ABSTRACT
Analytical and semi-analytical models for stream depletion with transient stream stage drawdown induced by groundwater pumping are developed to address a deficiency in existing models, namely, the use of a fixed stream stage condition at the stream-aquifer interface. Field data are presented to demonstrate that stream stage drawdown does indeed occur in response to groundwater pumping near aquifer-connected streams. A model that predicts stream depletion with transient stream drawdown is developed based on stream channel mass conservation and finite stream channel storage. The resulting models are shown to reduce to existing fixed-stage models in the limit as stream channel storage becomes infinitely large, and to the confined aquifer flow with a no-flow boundary at the streambed in the limit as stream storage becomes vanishingly small. The model is applied to field measurements of aquifer and stream drawdown, giving estimates of aquifer hydraulic parameters, streambed conductance, and a measure of stream channel storage. The results of the modeling and data analysis presented herein have implications for sustainable groundwater management.
ABSTRACT
Despite the success of programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibition in tumor therapy, many patients do not benefit. This failure may be attributed to the intrinsic functions of PD-L1. We perform a genome-wide CRISPR synthetic lethality screen to systematically explore the intrinsic functions of PD-L1 in head and neck squamous cell carcinoma (HNSCC) cells, identifying ferroptosis-related genes as essential for the viability of PD-L1-deficient cells. Genetic and pharmacological induction of ferroptosis accelerates cell death in PD-L1 knockout cells, which are also more susceptible to immunogenic ferroptosis. Mechanistically, nuclear PD-L1 transcriptionally activates SOD2 to maintain redox homeostasis. Lower reactive oxygen species (ROS) and ferroptosis are observed in patients with HNSCC who have higher PD-L1 expression. Our study illustrates that PD-L1 confers ferroptosis resistance in HNSCC cells by activating the SOD2-mediated antioxidant pathway, suggesting that targeting the intrinsic functions of PD-L1 could enhance therapeutic efficacy.
Subject(s)
B7-H1 Antigen , Ferroptosis , Animals , Humans , Mice , B7-H1 Antigen/metabolism , B7-H1 Antigen/genetics , Cell Line, Tumor , Clustered Regularly Interspaced Short Palindromic Repeats , CRISPR-Cas Systems , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/metabolism , Reactive Oxygen Species/metabolism , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/metabolism , Superoxide Dismutase/metabolism , Superoxide Dismutase/genetics , Synthetic Lethal MutationsABSTRACT
Cotton is a globally cultivated crop, producing 87% of the natural fiber used in the global textile industry. The pigment glands, unique to cotton and its relatives, serve as a defense structure against pests and pathogens. However, the molecular mechanism underlying gland formation and the specific role of pigment glands in cotton's pest defense are still not well understood. In this study, we cloned a gland-related transcription factor GhHAM and generated the GhHAM knockout mutant using CRISPR/Cas9. Phenotypic observations, transcriptome analysis, and promoter-binding experiments revealed that GhHAM binds to the promoter of GoPGF, regulating pigment gland formation in cotton's multiple organs via the GoPGF-GhJUB1 module. The knockout of GhHAM significantly reduced gossypol production and increased cotton's susceptibility to pests in the field. Feeding assays demonstrated that more than 80% of the cotton bollworm larvae preferred ghham over the wild type. Furthermore, the ghham mutants displayed shorter cell length and decreased gibberellins (GA) production in the stem. Exogenous application of GA3 restored stem cell elongation but not gland formation, thereby indicating that GhHAM controls gland morphogenesis independently of GA. Our study sheds light on the functional differentiation of HAM proteins among plant species, highlights the significant role of pigment glands in influencing pest feeding preference, and provides a theoretical basis for breeding pest-resistant cotton varieties to address the challenges posed by frequent outbreaks of pests.
