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1.
J Cell Mol Med ; 28(8): e18291, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38597412

RESUMEN

Natural immunoglobulin M (IgM) antibodies have been shown to recognize post-ischemic neoepitopes following reperfusion of tissues and to activate complement. Specifically, IgM antibodies and complement have been shown to drive hepatic ischemia reperfusion injury (IRI). Herein, we investigate the therapeutic effect of C2 scFv (single-chain antibody construct with specificity of a natural IgM antibody) on hepatic IRI in C57BL/6 mice. Compared with PBS-treated mice, C2 scFv-treated mice displayed almost no necrotic areas, significant reduction in serum ALT, AST and LDH levels, and significantly reduced in the number of TUNEL positive cells. Moreover, C2 scFv-treated mice exhibited a notable reduction in inflammatory cells after hepatic IRI than PBS-treated mice. The serum IL-6, IL-1ß, TNF-α and MPC-1 levels were also severely suppressed by C2 scFv. Interestingly, C2 scFv reconstituted hepatic inflammation and IRI in Rag1-/- mice. We found that C2 scFv promoted hepatic cell death and increased inflammatory cytokines and infiltration of inflammatory cells after hepatic IRI in Rag1-/- mice. In addition, IgM and complement 3d (C3d) were deposited in WT mice and in Rag1-/- mice reconstituted with C2 scFv, indicating that C2 scFv can affect IgM binding and complement activation and reconstitute hepatic IRI. C3d expression was significantly lower in C57BL/6 mice treated with C2 scFv compared to PBS, indicating that excessive exogenous C2 scFv inhibited complement activation. These data suggest that C2 scFv alleviates hepatic IRI by blocking complement activation, and treatment with C2 scFv may be a promising therapy for hepatic IRI.


Asunto(s)
Hígado , Daño por Reperfusión , Animales , Ratones , Ratones Endogámicos C57BL , Hígado/metabolismo , Inmunoglobulina M , Proteínas del Sistema Complemento , Proteínas de Homeodominio/metabolismo
2.
New Phytol ; 242(6): 2555-2569, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38594216

RESUMEN

Gibberellic acid (GA) plays a central role in many plant developmental processes and is crucial for crop improvement. DELLA proteins, the core suppressors in the GA signaling pathway, are degraded by GA via the 26S proteasomal pathway to release the GA response. However, little is known about the phosphorylation-mediated regulation of DELLA proteins. In this study, we combined GA response assays with protein-protein interaction analysis to infer the connection between Arabidopsis thaliana DELLAs and the C-TERMINAL DOMAIN PHOSPHATASE-LIKE 3 (CPL3), a phosphatase involved in the dephosphorylation of RNA polymerase II. We show that CPL3 directly interacts with DELLA proteins and promotes DELLA protein stability by inhibiting its degradation by the 26S proteasome. Consequently, CPL3 negatively modulates multiple GA-mediated processes of plant development, including hypocotyl elongation, flowering time, and anthocyanin accumulation. Taken together, our findings demonstrate that CPL3 serves as a novel regulator that could improve DELLA stability and thereby participate in GA signaling transduction.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Flores , Regulación de la Expresión Génica de las Plantas , Giberelinas , Unión Proteica , Giberelinas/metabolismo , Arabidopsis/crecimiento & desarrollo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Flores/crecimiento & desarrollo , Flores/genética , Proteolisis , Estabilidad Proteica , Fosfoproteínas Fosfatasas/metabolismo , Fosfoproteínas Fosfatasas/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Hipocótilo/crecimiento & desarrollo , Hipocótilo/metabolismo , Transducción de Señal , Antocianinas/metabolismo , Fosforilación
3.
Plant Dis ; 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38426893

