperforming the PointNet 93.75% and PointConv 92.25%. In conclusion, this study has demonstrated a novel and effective method for filled/unfilled grain recognition.
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Drought stress has been the major constraint on peanut yield and quality, and an understanding of the function of long non-coding (lncRNAs) in the peanut drought stress response is still in its infancy. In this study, two peanut varieties with contrasting drought tolerance were used to explore the functions of lncRNAs in the peanut drought response, and the results showed that the drought-tolerant variety presented greater antioxidant enzyme activity, osmotic adjustment ability, and photosynthesis under drought conditions. There were 4329 lncRNAs identified in the two varieties, of which 535 and 663 lncRNAs were differentially expressed in NH5 and FH18, respectively. The cis targets of the differentially expressed lncRNAs were putatively involved in secondary metabolite biosynthesis and other basic metabolic processes. A total of 673 competing endogenous RNA (ceRNA) pairs were selected specifically in NH5, and the associated ceRNA network revealed six lncRNAs, MSTRG.70535.2, MSTRG.86570.2, MSTRG.86570.1, MSTRG.100618.1, MSTRG.81214.2, and MSTRG.30931.1were considered as hub nodes. They were speculated to contribute to enhancing peanut drought tolerance, such as regulating transcription and plant growth processes, thereby improving the drought stress response. In this study, lncRNAs and mRNAs interaction networks were constructed to aid a comprehensive understanding of the peanut drought stress response and form a basis for future research.
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MicroRNAs , RNA Longo não Codificante , Arachis/genética , Biomarcadores , Secas , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs/genética , RNA Longo não Codificante/genéticaRESUMO
Background: The most common spinal disorder in elderly is lumbar spinal canal stenosis (LSCS). Previous studies showed that ligamentum flavum hypertrophy (LFH) with fibrosis as the main pathological change is one of the pathogenic factors leading to LSCS. Epidermal Growth Factor (EGF) is known to have an intimate relationship with fibrosis in various tissues. Nevertheless, currently, there are few studies regarding EGF in LFH. The effect of EGF on the development of LFH is unknown, and the underlying pathomechanism remains unclear. In this study, we investigated the role of EGF in LFH and its potential molecular mechanism. Methods: First, the expression levels of EGF, phosphorylation of EGF receptor (pEGFR), Transforming growth factor-ß1 (TGF-ß1), Phosphorylated Smad3 (pSmad3), collagen I and collagen III were examined via immunohistochemistry and Western blot in LF tissues from patients with LSCS or Non-LSCS. Second, primary LF cells were isolated from adults with normal LF thickness and were cultured with different concentrations of exogenous EGF with or without erlotinib/TGF-ß1-neutralizing antibody. Results: The results showed that EGF, pEGFR, TGF-ß1, pSmad3, collagen I and collagen III protein expression in the LSCS group was significantly higher than that in the Non-LSCS group. Meanwhile, pEGFR, TGF-ß1, pSmad3, collagen I and collagen III protein expression was significantly enhanced in LF cells after exogenous EGF exposure, which can be notably blocked by erlotinib. In addition, pSmad3, collagen I and collagen III protein expression was blocked by TGF-ß1-neutralizing antibody. Conclusions: EGF promotes the synthesis of collagen I and collagen III via the TGF-ß1/Smad3 signaling pathway, which eventually contributes to LFH.
