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Pentatricopeptide repeat (PPR) gene family constitutes one of the largest gene families in plants, which mainly participate in RNA editing and RNA splicing of organellar RNAs, thereby affecting the organellar development. Recently, some evidence elucidated the important roles of PPR proteins in the albino process of plant leaves. However, the functions of PPR genes in the woody mangrove species have not been investigated. In this study, using a typical true mangrove Kandelia obovata, we systematically identified 298 PPR genes and characterized their general features and physicochemical properties, including evolutionary relationships, the subcellular localization, PPR motif type, the number of introns and PPR motifs, and isoelectric point, and so forth. Furthermore, we combined genome-wide association studies (GWAS) and transcriptome analysis to identify the genetic architecture and potential PPR genes associated with propagule leaves colour variations of K. obovata. As a result, we prioritized 16 PPR genes related to the albino phenotype using different strategies, including differentially expressed genes analysis and genetic diversity analysis. Further analysis discovered two genes of interest, namely Maker00002998 (PLS-type) and Maker00003187 (P-type), which were differentially expressed genes and causal genes detected by GWAS analysis. Moreover, we successfully predicted downstream target chloroplast genes (rps14, rpoC1 and rpoC2) bound by Maker00002998 PPR proteins. The experimental verification of RNA editing sites of rps14, rpoC1, and rpoC2 in our previous study and the verification of interaction between Maker00002998 and rps14 transcript using in vitro RNA pull-down assays revealed that Maker00002998 PPR protein might be involved in the post-transcriptional process of chloroplast genes. Our result provides new insights into the roles of PPR genes in the albinism mechanism of K. obovata propagule leaves.
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This genetic association study examines the genetic aspects of necrobiotic xanthogranuloma in 3 patients in China.
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BACKGROUND: Chitinase-3 like-protein-1 (CHI3L1) is a member of the mammalian chitinase-like proteins and elevated serum CHI3L1 level has been proved to be associated with poor prognosis in hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between serum CHI3L1 levels and body composition parameters in patients with HCC after liver transplantation (LT). METHODS: This retrospective study enrolled 200 patients after LT for HCC. Blood samples were collected and serum concentrations of CHI3L1 were measured by enzyme-linked immunosorbent assay. Computer tomography (CT) were used to estimate skeletal muscle and adipose tissue mass. Spearman's rank correlation test was performed to assess associations between serum CHI3L1 levels and these body composition parameters. A Cox proportional-hazards regression model was performed to identify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) curves were constructed using the Kaplan-Meier method and compared by the log-rank test. RESULTS: Total 71 patients (35.5%) were diagnosed with myosteatosis according to skeletal muscle radiation attenuation (SMRA). The 5-year OS rates were 66.9% in non-myosteatosis group, significantly higher than 49.5% in myosteatosis group (p = 0.025), while the RFS of myosteatosis group (5-year RFS: 52.6%) or non-myosteatosis group (5-year RFS: 42.0%) shown no significant difference (p = 0.068). The serum CHI3L1 level were significantly negative correlated with SMRA (r = -0.3, p < 0.001). Interestingly, in patients with myosteatosis, Kaplan-Meier analysis revealed that elevated serum CHI3L1 levels were associated with worse OS (p < 0.001) and RFS (p = 0.047). However, in patients without myosteatosis, Kaplan-Meier analysis found elevated serum CHI3L1 levels were not associated with OS (p = 0.070) or RFS (p = 0.104). CONCLUSIONS: Elevated CHI3L1 was negatively correlated with SMRA, and predicted poorer prognosis in Chinese population after LT for HCC, especially in those patients with concomitant myosteatosis. Monitoring serum CHI3L1 can predict prognosis and effectively guide individual nutrition intervention.
