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Electrochemical nitrate reduction reaction (NO3RR) is emerging as a promising strategy for nitrate removal and ammonia (NH3) production using renewable electricity. Although great progresses have been achieved, the crystal phase effect of electrocatalysts on NO3RR remains rarely explored. Here, the epitaxial growth of unconventional 2H Cu on hexagonal close-packed (hcp) IrNi template, resulting in the formation of three IrNiCu@Cu nanostructures, is reported. IrNiCu@Cu-20 shows superior catalytic performance, with NH3 Faradaic efficiency (FE) of 86% at -0.1 (vs reversible hydrogen electrode [RHE]) and NH3 yield rate of 687.3 mmol gCu -1 h-1, far better than common face-centered cubic Cu. In sharp contrast, IrNiCu@Cu-30 and IrNiCu@Cu-50 covered by hcp Cu shell display high selectivity toward nitrite (NO2 -), with NO2 - FE above 60% at 0.1 (vs RHE). Theoretical calculations have demonstrated that the IrNiCu@Cu-20 has the optimal electronic structures for NO3RR due to the highest d-band center and strongest reaction trend with the lowest energy barriers. The high electroactivity of IrNiCu@Cu-20 originates from the abundant low coordination of Cu sites on the surface, which guarantees the fast electron transfer to accelerate the intermediate conversions. This work provides a feasible tactic to regulate the product distribution of NO3RR by crystal phase engineering of electrocatalysts.
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Herein, we present a novel and efficient method for the synthesis of two new polycyclic aromatic hydrocarbons, 1 and 2, through the electrocyclization-dehydrogenation of diradicaloids. The proposed oxidative electrocyclization via intermediate diradicaloids is monitored by electron paramagnetic resonance and ultraviolet-visible spectroscopy. Interestingly, 1 exhibits chirality because of its inherent helical skeleton, and 2 features long-wavelength absorption and near-infrared emission properties due to its extended π-conjugation.
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Ginseng, from the roots of Panax ginseng C. A. Meyer, is a widely used herbal medicine in Asian countries, known for its excellent therapeutic properties. The growth of P. ginseng is depend on specific and strict environments, with a preference for wetness but intolerance for flooding. Under excessive soil moisture, some irregular rust-like substances are deposited on the root epidermis, causing ginseng rusty symptoms (GRS). This condition leads to a significant reduce in yield and quality, resulting in substantial economic loses. However, there is less knowledge on the cause of GRS and there are no effective treatments available for its treatment once it occurs. Unsuitable environments lead to the generation of large amounts of reactive oxygen species (ROS). We investigated the key indicators associated with the stress response during different physiological stages of GRS development. We observed a significant change in ROS level, MDA contents, antioxidant enzymes activities, and non-enzymatic antioxidants contents prior to the GRS. Through the analysis of soil features with an abundance of moisture, we further determined the source of ROS. The levels of nitrate reductase (NR) and nitric oxide synthase (NOS) activities in the inter-root soil of ginseng with GRS were significantly elevated compared to those of healthy ginseng. These enzymes boost nitric oxide (NO) levels, which in turn showed a favorable correlation with the GRS. The activities of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase first rose and then decreased as GRS developed. Excess soil moisture causes a decrease in oxygen levels. This activated NR and NOS in the soil, resulting in a production of excess NO. The NO then diffused into the ginseng root and triggered a burst of ROS through NADPH located on the cell membrane. Additionally, Fe2+ in soil was oxidized to red Fe3+, and finally led to GRS. This conclusion was also verified by the Sodium Nitroprusside (SNP), a precursor compound producing NO. The presence of NO from NR and NOS in water-saturated soil is responsible for the generation of ROS. Among these, NO is the main component that contribute to the occurrence of GRS.
