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A robust and fully biobased covalent adaptable network (CAN) that allows recyclability, biocompatibility, and controlled biodegradability is reported. The CAN was fabricated through a simple photo-cross-linking method, wherein low-molecular-weight poly(lactic acid) (â¼3 kDa) was modified with end 1,2-dithiolane rings through a one-step Steglich esterification reaction with thioctic acid (TA). These incorporated 1,2-dithiolane rings undergo photoinduced ring-opening polymerization, thus enabling the cross-linking of poly(lactic acid) with abundant dynamic disulfide bonds. The resultant CAN demonstrates excellent transparency, effective UV-blocking capabilities below 320 nm, robust tensile strength (â¼39 MPa), and superior dimensional stability at 80 °C, alongside attractive biocompatibility. Moreover, owing to the dynamic exchange and redox-responsiveness of disulfide bonds, the material can be recycled by hot-pressing and a reduction-oxidation process while also being capable of controllably biodegrading at the end of its lifecycle. Furthermore, it exhibits reconfigurable shape memory properties with fast recovery. This study elucidates a straightforward approach to fabricating multifunctional and sustainable polymer materials with potential applications in diverse fields such as packaging, coating, and biomedicine.
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SCOPE: Polyphenols are the major active substances in red jujube fruit, and their anti-inflammatory and antioxidant activities suggest their potential utility in the prevention of ulcerative colitis (UC). METHODS AND RESULTS: In this study, the effect of polyphenol extracts from red jujube (Ziziphus jujuba Mill. "Junzao") (PERJ) on the dextron sulfate sodium (DSS)-induced UC mice is investigated. The result shows that PERJ effectively improves clinical symptoms, including food and water intake, the disease activity insex (DAI) and spleen index, and routine blood levels, and alleviates the shortening of the colon, in mice with DSS-induced UC. Meanwhile, PERJ remarkably decreases the expression of proinflammatory factors. Moreover, PERJ repairs intestinal barrier damage by increasing the expression level of mucin 2 and mucin 3, and the result is also confirmed in the histological assessment. Besides, the expression levels of Nod-like receptor family pyrin domain-containing 3 (NLRP3) and mitogen-activated protein kinase cascade (MAPKs) signaling pathway-related proteins are inhibited by the PERJ administration. Finally, 16S rRNA sequencing analyses reveal that PERJ reverses intestinal microbiota dysbiosis by enhancing the abundance of Firmicutes and decreasing that of Proteobacteria and Bacteroidetes. CONCLUSION: PERJ probably inhibits the development of UC by suppressing the NLRP3 and MAPKs signaling pathways and regulating gut microbiota homeostasis, and can be considered as a potential resource for preventing UC.
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Colitis Ulcerosa , Microbioma Gastrointestinal , Sistema de Señalización de MAP Quinasas , Extractos Vegetales , Ziziphus , Animales , Masculino , Ratones , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Sulfato de Dextran , Microbioma Gastrointestinal/efectos de los fármacos , Homeostasis/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Extractos Vegetales/farmacología , Polifenoles/farmacología , Ziziphus/químicaRESUMEN
Among various biomaterials employed for bone repair, composites with good biocompatibility and osteogenic ability had received increasing attention from biomedical applications. In this study, we doped selenium (Se) into hydroxyapatite (Se-HA) by the precipitation method, and prepared different amounts of Se-HA-loaded poly (amino acid)/Se-HA (PAA/Se-HA) composites (0, 10 wt%, 20 wt%, 30 wt%) byin-situmelting polycondensation. The physical and chemical properties of PAA/Se-HA composites were characterized by x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and their mechanical properties. XRD and FT-IR results showed that PAA/Se-HA composites contained characteristic peaks of PAA and Se-HA with amide linkage and HA structures. DSC and TGA results specified the PAA/Se-HA30 composite crystallization, melting, and maximum weight loss