Subject(s)
Biomarkers, Tumor , Carcinoma, Hepatocellular , Chitinase-3-Like Protein 1 , Liver Neoplasms , Humans , Chitinase-3-Like Protein 1/blood , Liver Neoplasms/blood , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Female , Middle Aged , Prognosis , Retrospective Studies , Biomarkers, Tumor/blood , Body Composition , Muscle, Skeletal/pathology , Muscle, Skeletal/metabolism , Muscle, Skeletal/diagnostic imaging , Liver Transplantation , Adult , Aged , Adipose Tissue/pathology , Adipose Tissue/metabolism , Kaplan-Meier Estimate , Tomography, X-Ray ComputedABSTRACT
Tumor recurrence is a life-threatening complication after liver transplantation (LT) for hepatocellular carcinoma (HCC). Precise recurrence risk stratification before transplantation is essential for the management of recipients. Here, we aimed to establish an inflammation-related prediction model for posttransplant HCC recurrence based on pretransplant peripheral cytokine profiling. Two hundred and ninety-three patients who underwent LT in two independent medical centers were enrolled, and their pretransplant plasma samples were sent for cytokine profiling. We identified four independent risk factors, including alpha-fetoprotein, systemic immune-inflammation index, interleukin 6, and osteocalcin in the training cohort (n = 190) by COX regression analysis. A prediction model named inflammatory fingerprint (IFP) was established based on the above factors. The IFP effectively predicted posttransplant recurrence (area under the receiver operating characteristic curve [AUROC]: 0.792, C-index: 0.736). The high IFP group recipients had significantly worse 3-year recurrence-free survival rates (37.9 vs. 86.9%, p < 0.001). Simultaneous T-cell profiling revealed that recipients with high IFP were characterized by impaired T cell function. The IFP also performed well in the validation cohort (n = 103, AUROC: 0.807, C-index: 0.681). In conclusion, the IFP efficiently predicted posttransplant HCC recurrence and helped to refine pretransplant risk stratification. Impaired T cell function might be the intrinsic mechanism for the high recurrence risk of recipients in the high IFP group.
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OBJECTIVE: To investigate the effects of selinexor, a inhibitor of nuclear export protein 1 (XPO1) on the proliferation inhibition and apoptosis of Kasumi-1 cells in acute myeloid leukemia (AML). METHODS: MTS method was used to detect the inhibitory effect of different concentrations of selinexor on the proliferation of Kasumi-1 cells at different time points. The apoptosis rate and cell cycle changes after treatment with different concentration of selinexor were detected by flow cytometry. RESULTS: Selinexor inhibited the growth of Kasumi-1 cells at different time points in a concentration-dependent manner (r 24 h=0.7592, r 48 h=0.9456, and r 72 h=0.9425). Selinexor inhibited Kasumi-1 cells growth in a time-dependent manner (r =0.9057 in 2.5 µmol/L group, r =0.9897 in 5 µmol/L group and r =0.9994 in 10 µmol/L group). Selinexor could induce apoptosis of Kasumi-1 cells in a dose-dependent manner (r =0.9732), and the apoptosis of Kasumi-1 cells was more obvious with the increase of drug concentration. The proportion of G0/G1 phase was significantly increased and the proportion of S phase was significantly decreased after the treatment of Kasumi-1 cells by selinexor. With the increase of drug concentration, the proportion of Kasumi-1 cells cycle arrest in G0/G1 phase was increased and the cell synthesis was decreased. CONCLUSION: Selinexor can promote the death of tumor cells by inhibiting Kasumi-1 cells proliferation, inducing apoptosis and blocking cell cycle.