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Óxido Nítrico , Panax , Raízes de Plantas , Espécies Reativas de Oxigênio , Solo , Panax/metabolismo , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/efeitos dos fármacos , Óxido Nítrico/metabolismo , Solo/química , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico , Antioxidantes/metabolismo , Óxido Nítrico Sintase/metabolismo , Nitrato Redutase/metabolismo , Doenças das PlantasRESUMO
BACKGROUND: Limited research has explored the potential association between the Triglyceride-Glucose (TyG) and mortality, especially in individuals with Helicobacter pylori (H. pylori) infection. This study seeks to investigate the correlation between the TyG index and H. pylori infection and investigate whether the associations between the TyG index exposure and all-cause mortality are mediated by H. pylori infection. METHODS: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, incorporating a final sample size of 2,187 participants. Both univariable and multivariable-adjusted logistic regression analyses were employed to examine the relationship between H. pylori infection and relevant covariates. To assess the association between TyG index, and all-cause mortality in individuals with or without H. pylori infection, Cox regression analysis, and restricted regression cubic spline analysis were implemented. RESULTS: A significant positive correlation was observed between the TyG index and an elevated risk of H. pylori infection [OR 1.157, 95% CI (1.383 ~ 1.664)]. This correlation persisted even after adjusting for confounding factors [OR 1.189, 95% CI (1.003, 1.411), P < 0.05]. Furthermore, in patients with positive H. pylori infection, a noteworthy nonlinear correlation between the TyG index and all-cause mortality was identified (P = 0.0361). With an increase in the TyG index, all-cause mortality exhibited a corresponding rise, particularly following adjustment for all potential confounding factors. Conversely, in patients with negative H. pylori infection, no significant association was observed between the TyG index and all-cause mortality after adjusting for potential confounding factors. CONCLUSION: A higher TyG index was linked to increased H. pylori infection risks. Participants in the higher quantile group of the TyG index are positively associated with higher all-cause mortality compared to the higher quantile group of the TyG index in H. pylori-positive participants instead of H. pylori-negative participants.
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Objectives: The centrifugal ultrafiltration-high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established to determine the free perampanel (PER) concentration in children with epilepsy. Methods: Free PER concentration was obtained using centrifugal ultrafiltration devices. The internal standard was PER-D5. The method was investigated for selectivity, carryover, lower limit of quantification, calibration curve, accuracy, precision, matrix effects, recovery, and stability. The Spearman's correlation coefficient was used to evaluate the correlation between the free and total PER concentrations. A nonparametric test was used to estimate the effects of PER along with other antiepileptic drugs on the total and free PER concentrations. Results: The free PER concentration was positively correlated with the total PER concentration in the 57 plasma samples (r = 0.793 > 0, P < 0.001). Additionally, the free PER concentrations were significantly (P < 0.05) increased in valproic acid (VPA) co-therapy (9.87 ± 5.83) compared with non-VPA co-therapy (5.03 ± 4.57). Conclusions: The proposed method is efficient, sensitive, and suitable for detecting free PER concentrations in children with epilepsy. Simultaneously, the free PER concentration response to clinical outcomes in children with epilepsy was more clinically significant, particularly when combined with VPA.
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AIMS: The relationship between frailty and mortality among individuals with varying diabetic statuses represents a burgeoning area of concern and scholarly interest within the medical community. However, there are limited studies that explore the relationship between frailty and mortality, as well as cause-specific mortality among individuals with non-diabetes, prediabetes, and diabetes patients. Hence, this study aims to investigate the relationship between the frailty statues and all-cause mortality, as well as cause-specific mortality in individuals with varying diabetic statuses using the data in the NHANES database. METHODS: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, incorporating a final sample size of 57, 098 participants. Both univariable and multivariable-adjusted logistic regression analyses, as well as Cox regression analysis were employed to examine the relationship between frailty index (FI) and mortality. RESULTS: This study, found a significant positive correlation between the frailty and the increased risk of all-cause mortality non-diabetic [OR 4.277, 95%CI (3.982, 4.594), P < 0.001], prediabetic [OR 2.312, 95%CI (2.133, 2.506), P < 0.001], and diabetic patients [OR 3.947, 95%CI (3.378, 4.611), P < 0.001]. This correlation still existed even after adjusting for confounding factors including age, sex, BMI, poverty, fasting insulin, education, smoke, alcohol drink, waist, hypertension, hyperlipidemia, fasting glucose, HbA1c, eGFR, creatinine and total bilirubin. Our result also suggested a significant positive correlation between the frailty index and the increased risk of CVD mortality among non-diabetic [OR 3.095, 95%CI (2.858, 3.352), P < 0.001] and prediabetic [OR 5.985, 95%CI (5.188, 6.904), P < 0.001] individuals. However, in patients with diabetes, the correlation between frailty and CVD mortality lost significance after adjusting for possible confounding factors [OR 1.139, 95%CI (0.794, 1.634), P > 0.05]. CONCLUSION: A nonlinear relationship has been identified between the FI and all-cause mortality, as well as CVD mortality in non-diabetic and pre-diabetic population. In diabetic patients, there was a significant positive correlation between the frailty and the increased risk of all-cause mortality, but not with CVD mortality. Renal function and liver function might potentially acted as an intermediary factor that elevated the risk of CVD mortality in frail patients with diabetes.
