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C1R has been identified to have a distinct function in cutaneous squamous cell carcinoma that goes beyond its role in the complement system. However, it is currently unknown whether C1R is involved in the progression of hepatocellular carcinoma (HCC). HCC tissues were used to examine C1R expression in relation to clinical and pathological factors. Malignant characteristics of HCC cells were assessed through in vitro and in vivo experiments. The mechanism underlying the role of C1R in HCC was explored through RNA-seq, methylation-specific PCR, immuno-precipitation, and dual-luciferase reporter assays. This study found that the expression of C1R decreased as the malignancy of HCC increased and was associated with poor prognosis. C1R promoter was highly methylated through DNMT1 and DNMT3a, resulting in a decrease in C1R expression. Downregulation of C1R expression resulted in heightened malignant characteristics of HCC cells through the activation of HIF-1α-mediated glycolysis. Additionally, decreased C1R expression was found to promote xenograft tumor formation. We found that C-reactive protein (CRP) binds to C1R, and the free CRP activates the NF-κB signaling pathway, which in turn boosts the expression of HIF-1α. This increase in HIF-1α leads to higher glycolysis levels, ultimately promoting aggressive behavior in HCC. Methylation of the C1R promoter region results in the downregulation of C1R expression in HCC. C1R inhibits aggressive behavior in HCC in vitro and in vivo by inhibiting HIF-1α-regulated glycolysis. These findings indicate that C1R acts as a tumor suppressor gene during HCC progression, opening up new possibilities for innovative therapeutic approaches.
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INTRODUCTION: Patients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus. CSPH is defined by hepatic venous pressure gradient (HVPG)≥10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)≥25 kPa can be used as a surrogate of HVPG≥10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS≥25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%-6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS≥25 kPa may benefit from carvedilol therapy. METHODS AND ANALYSIS: This study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS≥25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committees of the Sixth People's Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073864.
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Carvedilol , Hipertensão Portal , Cirrose Hepática , Carvedilol/uso terapêutico , Carvedilol/farmacologia , Humanos , Hipertensão Portal/tratamento farmacológico , Hipertensão Portal/etiologia , Cirrose Hepática/complicações , Método Duplo-Cego , China/epidemiologia , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Antagonistas Adrenérgicos beta/uso terapêutico , Feminino , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Pressão na Veia Porta/efeitos dos fármacos , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/prevenção & controle , Técnicas de Imagem por Elasticidade , Adulto , MasculinoRESUMO
Drought stress inhibits plant growth and agricultural production. Improving plant instantaneous water use efficiency (iWUE), which is strictly regulated by stomata, is an effective way to cope with drought stress. However, the mechanisms of iWUE regulation are poorly understood. Through genetic screening for suppressors of mpk12-4, an Arabidopsis (Arabidopsis thaliana) mutant with a major iWUE quantitative trait locus gene MITOGEN-ACTIVATED PROTEIN KINASE12 deleted, we identified HIGH LEAF TEMPERATURE1 (HT1). Genetic interaction and physiological analyses showed that MPK12 controls iWUE through multiple modules in a high CO2-induced stomatal closing pathway that regulate SLOW ANION CHANNEL-ASSOCIATED1 (SLAC1) activity. HT1 acts downstream of MPK12, whereas OPEN STOMATA1 (OST1) and GUARD CELL HYDROGEN PEROXIDE-RESISTANT1 (GHR1) function downstream of HT1 by activating SLAC1 in iWUE. Photosynthetic-CO2 response curves and biomass analyses under different water-supply conditions showed that HT1 dysfunction improved iWUE and also increased plant growth capacity, and products of HT1 putative orthologs from Brassica (Brassica napus) and rice (Oryza sativa) exhibited functions similar to that of Arabidopsis HT1 in iWUE and the CO2-signaling pathway. Our study revealed the mechanism of MPK12-mediated iWUE regulation in Arabidopsis and provided insight into the internal relationship between iWUE and CO2 signaling in guard cells and a potential target for improving crop iWUE and drought tolerance.
