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Nicosulfuron-resistant biotype (R) and -sensitive biotype (S) Amaranthus retroflexus L. seeds were subjected to different temperature, light, salt, osmotic potential, pH value and burial depth treatments. The difference in germination response of two populations to the above abiotic environmental factors was used to study the fitness cost of nicosulfuron-resistance evolution in A. retroflexus. The aim is to find a powerful tool for weed control in the presence of evolutionary resistance selection. The results of this experiment showed that the germination rate and germination index in S population were generally higher than that in R population. When the salt stress was 80 mM, the water potential was -0.1 Mpa ~ -0.4 Mpa, and under strong acid and alkali conditions, the germination index in S population was prominently higher than that in R population (p<0.05). The delayed seed germination in R population indicated that its nicosulfuron resistance may be linked to seed biochemical compositions that altered seed germination dynamics. The resistant and sensitive biotype of A. retroflexus had differently favourable adaptability in diverse environments. Salt, osmotic potential and pH value are not the major constraints for A. retroflexus germination, however, A. retroflexus are strongly responsive to temperature, light and burial depth. Considering that seeds of A. retroflexus are unable to reach the soil surface beyond the depth of 6 cm, deep inversion tillage before sowing may be an effective and economical weed management tool for the control of nicosulfuron resistant A. retroflexus.
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Amaranthus , Germinación , Amaranthus/crecimiento & desarrollo , Amaranthus/fisiología , Amaranthus/efectos de los fármacos , Semillas/crecimiento & desarrollo , Semillas/efectos de los fármacos , Semillas/fisiología , Herbicidas/farmacología , Concentración de Iones de Hidrógeno , Compuestos de Sulfonilurea/farmacología , Temperatura , Resistencia a los Herbicidas , Luz , PiridinasRESUMEN
BACKGROUND & AIMS: Crotonylation, a crotonyl-CoA-based non-enzymatic protein translational modification, affects diverse biological processes, such as spermatogenesis, tissue injury, inflammation, and neuropsychiatric diseases. Crotonylation is decreased in hepatocellular carcinomas (HCCs), but the mechanism remains unknown. In this study, we aim to describe the role of glutaryl-CoA dehydrogenase (GCDH) in tumor suppression. METHODS: Three cohorts containing 40, 248 and 17 pairs of samples were used to evaluate the link between GCDH expression levels and clinical characteristics of HCC, as well as responses to anti-programmed cell death protein 1 (PD-1) treatment. Subcutaneous xenograft, orthotopic xenograft, Trp53Δhep/Δhep; MYC- and Ctnnboe;METoe-driven mouse models were adopted to validate the effects of GCDH on HCC suppression. RESULTS: GCDH depletion promoted HCC growth and metastasis, whereas its overexpression reversed these processes. As GCDH converts glutaryl-CoA to crotonyl-CoA to increase crotonylation levels, we performed lysine crotonylome analysis and identified the pentose phosphate pathway (PPP) and glycolysis-related proteins PGD, TKT, and ALDOC as GCDH-induced crotonylation targets. Crotonyl-bound targets showed allosteric effects that controlled their enzymatic activities, leading to decreases in ribose 5-phosphate and lactate production, further limiting the Warburg effect. PPP blockade also stimulated peroxidation, synergizing with senescent modulators to induce senescence in GCDHhigh cells. These cells induced the infiltration of immune cells by the SASP (senescence-associated secretory cell phenotype) to shape an anti-tumor immune microenvironment. Meanwhile, the GCDHlow population was sensitized to anti-PD-1 therapy. CONCLUSION: GCDH inhibits HCC progression via crotonylation-induced suppression of the PPP and glycolysis, resulting in HCC cell senescence. The senescent cell further shapes an anti-tumor microenvironment via the SASP. The GCDHlow population is responsive to anti-PD-1 therapy because of the increased presence of PD-1+CD8+ T cells. IMPACT AND IMPLICATIONS: Glutaryl-CoA dehydrogenase (GCDH) is a favorable prognostic indicator in liver, lung, and renal cancers. In addition, most GCDH depletion-induced toxic metabolites originate from the liver, accumulate locally, and cannot cross the blood-brain barrier. Herein, we show that GCDH inhibits hepatocellular carcinoma (HCC) progression via crotonylation-induced suppression of the pentose phosphate pathway and glycolysis, resulting in HCC cell senescence. We also found that more PD-1+CD8+ T cells are present in the GCDHlow population, who are thus more responsive to anti-PD-1 therapy. Given that the GCDHlow and GCDHhigh HCC population can be distinguished based on serum glucose and ammonia levels, it will be worthwhile to evaluate the curative effects of pro-senescent and immune-therapeutic strategies based on the expression levels of GCDH.