temperatures at 203.33 °C, 162.54 °C, and 468.92 °C, respectively, which implied good thermal stability. SEM results showed that Se-HA was uniformly dispersed in PAA. The mechanical properties of PAA/Se-HA30 composites included bending, compressive, and yield strengths at 83.07 ± 0.57, 106.56 ± 0.46, and 99.17 ± 1.11 MPa, respectively. The cellular responses of PAA/Se-HA compositesin vitrowere studied using bone marrow mesenchymal stem cells (BMSCs) by cell counting kit-8 assay, and results showed that PAA/Se-HA30 composites significantly promoted the proliferation of BMSCs at the concentration of 2 mg ml-1. The alkaline phosphatase activity (ALP) and alizarin red staining results showed that the introduction of Se-HA into PAA enhanced ALP activity and formation of calcium nodule. Western blotting and Real-time polymerase chain reaction results showed that the introduction of Se-HA into PAA could promoted the expression of osteogenic-related proteins and mRNA (integrin-binding sialoprotein, osteopontin, runt-related transcription factor 2 and Osterix) in BMSCs. A muscle defect at the back and a bone defect at the femoral condyle of New Zealand white rabbits were introduced for evaluating the enhancement of bone regeneration of PAA and PAA/Se-HA30 composites. The implantation of muscle tissue revealed good biocompatibility of PAA and PAA/Se-HA30 composites. The implantation of bone defect showed that PAA/Se-HA30 composites enhanced bone formation at the defect site (8 weeks), exhibiting good bone conductivity. Therefore, the PAA-based composite was a promising candidate material for bone tissue regeneration.
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Durapatita , Selenio , Animales , Conejos , Durapatita/química , Aminoácidos/química , Espectroscopía Infrarroja por Transformada de Fourier , Regeneración Ósea , Osteogénesis , Osteoblastos , Proliferación CelularRESUMEN
l-threonine as an important precursor substance of l-isoleucine and improving its accumulation in Escherichia coli became an important idea to construct a chassis strain with high l-isoleucine production. Meanwhile, the effect of l-threonine metabolic pathway disruption in E. coli for the improved production of l-isoleucine remains unrevealed. In the present study, a mutant strain of E. coli was engineered by inactivating specific metabolic pathways (e.g., Δtdh, ΔltaE, and ΔyiaY) that were associated with l-threonine metabolism but unrelated to l-isoleucine synthesis. This was done with the aim to reduce the breakdown of l-threonine and, thereby, increase the production of l-isoleucine. The results obtained demonstrated a 72.3% increment in l-isoleucine production from 4.34 to 7.48 g·L-1 in the mutant strain compared with the original strain, with an unexpected 10.3% increment in bacterial growth as measured at OD600. Transcriptome analysis was also conducted on both the mutant strain NXU102 and the original strain NXU101 in the present study to gain a comprehensive understanding of their physiological attributes. The findings revealed a notable disparity in 1294 genes between the two strains, with 658 genes exhibiting up-regulation and 636 genes displaying down-regulation. The activity of tricarboxylic acid (TCA) cycle-related genes was found to decrease, but oxidative phosphorylation-related genes were highly up-regulated, which explained the increased activity of the mutant strain. For instance, l-lysine catabolism-related genes were found to be up-regulated, which reconfigured the carbon flow into the TCA cycle. The augmentation of acetic acid degradation pathway-related genes assisted in the reduction in acetic acid accumulation that could retard cell growth. Notably, substantial up-regulation of the majority of genes within the aspartate pathway could potentially account for the increased production of l-isoleucine in the present study. In this paper, a chassis strain with an l-isoleucine yield of 7.48 g·L-1 was successfully constructed by cutting off the threonine metabolic pathway. Meanwhile, transcriptomic analysis revealed that the cutting off of the threonine metabolic pathway induced perturbation of genes related to the pathways associated with the synthesis of l-isoleucine, such as the tricarboxylic acid cycle, glycolysis, and aspartic acid pathway.