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Plants rely on strigolactones (SLs) to regulate their development and form symbiotic relationships with microbes as part of the adaptive phosphorus (P) efficiency strategies. However, the impact of SLs on root-associated microbial communities in response to P availability remains unknown. Here, root microbiota of SL biosynthesis (max3-11) and perception (d14-1) were compared to wild-type Col-0 plants under different P concentrations. Using high-throughput sequencing, the relationship between SLs, P concentrations, and the root-associated microbiota was investigated to reveal the variation in microbial diversity, composition, and interaction. Plant genotypes and P availability played important but different roles in shaping the root-associated microbial community. Importantly, SLs were found to attract Acinetobacter in low P conditions, which included an isolated CP-2 (Acinetobacter soli) that could promote plant growth in cocultivation experiments. Moreover, SLs could change the topologic structure within co-occurrence networks and increase the number of keystone taxa (e.g., Rhizobiaceae and Acidobacteriaceae) to enhance microbial community stability. This study reveals the key role of SLs in mediating root-associated microbiota interactions.IMPORTANCEStrigolactones (SLs) play a crucial role in plant development and their symbiotic relationships with microbes, particularly in adapting to phosphorus levels. Using high-throughput sequencing, we compared the root microbiota of plants with SL biosynthesis and perception mutants to wild-type plants under different phosphorus concentrations. These results found that SLs can attract beneficial microbes in low phosphorus conditions to enhance plant growth. Additionally, SLs affect microbial network structures, increasing the stability of microbial communities. This study highlights the key role of SLs in shaping root-associated microbial interactions, especially in response to phosphorus availability.
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Lactonas , Microbiota , Fósforo , Raízes de Plantas , Fósforo/metabolismo , Raízes de Plantas/microbiologia , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Microbiota/efeitos dos fármacos , Lactonas/metabolismo , Lactonas/farmacologia , Arabidopsis/microbiologia , Arabidopsis/efeitos dos fármacos , Arabidopsis/metabolismo , Simbiose/efeitos dos fármacosRESUMO
Anthocyanin (AN) has good antioxidant and anti-inflammatory bioactivities, but its poor biocompatibility and low stability limit the application of AN in the food industry. In this study, core-shell structured carriers were constructed by noncovalent interaction using tannic acid (TA) and poloxamer 188 (F68) to improve the biocompatibility, stability and smart response of AN. Under different treatment conditions, TA-F68 and AN were mainly bound by hydrophobic interaction. The PDI is less than 0.1, and the particle size of nanoparticles (NPs) is uniform and concentrated. The retention of the complex was 15.50 % higher than that of AN alone after 9 d of light treatment. After heat treatment for 180 min, the retention rate after loading was 13.87 % higher than that of AN alone. The carrier reduce the damage of AN by the digestive environment, and intelligently and sustainedly release AN when the esterase is highly expressed. In vitro studies demonstrated that the nanocarriers had good biocompatibility and significantly inhibited the overproduction of reactive oxygen species induced by oxidative stress. In addition, AN-TA-F68 has great potential for free radical scavenging at sites of inflammation. In conclusion, the constructed nano-delivery system provides a potential application for oral ingestion of bioactive substances for intervention in ulcerative colitis.
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Antocianinas , Nanopartículas , Antocianinas/farmacologia , Polifenóis/farmacologia , Antioxidantes/farmacologiaRESUMO
BACKGROUND: Cetaceans, having experienced prolonged adaptation to aquatic environments, have undergone evolutionary changes in their respiratory systems. This process of evolution has resulted in the emergence of distinctive phenotypic traits, notably the abundance of elastic fibers and thickened alveolar walls in their lungs, which may facilitate alveolar collapse during diving. This structure helps selective exchange of oxygen and carbon dioxide, while minimizing nitrogen exchange, thereby reducing the risk of DCS. Nevertheless, the scientific inquiry into the mechanisms through which these unique phenotypic characteristics govern the diving behavior of marine mammals, including cetaceans, remains unresolved. RESULTS: This study entails an evolutionary analysis of 42 genes associated with pulmonary fibrosis across 45 mammalian species. Twenty-one genes in cetaceans exhibited accelerated evolution, featuring specific amino acid substitutions in 14 of them. Primarily linked to the development of the respiratory system and lung morphological construction, these genes play a crucial role. Moreover, among marine mammals, we identified eight genes undergoing positive selection, and the evolutionary rates of three genes significantly correlated with diving depth. Specifically, the SFTPC gene exhibited convergent amino acid substitutions. Through in vitro cellular experiments, we illustrated that convergent amino acid site mutations in SFTPC contribute positively to pulmonary fibrosis in marine mammals, and the presence of this phenotype can induce deep alveolar collapse during diving, thereby reducing the risk of DCS during diving. CONCLUSIONS: The study unveils pivotal genetic signals in cetaceans and other marine mammals, arising through evolution. These genetic signals may influence lung characteristics in marine mammals and have been linked to a reduced risk of developing DCS. Moreover, the research serves as a valuable reference for delving deeper into human diving physiology.