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Ligamento Amarelo , Estenose Espinal , Adulto , Idoso , Anticorpos Neutralizantes/metabolismo , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/metabolismo , Cloridrato de Erlotinib/metabolismo , Fibrose , Humanos , Hipertrofia/metabolismo , Ligamento Amarelo/metabolismo , Ligamento Amarelo/patologia , Transdução de Sinais , Proteína Smad3/genética , Proteína Smad3/metabolismo , Estenose Espinal/metabolismo , Estenose Espinal/patologia , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismoRESUMO
SphK1 gene has different roles in various types of cells in liver diseases, but most studies are based on global knockout mice, which hampers the study on the cellular and molecular mechanisms of SphK1. In order to further study the role of SphK1 in liver, SphK1 conditional knockout mice were constructed. A liver-specific SphK1 gene knockout mouse model was constructed by the Cre/Loxp recombinant enzyme system. PCR technologies and western blotting were used to identified the elimination of SphK1 gene in hepatocytes. SphK1flox/flox mice were used as a control group to verify the effectiveness of SphK1 liver-specific knockout mice from the profile, pathology, and serology of mice. The ablation of SphK1 in hepatic parenchymal cells was demonstrated by fluorescent in situ hybridization and the contents of S1P and Sph were measured by ELISA kit. The genotypes of liver in SphK1 conditional knockout mice were different from that of other organs. The mRNA and protein levels of SphK1 in liver tissue of SphK1 conditional knockout mice were almost depleted by compared with SphK1flox/flox mice. Physiology and pathology showed no significant difference between SphK1 liver conditional knockout mice and SphK1flox/flox mice. Additionally, SphK1 was eliminated in hepatocytes, leading to the reduce of S1P content in hepatocytes and liver tissues and the increase of Sph content in hepatocytes. The model of SphK1 gene liver conditional knockout mice was successfully constructed, providing a tool for the study of the roles of SphK1 in hepatocyte and liver diseases.
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Hepatócitos/metabolismo , Integrases/metabolismo , Lisofosfolipídeos/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/fisiologia , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Animais , Integrases/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
Plants tolerate cold stress by regulating gene networks controlling cellular and physiological traits to modify growth and development. Transcription factor (TF)-directed regulation of transcription within these gene networks is key to eliciting appropriate responses. Identifying TFs related to cold tolerance contributes to cold-tolerant crop breeding. In this study, a comparative transcriptome analysis was carried out to investigate global gene expression of entire TFs in two peanut varieties with different cold-tolerant abilities. A total of 87 TF families including 2328 TF genes were identified. Among them, 445 TF genes were significantly differentially expressed in two peanut varieties under cold stress. The TF families represented by the largest numbers of differentially expressed members were bHLH (basic helix-loop-helix protein), C2H2 (Cys2/His2 zinc finger protein), ERF (ethylene-responsive factor), MYB (v-myb avian myeloblastosis viral oncogene homolog), NAC (NAM, ATAF1/2, CUC2) and WRKY TFs. Phylogenetic evolutionary analysis, temporal expression profiling, protein-protein interaction (PPI) network, and functional enrichment of differentially expressed TFs revealed the importance of plant hormone signal transduction and plant-pathogen interaction pathways and their possible mechanism in peanut cold tolerance. This study contributes to a better understanding of the complex mechanism of TFs in response to cold stress in peanut and provides valuable resources for the investigation of evolutionary history and biological functions of peanut TFs genes involved in cold tolerance.
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Arachis/crescimento & desenvolvimento , Mineração de Dados/métodos , Perfilação da Expressão Gênica/métodos , Fatores de Transcrição/genética , Arachis/genética , Resposta ao Choque Frio , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Filogenia , Melhoramento Vegetal , Proteínas de Plantas/genética , Mapas de Interação de ProteínasRESUMO
Activation of hepatic stellate cells (HSCs) is an essential event in the initiation and progression of liver fibrosis. HSCs are believed to be the major source of collagen-producing myofibroblasts in fibrotic livers. A key feature in the pathogenesis of liver fibrosis is fibrillar Collagen I (Col 1) deposition. Osteopontin (OPN), an extracellular matrix (ECM) cytokine expressed in HSCs, could drive fibrogenesis by modulating the HSC pro-fibrogenic phenotype and Col 1 expression. Here, we aimed to investigate the molecular mechanism of OPN regulating the activation of HSCs. Our results showed that hepatic expression of OPN was increased in patients with liver fibrosis. In addition, hepatic OPN was positively correlated with Col 1 and α-SMA. Recombinant OPN (rOPN) upregulated Col 1 and α-SMA expression in LX-2 cells. However, OPN knockdown downregulated Col 1 expression. The 3'-UTR of the collagen 1 (Col 1) was identified to bind miR-129-5p. Transfection of miR-129-5p mimic in HSC resulted in a marked reduction of Col 1 expression. Conversely, a decrease in miR-129-5p in HSCs transfected by anti-sense miR-129-5p (AS-miR-129-5p) caused Col 1 upregulation. Furthermore, luciferase reporter assay showed that miR-129-5p directly target the 3'-UTR of Col1α1 mRNA via repressing its post-transcriptional activities. Finally, miR-129-5p level was decreased in fibrotic liver of human, and reduced by rOPN treatment. In contrast, miR-129-5p was induced in HSCs transfected by OPN siRNA. These data suggested that OPN induces Col 1 expression via suppression of miR-129-5p in HSCs.