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BACKGROUND: Water-free transportation (WFT), as a novel strategy for express delivery of live shrimp (Litopenaeus vannamei), was developed recently. However, air exposure during this transportation arouses a series of abiotic stress to the shrimp. In the present study, the influences of WFT stress on glycolysis and lipolysis metabolism and meat quality (umami flavor and drip loss) were investigated in comparison with conventional water transportation (WT). RESULTS: The results showed that type II muscle fibers with the feature of anaerobic metabolism were dominated in shrimp flesh. In addition, the increments of intracellular Ca2+ was detected in WFT and WT, which then activated the AMP-activated protein kinase pathway and promoted the consumption of glycogen, as well as the accumulation of lactate and lipolysis, under the enzymolysis of hexokinase, pyruvate kinase, lactate dehydrogenase and adipose triglyceride lipase. Glycogen glycolyzed to latate. Meanwhile, ATP degraded along with glycolysis resulting in the generation of ATP-related adenosine phosphates such as inosine monophosphate with umami flavor and phosphoric acid. More remarkable (P < 0.05) physiological changes (except lactate dehydrogenase and lactate) were observed in WFT compared to WT. Additionally, the fatty acid profile also slightly changed. CONCLUSION: The transport stress induced significant energy metabolism changes of shrimp flesh and therefore effected the flesh quality. The intensifications of freshness (K-value) of shrimp flesh were detected as a result of ATP degradation, which were more pronounced after WFT. However, the drip loss of shrimp flesh was more significantly increased (P < 0.05) after WFT compared to WT. © 2023 Society of Chemical Industry.
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Proteínas Quinasas Activadas por AMP , Penaeidae , Animales , Proteínas Quinasas Activadas por AMP/metabolismo , Glucógeno/metabolismo , Lactatos/metabolismo , Lactato Deshidrogenasas/metabolismo , Adenosina Trifosfato , Penaeidae/metabolismoRESUMEN
Electrochemical biosensors based on immobilized enzymes are among the most popular and commercially successful biosensors. The literature in this field suggests that modification of electrodes with nanomaterials is an excellent method for enzyme immobilization, which can greatly improve the stability and sensitivity of the sensor. However, the poor stability, weak reproducibility, and limited lifetime of the enzyme itself still limit the requirements for the development of enzyme electrochemical biosensors for food production process monitoring. Therefore, constructing sensing technologies based on enzyme electrochemical biosensors remains a great challenge. This article outlines the construction principles of four generations of enzyme electrochemical biosensors and discusses the applications of single-enzyme systems, multi-enzyme systems, and nano-enzyme systems developed based on these principles. The article further describes methods to improve enzyme immobilization by combining different types of nanomaterials such as metals and their oxides, graphene-related materials, metal-organic frameworks, carbon nanotubes, and conducting polymers. In addition, the article highlights the challenges and future trends of enzyme electrochemical biosensors, providing theoretical support and future perspectives for further research and development of high-performance enzyme chemical biosensors.
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Wounds on Chinese yam (Dioscorea opposita ) tubers can ocurr during harvest and handling, and rapid suberisation of the wound is required to prevent pathogenic infection and desiccation. However, little is known about the causal relationship among suberin deposition, relevant gene expressions and endogenous phytohormones levels in response to wounding. In this study, the effect of wounding on phytohormones levels and the expression profiles of specific genes involved in wound-induced suberisation were determined. Wounding rapidly increased the expression levels of genes, including PAL , C4H , 4CL , POD , KCSs , FARs , CYP86A1 , CYP86B1 , GPATs , ABCGs and GELPs , which likely involved in the biosynthesis, transport and polymerisation of suberin monomers, ultimately leading to suberin deposition. Wounding induced phenolics biosynthesis and being polymerised into suberin poly(phenolics) (SPP) in advance of suberin poly(aliphatics) (SPA) accumulation. Specifically, rapid expression of genes (e.g. PAL , C4H , 4CL , POD ) associated with the biosynthesis and polymerisation of phenolics, in consistent with SPP accumulation 3days after wounding, followed by the massive accumulation of SPA and relevant gene expressions (e.g. KCSs , FARs , CYP86A1 /B1 , GPATs , ABCGs , GELPs ). Additionally, wound-induced abscisic acid (ABA) and jasmonic acid (JA) consistently correlated with suberin deposition and relevant gene expressions indicating that they might play a central role in regulating wound suberisation in yam tubers.