Subject(s)
Gene Expression Regulation, Plant , Gossypium , Plant Proteins , Gossypium/genetics , Gossypium/parasitology , Gossypium/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , Animals , Gibberellins/metabolism , Gossypol/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Disease Resistance/genetics , Plant Diseases/parasitology , Plant Diseases/immunology , Moths/physiology , Larva/growth & developmentABSTRACT
BACKGROUND: The prognosis of high or markedly low diastolic blood pressure (DBP) with normalized on-treatment systolic blood pressure on major adverse cardiovascular events (MACEs) is uncertain. This study examined whether treated isolated diastolic hypertension (IDH) and treated isolated low DBP (ILDBP) were associated with MACEs in patients with hypertension. METHODS AND RESULTS: A total of 7582 patients with on-treatment systolic blood pressure <130 mm Hg from SPRINT (Systolic Blood Pressure Intervention Trial) were categorized on the basis of average DBP: <60 mm Hg (n=1031; treated ILDBP), 60 to 79 mm Hg (n=5432), ≥80 mm Hg (n=1119; treated IDH). MACE risk was estimated using Cox proportional-hazards models. Among the SPRINT participants, median age was 67.0 years and 64.9% were men. Over a median follow-up of 3.4 years, 512 patients developed a MACE. The incidence of MACEs was 3.9 cases per 100 person-years for treated ILDBP, 1.9 cases for DBP 60 to 79 mm Hg, and 1.8 cases for treated IDH. Comparing with DBP 60 to 79 mm Hg, treated ILDBP was associated with an 1.32-fold MACE risk (hazard ratio [HR], 1.32, 95% CI, 1.05-1.66), whereas treated IDH was not (HR, 1.18 [95% CI, 0.87-1.59]). There was no effect modification by age, sex, atherosclerotic cardiovascular disease risk, or cardiovascular disease history (all P values for interaction >0.05). CONCLUSIONS: In this secondary analysis of SPRINT, among treated patients with normalized systolic blood pressure, excessively low DBP was associated with an increased MACE risk, while treated IDH was not. Further research is required for treated ILDBP management.
Subject(s)
Cardiovascular Diseases , Hypertension , Hypotension , Aged , Female , Humans , Male , Blood Pressure/physiology , Cardiovascular Diseases/etiology , Heart Disease Risk Factors , Hypertension/drug therapy , Hypertension/epidemiology , Hypertension/complications , Risk FactorsABSTRACT
Identification of new mechanisms mediating insulin sensitivity is important to allow validation of corresponding therapeutic targets. In this study, we first used a cellular model of skeletal muscle cell iron overload and found that endoplasmic reticulum (ER) stress and insulin resistance occurred after iron treatment. Insulin sensitivity was assessed using cells engineered to express an Akt biosensor, based on nuclear FoxO localization, as well as western blotting for insulin signaling proteins. Use of salubrinal to elevate eIF2α phosphorylation and promote the unfolded protein response (UPR) attenuated iron-induced insulin resistance. Salubrinal induced autophagy flux and its beneficial effects on insulin sensitivity were not observed in autophagy-deficient cells generated by overexpressing a dominant-negative ATG5 mutant or via knockout of ATG7. This indicated the beneficial effect of salubrinal-induced UPR activation was autophagy-dependent. We translated these observations to an animal model of systemic iron overload-induced skeletal muscle insulin resistance where administration of salubrinal as pretreatment promoted eIF2α phosphorylation, enhanced autophagic flux in skeletal muscle and improved insulin responsiveness. Together, our results show that salubrinal elicited an eIF2α-autophagy axis leading to improved skeletal muscle insulin sensitivity both in vitro and in mice.