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Background: Due to the limited role of chronic pain medication in military personnel and the distress caused to the military population, mindfulness-based therapy has been considered for the follow-up treatment of military personnel with chronic pain. The purpose of this review is to explore the effect and the implementation of mindfulness-based therapy for the military population with chronic pain. Methods: The keywords for the search included "mindfulness" AND ("pain" OR "chronic pain") AND ("military" OR "veteran"). The PubMed, Embase, and Cochrane Library databases were searched. The Cochrane Collaboration tool was used to independently assess the risk of bias of the included randomized controlled trials, and the Newcastle-Ottawa Scale was used to independently assess the risk of bias of the included case-control studies. Results: A total of 175 papers were identified; 65 duplicates were excluded, and 59 papers that did not meet the inclusion criteria were excluded after reading the titles and abstracts. The remaining 51 papers were read in full, 42 of which did not meet the inclusion criteria. Nine papers met the inclusion criteria and were included in the study. The nine studies included 507 veterans and 56 active-duty female military personnel. All pain interventions were mindfulness-based therapy, and all of them were integrated into or adapted from standard mindfulness courses. The results all showed that after mindfulness-based therapy, the relevant indicators improved. Conclusions: Mindfulness-based therapy is an effective treatment method for the military population with chronic pain. The review indicates that future research should focus on the best setting for mindfulness-based therapy, including the course content and time.
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Japanese brome (Bromus japonicus) has become one of the main weeds in wheat fields in Hebei province of China and causes a large decrease of wheat production. A total of 44 putative resistant and 2 susceptible Japanese brome populations were collected in the 2021/2022 crop season from Hebei province of China to determine resistance levels to flucarbazonesodium and to investigate the diversity of acetolactate synthase (ALS) mutations, as well as to confirm the cross-and multiple-resistance levels to ALS and EPSPS (5-enolpyruvate shikimate-3-phosphate synthetase) inhibitors. Whole plant bioassay results showed that 15 out of 44 populations tested or 34% were resistant to flucarbazonesodium. The resistance indices of Japanese brome to flucarbazonesodium ranged from 43 to 1977. The resistant populations were mainly distributed in Baoding and Shijiazhuang districts, and there was only one resistant population in Langfang district. Resistant Japanese brome had diverse ALS mutations, including Pro-197-Ser, -Thr, -Arg and Asp-376-Glu. The incidence of Pro-197-Ser mutation was the highest at 68%. Application of the CYP450 inhibitor malathion suggested that CYP450 was involved in metabolic resistance in a population without an ALS mutation. The population with Pro-197-Thr mutation evolved weak cross-resistance to mesosulfuron-methyl and pyroxsulam, and it is in the process of evolving multiple-resistance to glyphosate.