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Dioscorea , Reguladores del Crecimiento de las Plantas , Dioscorea/genética , Dioscorea/metabolismo , Lípidos/genética , Expresión GénicaRESUMEN
Heat-moisture treatment (HMT) and annealing (ANN) were applied to modify the proso millet starch, and then the physicochemical properties as well as the in vitro digestion of the modified starch were investigated systematically. Results indicated that HMT and ANN did not change the typical A-type crystallinity. However, both processes cause cracks and dents on the surface of the granule. The gelatinization temperature increased while peak viscosity value, relative crystallinity and gelatinization enthalpy of proso millet starch decreased significantly after HTM and ANN. Meanwhile, a remarkable increase of the slowly digestible starch(SDS) and resistant starch(RS) content was noticed after HTM and ANN modification (the highest content of SDS and RS after HTM and ANN were 9.52 ± 0.82 %, 12.03 ± 1.36 % and 12.15 ± 0.89 %, 8.75 ± 1.63 %, respectively). Those results indicated that the ANN and HMT processes could modify the physicochemical properties and in vitro digestion of proso millet starch efficiently and showed potential application to produce healthy starch food with lower digestion.
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Panicum , Almidón , Almidón/química , Calor , Temperatura , Harina/análisisRESUMEN
The emulsification of ultrasonic-assisted prepared octenyl succinic anhydride (OSA) rice starch on curcumin was investigated in the present study. The results indicated that the encapsulation efficiency of curcumin in emulsions stabilized by OSA-ultrasonic treatment rice starch was improved, from 81.65 ± 0.14% to 89.03 ± 0.09%. During the in vitro oral digestion, the particle size and Zeta potential of the curcumin emulsion did not change significantly (p > 0.05). During the in vitro digestive stage of the stomach and small intestine, the particle size of the curcumin emulsion continued to increase, and the absolute potential continued to decrease. Our work showed that OSA-pre-treatment ultrasonic rice starch could improve curcumin bioavailability by increasing the encapsulation efficiency with stronger stability to avoid the attack of enzymes and high intensity ion, providing a way to develop new emulsion-based delivery systems for bioactive lipophilic compounds using OSA starch.
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Curcumina , Oryza , Emulsiones , Almidón , Anhídridos Succínicos , UltrasonidoRESUMEN
Fruits of six varieties of young citrus cultivated in China were collected for phytochemical composition analysis and antioxidant activity determination. The phenolic acids, synephrine, flavone, and flavanone were analyzed using HPLC, and the total phenolic content and antioxidant capacity were determined by Folin-Ciocalteu, Ferric ion reducing antioxidant power (FRAP), 2,2- 1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) analysis. The results indicated that Ougan variety had the highest total phenolic content (125.18 GAE mg/g DW), followed by the Huyou variety (107.33 mg/g DW), while Wanshuwenzhoumigan variety had the lowest (35.91 mg/g DW). Ferulic acid was the most dominant soluble phenolic acid in the selected young citrus, followed by p-coumaric acid and p-hydroxybenzoic acid, whereas nobiletin and tangeretin were the most abundant flavones in the Ponkan, Ougan, and Wanshuwenzhoumigan varieties. Antioxidant capacity that measured by ABTS, FRAP, and DPPH showed similar trends and was positively correlated with the total phenolic and total flavonoid contents (p < 0.05). Considering the high content of phenolics in the young fruits of Ougan and Huyou variety, those two varieties might be potential resources for extracting phytochemicals for health promotion.
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Antioxidantes , Citrus , Antioxidantes/química , Citrus/química , Flavonoides/química , Fenoles/química , Fitoquímicos/análisisRESUMEN
Cerebral small vessel disease (CSVD) is a generic term used for intracranial vascular disorders caused by the structural changes of cerebral microvessels, including the small arteries, arterioles, capillaries and venules. CSVD exhibits various neuroimaging features and is associated clinical characteristics. Although CSVD is recognized as the leading cause of vascular cognitive impairment (VCI), the underlying mechanism(s) remains elusive. Growing evidence indicates a significant association between altered neurovascular unit (NVU) functioning and the pathophysiology of evolving CSVD-induced VCI. Therefore, research is required to understand how NVU dysregulation contributes to cognitive impairment due to CSVD. In this review, we describe the link between the neuroimaging focal lesions and cognitive alterations. We also discuss the potential pathological role of NVU dysregulation in the entry of pathogens from the blood into the parenchyma by altering the blood-brain barrier (BBB), affecting the cerebral microvascular and consequently cause VCI. Next, we review the coupling of neural activity with cerebral blood flow to control the microvascular perfusion; and the disrupted clearance of metabolic byproducts with CSF-ISF exchange via perivascular pathways and glymphatic system. Finally, we discussed the possible therapeutic interventions in CSVD.