Subject(s)
Autophagy , Cinnamates , Endoplasmic Reticulum Stress , Eukaryotic Initiation Factor-2 , Insulin Resistance , Thiourea , Thiourea/analogs & derivatives , Unfolded Protein Response , Animals , Thiourea/pharmacology , Cinnamates/pharmacology , Autophagy/drug effects , Mice , Eukaryotic Initiation Factor-2/metabolism , Unfolded Protein Response/drug effects , Phosphorylation , Male , Endoplasmic Reticulum Stress/drug effects , Salicylates/pharmacology , Mice, Inbred C57BL , Iron/metabolism , Muscle, Skeletal/metabolism , Muscle, Skeletal/drug effects , Iron Overload/metabolism , Signal Transduction/drug effectsABSTRACT
Egg weight (EW) and age at first egg (AFE) are economically important traits in breeder chicken production. The genetic basis of these traits, however, is far from understood, especially for broiler breeders. In this study, genetic parameter estimation, genome-wide association analysis, meta-analysis, and selective sweep analysis were carried out to identify genetic loci associated with EW and AFE in 6,842 broiler breeders. The study found that the heritability of EW ranged from 0.42 to 0.44, while the heritability of AFE was estimated at 0.33 in the maternal line. Meta-analysis and selective sweep analysis identified two colocalized regions on GGA4 that significantly influenced EW at 32 wk (EW32W) and at 43 wk (EW43W) with both paternal and maternal lines. The genes AR, YIPF6, and STARD8 were located within the significant region (GGA4: 366.86-575.50 kb), potentially affecting EW through the regulation of follicle development, cell proliferation, and lipid transfer etc. The promising genes LCORL and NCAPG were positioned within the significant region (GGA4:75.35-75.42 Mb), potentially influencing EW through pleiotropic effects on growth and development. Additionally, 3 significant regions were associated with AFE on chromosomes GGA7, GGA19, and GGA27. All of these factors affected the AFE by influencing ovarian development. In our study, the genomic information from both paternal and maternal lines was used to identify genetic regions associated with EW and AFE. Two genomic regions and eight genes were identified as the most likely candidates affecting EW and AFE. These findings contribute to a better understanding of the genetic basis of egg production traits in broiler breeders and provide new insights into future technology development.
Subject(s)
Chickens , Genome-Wide Association Study , Ovum , Animals , Chickens/genetics , Chickens/physiology , Chickens/growth & development , Female , Genome-Wide Association Study/veterinary , Ovum/physiology , Genetic Loci , Quantitative Trait Loci , MaleABSTRACT
Semen volume is an important economic trait of broilers and one of the important indices for continuous breeding. The objective of this study was to identify genes related to semen volume through transcriptome analysis of the testis tissue of white feather broilers. The testis samples with the highest semen volume (H group, n = 5) and lowest semen volume (L group, n = 5) were selected from 400-day-old roosters for transcriptome analysis by RNA sequencing. During the screening of differentially expressed genes (DEGs) between the H and L groups, a total of 386 DEGs were identified, among which 348 were upregulated and 38 were downregulated. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the immune response, leukocyte differentiation, cell adhesion molecules and collagen binding played vital roles in spermatogenesis. The results showed that 4 genes related to spermatogenesis, namely, COL1A1, CD74, ARPC1B and APOA1, were significantly expressed in Group H, which was consistent with the phenotype results. Our findings may provide a basis for further research on the genetic mechanism of semen volume in white feather broilers.
Subject(s)
Chickens , Transcriptome , Male , Animals , Chickens/genetics , Feathers , Gene Expression Profiling/veterinary , Spermatogenesis/geneticsABSTRACT
Salmonella has been one of the most important factors restricting the development of the poultry industry and also poses great threat to public health. To get insight into molecular alterations that occur during bacterial infection, we sequenced the cecal tonsil transcriptome in 2 chicken breeds (Beijing-You and Cobb) known to have differing resistance to Salmonella. The 28-day-old chickens were orally challenged by 1.83 × 1011 CFU Salmonella Typhimurium, and the cecal tonsil transcriptome was sequenced 3 d postinfection. Analysis identified 201 and 170 differentially expressed genes response to Salmonella in 2 chicken breeds, respectively. They were involved in the Toll-like receptor signaling pathway and activated the production of pro-inflammatory cytokines and chemokines. The protein-protein interaction (PPI) network suggested MMP9 as a crucial protein that may be involved in extracellular matrix breakdown and leukocyte migration in the resistant breed (Beijing-You). Meanwhile, in susceptible chickens (Cobb), ACOD1 was the key gene in the PPI network and might promote the expression of genes related to oxidative stress response and gastrointestinal tract function. These findings provide insight into the differing resistance of these 2 chicken breeds.