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Fibrose Pulmonar , Animais , Humanos , Cetáceos/genética , Cetáceos/metabolismo , Pulmão/metabolismo , Mamíferos/metabolismo , Oxigênio/metabolismoRESUMO
The digestive instability of anthocyanins (ACNs) limits their application in food nutrition, especially precision nutrition. Blueberry ACNs-loaded nanoparticles (Lipo/GA-ACNs NPs) were prepared using gum arabic (GA) as the delivery carrier and liposomal vesicles (Lipo) prepared from soy lecithin as the targeting scaffold. The average particle size of the NPs was 99.4 nm, and the polydispersion index (PDI) was 0.46. The results showed that the presence of the Lipo-GA matrix enhanced the NPs' in vitro stability and antioxidant activity. In addition, the in vitro biocompatibility, uptake ability, lipid-lowering activity, and free-radical scavenging ability were improved to a certain extent. In a high-fat diet (HFD)-induced obese mouse model, oral administration of ACNs-LNP (LNP, liver-targeted nanoparticle) showed better effects on body weight, liver injury, and lipid droplet accumulation in the liver than ACNs. In addition, ACNs-LNP also played a role in regulating HFD-induced gut microbiota imbalance. These results provide a promising ACNs delivery strategy with the potential to be developed into a functional food that targets the liver to prevent fatty liver.
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Mirtilos Azuis (Planta) , Microbioma Gastrointestinal , Nanopartículas , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Antocianinas/farmacologia , Camundongos Obesos , Lecitinas , Goma Arábica/farmacologia , Gotículas Lipídicas , Camundongos Endogâmicos C57BLRESUMO
OBJECTIVES: In diabetes, chronic hyperglycemia increases the overactivation of oxidative phosphorylation of mitochondria in the liver, resulting in oxidative stress (OS) damage. The Nrf2 signaling pathway plays a key role in preventing hepatic oxidative injury and inflammation. This study aims to investigate the therapeutic effect and mechanism of Modified Buyang Huanwu Decoction (mBYHWD) on diabetic liver injury (DLI) by regulating oxidative stress mediated by Nrf2 signaling pathway. METHODS: The experiment was divided into three groups: a control group (db/m mice, Con), a diabetes model group (db/db mice, Mod), and a traditional Chinese medicine group (db/m mice, mBYHWD). Post-treatment, serum from each group was analyzed to assess changes of blood glucose, blood lipid, and liver function. These results were combined with data mining to explore the possible pathogenesis of DLI. Liver tissues were collected to observe the pathological morphology and detect related proteins. RESULTS: The results demonstrated that mBYHWD significantly reduced blood lipids and improved liver function following diabetic liver injury. The histopathological results demonstrated that mBYHWD could significantly ameliorate damage of diabetic hepatocytes. Protein analysis revealed that mBYHWD treatment significantly increased the expression of antioxidant proteins in diabetic liver tissue and inhibited inflammation. CONCLUSIONS: The therapeutic mechanism of mBYHWD on DLI may involve activating the Nrf2 signaling pathway to improve oxidative stress, inhibit inflammation, and reduce liver tissue fibrosis.