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Acetolactato Sintasa , Herbicidas , Sulfonamidas , Triazoles , Bromus/metabolismo , Herbicidas/farmacología , Mutación , China , Resistencia a los Herbicidas/genética , Acetolactato Sintasa/metabolismoRESUMEN
Background/purpose: Optimal sedation management for pediatric dental treatment demands special focus as it's tubeless and shares a same oral space. The study was to evaluate dexmedetomidine compared to midazolam for intranasal premedication in pediatric dental treatment under intravenous deep sedation. Materials and methods: A hundred children aged 3-7 years scheduled for elective dental treatment under intravenous deep sedation anesthesia were enrolled, of whom 50 children (Group D) were intranasally premedicated with 2.0 µg/kg dexmedetomidine and the remaining 50 children (Group M) received traditional 0.2 mg/kg midazolam. Acceptance rate of venipuncture was regarded as the primary endpoint. Results: The acceptance rate of venipuncture in Group D and Group M were 76% versus 52%, respectively (P = 0.021). More children in Group M complained about bitter/sour taste than Group D (62% vs. 8%, P < 0.001). Intraoperatively, children in Group M were found to have more choking cough than Group D (30% vs. 9%, P = 0.003), and patients in Group M required more suction (18 [36%] in Group M vs. 4 [8%] in Group D, P = 0.001). There were no significant differences between the groups in the incidences of temporal hypoxemia (SpO2 ≤ 90%), however, two children in Group M experienced hypoxemia over 10 s. Conclusion: Compared to the 0.2 mg/kg midazolam, children premedicated with 2.0 µg/kg intranasal dexmedetomidine showed superior venipuncture acceptance, had less intraoperative choking cough and required fewer suction. It seems to be a good alternative to midazolam as premedication for deep sedation in pediatric dental treatment.
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Hepatocellular carcinoma (HCC) is a typical tumor that undergoes metabolic reprogramming, differing from normal liver tissue in glucose, lipid, nucleic acid, and amino acid metabolism. Although ammonia is a toxic metabolic by-product, it has also been recently recognized as a signaling molecule to activate lipid metabolism, and it can be a nitrogen source for biosynthesis to support tumorigenesis. In this study, we revealed that ß-catenin activation increases ammonia production in HCC mainly by stimulating glutaminolysis. ß-Catenin/LEF1 activated the transcription of the glutamate dehydrogenase GLUD1, which then promoted ammonia utilization to enhance the production of glutamate, aspartate, and proline as evidenced by 15NH4Cl metabolic flux. ß-Catenin/TCF4 induced the transcription of SLC4A11, an ammonia transporter, to excrete excess ammonia. SLC4A11 was upregulated in HCC tumor tissues, and high SLC4A11 expression was associated with poor prognosis and advanced disease stages. Loss of SLC4A11 induced HCC cell senescence in vitro by blocking ammonia excretion and reduced ß-catenin-driven tumor growth in vivo. Furthermore, elevated levels of plasma ammonia promoted the progression of ß-catenin mutant HCC, which was impeded by SLC4A11 deficiency. Downregulation of SLC4A11 led to ammonia accumulation in tumor interstitial fluid and decreased plasma ammonia levels in HCC with activated ß-catenin. Altogether, this study indicates that ß-catenin activation reprograms ammonia metabolism and that blocking ammonia excretion by targeting SLC4A11 could be a promising approach to induce senescence in ß-catenin mutant HCC. SIGNIFICANCE: Ammonia metabolism reprogramming mediated by aberrant activation of ß-catenin induces resistance to senescence in HCC and can be targeted by inhibiting SLC4A11 as a potential therapy for ß-catenin mutant liver cancer.