RESUMEN

In September 2023, brown rot disease was observed on cloves of garlic (Allium sativum) variety "Zipi-1" (purple skin) collected from Jinxiang County, China during scientific research at the Beijing Academy of Agricultural and Forestry Sciences after being planted in nutrient soil for approximately 2 weeks in a growth chamber maintaining 22℃, 60% relative humidity, and 16 hours of light. Out of the 90 garlic cloves investigated, 18 showed signs of decay, characterized by a brown color and rot, with the surface covered in blue and white mold layers. Six symptomatic cloves were collected for isolating the pathogen using the method described in a previous study (Wu et al. 2021). After 2 d of incubation, individual spores were harvested from the fungal colonies and recultured. Single-spore cultures growing on PDA medium appeared white and flocculent when viewed from the top, and yellowish-brown when viewed from the bottom. After 5 d of cultivation, the colonies had a diameter of approximately 5.8 cm and microscopic examination revealed that the mycelium had a diameter of about 9-13 µm (Fig. S1a, b and c). Isolate As1 produced three types of spores: oval-shaped chlamydospores with a diameter of approximately 6 µm, while spindle-shaped microconidia and sickle-shaped macroconidia measuring approximately 6-7 × 20-30 µm and 8 × 50 µm, respectively (Fig. S1d and e). The mycelial characteristics and reproductive structures of the isolates fit the morphological description of Fusarium solani (Xie et al. 2022). To confirm the identification, TEF1, RPB1 and RPB2 regions of the genome were amplified from three separate isolates (As1, As2, and As3) using EF1/EF2, RPB1-Fa/G2R, RPB2-5F2/7cR, and RPB2-7cF/11aR primer pairs (O'Donnell et al. 2022). The results indicated that the sequences of the three isolates were completely identical. Furthermore, the BLASTn comparison results of the TEF1 (OR916018, 710bp, 100%), RPB1 (OR916019, 1797bp, 99.8%), and RPB2 (OR916020, 1874bp, 100%) sequences in the FUSARIUM-ID v.3.0 database revealed that As1 was identified as F. solani species complex 5 (O'Donnell et al. 2022). To assess the pathogenicity of As1, the surface of healthy garlic cloves (n = 30) was spread with 106 microconidia/mL As1 suspension, while a control group (n = 30) was inoculated with sterile water. All inoculated cloves were placed in an artificial climate chamber under same conditions described above. After 10 d, all inoculated cloves exhibited rot symptoms consistent with those of the initially infected cloves identified in September 2023, while the control plant cloves remained asymptomatic (Fig. S2). Based on morphological and molecular characters (TEF1, RPB1, and RPB2), the reisolated pathogen from diseased plants was identical to the As1 isolate used for inoculation, and the disease assays were repeated twice. Fusarium spp. has been reported as the causal agent of garlic rot disease in several countries such as Mexico, America, and Russia (Gálvez and Palmero 2022). Tai (1979) previously published a report on the presence of F. solani in garlic; however, the content in the book is rather basic, lacking detailed information on the isolation, identification, and the potential for causing garlic diseases, whether postharvest or during growth. Our research can be considered a supplement and improvement to the study by Tai (1979) and lays the groundwork for future studies on management strategies to combat plant diseases caused by F. solani.

4.
BMC Anesthesiol ; 24(1): 51, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38317099

RESUMEN

BACKGROUND: Sufentanil in combination with dezocine or esketamine is often used for postoperative analgesia. However, there is a lack of clinical evidence of efficacy. This study compares the analgesic effects of esketamine and dezocine combined with sufentanil for relieving pain after laparoscopic cholecystectomy(LC). METHODS: A total of 58 patients were randomly assigned to the esketamine group (ES group) and dezocine group (DE group). In the ES group, 1.5 mg/kg esketamine was used. In the DE group, 0.3 mg/kg dezocine was used. Primary outcome measures were Visual Analog Scale (VAS) score at 4 h, 8 h, 24 h and 48 h after surgery. The second outcome measures were Interleukin-6 (IL-6) and C-reactive protein (CRP) levels in the serum 10 minutes before anesthesia induction, and at 24 h and 48 h after surgery. RESULTS: The VAS scores at 4 h, 8 h, 24 h and 48 h after the surgery in the ES group vs DE group were 2.70 vs 3.50(P=0.013),2.35 vs 3.15(P=0.004),1.69 vs 2.58(P=0.002), and 1.50 vs 2.26(P=0.002), respectively. The serum IL-6 concentrations 10 minutes before anesthesia induction, and at 24 h and 48 h after surgery in the ES group and DE group were 34.39 and 34.12(P=0.901),112.33 and 129.60(P=0.014), and 89.69 and 108.46(P<0.001), respectively. The CRP levels in serum 10 minutes before anesthesia induction, and at 24 h and 48 h after the surgery in the ES group and DE group were 5.99 and 5.86(P=0.639), 28.80 and 35.37(P<0.001), and 23.17 and 30.11(P<0.001), respectively. CONCLUSION: For postoperative pain after LC, 1.5mg/kg esketamine provided better analgesia and reduced inflammation levels than 0.3mg/kg dezocine. TRIAL REGISTRATION: This trial was registered in the China Clinical Research Information Center in 31/05/2023 : https://www.chictr.org.cn/bin/home (Registration number: ChiCTR2300072011).


Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes , Colecistectomía Laparoscópica , Ketamina , Sufentanilo , Tetrahidronaftalenos , Humanos , Sufentanilo/uso terapéutico , Analgésicos Opioides/uso terapéutico , Estudios Prospectivos , Interleucina-6 , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Método Doble Ciego
5.
Osteoporos Int ; 35(1): 117-128, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37670164

RESUMEN

This study utilized deep learning to classify osteoporosis and predict bone density using opportunistic CT scans and independently tested the models on data from different hospitals and equipment. Results showed high accuracy and strong correlation with QCT results, showing promise for expanding osteoporosis screening and reducing unnecessary radiation and costs. PURPOSE: To explore the feasibility of using deep learning to establish a model for osteoporosis classification and bone density value prediction based on opportunistic CT scans and to verify its generalization and diagnostic ability using an independent test set. METHODS: A total of 1219 cases of opportunistic CT scans were included in this study, with QCT results as the reference standard. The training set: test set: independent test set ratio was 703: 176: 340, and the independent test set data of 340 cases were from 3 different hospitals and 4 different CT scanners. The VB-Net structure automatic segmentation model was used to segment the trabecular bone, and DenseNet was used to establish a three-classification model and bone density value prediction regression model. The performance parameters of the models were calculated and evaluated. RESULTS: The ROC curves showed that the mean AUCs of the three-category classification model for categorizing cases into "normal," "osteopenia," and "osteoporosis" for the training set, test set, and independent test set were 0.999, 0.970, and 0.933, respectively. The F1 score, accuracy, precision, recall, precision, and specificity of the test set were 0.903, 0.909, 0.899, 0.908, and 0.956, respectively, and those of the independent test set were 0.798, 0.815, 0.792, 0.81, and 0.899, respectively. The MAEs of the bone density prediction regression model in the training set, test set, and independent test set were 3.15, 6.303, and 10.257, respectively, and the RMSEs were 4.127, 8.561, and 13.507, respectively. The R-squared values were 0.991, 0.962, and 0.878, respectively. The Pearson correlation coefficients were 0.996, 0.981, and 0.94, respectively, and the p values were all < 0.001. The predicted values and bone density values were highly positively correlated, and there was a significant linear relationship. CONCLUSION: Using deep learning neural networks to process opportunistic CT scan images of the body can accurately predict bone density values and perform bone density three-classification diagnosis, which can reduce the radiation risk, economic consumption, and time consumption brought by specialized bone density measurement, expand the scope of osteoporosis screening, and have broad application prospects.


Asunto(s)
Enfermedades Óseas Metabólicas , Aprendizaje Profundo , Osteoporosis , Humanos , Densidad Ósea , Osteoporosis/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Estudios Retrospectivos
6.
Nat Commun ; 14(1): 7169, 2023 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-37935692

RESUMEN

The precise modification or functionalization of the protein C-terminus is essential but full of challenges. Herein, a chemical approach to modify the C-terminus is developed by fusing a cysteine protease domain on the C-terminus of the protein of interest, which could achieve the non-enzymatic C-terminal functionalization by InsP6-triggered cysteine protease domain self-cleavage. This method demonstrates a highly efficient way to achieve protein C-terminal functionalization and is compatible with a wide range of amine-containing molecules and proteins. Additionally, a reversible C-terminal de-functionalization is found by incubating the C-terminal modified proteins with cysteine protease domain and InsP6, providing a tool for protein functionalization and de-functionalization. Last, various applications of protein C-terminal functionalization are provided in this work, as demonstrated by the site-specific assembly of nanobody drug conjugates, the construction of a bifunctional antibody, the C-terminal fluorescent labeling, and the C-terminal transpeptidation and glycosylation.


Asunto(s)
Proteasas de Cisteína , Proteína C , Proteína C/metabolismo , Proteínas/metabolismo , Glicosilación , Proteasas de Cisteína/metabolismo , Cisteína/metabolismo
7.
Mitochondrial DNA B Resour ; 8(8): 890-894, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37622030

RESUMEN

Allium fistulosum L. (Linnaeus, Carolus, 1753) is an aromatic vegetable with health benefits and medicinal value. In this study, the complete mitochondrial genome of A. fistulosum was determined. Circular mitochondrial DNA (mtDNA) was 382,053 bp in size, encoded 44 genes, and contained 26 protein-coding genes (PCGs), 14 tRNAs, and four rRNAs. Phylogenetic analysis of amino acid sequences of the 26 PCGs revealed that the closest relationship was between A. fistulosum and Allium cepa. The high-quality mitochondrial genomic sequences of A. fistulosum presented in this study will serve as a useful resource for a range of genetic, functional, evolutionary, and comparative genomic studies on this species of the Amaryllidaceae family.