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Enfermedades de los Pequeños Vasos Cerebrales , Disfunción Cognitiva , Sistema Glinfático , Enfermedades de los Pequeños Vasos Cerebrales/patología , Disfunción Cognitiva/etiología , Sistema Glinfático/patología , Humanos , Microcirculación , NeuroimagenRESUMEN
OBJECTIVE: This study intended to investigate whether retinal nerve fiber layer (RNFL) thickness could become a potential marker in patients with Parkinson's disease with cognitive impairment (PD-CI). METHODS: Fifty-seven PD patients and 45 age-matched healthy controls (HCs) were recruited in our cross-sectional study and completed optical coherence tomography (OCT) evaluations. PD with normal cognition (PD-NC) and cognitive impairment (PD-CI) patients were divided following the 2015 Movement Disorder Society criteria. RNFL thickness was quantified in subfields of the 3.0-mm circle surrounding the optic disk; while a battery of neuropsychiatric assessments was conducted to estimate the Parkinsonism severity. General linear models and one-way ANOVA were adopted to assess RNFL thickness between subgroups with different cognitive statuses; logistic regression analyses were applied to determine the relation between RNFL and PD-CI cases. RESULTS: Compared with HCs, more thinning of the RNFL was observed in the inferior and temporal sectors in PD patients, especially in the PD-CI group. Inferior RNFL thickness was reduced in PD-CI compared with PD-NC patients. Logistic regression analysis found that inferior RNFL thickness was independently associated with PD-CI cases (odds ratio = 0.923, p = 0.014). Receiver operating characteristic analysis showed that the RNFL-involved combined model provided a high accuracy in screening cognitive deficiency in PD cases (area under the curve = 0.85, p < 0.001). CONCLUSION: Reduced RNFL thickness especially in the inferior sector is independently associated with PD-CI patients. Our study present new perspectives into verifying possible indicators for neuropathological processes or disease severity in Parkinsonians with cognitive dysfunction.
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Glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting enzyme of the pentose phosphate pathway (PPP), plays a pivotal role in plant stress responses. However, the function and mechanism of G6PDHs in crop plants challenged by fungal pathogens remain poorly understood. In this study, a wheat G6DPH gene responding to infection by Puccinia striiformis f. sp. tritici (Pst), designated TaG6PDH2, was cloned and functionally identified. TaG6PDH2 expression was significantly upregulated in wheat leaves inoculated with Pst or treated with abiotic stress factors. Heterologous mutant complementation and enzymatic properties indicate that TaG6PDH2 encodes a G6PDH protein. The transient expression of TaG6PDH2 in Nicotiana benthamiana leaves and wheat protoplasts revealed that TaG6PDH2 is a chloroplast-targeting protein. Silencing TaG6PDH2 via the barley stripe mosaic virus (BSMV)-induced gene silencing (VIGS) system led to compromised wheat resistance to the Pst avirulent pathotype CYR23, which is implicated in weakened H2O2 accumulation and cell death. In addition, TaG6PDH2 was confirmed to interact with the wheat glutaredoxin TaGrxS4. These results demonstrate that TaG6PDH2 endows wheat with increased resistance to stripe rust by regulating reactive oxygen species (ROS) production.