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Amoníaco , Carcinoma Hepatocelular , Senescencia Celular , Neoplasias Hepáticas , beta Catenina , Animales , Humanos , Masculino , Ratones , Amoníaco/metabolismo , beta Catenina/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Glutamato Deshidrogenasa/metabolismo , Glutamato Deshidrogenasa/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Ratones Desnudos , PronósticoRESUMEN
Hepatocellular carcinoma (HCC) stands as the fifth most prevalent malignant tumor on a global scale and presents as the second leading cause of cancer-related mortality. DNA damage-based radiotherapy (RT) plays a pivotal role in the treatment of HCC. Nevertheless, radioresistance remains a primary factor contributing to the failure of radiation therapy in HCC patients. In this study, we investigated the functional role of transketolase (TKT) in the repair of DNA double-strand breaks (DSBs) in HCC. Our research unveiled that TKT is involved in DSB repair, and its depletion significantly reduces both non-homologous end joining (NHEJ) and homologous recombination (HR)-mediated DSB repair. Mechanistically, TKT interacts with PARP1 in a DNA damage-dependent manner. Furthermore, TKT undergoes PARylation by PARP1, resulting in the inhibition of its enzymatic activity, and TKT can enhance the auto-PARylation of PARP1 in response to DSBs in HCC. The depletion of TKT effectively mitigates the radioresistance of HCC, both in vitro and in mouse xenograft models. Moreover, high TKT expression confers resistance of RT in clinical HCC patients, establishing TKT as a marker for assessing the response of HCC patients who received cancer RT. In summary, our findings reveal a novel mechanism by which TKT contributes to the radioresistance of HCC. Overall, we identify the TKT-PARP1 axis as a promising potential therapeutic target for improving RT outcomes in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animales , Ratones , Roturas del ADN de Doble Cadena , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patología , Transcetolasa/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patología , Reparación del ADN , ADN , Reparación del ADN por Unión de Extremidades , Reparación del ADN por Recombinación , Poli(ADP-Ribosa) Polimerasa-1/genéticaRESUMEN
A pilot project for groundwater recharge from rivers is currently being carried out in North China Plain. To investigate the influence of river recharge on groundwater hydrochemical characteristics, dynamic monitoring and analysis of groundwater samples were conducted at a typical recharge site in the Hutuo River alluvial-pluvial fan in the North China Plain from 2019 to 2021. Hydrochemical, isotopic, and multivariate statistical analyses were used to systematically reveal the spatiotemporal variation of groundwater chemistry and its driving factors during groundwater recharge process. The results showed that the groundwater hydrochemical types and characteristics in different recharge areas and recharge periods exhibited obvious spatiotemporal differences. The groundwater type varied from HCO3·SO4-Na·Mg to HCO3·SO4-Ca·Mg in an upstream ecological area, while the groundwater type changed from SO4·HCO3-Mg·Ca to HCO3·SO4-Ca·Mg in the downstream impacted by reclaimed water. Changes in the contents of Ca2+, Mg2+ and HCO3- were mostly controlled by the water-rock interactions and mixing-dilution of recharge water, while the increases in Na+, NO3-, Cl-, SO42- and NO3- contents were mainly due to the infiltration of reclaimed water. Nitrogen and oxygen isotope (δ15N and δ18O) tests and the Bayesian isotope mixing model results further demonstrated that nitrate pollution mainly originated from anthropogenic sources, and the major contribution came from manure and sewage, with an average proportion of 64.6 %. Principal component analysis indicated that water-rock interactions, river-groundwater mixing and redox environment alternation were dominant factors controlling groundwater chemical evolution in groundwater recharge process.
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Exploiting advanced amphiphilic solid catalysts is crucial to the development of Pickering emulsion catalysis. Herein, covalent organic framework (COF) nanoparticles constructed with highly hydrophobic monomers as linkers were found to show superior amphiphilicity and they were then developed as a new class of solid emulsifiers for Pickering emulsion catalysis. Employing amphiphilic COFs as solid emulsifiers, Pickering emulsions with controllable emulsion type and droplet sizes were obtained. COF materials have also been demonstrated to serve as porous surface coatings to replace traditional surface modifications for stabilizing Pickering emulsions. After implanting Pd nanoparticles into amphiphilic COFs, the obtained catalyst displayed a 3.9â times higher catalytic efficiency than traditional amphiphilic solid catalysts with surface modifications in the biphasic oxidation reaction of alcohols. Such an enhanced activity was resulted from the high surface area and regular porous structure of COFs. More importantly, because of their tunable pore diameters, Pickering emulsion catalysis with remarkable size selectivity was achieved. This work is the first example that COFs were applied in Pickering emulsion catalysis, providing a platform for exploring new frontiers of Pickering emulsion catalysis.