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Apoptosis , Cell Proliferation , Hydrazines , Leukemia, Myeloid, Acute , Triazoles , Hydrazines/pharmacology , Triazoles/pharmacology , Apoptosis/drug effects , Humans , Cell Proliferation/drug effects , Leukemia, Myeloid, Acute/drug therapy , Cell Line, Tumor , Cell Cycle/drug effects , Exportin 1 Protein , KaryopherinsABSTRACT
BACKGROUND: Sarcopenia is associated with unfavourable long-term survival in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). However, the impact of myosteatosis and muscle loss on patient prognosis has not been investigated. METHODS: Seven hundred fifty-six HCC patients who received LT at 3 transplant centres were included. Computed tomography (CT) images of recipients were collected to measure skeletal muscle index (SMI) and skeletal muscle radiodensity (SMRA). The impact of myosteatosis on the prognosis of sarcopenic and non-sarcopenic patients was studied separately. Muscle status was evaluated based on the presence of sarcopenia and myosteatosis. The muscle loss of 342 males was calculated as the relative change of SMI between pre- and post-LT evaluations. Cox regression models were used to identify predictors of overall survival (OS) and recurrence-free survival (RFS). RESULTS: The study comprised 673 males and 83 females. The median follow-up time was 31 months (interquartile range, 19-43 months). Prior to LT, 267 (39.7%) and 187 (27.8%) males were defined as sarcopenic (low-SMI) and myosteatotic (low-SMRA), respectively. For sarcopenic recipients, the presence of myosteatosis was followed by a 23.6% decrease in 5 year OS (P < 0.001) and a 15.0% decrease in 5 year RFS (P = 0.014). Univariate and multivariate analyses revealed that muscle status was an independent predictor of OS [hazard ratio (HR), 1.569; 95% confidence interval (CI), 1.317-1.869; P < 0.001] and RFS (HR, 1.369; 95% CI, 1.182-1.586; P < 0.001). Postoperatively, a muscle loss >14.2% was an independent risk factor for poor OS (HR, 2.286; 95% CI, 1.358-3.849; P = 0.002) and RFS (HR, 2.219; 95% CI, 1.418-3.471; P < 0.001) in non-sarcopenic recipients (N = 209). CONCLUSIONS: Pre-transplant myosteatosis aggravated the adverse impact of sarcopenia on liver transplant outcomes in male HCC patients. Post-transplant muscle loss might assist in prognostic stratification of recipients without pre-existing sarcopenia, intriguing new insights into individualized management.
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Alzheimer's disease (AD) is recognized as the leading cause of dementia, imposing a significant economic toll on society. Despite the emergence of novel therapeutic approaches for AD, their efficacy and safety mandates further validation through rigorous clinical trials. In this context, hypertension (HTN) has garnered considerable attention as an amendable risk factor for AD. Research indicates that hypertension during midlife is associated with an elevated risk of AD in later years, influencing both the onset and progression of the disease. Nevertheless, the relationship between AD and hypertension in the later stages of life remains a subject of debate. Moreover, the consequences of blood pressure reduction on cognitive function, along with the optimal pharmacological interventions and therapeutic thresholds for hypertension, have emerged as pivotal areas of inquiry. This review synthesizes findings on epidemiology, neuroimaging, and biomarkers, and the effects of antihypertensive medications to elucidate the link between hypertension and cognitive performance. We particularly investigate how hypertension and AD are related by plasma sulfide dysregulation, offering possible indicators for future diagnosis and therapy.