8.
J Mol Cell Cardiol ; 182: 57-72, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37482037

RESUMEN

Hypertension-induced tunica media thickening (TMT) is the most important fundamental for the subsequent complications like stroke and cardiovascular diseases. Pathogenically, TMT originates from both vascular smooth muscle cells (VSMCs) hypertrophy due to synthesizing more amount of intracellular contractile proteins and excess secretion of extracellular matrix. However, what key molecules are involved in the pathogenesis of TMT is unknown. We hypothesize that formin homology 2 domain-containing protein 1 (FHOD1), an amply expressed mediator for assembly of thin actin filament in VSMCs, is a key regulator for the pathogenesis of TMT. In this study, we found that FHOD1 expression and its phosphorylation/activation were both upregulated in the arteries of three kinds of hypertensive rats. Ang-II induced actin filament formation and hypertrophy through activation and upregulation of FHOD1 in VSMCs. Active FHOD1-mediated actin filament assembly and secretions of collagen-1α/collagen-3α played crucial roles in Ang-II-induced VSMCs hypertrophy in vitro and hypertensive TMT in vivo. Proteomics demonstrated that activated FL-FHOD1 or its C-terminal diaphanous-autoregulatory domain significantly upregulated RNF213 (ring finger protein 213), a 591-kDa cytosolic E3 ubiquitin ligase with its loss-of-functional mutations being a susceptibility gene for Moyamoya disease which has prominent tunica media thinning in both intracranial and systemic arteries. Mechanistically, activated FHOD1 upregulated its downstream effector RNF213 independently of its classical pathway of decreasing G-actin/F-actin ratio, transcription, and translation, but dependently on its C-terminus-mediated stabilization of RNF213 protein. FHOD1-RNF213 signaling dramatically promoted collagen-1α/collagen-3α syntheses in VSMCs. Our results discovered a novel signaling axis of FHOD1-RNF213-collagen-1α/collagen-3α and its key role in the pathogenesis of hypertensive TMT.


Asunto(s)
Actinas , Hipertensión , Animales , Ratas , Actinas/metabolismo , Hipertensión/etiología , Hipertrofia , Transducción de Señal/fisiología , Factores de Transcripción , Túnica Media/metabolismo
9.
Genes (Basel) ; 14(6)2023 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-37372466

RESUMEN

BAHD acyltransferases (BAHDs), especially those present in plant epidermal wax metabolism, are crucial for environmental adaptation. Epidermal waxes primarily comprise very-long-chain fatty acids (VLCFAs) and their derivatives, serving as significant components of aboveground plant organs. These waxes play an essential role in resisting biotic and abiotic stresses. In this study, we identified the BAHD family in Welsh onion (Allium fistulosum). Our analysis revealed the presence of AfBAHDs in all chromosomes, with a distinct concentration in Chr3. Furthermore, the cis-acting elements of AfBAHDs were associated with abiotic/biotic stress, hormones, and light. The motif of Welsh onion BAHDs indicated the presence of a specific BAHDs motif. We also established the phylogenetic relationships of AfBAHDs, identifying three homologous genes of CER2. Subsequently, we characterized the expression of AfCER2-LIKEs in a Welsh onion mutant deficient in wax and found that AfCER2-LIKE1 plays a critical role in leaf wax metabolism, while all AfCER2-LIKEs respond to abiotic stress. Our findings provide new insights into the BAHD family and lay a foundation for future studies on the regulation of wax metabolism in Welsh onion.


Asunto(s)
Ácidos Grasos , Cebollas , Cebollas/genética , Ácidos Grasos/metabolismo , Filogenia , Epidermis de la Planta/genética , Epidermis de la Planta/metabolismo , Ceras/metabolismo
10.
Mater Today Bio ; 21: 100694, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37346780

RESUMEN

In-situ renal tissue engineering is promising yet challenging for renal injury repair and regeneration due to the highly vascularized structure of renal tissue and complex high-oxidative stress and ischemic microenvironment. Herein, a novel biocompatible 3D porous hydrogel (DFO-gel) with sustained release capacity of hypoxia mimicking micromolecule drug deferoxamine (DFO) was developed for in-situ renal injury repair. In vitro and in vivo experimental results demonstrated that the developed DFO-gels can exert the synchronous benefit of scavenging excess reactive oxygen species (ROS) regulating inflammatory microenvironment and promoting angiogenesis for effective renal injury repair by up-regulating hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). The in-situ neogenesis of neonatal glomerular- and tubular-like structures in the implanted areas in the partially nephrectomized rats also suggested the potential for promoting renal injury repair and regeneration. This multifunctional hydrogel can not only exhibit the sustained release and promoted bio-uptake capacity for DFO, but also improve the renal injured microenvironment by alleviating oxidative and inflammatory stress, accelerating neovascularization, and promoting efficient anti-synechia. We believe this work offers a promising strategy for renal injury repair and regeneration.