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Objective: Unilateral mastectomy is known to induce postural alterations, yet the temporal development pattern of these changes remains elusive. This study aimed to explore the impact of unilateral mastectomy on body posture. Methods: A prospective, longitudinal, observational study with a one-group repeated-measures design was conducted. Patients undergoing unilateral mastectomy were recruited from a university-affiliated hospital in Western China and monitored for 12 months post-surgery. A trained nurse assessed seven postural baseline parameters on the day of suture removal and at 3, 6, and 12 months after unilateral mastectomy. Two parameters were in the sagittal plane (forward head posture and trunk rotation angle), and five were in the coronal plane (neck tilt, shoulder asymmetry, scapular asymmetry, scapular asymmetry relative to the spine, and pelvic tilt). Results: The final analysis included 159 patients. Baseline prevalence of most postural abnormalities ranged from 50.94% to 59.75%, with mean deviations between 2.74 and 4.51 mm. At 12 months post-mastectomy, prevalence and mean deviations increased by more than 30% and 3.50 mm, respectively, compared to baseline. Postural abnormalities increased gradually in the first 3 months, notably between the 3rd and 6th months, and slowed between the 6th and 12th months. On the mastectomy side, coronal plane abnormalities significantly increased within 12 months: earlobe to acromion distance (Wald χ2 = 45.283, P < 0.001), depressed shoulder height (Wald χ2 = 42.253, P < 0.001), depressed scapula height (Wald χ2 = 31.587, P < 0.001), scapula to spine distance (Wald χ2 = 45.283, P < 0.001), and elevated pelvic height (Wald χ2 = 48.924, P < 0.001). Conclusions: Postural changes are common post-unilateral mastectomy, with prevalence and deviation increasing gradually, particularly between 3 and 6 months post-mastectomy. Early rehabilitation initiation is recommended to mitigate postural changes. Trial registration: ChiCTR2000040897.
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Diabetic kidney disease (DKD) is a major microvascular complication of diabetes, and hyperglycemic memory associated with diabetes carries the risk of disease occurrence, even after the termination of blood glucose injury. The existence of hyperglycemic memory supports the concept of an epigenetic mechanism involving n6-methyladenosine (m6A) modification. Several studies have shown that m6A plays a key role in the pathogenesis of DKD. This review addresses the role and mechanism of m6A RNA modification in the progression of DKD, including the regulatory role of m6A modification in pathological processes, such as inflammation, oxidative stress, fibrosis, and non-coding (nc) RNA. This reveals the importance of m6A in the occurrence and development of DKD, suggesting that m6A may play a role in hyperglycemic memory phenomenon. This review also discusses how some gray areas, such as m6A modified multiple enzymes, interact to affect the development of DKD and provides countermeasures. In conclusion, this review enhances our understanding of DKD from the perspective of m6A modifications and provides new targets for future therapeutic strategies. In addition, the insights discussed here support the existence of hyperglycemic memory effects in DKD, which may have far-reaching implications for the development of novel treatments. We hypothesize that m6A RNA modification, as a key factor regulating the development of DKD, provides a new perspective for the in-depth exploration of DKD and provides a novel option for the clinical management of patients with DKD.
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Diabetes Mellitus , Nefropatias Diabéticas , Humanos , Metilação de RNA , Adenosina , Glicemia , Epigênese Genética , RNARESUMO
Dopaminergic neurons in the substantia nigra (SN) expressing SUR1/Kir6.2 type ATP-sensitive potassium channels (K-ATP) are more vulnerable to rotenone or metabolic stress, which may be an important reason for the selective degeneration of neurons in Parkinson's disease (PD). Baicalein has shown neuroprotective effects in PD animal models. In this study, we investigated the effect of baicalein on K-ATP channels and the underlying mechanisms in rotenone-induced apoptosis of SH-SY5Y cells. K-ATP currents were recorded from SH-SY5Y cells using whole-cell voltage-clamp recording. Drugs dissolved in the external solution at the final concentration were directly pipetted onto the cells. We showed that rotenone and baicalein opened K-ATP channels and increased the current amplitudes with EC50 values of 0.438 µM and 6.159 µM, respectively. K-ATP channel blockers glibenclamide (50 µM) or 5-hydroxydecanoate (5-HD, 250 µM) attenuated the protective effects of baicalein in reducing reactive oxygen species (ROS) content and increasing mitochondrial membrane potential and ATP levels in rotenone-injured SH-SY5Y cells, suggesting that baicalein protected against the apoptosis of SH-SY5Y cells by regulating the effect of rotenone on opening K-ATP channels. Administration of baicalein (150, 300 mg·kg-1·d-1, i.g.) significantly inhibited rotenone-induced overexpression of SUR1 in SN and striatum of rats. We conducted surface plasmon resonance assay and molecular docking, and found that baicalein had a higher affinity with SUR1 protein (KD = 10.39 µM) than glibenclamide (KD = 24.32 µM), thus reducing the sensitivity of K-ATP channels to rotenone. Knockdown of SUR1 subunit reduced rotenone-induced apoptosis and damage of SH-SY5Y cells, confirming that SUR1 was an important target for slowing dopaminergic neuronal degeneration in PD. Taken together, we demonstrate for the first time that baicalein attenuates rotenone-induced SH-SY5Y cell apoptosis through binding to SUR1 and activating K-ATP channels.