Subject(s)
Chickens , Salmonella typhimurium , Animals , Salmonella typhimurium/genetics , Chickens/genetics , Palatine Tonsil , Beijing , Gene ExpressionABSTRACT
OBJECTIVE: The authors aimed to investigate the evolutionary characteristics of the Zabramski classification of cerebral cavernous malformations (CCMs) and the value of the Zabramski classification in predicting clinical outcome in patients with sporadic CCM. METHODS: This retrospective study consecutively included cases of sporadic CCM that had been untreated from January 2001 through December 2021. Baseline and follow-up patient information was recorded. The evolution of the Zabramski classification of a sporadic CCM was defined as the initial lesion type changing into another type for the first time on MRI follow-up. The primary outcome was the occurrence of a hemorrhage event, which was defined as a symptomatic event with radiological evidence of overt intracerebral hemorrhage. RESULTS: Among the 255 included cases, 55 (21.6%) were classified as type I CCM, 129 (50.6%) as type II CCM, and 71 (27.8%) as type III CCM, based on initial MRI. During a mean follow-up of 58.8 ± 33.6 months, 51 (20.0%) patients had lesion classification transformation, whereas 204 (80.0%) patients maintained their initial type. Among the 51 transformed lesions, 29 (56.9%) were type I, 11 (21.6%) were type II, and 11 (21.6%) were type III. Based on all follow-up imaging, of the initial 55 type I lesions, 26 (47.3%) remained type I and 27 (49.1%) regressed to type III because of hematoma absorption; 91.5% of type II and 84.5% of type III lesions maintained their initial type during MRI follow-up. The classification change rate of type I lesions was statistically significantly higher than those of type II and III lesions. After a total follow-up of 1157.7 patient-years, new clinical hemorrhage events occurred in 40 (15.7%) patients. The annual cumulative incidence rate for symptomatic hemorrhage in all patients was 3.4 (95% CI 2.5-4.7) per 100 person-years. Kaplan-Meier survival analysis showed that the annual cumulative incidence rate for symptomatic hemorrhage of type I CCM (15.3 per 100 patient-years) was significantly higher than those of type II (0.6 per 100 patient-years) and type III (2.3 per 100 patient-years). CONCLUSIONS: This study suggests that the Zabramski classification is helpful in estimating clinical outcome and can assist with surgical decision-making in patients with sporadic CCM.
Subject(s)
Hemangioma, Cavernous, Central Nervous System , Humans , Retrospective Studies , Hemangioma, Cavernous, Central Nervous System/complications , Hemangioma, Cavernous, Central Nervous System/diagnostic imaging , Hemangioma, Cavernous, Central Nervous System/epidemiology , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/etiology , Cerebral Hemorrhage/epidemiology , Magnetic Resonance Imaging/adverse effects , Kaplan-Meier EstimateABSTRACT
Tourette syndrome(TS)is a chronic neurodevelopmental disorder.Acupuncture can effectively improve the clinical symptoms of TS patients.This article systematically summarized the clinical research status of acupuncture for the treatment of TS in recent years from the aspects of characteristic acupuncture methods,characteristic needles and comprehensive therapies,and put forward suggestions and prospects for systematically elaborating the peripheral-central mechanism of acupuncture for TS around the intestinal immunity and brain network mechanism in the future,so as to provide reference for optimizing clinical research and treatment.
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Objective:To systematically evaluate the risk prediction model of ICU-acquired dysphagia in critically ill patients, and to provide a reference basis for medical practitioners to select or develop suitable risk assessment tools.Methods:Cross-sectional studies, case-control studies, and cohort studies of ICU-acquired dysphagia risk prediction models were searched in eight databases, including Wanfang database, China Biomedical Literature Database, VIP database, China National Knowledge Infrastructure, PubMed, Embase, CINAHL, and the Cochrane Library in both English and Chinese, and the search timeframe was from the construction of the database to July 5th, 2023. and the search was limited to Chinese and English. Literature was independently screened and data were extracted by 2 investigators, and the risk of bias assessment tool for predictive modeling studies was applied to analyze the risk of bias and applicability of the included literature.Results:A total of 8 high-quality papers were included, including 8 predictive models of risk of ICU-acquired dysphagia. The area under the subject operating characteristic curve for the models ranged from 0.750 to 0.980, with 6 models reporting calibration and 2 models having a Hosmer-Lemeshow test P>0.05, indicating good agreement. 2 models were externally validated. Independent predictors reported repeatedly for multivariate models were age ≥ 65 years, chronic lung disease, cerebrovascular disease, comorbid arrhythmias, use of sedative medications and duration of use, Acute Physiology and Chronic Health Evaluation Ⅱ score ≥ 15, presence of a nasogastric tube, duration of indwelling gastric tube ≥ 72 h, and duration of endotracheal intubation ≥ 72 h. Smaller sample sizes (outcome events), insufficient attention to missing data, variable screening processes irrationality, and model overfitting increased the risk of model bias. Conclusions:The included models showed overall good discrimination and applicability, but their risk of bias was high, and external validation was carried out in only a very few studies. Future studies should refer to transparent reports of multivariate predictive models to develop, update, and validate the models to obtain high-quality predictive models of the risk of ICU-acquired dysphagia, which can provide a reference basis for the development of relevant preventive strategies.