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A homogeneous polysaccharide from Bletilla striata fresh tuber (BSPS) was prepared and extensively characterized using HP-GPC, colorimetry, FT-IR, methylation, GC-MS, NMR, Congo red experiment, SEM, and AFM. The molecular weight of BSPS was 722.90 kDa. BSPS consisted of glucose and mannose in the molar ratio of 1 : 2.5. BSPS had a linear chain structure consisting mainly of â4)-ß-d-Glcp-(1â and â4)-ß-d-Manp-(1â residues. O-acetyl group linked to C2 of â4)-ß-d-Manp-(1â residue. Its monosaccharide molar ratio, molecular weight, and O-acetyl substituted position were different from that of the polysaccharide from B. striata dried tuber reported previously. Furthermore, BSPS at concentrations of 3.125-25 µg/mL significantly promoted the viability (ca. 10%), differentiation (1.5-4 folds), migration (15%-70%), and invasion (1.84-4.65 folds) of C2C12 cells. Of note, BSPS remarkably accelerated the epidermal regeneration and wound healing in mice. This study for the first time reported the structure of polysaccharides in B. striata fresh tubers. The results demonstrated that BSPS could be explored as a novel natural wound-healing drug.
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In plants, microRNAs (miRNAs) are a class of important small RNAs involved in their growth and development, and play a very significant role in regulating their tissue coloring. In this paper, the mechanisms on miRNA regulation of plant coloring are mainly reviewed from three aspects: macroscopic physiological and molecular foundations related to tissue coloring, miRNA biosynthesis and function, and specific analysis of miRNA regulation studies on leaf color, flower color, fruit color, and other tissue color formation in plants. Furthermore, we also systematically summarize the miRNA regulatory mechanisms identified on pigments biosynthesis and color formation in plants, and the regulatory mechanisms of these miRNAs mentioned on the existing researches can be divided into four main categories: directly targeting the related transcription factors, directly targeting the related structural genes, directly targeting the related long noncoding RNAs (LncRNAs) and miRNA-mediated production of trans-acting small interfering RNAs (ta-siRNAs). Together, these research results aim to provide a theoretical reference for the in-depth study of plant coloring mechanism and molecular breeding study of related plants in the future.
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The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure (BP). We administered hydroxylamine hydrochloride (HA), a cystathionine-ß-synthase (CBS) inhibitor, into the PVN to suppress endogenous hydrogen sulfide (H2S) and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the NS+PVN vehicle group, the NS+PVN HA group, the HS+PVN vehicle group, and the HS+PVN HA group, with 10 rats in each group. The rats in the NS (normal salt) groups were fed a normal-salt diet containing 0.3% NaCl, while the HS (high salt) groups were fed a high-salt diet containing 8% NaCl. The mean arterial pressure (MAP) was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini-pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H2S in the PVN and plasma norepinephrine (NE) using ELISA. Additionally, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time PCR. In the current study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of high salt-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system.
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Overexpression of Dunaliella parva (D. parva) malic enzyme (ME) gene (DpME) significantly increased DpME expression and ME enzyme activity in transgenic D. parva. Nitrogen limitation had an inhibitory effect on protein content, and DpME overexpression could improve protein content. Nitrogen limitation increased carbohydrate content, and Dunaliella parva overexpressing malic enzyme gene under nitrogen limitation (DpME-N-) group showed the lowest starch content among all groups. Dunaliella parva overexpressing malic enzyme gene under nitrogen sufficient condition (DpME) and DpME-N- groups showed considerably high mRNA levels of DpME. ME activity was significantly enhanced by DpME overexpression, and nitrogen limitation caused a smaller increase. DpME overexpression and nitrogen limitation obviously enhanced lipid accumulation, and DpME overexpression had more obvious effect. Compared with control (wild type), lipid content (68.97%) obviously increased in DpME-N- group. This study indicated that the combination of DpME overexpression and nitrogen limitation was favorable to the production of microalgae biodiesel.