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Flavanonas , Neuroblastoma , Canais de Potássio Corretores do Fluxo de Internalização , Humanos , Ratos , Animais , Canais KATP , Rotenona/farmacologia , Receptores de Sulfonilureias , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Glibureto/farmacologia , Simulação de Acoplamento Molecular , Apoptose , Neurônios Dopaminérgicos/metabolismo , Trifosfato de Adenosina/farmacologiaRESUMO
Anthocyanins (ACNs) systems encapsulated in nanomaterials have received widespread attention and rapid development due to its good delivery potential. Here, the favorable benefits of four natural polysaccharide food additives coated ACNs-liposome nanoparticles (ACNs-Lipo NPs) on the stability and possible lipid-lowering effects of ACNs are discussed in this work. The polysaccharides were coupled to the ACNs-Lipo NPs and self-assembled to create ACNs-Lipo@polysaccharide NPs. The impact of various polysaccharides on the physical, chemical, and stability characteristics of NPs was examined. We found that the NPs prepared with gum arabic (GA) had the best stability. FT-IR and XRD analysis revealed electrostatic adsorption and hydrogen binding forces between the components, as well as an amorphous structure. A series of tests in vitro confirmed the excellent stability, bioavailability, antioxidant activity, and biocompatibility of NPs. Finally, cellular antioxidant activity (CAA) and oleic acid (OA)-induced lipid deposition cell models revealed that ACNs-Lipo@GA might be more readily absorbed by cells, resulting in improved antioxidant activity and lipid-lowering impact, with possible targeted delivery qualities and lipid-lowering effect.
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Antioxidantes , Nanopartículas , Antioxidantes/química , Antocianinas/química , Lipossomos , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas/química , Polissacarídeos/farmacologia , LipídeosRESUMO
OBJECTIVE: Seizures are one of the complications that can occur after cranioplasty (CP). In some regions, titanium mesh remains the material of choice for CP. However, risk factors for seizures after titanium CP have been less studied. The purpose of this study was to identify potential risk factors for early seizures (≤7 days) and late seizures (>8 days) after titanium CP in a single institution. METHODS: A retrospective review was conducted of 241 consecutive patients who received titanium CP at the First Affiliated Hospital of Harbin Medical University from January 2016 to December 2020. Univariate and multivariable logistic regression analyses were performed to determine the independent risk factors for new-onset seizures after titanium CP. RESULTS: Fifteen patients (6.22%) experienced early post-CP seizures, and late post-CP seizures were observed in 81 patients (33.61%). A flaccid concave cranial defect (P = 0.042) was associated with early post-CP seizures, whereas hypertension (P < 0.001) was the only significant predictor for late seizures after titanium CP. CONCLUSIONS: Seizure is a common complication after titanium CP, especially in patients who do not receive prophylactic antiepileptic drugs before the procedure. Risk factors for new-onset seizures at different periods after titanium CP were found to be different. In addition, radiologic factors before titanium CP may play a role in early new-onset seizures after titanium CP and should not be ignored.
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Craniectomia Descompressiva , Titânio , Humanos , Titânio/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Craniectomia Descompressiva/efeitos adversos , Convulsões/epidemiologia , Convulsões/etiologia , Convulsões/prevenção & controle , Fatores de Risco , Crânio/cirurgia , Estudos RetrospectivosRESUMO
Background: Chemotherapy-induced thrombocytopenia (CIT) is a common hematological complication in patients with cancer. Hetrombopag is a novel thrombopoietin receptor agonist that has shown an additive effect in stimulating platelet production when combined with recombinant human thrombopoietin (rhTPO). Objectives: This multicenter retrospective cohort study aimed to evaluate the efficacy and safety of hetrombopag plus rhTPO compared with rhTPO alone for CIT. Methods: A total of 294 patients with solid tumors and CIT (platelet count, <50 × 109/L) who received either rhTPO plus hetrombopag (146 patients) or rhTPO alone (148 patients) at 3 centers from January to December 2022 were included in the study. The primary outcome was a platelet count at least 50 × 109/L higher than the baseline value within 14 days. Chemotherapy dose reductions/delays, bleeding, and adverse events were reported. Results: One hundred twenty patients (82.2%) in the rhTPO-hetrombopag group vs 100 patients (67.6%) in the rhTPO group achieved the primary outcome (P = .005). This significant difference persisted in adjusted analysis (odds ratio, 2.01; 95% CI, 1.12-3.60). A total of 115 patients (78.8%) in the rhTPO-hetrombopag group and 101 patients (68.2%) in the rhTPO group avoided chemotherapy dose reductions/delays (P = .041). There was no significant difference in bleeding rates, and adverse events were mild and similar between the 2 groups. No deaths occurred. Conclusion: Compared to rhTPO alone, our findings suggest that the combination of hetrombopag and rhTPO is safe and more effective in patients with CIT.