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Colágeno Tipo I/genética , Cirrose Hepática/genética , MicroRNAs/genética , Osteopontina/genética , Regiões 3' não Traduzidas/genética , Linhagem Celular , Proliferação de Células/genética , Cadeia alfa 1 do Colágeno Tipo I , Regulação da Expressão Gênica , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Humanos , Fígado/metabolismo , Cirrose Hepática/patologia , Osteopontina/farmacologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Transdução de Sinais/genéticaRESUMO
Background: HER2-positive breast cancer is one of the most prevalent subtypes of breast cancer and represents a significant health concern for women worldwide due to its high morbidity and mortality rates. Recent studies have consistently underscored the pivotal role of angiogenesis in the development and progression of HER2-positive breast cancer. Here, we developed a prognostic signature based on angiogenesis-related genes (ARGs) to categorize HER2-positive breast cancer patients and provide insights into their survival outcomes. Methods: Kaplan-Meier survival curve, time-dependent receiver operating characteristic (ROC) and nomogram were performed to investigate the prognostic performance of the signature. In addition, we comprehensively analyzed the correlation of the prognostic signature with immune cell infiltration, immune checkpoint inhibitors (ICIs) therapy. Finally, Immunohistochemistry (IHC) and immunoblotting were used to investigate XBP1 expression in HER2-positive breast cancer tissues. Colony formation assay was performed to examine cell proliferation of HER2-positive breast cancer cells. Results: The Kaplan-Meier curves and the ROC curves demonstrated that the ARGs had good performance in predicting the prognosis of HER2-positive breast cancer patients. In addition, we observed that the low-risk group was remarkably associated with immune infiltration and better response to ICIs. Further experimental results show that XBP1 is upregulated in human HER2-positive breast cancer, and its knockdown significantly inhibited cell proliferation. Conclusions: Our study demonstrated that the ARGs could serve as a novel biomarker for predicting the prognosis of patients with HER2-positive breast cancer and providing new insights into immunotherapy strategies for these patients.
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Inadequate osseointegration at the interface is a key factor in orthopedic implant failure. Mechanistically, traditional orthopedic implant interfaces fail to precisely match natural bone regeneration processes in vivo. In this study, a novel biomimetic coating on titanium substrates (DPA-Co/GFO) through a mussel adhesion-mediated ion coordination and molecular clicking strategy is engineered. In vivo and in vitro results confirm that the coating exhibits excellent biocompatibility and effectively promotes angiogenesis and osteogenesis. Crucially, the biomimetic coating targets the integrin α2ß1 receptor to promote M2 macrophage polarization and achieves a synergistic effect between immunomodulation and vascularized bone regeneration, thereby maximizing osseointegration at the interface. Mechanical push-out tests reveal that the pull-out strength in the DPA-Co/GFO group is markedly greater than that in the control group (79.04 ± 3.20 N vs 31.47 ± 1.87 N, P < 0.01) and even surpasses that in the sham group (79.04 ± 3.20 N vs 63.09 ± 8.52 N, P < 0.01). In summary, the novel biomimetic coating developed in this study precisely matches the natural process of bone regeneration in vivo, enhancing interface-related osseointegration and showing considerable potential for clinical translation and applications.