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Basidiomycota , Triticum , Triticum/metabolismo , Glucosafosfato Deshidrogenasa/genética , Glucosafosfato Deshidrogenasa/metabolismo , Peróxido de Hidrógeno/metabolismo , Basidiomycota/genética , Silenciador del Gen , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Resistencia a la Enfermedad/genéticaRESUMEN
Cardiovascular autonomic dysfunctions (CAD) are prevalent in Parkinson's disease (PD). It contributes to the development of cognitive dysfunction, falls and even mortality. Significant progress has been achieved in the last decade. However, the underlying mechanisms and effective treatments for CAD have not been established yet. This review aims to help clinicians to better understand the pathogenesis and therapeutic strategies. The literatures about CAD in patients with PD were reviewed. References for this review were identified by searches of PubMed between 1972 and March 2021, with the search term "cardiovascular autonomic dysfunctions, postural hypotension, orthostatic hypotension (OH), supine hypertension (SH), postprandial hypotension, and nondipping". The pathogenesis, including the neurogenic and non-neurogenic mechanisms, and the current pharmaceutical and non-pharmaceutical treatment for CAD, were analyzed. CAD mainly includes four aspects, which are OH, SH, postprandial hypotension and nondipping, among them, OH is the main component. Both non-neurogenic and neurogenic mechanisms are involved in CAD. Failure of the baroreflex circulate, which includes the lesions at the afferent, efferent or central components, is an important pathogenesis of CAD. Both non-pharmacological and pharmacological treatment alleviate CAD-related symptoms by acting on the baroreflex reflex circulate. However, pharmacological strategy has the limitation of failing to enhance baroreflex sensitivity and life quality. Novel OH treatment drugs, such as pyridostigmine and atomoxetine, can effectively improve OH-related symptoms via enhancing residual sympathetic tone, without adverse reactions of supine hypertension. Baroreflex impairment is a crucial pathological mechanism associated with CAD in PD. Currently, non-pharmacological strategy was the preferred option for its advantage of enhancing baroreflex sensitivity. Pharmacological treatment is a second-line option. Therefore, to find drugs that can enhance baroreflex sensitivity, especially via acting on its central components, is urgently needed in the scientific research and clinical practice.
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Wounding induces a cascade of correlative physiological responses that lead to the repair of damaged tissue. In this study, the effect of wounding on suberin, endogenous hormones and their metabolic genes expression was observed during the wound healing of kiwifruit (Actinidia chinensis Planch.). In addition, the role of abscisic acid (ABA) in wound suberisation was investigated by analysing the coordinated regulation between ABA and other hormones. The wound healing process in kiwifruit could be divided into two stages including: (1) initial accumulation of suberin polyphenolic (SPP) and long carbon chain suberin polyaliphatic monomers (LSPA) before 24h; and (2) massive synthesis of SPP and very long carbon chain suberin polyaliphatic monomers (VLSPA) after 24h. ABA content rapidly increased and induced the jasmonic acid (JA) biosynthesis at the early stage of wound healing. ABA level gradually decreased with the expression of AchCYP707A genes, while the contents of trans-zeatin (t-ZT) and indole-3-acetic acid (IAA) steadily increased at the late stage of wound healing. Exogenous ABA stimulated JA and suberin monomers accumulation, but suppressed both t-ZT and IAA biosynthesis. The role of ABA in wound healing of kiwifruit might be involved in the coordination of both JA-mediated suberin monomers biosynthesis and t-ZT- and IAA-mediated formation of suberised cells via an interaction mechanism.
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Ácido Abscísico , Actinidia , Actinidia/metabolismo , Ciclopentanos , Citocininas , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos , Oxilipinas , Proteínas de Plantas/genéticaRESUMEN
The relationship between fibrinogen and white matter hyperintensities (WMHs) are inconsistent. Whether there are different relationships between WMHs and fibrinogen in disparate subtypes of cerebral small vessel disease (CSVD) remains unknown. Here, we investigated the roles of plasma fibrinogen in sporadic CSVD (sCSVD) and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) patients. We performed a cross-sectional study that included 74 CSVD patients (19 CADASIL and 55 sporadic) and 74 age- and gender-matched healthy controls (HCs). Plasma fibrinogen was determined, and the severity of WMHs in CSVD patients was rated according to Fazekas scales. Univariate analysis and ordinal logistic regression were performed to evaluate the relationship between fibrinogen and the severity of WMHs in CSVD. Both CADASIL and sCSVD patients showed significantly higher plasma fibrinogen levels than HCs. No significant difference in the plasma fibrinogen level was observed between CADASIL and sCSVD. Univariate analysis and ordinal logistic regression indicated that fibrinogen is an independent risk factor for the severity of WMHs in CADASIL patients (odds ratio [OR] =1.064; 95% Confidence interval (CI, 1.004-1.127); p =0.037). However, age (odds ratio [OR] =1.093; 95% CI (1.033-1.156); P = 0.002), but not fibrinogen (odds ratio [OR] =1.004; 95% CI (0.997-1.011); P=0.262), is an independent risk factor for the severity of WMHs in sCSVD patients. Our results suggest that high levels of plasma fibrinogen are associated with the severity of WMHs in CADASIL but not in sCSVD patients, indicating that the role of fibrinogen may be different in disparate subtypes of CSVD. A better understanding of fibrinogen may yield insights into the pathogenesis of CSVD.