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The full combination of high sensitivity indication and long-lasting bacteriostatic function is an innovative need to meet the practicality of intelligent film packaging systems for food products. Hence, Blueberry anthocyanins (BA) copigmentated by ferulic acid (FA) was used as an indicator, and cinnamon essential oil (CO) encapsulated by ß-cyclodextrin (ß-CD) as a bacteriostat, potato starch (PS) as a film-forming substrate to prepared a dual-function starch-based intelligent active packaging film with pH indicator and antibacterial function. FA had the best copigmentation effect with a threefold increase in a value compared to other phenolic acids. The ΔE value increased from 3.24 to 5.13 at pH 2-8, and the change was still prominent in acid-base alternating test, indicating a high response sensitivity. Notably, the yellow gamut of indicating terminus increased its visibility to the naked eye. The release behavior of CO from film was in line with Fick's diffusion. Meanwhile, the release of CO delayed to about 90 h through ß-cyclodextrin encapsulation, showing a high growth-inhibition rate in E. coli and S. aureus of almost 100 %. In this study, a dual-function film with indication and bacteriostasis was prepared and enhanced with both, expanding its wide application in intelligent packaging of fresh food.
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Óleos Voláteis , beta-Ciclodextrinas , Tiram/farmacologia , Amido/farmacologia , Antocianinas/farmacologia , Escherichia coli , Staphylococcus aureus , Óleos Voláteis/farmacologia , beta-Ciclodextrinas/farmacologia , Conservação de Alimentos , Embalagem de Alimentos , Concentração de Íons de HidrogênioRESUMO
The mechanisms through which stocking rates affect soil organic carbon in desert steppe landscapes are not fully understood. To address this research gap, we investigated changes in the biomass of Stipa breviflora plant communities and soils in a desert steppe. Through our research findings, we can establish an appropriate stocking rate for Stipa breviflora desert steppe. The establishment serves as a theoretical foundation for effectively maintaining elevated productivity levels and increasing the carbon sink, thereby offering a valuable contribution towards mitigate climate change. This study examined the effects of different stocking rates on soil organic carbon input, sequestration, and output and found: (1) For soil organic carbon input, the aboveground and litter biomass of plant communities decreased with increasing stocking rate. (2) Grazing treatments did not affect soil organic carbon retention. (3) Regarding soil organic carbon output, the grazing treatments exhibited no significant alteration in soil respiration when compared to the no grazing. In summary, the primary mechanisms through which increasing stocking rates affect the soil organic carbon pool are decreased inputs from plants and increased output through wind erosion. Therefore, decreasing grazing intensity is key to improving soil organic carbon retention in the desert steppe.
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Ecossistema , Solo , Biomassa , Carbono/análise , Plantas , Poaceae , China , PradariaRESUMO
Nitric oxide (NO) is a key signaling molecule affecting the response of plants to salt stress; however, the underlying molecular mechanism is poorly understood. In this study, we conducted a phenotype analysis and found that the small GTPase RABG3E (RAB7) promotes salt tolerance in Arabidopsis thaliana. NO promotes the S-nitrosylation of RAB7 at Cys-171, which in turn helps maintain the ion balance in salt-stressed plants. Furthermore, the S-nitrosylation of RAB7 at Cys-171 enhances the enzyme's GTPase activity, thereby promoting vesicle trafficking and increasing its interaction with phosphatidylinositol phosphates-especially phosphatidylinositol-4-phosphate (PI4P). Exogenously applied PI4P increases vesicle trafficking and promotes salt tolerance depending on the S-nitrosylation of RAB7 at Cys-171. These findings illustrate a unique mechanism in salt tolerance, by which NO regulates vesicle trafficking and ion homeostasis through the S-nitrosylation of RAB7 and its interaction with PI4P.