ABSTRACT
Groundwater constitutes a critical component in providing fresh water for various human endeavors. Never-theless, its susceptibility to contamination by pollutants represents a significant challenge. A comprehensive understanding of the dynamics of solute transport in groundwater and soils is essential for predicting the spatial and temporal distribution of these contaminants. Presently, conventional models such as the mobile-immobile (MIM) model and the rate-limited sorption (RLS) model are widely employed to describe the non-Fickian behavior of solute transport. In this research, we present a novel approach to solute transport that is founded on the temporally relaxed theory of Fick's Law. Our methodology introduces two relaxation times to account for solute particle collisions and attachment, leading to the derivation of a new advection-dispersion equation. Our findings indicate that the relaxation times possess similar properties to the transport parameters in the MIM and RLS models, and our solution can be applied to accurately predict transport parameters from soil column experiments. Additionally, we discovered that the relaxation times are proportional to the magnitude of Peclet number. This innovative approach provides a deeper insight into solute transport and its impact on groundwater contamination.
ABSTRACT
BACKGROUND: Although replantation of amputated facial segments remains challenging in reconstructive surgery, it offers excellent aesthetic and functional outcomes. METHODS: From May 2004 to October 2019, 12 patients underwent replantation of amputated facial tissues by supermicrosurgery. The case details, such as the rationale for replantation, the operation method, and postoperative therapy, are described. Four cases are discussed to demonstrate the replantation of different facial parts. RESULTS: Facial tissue replantation was successful in all 12 patients without secondary surgery. The cases included the nose (1 patient), ears (8 patients), lips (2 patients), and one of the soft tissue segments surrounding the lower jaw. Venous congestion occurred in three patients who received a solitary arterial repair and were treated with bloodletting. All patients expressed satisfaction with the cosmetic and functional results at the final follow-up. CONCLUSIONS: Supermicrosurgical facial tissue replantation is a promising and effective procedure for providing patients with the best aesthetic and functional outcomes.
Subject(s)
Amputation, Traumatic , Plastic Surgery Procedures , Humans , Amputation, Traumatic/surgery , Microsurgery/methods , Replantation/methods , Nose/surgeryABSTRACT
The weight of breast muscle (WBM) is a highly monitored indicator in broiler breeding that can be obtained after slaughtering. Currently, due to the lack of accurate in vivo phenotypes for both genomic and phenotypic selection, genetic gains in WBM fall short of initial expectations. In this study, 1,006 market-age (42 d) broilers from 3 generations over 2 yr were randomly selected, and the breast width (BW), fossil bone length (FBL), breast muscle thickness (BMT), and live weight (LW) were measured exactly in vivo. Eight models, including multiple linear regression (MLR), ridge regression (RR), least absolute shrinkage and selection operator (LASSO), and elastic net (EN), were fitted to explore the best regression relationships between breast muscle weight and these indicators. Support vector machine (SVM) methods with both linear kernels and radial kernels were used to fit the models, while 2 decision tree-based machine learning algorithms, random forest (RF), and extreme gradient boosting (XGBoost), were used to establish the prediction model. The predictive effects of different combinations of independent variables were compared, leading to the conclusion that the EN model achieves the best predictive power when all 4 live features are used as inputs and is slightly better than the other models (R2 = 0.7696). This method could be applied in practical production and breeding work, leading to substantial cost savings and enhancements in the breeding process.