11.
Carbohydr Polym ; 314: 120919, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37173055

RESUMEN

Hybrid LiMg batteries stand out by combining the rapid lithium diffusion kinetics and the advantages of magnesium. However, the uneven Mg deposits may result in continuous parasitic reactions and penetrate the separator. Herein, cellulose acetate (CA), with functional groups, was applied to engineer coordination with MOFs and construct the evenly-distributed and ample nucleation sites. Moreover, the hierarchical MOFs@CA network was fabricated via the metal ion pre-anchored strategy to regulate the uniform Mg2+ flux and improve ion-conductivity simultaneously. Furthermore, the hierarchical CA networks with well-ordered MOFs provided efficient MOF-to-MOF ion-transportation channels and served as ion sieves to inhibit anion transportation, thereby mitigating polarization. The super dendrite-inhibition and interfacial compatibility was confirmed and the assembled Mo6S8//Mg batteries exhibited high capacity about 105 mAh g-1 and capacity decay of 4 % after 600 cycles at 30 C, which surpassed the state-of-the-art LMBs system employing Mo6S8 electrode. The fabricated GPE sheds fresh strategy for the design of CA-based GPEs and bright light on the promise of high-performance LMBs.

12.
Zhongguo Gu Shang ; 36(3): 255-61, 2023 Mar 25.
Artículo en Chino | MEDLINE | ID: mdl-36946019

RESUMEN

OBJECTIVE: To investigate the biomechanical characteristics of different internal fixations for Pauwels type Ⅲ femoral neck fracture with defect, and provide reference for the treatment of femoral neck fracture. METHODS: Three-dimensional (3D) finite element models of femoral neck fractures were established based on CT images, including fracture and fracture with defects. Four internal fixations were simulated, namely, inverted cannulated screw(ICS), ICS combined with medial buttress plate, the femoral neck system (FNS) and FNS combined with medial buttress plate. The von Mises stress, model stiffness and fracture displacements of fracture models under 2 100 N axial loads were measured and compared. RESULTS: When femoral neck fracture was fixed by ICS and FNS, the peak stress was mainly concentrated on the surface of the screw near the fracture line, and the peak stress of FNS is higher than that of ICS;When the medial buttress plate was combined, the peak stress was increased and transferred to medial buttress plate, with more obvious of ICS fixation. For the same fracture model, the stiffness of FNS was higher than that of ICS. Compared with femoral neck fracture with defects, fracture model showed higher stiffness in the same internal fixation. The use of medial buttress plate increased model stiffness, but ICS increased more than FNS. The fracture displacement of ICS model exceeded that of FNS. CONCLUSION: For Pauwels type Ⅲ femoral neck fracture with defects, FNS had better biomechanical properties than ICS. ICS combined with medial buttress plate can better enhance fixation stability and non-locking plate is recommended. FNS had the capability of shear resistance and needn't combine with medial buttress plate.


Asunto(s)
Fracturas del Cuello Femoral , Humanos , Fracturas del Cuello Femoral/cirugía , Fijación Interna de Fracturas/métodos , Tornillos Óseos , Placas Óseas , Fenómenos Biomecánicos , Análisis de Elementos Finitos
13.
J Med Chem ; 66(1): 1011-1026, 2023 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-36584232

RESUMEN

The inadequate understanding of the structure-activity relationship (SAR) of glycosite-specific antibody-drug conjugates (ADCs) hinders its design and development. Herein, we revealed the systemic SAR and structure-toxicity relationship (STR) of gsADCs by constructing 50 gsADC structures bearing three glycan subtypes and diverse linker-drug combinations. According to the results, extra hydrophilic linkers are indispensable for the intact glycan-based gsADCs to achieve better in vivo efficacy. Meanwhile, the gsADCs that conjugate linker-drug complexes onto the terminal sialic acid are more stable and potent than the ones conjugated onto the terminal galactose in vivo. Notably, the LacNAc-based gsADCs, which shortened the spacer and located the linker-drug more inside the immunoglobulin class G (IgG) Fc cavity, showed excellent hydrophilicity, in vivo activity, pharmacokinetics, and safety. Conclusively, we found that hiding the linker-toxin into the Fc cavity can significantly enhance the therapeutic index of LacNAc-based gsADCs, which will benefit the further design of ADCs with optimal druggability.