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Metabolismo dos Lipídeos , Malato Desidrogenase , Nitrogênio , Nitrogênio/metabolismo , Malato Desidrogenase/metabolismo , Malato Desidrogenase/genética , Clorofíceas/genética , Clorofíceas/metabolismoRESUMO
This study reports the structure-activity relationships of a unique subclass IIb bacteriocin, plantaricin EvF, which consists of two peptide chains and possesses potent antimicrobial activity. Because the plantaricin Ev peptide chain lacks an α-helix structure, plantaricin EvF is unable to exert its antimicrobial activity through helix-helix interactions like typical subclass IIb bacteriocins. We have shown by various structural evaluation methods that plantaricin Ev can be stabilized by hydrogen bonding at amino acid residues R3, V12, and R13 to the N-terminal region of plantaricin F. This binding gives plantaricin EvF a special spade-shaped structure that exerts antimicrobial activity. In addition, the root-mean-square deviations (RMSDs) of the amino acid residues Y6, F8, and R13 of plantaricin Ev pre- and post-binding were 1.512, 1.723, and 1.369, respectively, indicating that they underwent large structural changes. The alanine scanning experiments demonstrated the important role of the above key amino acids in maintaining the structural integrity of plantaricin EvF. This study not only reveals the unique structural features of plantaricin EvF, but also provides an insight into the structure-activity relationships of subclass IIb bacteriocins.
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This study explores the relationship between economic growth (GDP), biomass energy consumption (BEC), Rule of Law, and Government Effectiveness on climate change (CO2 emissions) in the Republic of Congo from 1990 to 2020. We employed a nonlinear autoregressive distributed Lag (NARDL) model to analyse data from World Bank databases. Higher GDP leads to lower CO2 emissions in the long run. Increased BEC also reduces emissions, but a decrease can have a small negative impact. Interestingly, a stronger Rule of Law and Government Effectiveness is associated with higher CO2 emissions in the short run, potentially due to relaxed environmental regulations. However, a stronger Rule of Law and Government Effectiveness leads to lower emissions in the long run, suggesting a potential shift towards sustainable practices. These findings provide valuable insights for policymakers aiming to achieve economic growth and climate stability in the Republic of Congo.
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RATIONALE AND OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) is the most common malignant neoplasm affecting the kidney, exhibiting a dismal prognosis in metastatic instances. Elucidating the composition of ccRCC holds promise for the discovery of highly sensitive biomarkers. Our objective was to utilize habitat imaging techniques and integrate multimodal data to precisely predict the risk of metastasis, ultimately enabling early intervention and enhancing patient survival rates. MATERIAL AND METHODS: A retrospective analysis was performed on a cohort of 263 patients with ccRCC from three hospitals between April 2013 and March 2021. Preoperative CT images, ultrasound images, and clinical data were comprehensively analyzed. Patients from two campuses of Qilu Hospital of Shandong University were assigned to the training dataset, while the third hospital served as the independent testing dataset. A robust consensus clustering method was used to classify the primary tumor space into distinct sub-regions (i.e., habitats) using contrast-enhanced CT images. Radiomic features were extracted from these tumor sub-regions and subsequently reduced to identify meaningful features for constructing a predictive model for ccRCC metastasis risk assessment. In addition, the potential value of radiomics in predicting ccRCC metastasis risk was explored by integrating ultrasound image features and clinical data to construct and compare alternative models. RESULTS: In this study, we performed k-means clustering within the tumor region to generate three distinct tumor subregions. We quantified the Hounsfiled Unit (HU) value, volume fraction, and distribution of high- and low-risk groups in each subregion. Our investigation focused on 252 patients with Habitat1 + Habitat3 to assess the discriminative power of these two subregions. We then developed a risk prediction model for ccRCC metastasis risk classification based on radiomic features extracted from CT and ultrasound images, and clinical data. The Combined model and the CT_Habitat3 model showed AUC values of 0.935 [95%CI: 0.902-0.968] and 0.934 [95%CI: 0.902-0.966], respectively, in the training dataset, while in the independent testing dataset, they achieved AUC values of 0.891 [95%CI: 0.794-0.988] and 0.903 [95%CI: 0.819-0.987], respectively. CONCLUSION: We have identified a non-invasive imaging predictor and the proposed sub-regional radiomics model can accurately predict the risk of metastasis in ccRCC. This predictive tool has potential for clinical application to refine individualized treatment strategies for patients with ccRCC.