Subject(s)
Alzheimer Disease , Hypertension , Neuroimaging , Humans , Alzheimer Disease/physiopathology , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/metabolism , Hypertension/physiopathology , Hypertension/complications , Neuroimaging/methods , Brain/diagnostic imaging , Brain/physiopathology , Brain/metabolismSubject(s)
Ferroptosis , Ferroptosis/drug effects , Humans , Neoplasms/pathology , Neoplasms/metabolism , Lipids/chemistry , Cell Death , AnimalsABSTRACT
Objective: To systematically evaluate the efficacy of hyperbaric oxygen therapy (HBOT) as an adjunct therapy for treating sleep disorders in patients with Parkinson's disease (PD). Methods: We conducted comprehensive searches in eight databases from inception through September 2023, including PubMed, Cochrane Library, Embase, Web of Science, SinoMed, China National Knowledge Infrastructure (CNKI), China Science and Technology Periodical Database (VIP), and Wanfang Database. The objective was to identify randomized controlled trials (RCTs) evaluating HBOT's effectiveness in alleviating sleep disorder symptoms in PD patients as an adjunct therapy. Literature screening and data extraction were independently executed by the authors. Meta-analyses were performed using Review Manager 5.3 software, and publication bias and sensitivity analyses were assessed using Stata 17.0 software. Results: Seven RCTs involving 461 participants were included. The findings revealed that the addition of HBOT significantly enhanced sleep efficiency (MD = 15.26, 95% CI [10.89, 19.63], p < 0.00001), increased time in bed (MD = 69.65, 95% CI [43.01, 96.30], p < 0.00001), total sleep time (MD = 75.87, 95% CI [25.42, 126.31], p = 0.003), slow-wave sleep (SWS) time (MD = 6.14, 95% CI [3.95, 8.34], p < 0.00001), and rapid eye movement sleep (REM) time (MD = 4.07, 95% CI [2.05, 6.08], p < 0.0001), and reduced awakening frequency (MD = -11.55, 95% CI [-15.42, -7.68], p < 0.00001) and sleep latency (MD = -6.60, 95% CI [-9.43, -3.89], p < 0.00001). Additionally, significant improvements were observed in the Pittsburgh Sleep Quality Index (PSQI) (MD = -2.52, 95% CI [-2.85, -2.18], p < 0.00001), Epworth Sleepiness Scale (ESS) (MD = -2.90, 95% CI [-3.34, -2.47], p < 0.00001), Unified Parkinson's Disease Rating Scale Part III (UPDRS III) (MD = -1.32, 95% CI [-2.16, -0.47], p = 0.002), and Hoehn and Yahr grading (H-Y grading) (MD = -0.15, 95% CI [-0.28, -0.01], p = 0.03). Conclusion: The current meta-analysis supports the efficacy of HBOT as an adjunct therapy in managing sleep disorders in PD patients. It is recommended for PD patients experiencing sleep disturbances.Systematic review registration:https://www.crd.york.ac.uk/, identifier: CRD42023462201.
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OBJECTIVE: To assess the role of Machine Learning (ML) in identification critical factors of dementia and mild cognitive impairment. METHODS: 371 elderly individuals were ultimately included in the ML analysis. Demographic information (including gender, age, parity, visual acuity, auditory function, mobility, and medication history) and 35 features from 10 assessment scales were used for modeling. Five machine learning classifiers were used for evaluation, employing a procedure involving feature extraction, selection, model training, and performance assessment to identify key indicative factors. RESULTS: The Random Forest model, after data preprocessing, Information Gain, and Meta-analysis, utilized three training features and four meta-features, achieving an area under the curve of 0.961 and a accuracy of 0.894, showcasing exceptional accuracy for the identification of dementia and mild cognitive impairment. CONCLUSIONS: ML serves as a identification tool for dementia and mild cognitive impairment. Using Information Gain and Meta-feature analysis, Clinical Dementia Rating (CDR) and Neuropsychiatric Inventory (NPI) scale information emerged as crucial for training the Random Forest model.