Asunto(s)
Antineoplásicos , Inmunoconjugados , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Inmunoconjugados/química , Anticuerpos Monoclonales/química , Fragmentos Fc de Inmunoglobulinas , Polisacáridos , Inmunoglobulina G , Índice Terapéutico , Antineoplásicos/química
14.
J Mater Chem B ; 10(45): 9424-9437, 2022 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-36378134

RESUMEN

Acute kidney injury (AKI) and chronic kidney disease (CKD) are serious global public health issues. Both interconnect closely, and AKI-CKD transition significantly increases the morbidity of CKD and inevitably progresses to end stage renal disease. However, with the current drug delivery system it is hard to achieve precise delivery and apply it to clinical practice due to the local fibrotic milieu of the AKI-CKD transition procedure. Consequently, new treatment options to halt or even reverse AKI-CKD transition are urgently needed. Curcumin and Ac-SDKP were proved to be capable of ameliorating renal injury and restoring renal biological function. However, due to the water-insolubility, poor absorption and ease of degradation features, their utilization based on traditional drug delivery systems was still confined to the laboratory. A new approach for the targeted delivery of curcumin and Ac-SDKP into kidneys is needed. Hydrogels, owing to their capability of targeted-drug delivery and bio-favorable nature, emerge as a promising resolution. Herein, we developed a bioinspired double network hydrogel scaffold loaded with curcumin and N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) to explore the feasibility of drug-loaded hydrogels for treatment of AKI-CKD transition. This double network hydrogel (GCS) was prepared based on gelatin and curcumin-zinc with polydopamine (DOPA) coating and then immobilized with Ac-SDKP on the surface. The prepared hydrogels possessed appropriate porosity, suitable mechanical properties, and excellent biocompatibility. In vitro, the GCS hydrogel was demonstrated to be pro-angiogenic, anti-oxidative and anti-fibrotic. In vivo, after the GCS hydrogel was implanted into partially nephrectomized rat kidneys, local renal fibrosis was observed to be improved significantly, and neo-blood vessels and neonatal renal tubules appeared around the implanted area. We speculated that the GCS hydrogel could ameliorate renal fibrosis and injury significantly and stimulate regeneration in situ. Taken together, this study demonstrated the promising potential of this bioinspired hydrogel scaffold for renal injury repair and renal regeneration.


Asunto(s)
Lesión Renal Aguda , Curcumina , Insuficiencia Renal Crónica , Ratas , Animales , Hidrogeles/farmacología , Hidrogeles/metabolismo , Biomimética , Curcumina/farmacología , Curcumina/uso terapéutico , Curcumina/metabolismo , Riñón/metabolismo , Fibrosis , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Regeneración
15.
Injury ; 53(12): 3904-3911, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36182591

RESUMEN

OBJECTIVES: We have proposed a novel intramedullary nail (Ni-Nail) by incorporating a sustentaculum tali screw to improve the fixation stability of minimally invasive treatment for calcaneal fractures. This study aimed to evaluate the biomechanical characters of the Ni-Nail system and compare it with traditional C-Nail system. METHODS: A finite element model of a Sanders type-IIIAB calcaneal fracture was reconstructed and fixed using two intramedullary nail systems, which was validated by a cadaver study. A vertical loading of 700 N was applied to the subtalar joint surfaces, and 525 N Achilles tendon tension was applied to the superior border of the Achilles tuberosity. The von Mises stresses and fracture displacements of both fixation models were evaluated. RESULTS: The maximum von Mises stress of the screws of Ni-Nail and C-Nail were 27.92 MPa and 57.42 MPa, respectively, while that of the main nail were 67.44 MPa and 53.01 MPa. In addition, the maximum fracture displacement of the Ni-Nail was larger than that of C-Nail by 15.6% (0.37 mm vs.0.32 mm). CONCLUSIONS: Our static simulation analysis showed that both Ni-Nail and C-Nail demonstrated similar biomechanical stability for calcaneal fixation. The Ni-Nail features a simple structure that is easier to operate and less traumatizing. Future studies may consider to further evaluate the clinical effectiveness by clinical trials and follow-ups.


Asunto(s)
Traumatismos del Tobillo , Calcáneo , Fracturas Óseas , Fracturas Intraarticulares , Humanos , Calcáneo/cirugía , Fracturas Intraarticulares/diagnóstico por imagen , Fracturas Intraarticulares/cirugía , Placas Óseas , Fijación Interna de Fracturas , Tornillos Óseos , Fracturas Óseas/cirugía
16.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(9): 1078-1083, 2022 Sep 15.
Artículo en Chino | MEDLINE | ID: mdl-36111468