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Regeneração Óssea , Imunomodulação , Osseointegração , Titânio , Animais , Osseointegração/efeitos dos fármacos , Osseointegração/fisiologia , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/fisiologia , Imunomodulação/efeitos dos fármacos , Titânio/química , Bivalves , Peptídeos/farmacologia , Peptídeos/química , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Modelos Animais , Materiais Biomiméticos/farmacologia , Materiais Biomiméticos/químicaRESUMO
Implant-associated infections (IAIs) pose a significant threat to orthopedic surgeries. Bacteria colonizing the surface of implants disrupt bone formation-related cells and interfere with the osteoimmune system, resulting in an impaired immune microenvironment and osteogenesis disorders. Inspired by nature, a zeolitic imidazolate framework (ZIF)-sealed smart drug delivery system on Ti substrates (ZSTG) was developed for the "natural-artificial dual-enzyme intervention (NADEI)" strategy to address these challenges. The subtle sealing design of ZIF-8 on the TiO2 nanotubes ensured glucose oxidase (GOx) activity and prevented its premature leakage. In the acidic infection microenvironment, the degradation of ZIF-8 triggered the rapid release of GOx, which converted glucose into H2O2 for disinfection. The Zn2+ released from degraded ZIF-8, as a DNase mimic, can hydrolyze extracellular DNA, which further enhances H2O2-induced disinfection and prevents biofilm formation. Importantly, Zn2+-mediated M2 macrophage polarization significantly improved the impaired osteoimmune microenvironment, accelerating bone repair. Transcriptomics revealed that ZSTG effectively suppressed the inflammatory cascade induced by lipopolysaccharide while promoting cell proliferation, homeostasis maintenance, and bone repair. In vitro and in vivo results confirmed the superior anti-infective, osteoimmunomodulatory, and osteointegrative capacities of the ZSTG-mediated NADEI strategy. Overall, this smart bionic platform has significant potential for future clinical applications to treat IAIs.
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Anti-Infecciosos , Zeolitas , Osseointegração , Peróxido de Hidrogênio/farmacologia , Macrófagos , Anti-Infecciosos/farmacologia , OsteogêneseRESUMO
Lumbar spinal canal stenosis is primarily caused by ligamentum flavum hypertrophy (LFH), which is a significant pathological factor. Nevertheless, the precise molecular basis for the development of LFH remains uncertain. The current investigation observed a notable increase in thrombospondin-1 (THBS1) expression in LFH through proteomics analysis and single-cell RNA-sequencing analysis of clinical ligamentum flavum specimens. In laboratory experiments, it was demonstrated that THBS1 triggered the activation of Smad3 signaling induced by transforming growth factor ß1 (TGFß1), leading to the subsequent enhancement of COL1A2 and α-SMA, which are fibrosis markers. Furthermore, experiments conducted on a bipedal standing mouse model revealed that THBS1 played a crucial role in the development of LFH. Sestrin2 (SESN2) acted as a stress-responsive protein that suppressed the expression of THBS1, thus averting the progression of fibrosis in ligamentum flavum (LF) cells. To summarize, these results indicate that mechanical overloading causes an increase in THBS1 production, which triggers the TGFß1/Smad3 signaling pathway and ultimately results in the development of LFH. Targeting the suppression of THBS1 expression may present a novel approach for the treatment of LFH.