Subject(s)
Algorithms , Chickens , Animals , Ultrasonography/veterinary , Genomics , Pectoralis Muscles/diagnostic imagingABSTRACT
Inflammation plays an important role in the pathophysiology of cardiometabolic diseases. Sterile inflammation, a non-infectious and damage-associated molecular pattern (DAMP)-induced innate response, is now well-established to be closely associated with development and progression of cardiometabolic diseases. The NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome is well-established as a major player in sterile inflammatory responses. It is a multimeric cytosolic protein complex which regulates the activation of caspase-1 and subsequently promotes cleavage and release of interleukin (IL)-1 family cytokines, which have a deleterious impact on the development of cardiometabolic diseases. Therefore, targeting NLRP3 itself or the downstream consequences of NLRP3 activation represent excellent potential therapeutic targets in inflammatory cardiometabolic diseases. Here, we review our current understanding of the role which NLRP3 inflammasome regulation plays in cardiometabolic diseases such as obesity, diabetes, non-alcoholic steatohepatitis (NASH), atherosclerosis, ischemic heart disease and cardiomyopathy. Finally, we highlight the potential of targeting NLPR3 or related signaling molecules as a therapeutic approach.
Subject(s)
Cardiovascular Diseases , Non-alcoholic Fatty Liver Disease , Humans , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Inflammation/metabolism , Non-alcoholic Fatty Liver Disease/chemically induced , Non-alcoholic Fatty Liver Disease/metabolismABSTRACT
Quantification of leukocyte profiles is among the simplest measures of animal immune function. However, the relationship between H/L ratio and innate immunity and the measure's utility as an index for heterophil function remains to be analyzed. Variants associated with H/L ratio were fine-mapped based on the resequencing of 249 chickens of different generations and an F2 segregating population generated by crossing selection and control lines. H/L ratio in the selection line was associated with a selective sweep of mutations in protein tyrosine phosphatase, receptor type J (PTPRJ), which affects proliferation and differentiation of heterophils through its downstream regulatory genes. The SNP downstream of PTPRJ (rs736799474) have a universal effect on H/L, with CC homozygotes exhibiting improved heterophil function because of downregulated PTPRJ expression. In short, we systematically elucidated the genetic basis of the change in heterophil function resulting from H/L selection by identifying the regulatory gene (PTPRJ) and causative SNP.
Subject(s)
Chickens , Phosphoric Monoester Hydrolases , Animals , Chickens/genetics , Neutrophils , Leukocytes , LymphocytesABSTRACT
Primary liver cancer (PLC) includes hepatocellular carcinoma and intrahepatic cholangiocarcinoma and is the sixth most common cancer worldwide with poor prognosis. PLC is characterized by an abundant stromal reaction in which cancer-associated fibroblasts (CAFs) are one of the major stromal components. Solid evidence has demonstrated the crucial role of CAFs in tumor progression, and CAF abundance is often correlated with poor clinical outcomes. Although CAFs are regarded as an attractive and promising target for PLC treatment, a poor understanding of CAF origins and heterogeneity and a lack of specific CAF markers are the major hurdles to efficient CAF-specific therapy. In this review, we examine recent advances in the understanding of CAF diversity in the context of biomarkers, subtypes, and functions in PLC. The regulatory roles of CAFs in extracellular matrix remodeling, metastasis, cancer stemness, and therapeutic resistance are summarized. With an increasing link between CAF abundance and reduced antitumor immune responses, we provide updated knowledge on the crosstalk between CAFs and immune cells within the tumor microenvironment, which leads to immune resistance. In addition, we present current CAF-targeted therapies and describe some future perspectives. A better understanding of CAF biology will shed light on a novel therapeutic strategy against PLC.
Subject(s)
Bile Duct Neoplasms , Cancer-Associated Fibroblasts , Carcinoma, Hepatocellular , Cholangiocarcinoma , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Cancer-Associated Fibroblasts/pathology , Liver Neoplasms/pathology , Bile Ducts, Intrahepatic , Tumor MicroenvironmentABSTRACT
In the last few years, several articles have studied heat as a groundwater tracer and developed analytical geothermal solutions to predict the subsurface temperature and groundwater fluxes. These solutions can be sorted into steady-state and transient solutions. The steady-state solutions cannot describe the time-varying subsurface temperature, while the transient solutions ignore subsurface thermal boundary effects. Moreover, soil type may be another crucial factor significantly affecting the prediction results. This study compares six existing classical analytical solutions to examine the effects of soil types and subsurface thermal boundaries on simulating temperature-depth profiles and estimating groundwater fluxes. Several synthetic cases are built by considering the common soil types, sand and clay, to demonstrate their effects on predicting the profiles. A field case is used to show the effect of subsurface thermal boundaries on the groundwater flux estimated by an inverse approach. The study results indicate that the soil types have significant influences on simulating the profiles, and the influences grow with time. Some existing solutions may give inaccurate estimations of the field groundwater flux since they merely consider the heat source from the temperature variations on the ground surface but ignore possible thermal boundary effects in the subsurface. These findings will be valuable to those applying heat as a tracer to investigate infiltration.