RESUMEN

Objective: To analyze the characteristics of femoral neck fractures in young and middle-aged adults by means of medical image analysis and fracture mapping technology to provide reference for fracture treatment. Methods: A clinical data of 159 young and middle-aged patients with femoral neck fractures who were admitted between December 2018 and July 2019 was analyzed. Among them, 99 patients were male and 60 were female. The age ranged from 18 to 60 years, with an average age of 47.9 years. There were 77 cases of left femoral neck fractures and 82 cases of right sides. Based on preoperative X-ray film and CT, the fracture morphology was observed and classified according to the Garden classification standard and Pauwels' angle, respectively. Mimics19.0 software was used to reconstruct the three-dimensional models of femoral neck fracture, measure the angle between the fracture plane and the sagittal plane of the human body, and observe whether there was any defect at the fracture end and its position on the fracture surface. Through reconstruction, virtual reduction, and image overlay, the fracture map was established to observe the fracture line and distribution. Results: According to Garden classification standard, there were 6 cases of type Ⅰ, 61 cases of type Ⅱ, 54 cases of type Ⅲ, and 38 cases of type Ⅳ. According to the Pauwels' angle, there were 12 cases of abduction type, 78 cases of intermediate type, and 69 cases of adduction type. The angle between fracture plane and sagittal plane of the human body ranged from -39° to +30°. Most of them were Garden type Ⅱ, Ⅳ and Pauwels intermediate type. The fracture blocks were mainly in the form of a triangle with a long base and mainly distributed below the femoral head and neck junction area. Twenty-six cases (16.35%) were complicated with bone defects, which were mostly found in Garden type Ⅲ, Ⅳ, and Pauwels intermediate type, located at the back of femoral neck and mostly involved 2-4 quadrants. The fracture map showed that the fracture line of the femoral neck was distributed annularly along the femoral head and neck junction. The fracture line was dense above the femoral neck and scattered below, involving the femoral calcar. Conclusion: The proportion of displaced fractures (Garden type Ⅲ, Ⅳ) and unstable fractures (Pauwels intermediate type, adduction type) is high in femoral neck fractures in young and middle-aged adults, and comminuted fractures and bone defects further increase the difficulty of treatment. In clinical practice, it is necessary to choose treatment plan according to fracture characteristics. Anatomic reduction and effective fixation are the primary principles for the treatment of femoral neck fracture in young and middle-aged adults.


Asunto(s)
Fracturas del Cuello Femoral , Fracturas Conminutas , Adolescente , Adulto , Femenino , Fracturas del Cuello Femoral/diagnóstico por imagen , Fracturas del Cuello Femoral/cirugía , Cuello Femoral , Fijación Interna de Fracturas/métodos , Humanos , Masculino , Persona de Mediana Edad , Tecnología , Adulto Joven
17.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(9): 994-1000, 2022.
Artículo en Chino | MEDLINE | ID: mdl-36111717

RESUMEN

OBJECTIVES: To study the changes in the mortality rate and cause of death of hospitalized neonates in grade A tertiary hospitals in Weifang City of Shandong Province during a 10-year period. METHODS: A retrospective analysis was performed on 461 neonates who died in three grade A tertiary hospitals in Weifang City of Shandong Province from January 1, 2012 to December 31, 2021. The related clinical data were collected to examine the changes of neonatal mortality with time, gestational age (GA) and birth weight (BW). The main causes of death of the neonates were compared between the first 5 years (2012-2016) and the last 5 years (2017-2021) in the period. RESULTS: A total of 43 037 neonates were admitted from 2012 to 2021, among whom 461 died, resulting in a mortality rate of 1.07%. The mortality rate in the last 5 years was significantly lower than that in the first 5 years [0.96% (211/22 059 vs 1.19% (250/20 978); P<0.05]. The mortality rate of neonates decreased with the increases in GA and BW (P<0.05). In the first 5 years, the top three main causes of neonatal death were respiratory distress syndrome (RDS), sepsis, and pneumorrhagia, while in the last 5 years, the top three causes were sepsis, pneumorrhagia, and RDS. The leading cause of death was severe asphyxia for the neonates with a GA of <26 weeks and a BW of <750 g in both the first and last 5 years. For the neonates with a GA of 26-<28 weeks, the leading cause of death changed from RDS in the first 5 years to pneumorrhagia in the last 5 years. For the neonates with a BW of 750-<1 000 g, the leading cause of death changed from pneumorrhagia in the first 5 years to RDS in the last 5 years. For the neonates with a GA of 28-<32 weeks and a BW of 1 000-<1 500 g, the leading cause of death was RDS in both the first and last 5 years. For the neonates with a GA of 32-<37 weeks and a BW of 1 500-<2 500 g, the leading cause of death changed from RDS in the first 5 years to sepsis in the last 5 years. The leading cause of death was sepsis for the neonates with a GA of 37-<42 weeks and a BW of 2 500-<4 000 g in both the first and last 5 years. CONCLUSIONS: The mortality rate of neonates in the grade A tertiary hospitals in Weifang City of Shandong Province has been decreasing in the past 10 years, and it decreases with the increases in GA and BW. Sepsis, RDS, and pneumorrhagia are the leading causes of neonatal death. The mortality rate caused by RDS decreases from the first 5 years to the last 5 years, while the mortality rate caused by sepsis or pneumorrhagia increases from the first 5 years to the last 5 years. Therefore, reducing the incidence rates of sepsis, RDS, and pneumorrhagia is the key to reducing neonatal mortality.