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Ligamento Amarelo , Proteína Smad3 , Trombospondinas , Fator de Crescimento Transformador beta1 , Animais , Camundongos , Fibrose , Hipertrofia/metabolismo , Ligamento Amarelo/metabolismo , Ligamento Amarelo/patologia , Transdução de Sinais , Estresse Mecânico , Trombospondinas/genética , Trombospondinas/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismoRESUMO
The role of co-agonists of glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) in chronic kidney disease (CKD) remains unclear. Herein we found that GLP-1R and GCGR expression levels were lower in the kidneys of mice with CKD compared to healthy mice and were correlated with disease severity. Interestingly, GLP-1R or GCGR knockdown aggravated the progression of kidney injury in both diabetic db/db mice and non-diabetic mice undergoing unilateral ureteral obstruction (UUO). Based on the importance of GLP-1R and GCGR in CKD, we reported a novel monomeric peptide, 1907-B, with dual-agonism on both GLP-1R and GCGR. The data confirmed that 1907-B had a longer half-life than long-acting semaglutide in rats or cynomolgus monkeys (â¼2-3 fold) and exhibited better therapeutic contribution to CKD than best-in-class monoagonists, semaglutide, or glucagon, in db/db mice and UUO mice. Various lock-of-function models, including selective pharmacological activation and genetic knockdown, confirmed that 1907-B's effects on ameliorating diabetic nephropathy in db/db mice, as well as inhibiting kidney fibrosis in UUO mice, were mediated through GLP-1 and glucagon signaling. These findings highlight that 1907-B, a novel GLP-1R and GCGR co-agonist, exerts multifactorial improvement in kidney injuries and is an effective and promising therapeutic option for CKD treatment.
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Poor wound healing after diabetes mellitus remains a challenging problem, and its pathophysiological mechanisms have not yet been fully elucidated. Persistent bleeding, disturbed regulation of inflammation, blocked cell proliferation, susceptible infection and impaired tissue remodeling are the main features of diabetic wound healing. Conventional wound dressings, including gauze, films and bandages, have a limited function. They generally act as physical barriers and absorbers of exudates, which fail to meet the requirements of the whol diabetic wound healing process. Wounds in diabetic patients typically heal slowly and are susceptible to infection due to hyperglycemia within the wound bed. Once bacterial cells develop into biofilms, diabetic wounds will exhibit robust drug resistance. Recently, the application of stimuli-responsive hydrogels, also known as "smart hydrogels", for diabetic wound healing has attracted particular attention. The basic feature of this system is its capacities to change mechanical properties, swelling ability, hydrophilicity, permeability of biologically active molecules, etc., in response to various stimuli, including temperature, potential of hydrogen (pH), protease and other biological factors. Smart hydrogels can improve therapeutic efficacy and limit total toxicity according to the characteristics of diabetic wounds. In this review, we summarized the mechanism and application of stimuli-responsive hydrogels for diabetic wound healing. It is hoped that this work will provide some inspiration and suggestions for research in this field.
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Kidney fibrosis is a serious consequence of chronic kidney disease (CKD), and currently, there is no effective pharmacological treatment available. Cellular communication network-2 (CCN2/CTGF) is an extracellular matrix (ECM) protein that regulates the fibrotic process by activating the epidermal growth factor receptor (EGFR) signaling pathway. We herein present the discovery and structure-activity relationship study of novel peptides targeting CCN2 to develop potent and stable specific inhibitors of the CCN2/EGFR interaction. Remarkably, the 7-mer cyclic peptide OK2 exhibited potent activities to inhibit CCN2/EGFR-induced STAT3 phosphorylation and cellular ECM protein synthesis. Subsequent in vivo studies demonstrated that OK2 significantly alleviated renal fibrosis in a unilateral ureteral obstruction (UUO) mouse model. Moreover, this study first revealed that the peptide candidate could efficiently block CCN2/EGFR interaction through binding to the CT domain of CCN2, providing a new alternative strategy for peptide-based targeting of CCN2 and modulating CCN2/EGFR-mediated biological functions in kidney fibrosis.