Subject(s)
Cognitive Dysfunction , Dementia , Machine Learning , Humans , Cognitive Dysfunction/diagnosis , Female , Aged , Male , Dementia/diagnosis , China , Aged, 80 and over , Neuropsychological Tests/standards , Neuropsychological Tests/statistics & numerical data , East Asian PeopleABSTRACT
BACKGROUND: The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) as neoadjuvant therapy before liver transplantation (LT) for advanced-stage hepatocellular carcinoma (HCC) and to analyze the prognostic factors. AIM: To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC. METHODS: A total of 99 individuals diagnosed with advanced HCC were studied retrospectively. The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT: DEB-TACE group (n = 45) and control group (n = 54). The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus (PVTT). The DEB-TACE group consisted of two subgroups: Group A (n = 31) without PVTT and group B (n = 14) with PVTT. The control group also had two subgroups: Group C (n = 37) without PVTT and group D (n = 17) with PVTT. Data on patient demographics, disease characteristics, therapy response, and adverse events (AEs) were collected. The overall survival (OS) and recurrence-free survival (RFS) rates were assessed using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS. RESULTS: The DEB-TACE group exhibited an overall response rate of 86.6%. Following therapy, there was a significant decrease in the median alpha-fetoprotein (AFP) level (275.1 ng/mL vs 41.7 ng/mL, P < 0.001). The main AE was post-embolization syndrome. The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group (68.9% vs 38.9%, P = 0.003; 86.7% vs 63.0%, P = 0.008). Within the subgroups, group A had higher 2-year rates of RFS and OS compared to group C (71.0% vs 45.9%, P = 0.038; 83.8% vs 62.2%, P = 0.047). The 2-year RFS rate of group B was markedly superior to that of group D (64.3% vs 23.5%, P = 0.002). Results from multivariate analyses showed that pre-LT DEB-TACE [hazard ratio (HR) = 2.73, 95% confidence interval (CI): 1.44-5.14, P = 0.04], overall target tumor diameter ≤ 7 cm (HR = 1.98, 95%CI: 1.05-3.75, P = 0.035), and AFP level ≤ 400 ng/mL (HR = 2.34; 95%CI: 1.30-4.19, P = 0.009) were significant risk factors for RFS. Additionally, pre-LT DEB-TACE (HR = 3.15, 95%CI: 1.43-6.96, P = 0.004) was identified as a significant risk factor for OS. CONCLUSION: DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.
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Melatonin (N-acetyl-5-methoxytryptamine) is reported to improve mood disorders in perimenopausal women and gut microbiome composition is altered during menopausal period. The possible role of microbiome in the treatment effect of melatonin on menopausal depression remains unknown. Here, it is shown that melatonin treatment reverses the gut microbiota dysbiosis and depressive-like behaviors in ovariectomy (OVX) operated mice. This effect of melatonin is prevented by antibiotic cocktails (ABX) treatment. Transferring microbiota harvested from adolescent female mice to OVX-operated mice is sufficient to ameliorate depressive-like behaviors. Conversely, microbiota transplantation from OVX-operated mice or melatonin-treated OVX-operated mice to naïve recipient mice exhibits similar phenotypes to donors. The colonization of Alistipes Inops, which is abundant in OVX-operated mice, confers the recipient with depressive-like behaviors. Further investigation indicates that the expansion of Alistipes Inops induced by OVX leads to the degradation of intestinal tryptophan, which destroys systemic tryptophan availability. Melatonin supplementation restores systemic tryptophan metabolic disorders by suppressing the growth of Alistipes Inops, which ameliorates depressive-like behaviors. These results highlight the previously unrecognized role of Alistipes Inops in the modulation of OVX-induced behavioral disorders and suggest that the application of melatonin to inhibit Alistipes Inops may serve as a potential strategy for preventing menopausal depressive symptoms.
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Propylparaben (PrPB) is a known endocrine disrupting chemicals that is widely applied as preservative in pharmaceuticals, food and cosmetics. PrPB has been detected in human urine samples and human serum and has been proven to cause functional decline in reproduction. However, the direct effects of PrPB on mammalian oocyte are still unknown. Here, we demonstrationed that exposure to PrPB disturbed mouse oocyte maturation in vitro, causing meiotic resumption arrest and first polar body extrusion failure. Our results indicated that 600⯵M PrPB reduced the rate of oocyte germinal vesicle breakdown (GVBD). Further research revealed that PrPB caused mitochondrial dysfunction and oxidative stress, which led to oocyte DNA damage. This damage further disturbed the activity of the maturation promoting factor (MPF) complex Cyclin B1/ Cyclin-dependent kinase 1 (CDK1) and induced G2/M arrest. Subsequent experiments revealed that PrPB exposure can lead to spindle morphology disorder and chromosome misalignment due to unstable microtubules. In addition, PrPB adversely affected the attachment between microtubules and kinetochore, resulting in persistent activation of BUB3 amd BubR1, which are two spindle-assembly checkpoint (SAC) protein. Taken together, our studies indicated that PrPB damaged mouse oocyte maturation via disrupting MPF related G2/M transition and SAC depended metaphase-anaphase transition.