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Traditionally, fresh S. japonicum flowers (SJF) and S. japonicum flowers buds (SJFB) are dried prior to further processing and use. Here, we investigated the ways in which drying techniques, including sun drying (SD), steam drying (STD), microwave drying (MD), hot air drying (HAD, 40 °C, 60 °C, 80 °C, 100 °C), and freeze drying (FD), alter the flavonoid composition of freshly-harvested SJF and SJFB. The flavonoid content of dried samples was determined by Ultra High Performance Liquid Chromatography-Diode Array Detector (UPLC-DAD). Overall, different drying techniques had significantly different effects on the RU content, ranging from 10.63 % (HAD-80 °C) to 34.13 % (HAD-100 °C) in SJF and from 18.91 % (HAD-100 °C) to 29.16 % (HAD-40 °C) and 30.53 % (SD) in SJFB. To clarify the mechanism by which drying affects the RU content of S. japonicum flowers, we studied the activity of a rutin-hydrolyzing enzyme (RHE) isolated from SJF and SJFB using multiple separation and assay methods. According to the Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) results, the apparent molecular weight of the purified RHE was approximately 38 kDa. According to UPLC-DAD, RHE catalyzes the production of quercetin (QU) from rutin (RU), but not from other flavonoid glycosides. Drying fresh SJF and SJFB at low and high temperatures can inhibit RHE activity and prevent RU hydrolysis. Therefore, subjecting freshly-harvest SJF to HAD-100 °C, and freshly-harvest SJFB to SD or HAD-40 °C, can greatly increase the RU content. In particular, HAD is viable for large-scale application due to its simplicity and industrial feasibility.
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Fertilization introduces parental genetic information into the zygote to guide embryogenesis. Parental contributions to postfertilization development have been discussed for decades, and the data available show that both parents contribute to the zygotic transcriptome, suggesting a paternal role in early embryogenesis1-6. However, because the specific paternal effects on postfertilization development and the molecular pathways underpinning these effects remain poorly understood, paternal contribution to early embryogenesis and plant development has not yet been adequately demonstrated7. Here our research shows that TREE1 and its homologue DAZ3 are expressed exclusively in Arabidopsis sperm. Despite presenting no evident defects in sperm development and fertilization, tree1 daz3 unexpectedly led to aberrant differentiation of the embryo root stem cell niche. This defect persisted in seedlings and disrupted root tip regeneration, comparable to congenital defects in animals. TREE1 and DAZ3 function by suppression of maternal RKD2 transcription, thus mitigating the detrimental maternal effects from RKD2 on root stem cell niche. Therefore, our findings illuminate how genetic deficiencies in sperm can exert enduring paternal effects on specific plant organ differentiation and how parental-of-origin genes interact to ensure normal embryogenesis. This work also provides a new concept of how gamete quality or genetic deficiency can affect specific plant organ formation.
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While immune checkpoint blockade (ICB) has shown promise for clinical cancer therapy, its efficacy has only been observed in a limited subset of patients and the underlying mechanisms regulating innate and acquired resistance to ICB of tumor cells remain poorly understood. Here, we identified ependymin-related protein 1 (EPDR1) as an important tumor-intrinsic regulator of PD-L1 expression and tumor immune evasion. Aberrant expression of EPDR1 in hepatocellular carcinoma is associated with immunosuppression. Mechanistically, EPDR1 binds to E3 ligase TRIM21 and disrupts its interaction with IkappaB kinase-b, suppressing its ubiquitylation and autophagosomal degradation and enhancing NF-κB-mediated transcriptional activation of PD-L1. Further, we validated through a mouse liver cancer model that EPDR1 mediates exhaustion of CD8+ T cells and promotes tumor progression. In addition, we observed a positive correlation between EPDR1 and PD-L1 expression in both human and mouse liver cancer samples. Collectively, our study reveals a previously unappreciated role of EPDR1 in orchestrating tumor immune evasion and cancer progression.