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Descurainia sophia (flixweed) is a troublesome weed in winter wheat fields in North China. Resistant D. sophia populations with different acetolactate synthetase (ALS) mutations have been reported in recent years. In addition, metabolic resistance to ALS-inhibiting herbicides has also been identified. In this study, we collected and purified two resistant D. sophia populations (R1 and R2), which were collected from winter wheat fields where tribenuron-methyl provided no control of D. sophia at 30 g a.i. ha-1. Whole plant bioassay and ALS activity assay results showed the R1 and R2 populations had evolved high-level resistance to tribenuron-methyl and florasulam and cross-resistance to imazethapyr and pyrithiobacsodium. The two ALS genes were cloned from the leaves of R1 and R2 populations, ALS1 (2004 bp) and ALS2 (1998 bp). A mutation of Trp 574 to Leu in ALS1 was present in both R1 and R2. ALS1 and ALS2 were cloned from R1 and R2 populations respectively and transferred into Arabidopsis thaliana. Homozygous T3 transgenic seedlings with ALS1 of R1 or R2 were resistant to ALS-inhibiting herbicides and the resistant levels were the same. Transgenic seedlings with ALS2 from R1 or R2 were susceptible to ALS-inhibiting herbicides. Treatment with cytochrome P450 inhibitor malathion decreased the resistant levels to tribenuron-methyl in R1 and R2. RNA-Seq was used to identify target cytochrome P450 genes possibly involved in resistance to ALS-inhibiting herbicides. There were five up-regulated differentially expressed cytochrome P450 genes: CYP72A15, CYP83B1, CYP81D8, CYP72A13 and CYP71A12. Among of them, CYP72A15 had the highest expression level in R1 and R2 populations. The R1 and R2 populations of D. sophia have evolved resistance to ALS-inhibiting herbicides due to Trp 574 Leu mutation in ALS1 and possibly other mechanisms. The resistant function of CYP72A15 needs further research.
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Acetolactato Sintasa , Arilsulfonatos , Brassicaceae , Herbicidas , Acetolactato Sintasa/antagonistas & inhibidores , Acetolactato Sintasa/metabolismo , Brassicaceae/efectos de los fármacos , Brassicaceae/genética , Sistema Enzimático del Citocromo P-450/genética , Resistencia a los Herbicidas/genética , Herbicidas/farmacología , MutaciónRESUMEN
BACKGROUND AND AIMS: Molecular classification is a promising tool for prognosis prediction and optimizing precision therapy for HCC. Here, we aimed to develop a molecular classification of HCC based on the fatty acid degradation (FAD) pathway, fully characterize it, and evaluate its ability in guiding personalized therapy. APPROACH AND RESULTS: We performed RNA sequencing (RNA-seq), PCR-array, lipidomics, metabolomics, and proteomics analysis of 41 patients with HCC, in which 17 patients received anti-programmed cell death-1 (PD-1) therapy. Single-cell RNA sequencing (scRNA-seq) was performed to explore the tumor microenvironment. Nearly, 60 publicly available multiomics data sets were analyzed. The associations between FAD subtypes and response to sorafenib, transarterial chemoembolization (TACE), immune checkpoint inhibitor (ICI) were assessed in patient cohorts, patient-derived xenograft (PDX), and spontaneous mouse model ls. A novel molecular classification named F subtype (F1, F2, and F3) was identified based on the FAD pathway, distinguished by clinical, mutational, epigenetic, metabolic, and immunological characteristics. F1 subtypes exhibited high infiltration with immunosuppressive microenvironment. Subtype-specific therapeutic strategies were identified, in which F1 subtypes with the lowest FAD activities represent responders to compounds YM-155 and Alisertib, sorafenib, anti-PD1, anti-PD-L1, and atezolizumab plus bevacizumab (T + A) treatment, while F3 subtypes with the highest FAD activities are responders to TACE. F2 subtypes, the intermediate status between F1 and F3, are potential responders to T + A combinations. We provide preliminary evidence that the FAD subtypes can be diagnosed based on liquid biopsies. CONCLUSIONS: We identified 3 FAD subtypes with unique clinical and biological characteristics, which could optimize individual cancer patient therapy and help clinical decision-making.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Animales , Ratones , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Sorafenib/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Multiómica , Medicina de Precisión , Ácidos Grasos , Microambiente TumoralRESUMEN