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Asthma is a chronic respiratory disease characterized by airway inflammation and remodeling. Epithelial-mesenchymal transition (EMT) of bronchial epithelial cells is considered to be a crucial player in asthma. Methyltransferase-like 14 (METTL14), an RNA methyltransferase, is implicated in multiple pathological processes, including EMT, cell proliferation and migration. However, the role of METTL14 in asthma remains uncertain. This research aimed to explore the biological functions of METTL14 in asthma and its underlying upstream mechanisms. METTL14 expression was down-regulated in asthmatic from three GEO datasets (GSE104468, GSE165934, and GSE74986). Consistent with this trend, METTL14 was decreased in the lung tissues of OVA-induced asthmatic mice and transforming growth factor-ß1 (TGF-ß1)-stimulated human bronchial epithelial cells (Beas-2B) in this study. Overexpression of METTL14 caused reduction in mesenchymal markers (FN1, N-cad, Col-1 and α-SMA) in TGF-ß1-treated cells, but caused increase in epithelial markers (E-cad), thus inhibiting EMT. Also, METTL14 suppressed the proliferation and migration ability of TGF-ß1-treated Beas-2B cells. Two transcription factors, ETS1 and RBPJ, could both bind to the promoter region of METTL14 and drive its expression. Elevating METTL14 expression could reversed EMT, cell proliferation and migration promoted by ETS1 or RBPJ deficiency. These results indicate that the ETS1/METTL14 and RBPJ/METTL14 transcription axes exhibit anti-EMT, anti-proliferation and anti-migration functions in TGF-ß1-induced bronchial epithelial cells, implying that METTL14 may be considered an alternative candidate target for the treatment of asthma.
Subject(s)
Asthma , Bronchi , Epithelial Cells , Epithelial-Mesenchymal Transition , Methyltransferases , Proto-Oncogene Protein c-ets-1 , Transforming Growth Factor beta1 , Humans , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/genetics , Methyltransferases/metabolism , Methyltransferases/genetics , Animals , Bronchi/metabolism , Bronchi/pathology , Bronchi/cytology , Epithelial Cells/metabolism , Epithelial Cells/pathology , Mice , Proto-Oncogene Protein c-ets-1/metabolism , Proto-Oncogene Protein c-ets-1/genetics , Asthma/pathology , Asthma/metabolism , Asthma/genetics , Cell Line , Cell Proliferation , Mice, Inbred BALB C , Cell Movement , Gene Expression Regulation/drug effectsABSTRACT
Mercury (Hg) pollution in soil has grown into a severe environmental issue. Effective in situ immobilization techniques are crucially demanded. In this study, we explored the application of carboxymethyl cellulose stabilized iron sulfide nanoparticles (CMC-FeS) for in situ immobilization of Hg in soil. CMC-FeS (a CMC-to-FeS molar ratio of 0.0004) was prepared via the reaction between FeSO4 and Na2S using CMC as a stabilizer. Remedying the Hg-polluted soil using 0.03 % CMC-FeS via batch experiments effectively reduced the acid leachable Hg by 97.5 % upon equilibrium after 71 days. Column elution tests demonstrated that the addition of CMC-FeS decreased the peak Hg concentration by 89.9 % and the total Hg mass eluted by 94.9 % after 523 pore volumes. CMC-FeS immobilized Hg in soil via chemical precipitation, ion exchange, and surface complexation. After the CMC-FeS treatment, Hg was transformed from more available exchangeable, carbonate-bound, and organic material-bound forms into the less available residual fraction, reducing the environmental risk of soil Hg from medium to low. The application of CMC-FeS boosted the soil enzyme activities and enhanced the soil bacterial diversity whereas decreased the production of methylmercury. CMC-FeS also facilitated long-term immobilization of Hg in soil. The acid leachable Hg and relative Hg bioaccessibility was decreased. Lift cycle assessment indicated that the preparation and application of CMC-FeS for in situ Hg remediation in soil met green chemistry principles. The present study confirms that CMC-FeS can be applied as an efficient and "green" amending agent for long-term Hg immobilization in soil/sediment.