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BACKGROUND: Osteoporosis is a major global health issue, weakening bones and increasing fracture risk. Dual-energy X-ray absorptiometry (DXA) is the standard for measuring bone mineral density (BMD) and diagnosing osteoporosis, but its costliness and complexity impede widespread screening adoption. Predictive modeling using genetic and clinical data offers a cost-effective alternative for assessing osteoporosis and fracture risk. This study aims to develop BMD prediction models using data from the UK Biobank (UKBB) and test their performance across different ethnic and geographical populations. METHODS AND FINDINGS: We developed BMD prediction models for the femoral neck (FNK) and lumbar spine (SPN) using both genetic variants and clinical factors (such as sex, age, height, and weight), within 17,964 British white individuals from UKBB. Models based on regression with least absolute shrinkage and selection operator (LASSO), selected based on the coefficient of determination (R2) from a model selection subset of 5,973 individuals from British white population. These models were tested on 5 UKBB test sets and 12 independent cohorts of diverse ancestries, totaling over 15,000 individuals. Furthermore, we assessed the correlation of predicted BMDs with fragility fractures risk in 10 years in a case-control set of 287,183 European white participants without DXA-BMDs in the UKBB. With single-nucleotide polymorphism (SNP) inclusion thresholds at 5×10-6 and 5×10-7, the prediction models for FNK-BMD and SPN-BMD achieved the highest R2 of 27.70% with a 95% confidence interval (CI) of [27.56%, 27.84%] and 48.28% (95% CI [48.23%, 48.34%]), respectively. Adding genetic factors improved predictions slightly, explaining an additional 2.3% variation for FNK-BMD and 3% for SPN-BMD over clinical factors alone. Survival analysis revealed that the predicted FNK-BMD and SPN-BMD were significantly associated with fragility fracture risk in the European white population (P < 0.001). The hazard ratios (HRs) of the predicted FNK-BMD and SPN-BMD were 0.83 (95% CI [0.79, 0.88], corresponding to a 1.44% difference in 10-year absolute risk) and 0.72 (95% CI [0.68, 0.76], corresponding to a 1.64% difference in 10-year absolute risk), respectively, indicating that for every increase of one standard deviation in BMD, the fracture risk will decrease by 17% and 28%, respectively. However, the model's performance declined in other ethnic groups and independent cohorts. The limitations of this study include differences in clinical factors distribution and the use of only SNPs as genetic factors. CONCLUSIONS: In this study, we observed that combining genetic and clinical factors improves BMD prediction compared to clinical factors alone. Adjusting inclusion thresholds for genetic variants (e.g., 5×10-6 or 5×10-7) rather than solely considering genome-wide association study (GWAS)-significant variants can enhance the model's explanatory power. The study highlights the need for training models on diverse populations to improve predictive performance across various ethnic and geographical groups.
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Compound pollution at industrial sites impedes urban development, especially when there is a lack of understanding about the spatial variations of internal pollution in industrial areas producing light-weight materials. In this study, spatial distribution and ecological risks of potentially toxic elements (PTEs), volatile organic compounds (VOCs), and petroleum hydrocarbons (C10-40) in the soil and groundwater of an Al/Cu (aluminum/copper) industrial site have been analyzed comprehensively. Results revealed the progressive clustering of pollutants in different soil layers, which indicated varying levels of penetration and migration of pollutants from the surface downward. Furthermore, severity of pollution varied according to pollutant type, with Cu (5-10,228â¯mgâ¯kg-1) often exceeding the background levels significantly (>40). Cd (0.03-2.60â¯mgâ¯kg-1) and Hg (0.01-3.73â¯mgâ¯kg-1) were found at elevated concentrations in deeper soil layers, suggesting distinct variations of PTEs across different soil depths. Among the more hazardous VOCS, polychlorinated biphenyls (1.80-234⯵gâ¯kg-1) were particularly prevalent in the deeper layers of soil. Petroleum hydrocarbons (C10-40) were widely detected (6-582â¯mgâ¯kg-1), showing significant migration potential from surface to deep soil. These findings suggest that prolonged industrial activities lead to deep-seated accumulation of pollutants, which also impacts the groundwater, contributing to long-term dispersion of contaminants. Furthermore, multivariate statistical analysis indicated certain positive correlations among the distribution of Cu, Pb and petroleum hydrocarbons, indicating possible coupling of these pollutants. Severe Cu pollution caused an ecological risk in the surface soil layer (covering >20â¯% area of high pollution site, contributing >40â¯% ecological risk). While the Hg and Cd posed significant risks in the deeper soil layers, showing higher risk coefficients and mobility. The study provides crucial insights into the transformation of urban areas with a history of industrial uses into community spaces and highlights the risks posed by the remaining pollutants.