Background: Hepatocellular carcinoma (HCC) is one of the most serious malignant tumors threatening human life with a high mortality rate. The liver regenerative capacity after hepatectomy in early-stage HCC patients is influenced by various factors, including surgical methods and energy metabolism. This study aims to provide a prognostic model based on genes related to liver regeneration that can predict the prognosis of non-tumor tissues in HCC patients. Patients and Methods: A total of 584 non-tumor tissues from HCC patients were collected from three independent databases. Kaplan-Meier survival curves were used to identify prognostic liver-regeneration genes. Subsequently, a prognostic indicator, designated as the Liver Regeneration score (LR score), was determined using single-sample gene set enrichment analysis (ssGSEA). Independent cohorts were used to verify the relationship between LR score and prognosis in non-tumor tissues of HCC patients. Furthermore, a liver regeneration-related model was established to validate key genes identified through LASSO Cox regression analysis. Results: We constructed a gene set comprising 24 liver regeneration-related genes, and the LR score was utilized to predict the prognosis of HCC patients based on its levels in non-tumor tissues. In non-tumor tissues of HCC patients, higher LR scores were associated with improved prognosis. Higher LR scores in non-tumor tissues indicate improved liver metabolism in HCC patients, revealed by Enrichment analysis. LASSO Cox regression analysis identified two key genes, DHTKD1 (dehydrogenase E1 and transketolase domain containing 1) and PHYH (phytanoyl-CoA 2-hydroxylase), and higher expression levels of these genes in non-tumor tissues were correlated with better prognosis. The expression levels of these two genes also changed corresponding to the progression of liver regeneration. Conclusion: In summary, our study has introduced a novel LR gene signature for HCC patients, providing a predictive model for estimating clinical prognosis from non-tumor tissues. The LR score demonstrates promise as a reliable indicator for predicting overall survival in HCC.
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PURPOSE: The pathological diagnosis and prognosis prediction of hepatocellular carcinoma (HCC) is challenging due to the lack of specific biomarkers. This study aimed to validate the diagnostic and prognostic efficiency of Kidney-type glutaminase (GLS1) for HCC in prospective cohorts with a large sample size. METHODS: A total of 1140 HCC patients were enrolled in our prospective clinical trials. Control cases included 114 nontumour tissues. The registered clinical trial (ChiCTR-DDT-14,005,102, chictr.org.cn) was referred to for the exact protocol. GLS1 immunohistochemistry was performed on the whole tumour section. The diagnostic and prognostic performances of GLS1 was evaluated by the receiver operating characteristic curve and Cox regression model. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and area under the curve of GLS1 for the diagnosis of HCC were 0.746, 0.842, 0.979, 0.249, 0.588, and 0.814, respectively, which could be increased to 0.846, 0.886, 0.987,0.366, 0.732, and 0.921 when combined with glypican 3 (GPC3) and alpha-fetoprotein (AFP), indicating better diagnostic performance. Further, we developed a nomogram with GPC3 and GLS1 for identifying HCC which showed good discrimination and calibration. GLS1 expression was also related with age, T stage, TNM stage, Edmondson-Steiner grade, microvascular invasion, Ki67, VEGFR2, GPC3, and AFP expression in HCC. GLS1 expression was negatively correlated with disease-free survival (P < 0.001) probability of patients with HCC. CONCLUSIONS: It was validated that GLS1 was a sensitive and specific biomarker for pathological diagnosis of HCC and had prognostic value, thus having practical value for clinical application.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , alfa-Fetoproteínas , Estudios Prospectivos , Neoplasias Hepáticas/patología , Glutaminasa , Biomarcadores de Tumor , Pronóstico , Riñón/patología , GlipicanosRESUMEN