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Rodents, such as those that feed on plants and nest in plant roots, can significantly affect the growth and development of desert plants. The aim of this study was to investigate the effects of Rhombomys opimus disturbance on the photosynthetic characteristics and nutrient status of Haloxylon ammodendron at different growth stages in the Gurbantunggut Desert. The effects of great gerbil disturbance on the photosynthetic characteristics of H. ammodendron at different growth stages were investigated by measuring the gas exchange parameters, instantaneous water use efficiency, and chlorophyll fluorescence parameters of H. ammodendron at different ages (young, middle, and adult) under the disturbance of great gerbils. The soil nutrients in the assimilated branches and rhizosphere of H. ammodendron at different growth stages were tracked to reveal the relationship between the H. ammodendron nutrient content and gerbil disturbance. The results showed that great gerbil disturbance decreased the organic carbon content in the rhizosphere soil of adult H. ammodendron and increased the total nitrogen content in the rhizosphere soil and the nitrogen and potassium contents in the assimilated branches at each growth stage. The net photosynthetic rate and instantaneous water use efficiency of H. ammodendron decreased at each growth stage, and the maximum photochemical efficiency and non-photochemical quenching parameters of the young H. ammodendron decreased. However, the actual photochemical efficiency and photochemical parameters of the middle H. ammodendron increased. It was concluded that the disturbance of great gerbils decreased the photosynthetic capacity of H. ammodendron and increased the content of total nitrogen in the soil and nitrogen and potassium in the plant. This study revealed that the Gurbantunggut Desert great gerbil and H. ammodendron do not have a simple predation relationship. It laid a foundation for the study of the moderate disturbance threshold and better use of the mutually beneficial relationship between the two.
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BACKGROUND: To improve liver organ allocation, the model for end-stage liver disease (MELD) score was adopted in candidates reflecting the severity of liver disease and the physical condition of patients. Inflammatory markers are prognostic factors for various cancers and play prognostic roles in patients after liver transplantation (LT) for hepatocellular carcinoma (HCC). Researchers focused more on pre-LT inflammatory markers, while the role of dynamic change of these inflammatory markers is still unknown. The purpose of this study was to estimate the prognostic value of pre-LT and post-LT inflammatory markers. MATERIAL AND METHODS: We collected the pre-LT complete blood count and the post-LT result with highest count of white blood cells within 48 h. Platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio and systemic immune-inflammation index were calculated, and their prognostic roles were analyzed for their MELD scores. RESULTS: This retrospective two-center cohort study enrolled 290 patients after LT for HCC. Multivariate analysis identified pre-LT PLR as independent risk factor for recurrence-free survival (RFS) [HR (95%CI): 1.002 (1.000-1.003), p = 0.023]. A high pre-LT PLR or post-LT PLR were associated with poorer RFS (p < 0.001 and p = 0.004, respectively). Based on the MELD scores, the pre-LT PLR value was able to predict the RFS in high MELD group (p < 0.001) but had no predictive power in low MELD group (p = 0.076). On the contrary, the post-LT PLR value was better to predict the overall RFS value in low MELD group (p = 0.007) but could not predict the overall RFS value in high MELD group (p = 0.136). CONCLUSIONS: Both pre-LT PLR and post-LT PLR demonstrated prognostic value in patients following LT for HCC. Monitoring PLR values based on the MELD score can improve the predictive prognosis and more effectively guide the individual decisions for the postoperative intervention.