Asunto(s)
Muerte Perinatal , Síndrome de Dificultad Respiratoria del Recién Nacido , Sepsis , Peso al Nacer , Causas de Muerte , Femenino , Humanos , Recién Nacido , Estudios Retrospectivos
18.
Carbohydr Polym ; 296: 119950, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36087996

RESUMEN

Sulfurized polyacrylonitrile (SPAN) have been regarded as a promising cathode in high-energy-density lithium-sulfur batteries. However, severe safety issues derived from the electrolyte leakage and the uncontrollable lithium dendrite growth have seriously hindered the practical usage of Li-SPAN batteries. To address these issues, an eco-friendly and porous cellulose gel electrolyte (GE) was designed and prepared by UV photopolymerization and phase inversion methods. Also, covalent functional black phosphorous nanosheets (denoted as BP-Li) were fabricated and chosen as superior Li+ conductors in cellulose GE, ensuring the rapid ion transmission and suppressing the growth of lithium dendrites. As expected, the cellulose/BP-Li GE exhibited satisfactory ionic conductivity up to 5.21 × 10-3 S cm-1 with the high lithium ion transference number of 0.72. The Li-SPAN battery assembled with cellulose/BP-Li GE delivered high capacity of 938.8 mAh g-1 after 500 cycles with the capacity retention of 72.8 %. Hence, the cellulose/BP-Li GE displayed its promising usage in Li-SPAN batteries.


Asunto(s)
Litio , Fósforo , Resinas Acrílicas , Celulosa , Electrólitos , Iones
19.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 39(4): 672-678, 2022 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-36008330

RESUMEN

This study aims to analyze the biomechanical stability of Magic screw in the treatment of acetabular posterior column fractures by finite element analysis. A three-dimensional finite element model of the pelvis was established based on the computed tomography (CT) and magnetic resonance imaging (MRI) data of a volunteer and its effectiveness was verified. Then, the posterior column fracture model of the acetabulum was generated. The biomechanical stability of the four internal fixation models was compared. The 500 N force was applied to the upper surface of the sacrum to simulate human gravity. The maximum implant stresses of retrograde screw fixation, single-plate fixation, double-plate fixation and Magic screw fixation model in standing and sitting position were as follows: 114.10, 113.40 MPa; 58.93, 55.72 MPa; 58.76, 47.47 MPa; and 24.36, 27.50 MPa, respectively. The maximum stresses at the fracture end were as follows: 72.71, 70.51 MPa; 48.18, 22.80 MPa; 52.38, 27.14 MPa; and 34.05, 30.78 MPa, respectively. The fracture end displacement of the retrograde tension screw fixation model was the largest in both states, and the Magic screw had the smallest displacement variation in the standing state, but it was significantly higher than the two plate fixations in the sitting state. Magic screw can satisfy the biomechanical stability of posterior column fracture. Compared with traditional fixations, Magic screw has the advantages of more uniform stress distribution and less stress, and should be recommended.


Asunto(s)
Fracturas Óseas , Fracturas de la Columna Vertebral , Fenómenos Biomecánicos , Placas Óseas , Tornillos Óseos , Análisis de Elementos Finitos , Fijación Interna de Fracturas/métodos , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Humanos
20.
Front Plant Sci ; 13: 891066, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35665193

RESUMEN

Naringenin is an essential precursor for all flavonoids, and effectively promoting naringenin production is crucial in metabolic engineering. The interaction between plant metabolic enzymes ensures metabolic flux. The effect can effectively improve the natural product synthesis of engineering microbial systems. In this study, chalcone isomerase genes in Allium fistulosum have been identified. The expression of AfCHIL is closely related to the accumulation of anthocyanins, and the expression of AfCHIL and AfCHS was highly synchronized. Yeast two-hybrid and firefly luciferase complementation imaging assay further confirmed AfCHIL physically interacted with AfCHS/AfCHI. The bioconversion experiment confirmed that AfCHIL reduced the derailment produced by AfCHS and increased the yield of naringenin. In addition, a system of biosynthesis naringenin involved in AfCHS was constructed, and these results suggested that the potential function between CHS with CHIL advanced naringenin production effectively. In conclusion, this study illustrated the function of AfCHIs in Allium fistulosum and provided new insight into improving the synthesis efficiency of naringenin.

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