Ecological water replenishment (EWR) is an essential approach for improving the quantity and quality of regional water. The Chaobai River is a major river in Beijing that is replenished with water from multiple sources, including reclaimed water (RW), the South-North Water Transfer Project (SNTP), reservoir discharge (RD). The effects of multiple water source recharge (MWSR) on groundwater quality remain unclear. In this study, hydrochemical ions, isotopes (δ2H-H2O, δ18O-H2O, δ15N-NO3-, and δ18O-NO3-), mixing stable isotope analysis in R (MixSIAR), and hydrogeochemical modeling were used to quantify the contributions and impacts of different water sources on groundwater and to propose a conceptual model. The results showed that during the period before reservoir discharge, RW and SNTP accounted for 38 %-41 % and 54 % of the groundwater in their corresponding recharge areas, respectively. The groundwater in the RW recharge area contained high levels of Na+ and Cl- leading to the precipitation of halite, and was the main factor for the spatial variation in groundwater hydrochemical components. The surface water changed from Na·K - Cl·SO4 type to Ca·Mg - HCO3 type which was similar to groundwater after reservoir discharge. RD accounted for 30 % of the groundwater; however, it did not change the hydrochemical type of groundwater. Dual nitrate stable isotopes and MixSIAR demonstrated that RW was the primary source of NO3- in groundwater, contributing up to 76-89 %, and reservoir discharge effectively reduced the contribution of RW. δ15N-NO3- or δ18O-NO3- in relation to NO3-N suggests that denitrification is the main biogeochemical process of nitrogen in groundwater, whereas water recharge from the SNTP and RD reduces denitrification and dilutes NO3-. This study provides insights into the impact of anthropogenically controlled ecological water replenishment from different water sources on groundwater and guides the reasonable allocation of water resources.
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Digitaria sanguinalis is a competitive and annual grass weed that commonly infests crops across the world. In recent years, the control of D. sanguinalis by nicosulfuron has declined in Hebei Province, China. To determine the resistance mechanisms of D. sanguinalis to nicosulfuron, a population of D. sanguinalis where nicosulfuron had failed was collected from a maize field of Hebei Province, China. Whole-plant dose-response experiments demonstrated that the resistant population (HBMT-15) displayed 6.9-fold resistance to nicosulfuron compared with the susceptible population (HBMT-5). Addition of the glutathione S-transferase (GSTs) inhibitor 4-chloro-7-nitrobenzoxadiazole (NBD-Cl) significantly reduced the resistance level of the HBMT-15 population to nicosulfuron, and the GSTs activity of the HBMT-15 population was higher than the HBMT-5 population after nicosulfuron treatment. In vitro acetolactate synthase (ALS) enzyme experiments revealed that the nicosulfuron I50 value for the HBMT-15 population was 41 times higher than that of the HBMT-5 population. An Asp376 to Glu substitution in the ALS gene was identified in the HBMT-15 population. The HBMT-15 population had a moderate (2- to 4-fold) level of cross-resistance to three other ALS inhibitors (imazethapyr, pyroxsulam, and flucarbazonesodium), but was susceptible to pyrithiobacsodium. This study demonstrated that both an Asp376 to Glu substitution in the ALS gene and GSTs-involved metabolic resistance to ALS inhibitors coexisted in a D. sanguinalis population.