Subject(s)
Blood Platelets , Carcinoma, Hepatocellular , End Stage Liver Disease , Liver Neoplasms , Liver Transplantation , Lymphocytes , Humans , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/surgery , Liver Neoplasms/mortality , Liver Neoplasms/diagnosis , Liver Neoplasms/immunology , Male , Female , Middle Aged , Prognosis , Retrospective Studies , Lymphocytes/immunology , End Stage Liver Disease/surgery , End Stage Liver Disease/diagnosis , End Stage Liver Disease/mortality , Platelet Count , Adult , Lymphocyte Count , Aged , Severity of Illness IndexABSTRACT
The role of the mitochondrial electron transport chain (ETC) in regulating ferroptosis is not fully elucidated. Here, we reveal that pharmacological inhibition of the ETC complex I reduces ubiquinol levels while decreasing ATP levels and activating AMP-activated protein kinase (AMPK), the two effects known for their roles in promoting and suppressing ferroptosis, respectively. Consequently, the impact of complex I inhibitors on ferroptosis induced by glutathione peroxidase 4 (GPX4) inhibition is limited. The pharmacological inhibition of complex I in LKB1-AMPK-inactivated cells, or genetic ablation of complex I (which does not trigger apparent AMPK activation), abrogates the AMPK-mediated ferroptosis-suppressive effect and sensitizes cancer cells to GPX4-inactivation-induced ferroptosis. Furthermore, complex I inhibition synergizes with radiotherapy (RT) to selectively suppress the growth of LKB1-deficient tumors by inducing ferroptosis in mouse models. Our data demonstrate a multifaceted role of complex I in regulating ferroptosis and propose a ferroptosis-inducing therapeutic strategy for LKB1-deficient cancers.
Subject(s)
AMP-Activated Protein Kinases , Electron Transport Complex I , Ferroptosis , Animals , Female , Humans , Mice , AMP-Activated Protein Kinase Kinases/genetics , AMP-Activated Protein Kinases/metabolism , AMP-Activated Protein Kinases/genetics , Cell Line, Tumor , Electron Transport Complex I/metabolism , Electron Transport Complex I/genetics , Ferroptosis/genetics , Ferroptosis/drug effects , Mitochondria/metabolism , Mitochondria/genetics , Mitochondria/drug effects , Neoplasms/genetics , Neoplasms/pathology , Neoplasms/metabolism , Neoplasms/drug therapy , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase/genetics , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Signal Transduction , Xenograft Model Antitumor AssaysABSTRACT
Emulsified meat products contain high animal fat content, and excessive intake of animal fat is not good for health, so people are paying more and more attention to reduced-fat meat products. This study investigated the impact of varying proportions of pork back-fat and/or resistant starch on the proximate composition, water and fat retention, texture properties, color, and rheology characteristic of pork batter. The results found that replacing pork back-fat with resistant starch and ice water significantly decreased the total lipid and energy contents of cooked pork batter (p < 0.05) while improving emulsion stability, cooking yield, texture, and rheology properties. Additionally, when the pork back-fat replacement ratio was no more than 50%, there was a significant increase in emulsion stability, cooking yield, hardiness, springiness, cohesiveness, chewiness, and L* and G' values (p < 0.05). Furthermore, resistant starch and ice water enhanced myosin head and tail thermal stability and increased G' value at 80 °C. However, the initial relaxation times significantly decreased (p < 0.05) and the peak ratio of P21 significantly increased from 84.62% to 94.03%, suggesting reduced fluidity of water. In conclusion, it is feasible to use resistant starch and ice water as a substitute for pork back-fat in order to produce reduced-fat pork batter with favorable gel and rheology properties.