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Proteínas de Arabidopsis , Arabidopsis , Tolerância ao Sal , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Transdução de Sinais , Óxido NítricoRESUMO
BACKGROUND: Mesenchymal stromal cells (MSCs) have broad potential as a cell therapy including for the treatment of drug-resistant inflammatory conditions with abnormal T cell proliferation such as graft-versus-host disease (GVHD). Clinical success, however, has been complicated by the heterogeneity of culture-expanded MSCs as well as donor variability. Here, we devise culture conditions that promote expansion of MSCs with enhanced immunomodulatory functions both in vitro and in animal models of GVHD. METHODS: Human bone marrow-derived MSCs were expanded at high-confluency (MSCHC) and low-confluency state (MSCLC). Their immunomodulatory properties were evaluated with in vitro co-culture assays based on suppression of activated T cell proliferation and secretion of pro-inflammatory cytokines from activated T cells. Metabolic state of these cells was determined, while RNA sequencing was performed to explore transcriptome of these MSCs. Ex vivo expanded MSCHC or MSCLC was injected into human peripheral blood mononuclear cells (PBMC)-induced GVHD mouse model to determine their in vivo therapeutic efficacy based on clinical grade scoring, human CD45+ blood count and histopathological examination. RESULTS: As compared to MSCLC, MSCHC significantly reduced both the proliferation of anti-CD3/CD28-activated T cells and secretion of pro-inflammatory cytokines upon MSCHC co-culture across several donors even in the absence of cytokine priming. Mechanistically, metabolic analysis of MSCHC prior to co-culture with activated T cells showed increased glycolytic metabolism and lactate secretion compared to MSCLC, consistent with their ability to inhibit T cell proliferation. Transcriptome analysis further revealed differential expression of immunomodulatory genes including TRIM29, BPIFB4, MMP3 and SPP1 in MSCHC as well as enriched pathways including cytokine-cytokine receptor interactions, cell adhesion and PI3K-AKT signalling. Lastly, we demonstrate in a human PBMC-induced GVHD mouse model that delivery of MSCHC showed greater suppression of inflammation and improved outcomes compared to MSCLC and saline controls. CONCLUSION: Our study provides evidence that ex vivo expansion of MSCs at high confluency alters the metabolic and transcriptomic states of these cells. Importantly, this approach maximizes the production of MSCs with enhanced immunomodulatory functions without priming, thus providing a non-invasive and generalizable strategy for improving the use of MSCs for the treatment of inflammatory diseases.
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Leucócitos Mononucleares , Células-Tronco Mesenquimais , Animais , Camundongos , Humanos , Medula Óssea , Fosfatidilinositol 3-Quinases , Citocinas , Modelos Animais de Doenças , Proteínas de Ligação a DNA , Fatores de Transcrição , Peptídeos e Proteínas de Sinalização IntercelularRESUMO
Smartphone addiction is widespread among college students. Physical exercise and core self-evaluation are two potential factors that may influence smartphone addiction. This study aimed to investigate the relationship between physical exercise and college students' smartphone addiction, as well as the mediating effect of core self-evaluation. Here, 643 undergraduate university students are surveyed via questionnaire using the Physical Activity Rating Scale, the Smartphone Addiction Scale for College Students, and the Core Self-Evaluations Scale. The participants include 363 males (56.5%) and 280 females (43.5%), with ages ranging from 17 to 25 years old (mean = 19.68, SD = 1.40). The obtained data are analyzed using SPSS26.0 and the PROCESS plugins. The main findings of the study are as follows: (1) There is a significant negative correlation between physical exercise and smartphone addiction (r = -0.30, p < 0.01), a significant positive correlation between physical exercise and core self-evaluation (r = 0.25, p < 0.01), and a significant negative correlation between core self-evaluation and smartphone addiction (r = -0.52, p < 0.01). (2) There is a mediating effect of core self-evaluation between physical exercise and smartphone addiction. The current study can provide new evidence for the impact of physical exercise on smartphone addiction and highlights the importance of core self-evaluation. Moreover, research ideas and methodological guidance are provided for the following interventions and treatments targeting college students' smartphone addiction.