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Acetolactato Sintasa , Herbicidas , Digitaria/genética , Compuestos de Sulfonilurea/farmacología , Piridinas , Mutación , Acetolactato Sintasa/metabolismo , Inhibidores Enzimáticos/farmacología , Herbicidas/farmacología , Resistencia a los Herbicidas/genéticaRESUMEN
Background/purpose: Intravenous sedation with propofol in the dental treatment offers an alternative to inhalation sedation or general anesthesia. The aim of this study was to evaluate the safety and identify risk factors for intraoperative complications. Materials and methods: Uncooperative children who could not complete dental treatment under non-pharmacological behavior management or mild-to-moderate sedation in the outpatient pediatric department were selected. Details and time of dental treatment; intraoperative vital signs data, including blood pressure, heart rate, respiratory rate, pulse oxygen saturation (SpO2), end-tidal carbon dioxide, and electrocardiogram; and incidence of intraoperative and postoperative complications were recorded. Results: Overall, 344 children were selected, with 342 completing dental treatment. The dental treatment time was 20-155 (median, 85; interquartile range, 70-100) min. The number of treated teeth was at least 1 and at most 13 (median, 6; interquartile range, 5-8). Among 342 children, 35 (10.2%) had their treatment interrupted temporarily due to choking cough. No serious complications occurred; the incidence rate of minor complications was 47/342 (13.7%). Tachycardia was observed in 5/342 (1.5%) cases, oxygen desaturation (SpO2 < 95%) in 18, and hypoxemia (SpO2 ≤ 90%) in 25. The treatment duration was significant longer in cases with than without complications (P < 0.05), and children coughing during treatment were more likely to have complications (P < 0.05). Postoperative restlessness occurred in six children, but there was no vomiting, aspiration, or respiratory obstruction. Conclusion: Decreased oxygen saturation is the most common complications. Cough during treatment and longer treatment duration were risk factors for complications.
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Oxoglutarate dehydrogenase-like (OGDHL) is considered to be the isoenzyme of oxyglutarate dehydrogenase (OGDH) in the OGDH complex, which degrades glucose and glutamate. OGDHL was reported to reprogram glutamine metabolism to suppress HCC progression in an enzyme-activity-dependent manner. However, the potential subcellular localization and non-canonical function of OGDHL is poorly understood. We investigated the expression of OGDHL and its effect on HCC progression. By employing a variety of molecular biology techniques, we revealed the underlying mechanism of OGDHL-induced DNA damage in HCC cells in vitro and in vivo. AAV loaded with OGDHL exerts therapeutic effect on mouse HCC and prolongs survival time. OGDHL induces DNA damage in HCC cells in vitro and in vivo. We also observed that OGDHL possesses nuclear localization in HCC cells and OGDHL-induced DNA damage was independent of its enzymatic activity. Mechanistically, it was demonstrated that OGDHL binds to CDK4 in the nucleus to inhibit the phosphorylation of CDK4 by CAK, which in turn attenuates E2F1 signaling. Inhibition of E2F1 signaling downregulates pyrimidine and purine synthesis, thereby inducing DNA damage through dNTP depletion. We clarified the nuclear localization of OGDHL and its non-canonical function to induce DNA damage, which demonstrated that OGDHL may serve as a select potential therapeutic target for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratones , Animales , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Complejo Cetoglutarato Deshidrogenasa/metabolismo , Transducción de Señal , Daño del ADN , Línea Celular Tumoral , Proliferación CelularRESUMEN
The groundwater quality impacts associated with anthropogenic groundwater recharge (AGR) are of great concern for water management. However, the impacts of AGR on the molecular properties of dissolved organic matter (DOM) in aquifers are poorly understood. Herein, Fourier transform ion cyclotron resonance mass spectrometry was used to unravel the molecular characteristics of DOM in groundwaters from recharge areas by reclaimed water (RWRA) and natural water from South-to-North Water Diversion Project (SNWRA). Compared with RWRA groundwater, significantly fewer nitrogenous compounds, more sulfur-containing compounds, higher concentrations of NO3-N, and lower pH were observed in SNWRA groundwater, indicating the occurrence of deamination, sulfurization, and nitrification. The occurrence of these processes was further supported by transformations of more molecules related to nitrogen and sulfur in SNWRA groundwater relative to RWRA groundwater. The intensities of most common molecules in all samples were significantly correlated with the water quality indicators (e.g., Cl- and NO3-N) and fluorescent indicators (e.g., humic-like components (C1%)), indicating that those common molecules may have the potential to track the environmental impact of AGR on groundwater, especially these specific molecules having great mobility and being significantly correlated with other inert tracers like C1% and Cl-. This study is helpful to understand the environmental risks and regional applicability of AGR.