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OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy because it is often diagnosed at a late-stage. Signal transducer and activator of transcription 5 (STAT5) is a transcription factor implicated in the progression of various cancer types. However, its role in KRAS-driven pancreatic tumourigenesis remains unclear. DESIGN: We performed studies with LSL-Kras G12D; Ptf1a-Cre ERT (KCERT) mice or LSL-KrasG12D; LSL-Trp53R172H ; Pdx1-Cre (KPC) mice crossed with conditional disruption of STAT5 or completed deficiency interleukin (IL)-22. Pancreatitis was induced in mice by administration of cerulein. Pharmacological inhibition of STAT5 on PDAC prevention was studied in the orthotopic transplantation and patient-derived xenografts PDAC model, and KPC mice. RESULTS: The expression and phosphorylation of STAT5 were higher in human PDAC samples than control samples and high levels of STAT5 in tumour cells were associated with a poorer prognosis. The loss of STAT5 in pancreatic cells substantially reduces the KRAS mutation and pancreatitis-derived acinar-to-ductal metaplasia (ADM) and PDAC lesions. Mechanistically, we discovered that STAT5 binds directly to the promoters of ADM mediators, hepatocyte nuclear factor (HNF) 1ß and HNF4α. Furthermore, STAT5 plays a crucial role in maintaining energy metabolism in tumour cells during PDAC progression. IL-22 signalling induced by chronic inflammation enhances KRAS-mutant-mediated STAT5 phosphorylation. Deficiency of IL-22 signalling slowed the progression of PDAC and ablated STAT5 activation. CONCLUSION: Collectively, our findings identified pancreatic STAT5 activation as a key downstream effector of oncogenic KRAS signalling that is critical for ADM initiation and PDAC progression, highlighting its potential therapeutic vulnerability.
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BACKGROUND: Sudden sensorineural hearing loss (SSNHL), characterized by a rapid and unexplained loss of hearing, particularly at moderate to high frequencies, presents a significant clinical challenge. The therapeutic use of methylprednisolone sodium succinate (MPSS) via different administration routes, in combination with conventional medications, remains a topic of interest. AIM: To compare the therapeutic efficacy of MPSS administered via different routes in combination with conventional drugs for the treatment of mid- to high-frequency SSNHL. METHODS: The medical records of 109 patients with mid- to high-frequency SSNHL were analyzed. The patients were divided into three groups based on the route of administration: Group A [intratympanic (IT) injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection], Group B (intravenous injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection), and Group C (single IT injection of MPSS). The intervention effects were compared and analyzed. RESULTS: The posttreatment auditory thresholds in Group A (21.23 ± 3 .34) were significantly lower than those in Groups B (28.52 ± 3.36) and C (30.23 ± 4.21; P < 0.05). Group A also exhibited a significantly greater speech recognition rate (92.23 ± 5.34) than Groups B and C. The disappearance time of tinnitus, time to hearing recovery, and disappearance time of vertigo in Group A were significantly shorter than those in Groups B and C (P < 0.05). The total effective rate in Group A (97.56%) was significantly greater than that in Groups B and C (77.14% and 78.79%, χ 2 = 7.898, P = 0.019). Moreover, the incidence of adverse reactions in Groups A and C was significantly lower than that in Group B (4.88%, 3.03% vs 2.57%, χ 2 = 11.443, P = 0.003), and the recurrence rate in Group A was significantly lower than that in Groups B and C (2.44% vs 20.00% vs 21.21%, χ 2 = 7.120, P = 0.028). CONCLUSION: IT injection of MPSS combined with conventional treatment demonstrates superior efficacy and safety compared to systemic administration via intravenous infusion and a single IT injection of MPSS. This approach effectively improves patients' hearing and reduces the risk of disease recurrence.