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Patients with non-disabling middle cerebral artery (MCA) stenosis (ND-MCAS) are at risk for disabling ischemic cerebrovascular events (DICE) despite aggressive medical therapy. In this study, we aimed to verify whether cerebral circulation time (CCT) was a potential predictor of DICE in patients with ND-MCAS. From January 2015 to January 2020, 46 patients with ND-MCAS treated with aggressive medical therapy were enrolled for digital subtraction angiography (DSA) in this convenience sampling study. They were divided into the DICE (-) and DICE (+) groups based on the occurrence of DICE within 3 months after DSA. The CCT was defined as the time from the appearance of the MCA to the peak intensity of the Trolard vein during DSA. The rCCT (relative CCT) was defined as the ratio of the CCT of the stenotic side (sCCT) to the CCT of the healthy side (hCCT). The differences in sCCT, hCCT, and rCCT between the two groups were analyzed with Mann-Whitney U tests. Logistic regression analysis was performed to evaluate the association between the risk factors and DICE. Receiver operating characteristic (ROC) curves were constructed to assess the predictive value of rCCT in identifying DICE in ND-MCAS patients. The results showed that DICE appeared in 5 of the 46 patients within 3 months. rCCT were significantly increased in the DICE (+) group compared with the DICE (-) group [1.08 (1.05, 1.14) vs. 1.30 (1.22, 1.54), p < 0.001]. Logistic regression analysis found that prolonged rCCT was an independent positive prognostic factor for DICE (odds ratio = 1.273, p = 0.019) after adjustment for potential confounders (age, diabetes, antithrombotic use, and stenosis degree). ROC analysis showed that rCCT provided satisfactory accuracy in distinguishing the DICE (+) group from the DICE (-) group among ND-MCAS patients (area under the curve = 0.985, p < 0.001), with an optimal cutoff point of 1.20 (100% sensitivity, 97.6% specificity). In conclusion, prolonged rCCT is independently associated with the occurrence of DICE in ND-MCAS patients and may be used to identify individuals at risk of DICE.
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Brief pretreatment of cold shock at 13 °C for 3 min proved to be an inducer of heat shock protein 70 (HSP70) and improved stress tolerance as a molecular chaperone. With the improvement of air exposure tolerance, HSP70 in shrimp hemocytes was upregulated in mRNA and protein levels after cold shock. Both HSP70 RNA interference (RNAi) gene knockdown and recombinant HSP70 (rHSP70) injection were successfully established in order to investigate the role of HSP70 in response to air exposure stress. Shrimp receiving rHSP70 showed an improved survival rate (80%) with no significant difference (p > 0.05) compared to cold shock treated shrimp (control, 90%) under air exposure, but the survival rate of HSP70-knockdown shrimp was significantly lower (62%, p < 0.05). Reactive oxygen species (ROS) content, relative expression of cytochrome c, caspase-3 activity, and apoptosis rate in hemocytes of HSP70 enriched shrimp (i.e., cold shock and rHSP70 injection) were significantly lower (p < 0.05) than HSP70-knockdown shrimp. Results suggested that HSP70 could be induced by cold shock and contributed to improve the tolerance of shrimp suffering air exposure by blocking the apoptosis pathway through scavenging intracellular ROS, inhibiting cytochrome c expression, inhibiting release from mitochondria, and inactivating caspase-3. This work updates the understanding of cold shock mechanism in water-free transportation of aquatic animals.