Subject(s)
Groundwater , Soil , Temperature , Environmental Monitoring/methods , Hot TemperatureABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Medical abortions using mifepristone and misoprostol have been approved in many countries for early pregnancy loss. Despite its high success rate, this medication regimen can result in incomplete abortion, which is responsible for endometrial damage, prolonged uterine bleeding, abdominal pain, etc. Buxue Yimu Pills (BYP) is a famous Chinese medicine prescription that is widely used in the field of gynecology and obstetrics for treating patients with postpartum complications. However, the therapeutic effect and mechanism of BYP remain to be explored. AIM OF THE STUDY: This study aimed to clarify the therapeutic effect and mechanism of action of BYP in postpartum complications using mifepristone and misoprostol-induced incomplete abortion in rats. MATERIALS AND METHODS: Experimental medical-induced incomplete abortion model rats were constructed using mifepristone and misoprostol, and further treated with saline or BYP by intragastric administration. Detailed information regarding the changes in mRNA and protein levels in the uterine tissues of rats regulated by BYP was illustrated by RNA sequencing (RNA-seq) analysis and quantitative proteomics analysis. The differentially expressed genes and proteins were further subjected to Gene Ontology (GO) and pathway enrichment analyses and further verified using quantitative Real-time PCR (qRT-PCR) analysis and western blot assay. RESULTS: BYP administration markedly alleviated the increase in serum prostaglandin F2α (PGF2α) and expression of PGF2α receptor (PGF2αR) in uterine tissues and inhibited the decrease in serum chorionic gonadotrophin (CG). Compared with the model group, 674 genes were upregulated and 344 genes were downregulated by BYP administration; 108 proteins were upregulated and 48 proteins were downregulated by BYP administration. qRT-PCR analysis of the uterine tissues showed that BYP treatment reversed the variation tendency of genes, including Mmp7, Mmp14, Timp2, Col6a4, Jak2, Wnt7a, and Mylk compared with the model group. Western blot analysis showed that BYP administration affected PKCδ, Collagen VI, MMP7, TIMP2, MLCK, and p-MLC protein levels. CONCLUSION: BYP administration facilitated uterine recovery in medical-induced incomplete abortion rats, and this therapeutic effect involved various targets and biological processes, including the TIMP2/MMP7 and MLCK/p-MLC signaling pathways, etc.
Subject(s)
Abortion, Incomplete , Abortion, Induced , Abortion, Spontaneous , Misoprostol , Animals , Female , Pregnancy , Rats , Dinoprost , Matrix Metalloproteinase 7 , Mifepristone/pharmacology , Mifepristone/therapeutic use , Misoprostol/pharmacology , Misoprostol/therapeutic use , Proteomics , TranscriptomeABSTRACT
The discovery of more efficient and stable catalysts for oxygen evolution reaction (OER) is vital in improving the efficiency of renewable energy generation devices. Given the large numbers of possible binary and ternary metal oxide OER catalysts, high-throughput methods are necessary to accelerate the rate of discovery. Herein, Mn-based spinel oxide, Fe10 Co40 Mn50 O, is identified for the first time using high-throughput methods demonstrating remarkable catalytic activity (overpotential of 310 mV on fluorine-doped tin oxide (FTO) substrate and 237 mV on Ni foam at 10 mA cm-2 ). Using a combination of soft X-ray absorption spectroscopy and electrochemical measurements, the high catalytic activity is attributed to 1) the formation of multiple active sites in different geometric sites, tetrahedral and octahedral sites; and 2) the formation of active oxyhydroxide phase due to the strong interaction of Co2+ and Fe3+ . Structural and surface characterizations after OER show preservation of Fe10 Co40 Mn50 O surface structure highlighting its durability against irreversible redox damage on the catalytic surface. This work demonstrates the use of a high-throughput approach for the rapid identification of a new catalyst, provides a deeper understanding of catalyst design, and addresses the urgent need for a better and stable catalyst to target greener fuel.