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Fator de Crescimento do Tecido Conjuntivo , Peptídeos Cíclicos , Camundongos , Animais , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/uso terapêutico , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Receptores ErbB/metabolismo , Rim/metabolismo , FibroseRESUMO
BACKGROUND: Total hip arthroplasty (THA) using the direct anterior approach (DAA) is becoming increasingly popular due to its potential benefits over the posterolateral approach (PLA). However, few studies have compared the efficacies of these two surgical approaches in hip fusion treatment. This study compared early clinical direct anterior and posterolateral THA outcomes in hip fusion treatment. METHODS: Here, 127 hips (65 DAA, 62 PLA) were retrospectively evaluated. Early postoperative functional outcomes of DAA and PLA groups were assessed using Harris score and Oxford Hip Score (OHS) and standard anteroposterior hip radiographs. Surgical characteristics, perioperative results, and complications within 6 months postoperatively were recorded. RESULTS: Though baseline values were similar, Harris and OHS scores were better in the DAA group than in the PLA group at 1 and 3 months postoperatively. The average cup anteversion angle was significantly greater in the DAA group than in the PLA group (12.7° vs. 11.1°). More hips undergoing DAA were successfully orientated in both inclination and anteversion angles (46 vs. 32). Early postoperative hip function predictors were preoperative fused hip position, surgical approach, and range of motion. DAA was associated with reduced postoperative blood loss and shorter hospital stays. Furthermore, 14 vs. 8 complications occurred in the DAA vs. PLA group. Lateral femoral cutaneous nerve injuries were observed in eight hips (12.3%) of the DAA group. CONCLUSION: For fused or ankylosed hips, THA using DAA in the lateral decubitus position may result in excellent prosthesis positioning and faster postoperative recovery throughout early follow-up vs. PLA.
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With 2-COOH and 4-SH donors all packed onto the benzene ring, tetrasulfanyl terephthalic acid (TST) is a simple yet fully equipped ligand to move the field of metal-coordination materialsâit is now accomplished. The hard-soft carboxyl-thiol synergy is leveraged here in selectively bonding the carboxyl units to Zr(IV) ions to form the same cubic net of UiO-66 (this being based on the terephthalic linker)âwith the free-standing dithiolene units equipping the grid of ZrTST. The 3D network of ZrTST averages about 7.6 connections [as in Zr6O4(OH)4(C8H4O4S4)3.8], with the other 4.4 sealed by acetate ions. The ZrTST solid is stable in boiling water (it is formed in water/acetic acid/ethane dithiol) and remains ordered even above 300 °C. The thiol-enabled ZrTST (powder) takes up mercury from water with a high distribution coefficient Kd (e.g., 1.2 × 106 mL·g-1); it also shows proton conductivity (1.9 × 10-3 S·cm-1 at 90 °C and 90% relative humidity), which, most notably, increases to a highest value of 3.7 × 10-1 S·cm-1 after oxidizing the -SH into the -SO3H groups.
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Implant-associated infection (IAI) is increasingly emerging as a serious threat with the massive application of biomaterials. Bacteria attached to the surface of implants are often difficult to remove and exhibit high resistance to bactericides. In the quest for novel antimicrobial strategies, conventional antimicrobial materials often fail to exert their function because they tend to focus on direct bactericidal activity while neglecting the modulation of immune systems. The inflammatory response induced by host immune cells was thought to be a detrimental force impeding wound healing. However, the immune system has recently received increasing attention as a vital player in the host's defense against infection. Anti-infective strategies based on the modulation of host immune defenses are emerging as a field of interest. This review explains the importance of the immune system in combating infections and describes current advanced immune-enhanced anti-infection strategies. First, the characteristics of traditional/conventional implant biomaterials and the reasons for the difficulty of bacterial clearance in IAI were reviewed. Second, the importance of immune cells in the battle against bacteria is elucidated. Then, we discuss how to design biomaterials that activate the defense function of immune cells to enhance the antimicrobial potential. Based on the key premise of restoring proper host-protective immunity, varying advanced immune-enhanced antimicrobial strategies were discussed. Finally, current issues and perspectives in this field were offered. This review will provide scientific guidance to enhance the development of advanced anti-infective biomaterials.