Reshaping the Tumor Microenvironment of KRASG12D Pancreatic Ductal Adenocarcinoma with combined SOS1 and MEK Inhibition for Improved Immunotherapy Response.

KRAS inhibitors have demonstrated exciting pre-clinical and clinical responses, although resistance occurs rapidly. Here, we investigate the effects of KRAS-targeting therapies on the tumor microenvironment using a library of KRASG12D, p53 mutant, murine PDAC-derived cell lines (KPCY) to leverage immune-oncology combination strategies for long-term tumor efficacy. Our findings show that SOS1 and MEK inhibitors (SOS1i+MEKi) suppressed tumor growth in syngeneic models and increased intra-tumoral CD8+ T cells without durable responses. scRNA-sequencing revealed an increase in inflammatory cancer associated fibroblasts (iCAFs), M2 macrophages, and a decreased dendritic cell quality that ultimately resulted in a highly immunosuppressive microenvironment driven by IL6+ iCAFs. Agonist CD40 treatment was effective to revert macrophage polarization and overcome the lack of mature antigen presenting DCs after SOS1i+MEKi therapy. Treatment increased the overall survival of KPCY tumor-bearing mice. The addition of checkpoint blockade to SOS1i+MEKi combination resulted in tumor free mice with established immune memory. Our data suggests that KRAS inhibition affects myeloid cell maturation and highlights the need for combining KRAS cancer-targeted therapy with myeloid activation to enhance and prolong anti-tumor effects.

Optimized decomposition of fresh tomato remnants in facility soil.

To return vegetable remnants to soil in situ and understand parameters that determine their decomposition efficiency, the tomato remnant length, soil moisture, soil temperature and dosage of a microbial decomposer (MD) have been evaluated through a laboratory experiment using a nylon mesh bag in this study. The results showed that the residual remnant weight, and total carbon content increased 28.49 % and 32.65 %, respectively with two different remnant lengths (∼0.5 cm and ∼2.5 cm), while the decay rate and organic carbon breakdown rate decreased by 6.14 % and 7.48 %, respectively. When the relative water content in soil increased, the residual remnant weight and total carbon content first decreased and then increased, while the trend of the decay rate (16.94 % with 80 % soil water content) and organic carbon breakdown rate (9.96 % with 60 % soil water content) were opposite. At a high MD dosage (7 % or 9 % of the total compost weight), both rates of remnants were greater than those at the low dosage (1 %), with an increase of 38.63 % or 36.19 % and 15.89 % or 15.78 %, respectively. With an increase in soil temperature, both residual remnant weight and total carbon content decreased first and then increased, while both decomposition rate and organic carbon breakdown rate increased first and then decreased by 27.35 % and 22.78 %, respectively at 45 °C, compared with those at 30 °C. It was concluded that the decomposition rate was significantly correlated with the remnant length and the MD dosage, while the organic carbon breakdown rate was significantly associated with all four parameters evaluated. The optimal decomposing efficiency was achieved through cutting tomato remnants to a length of ∼0.5 cm, maintaining soil relative moisture content at 89 %, keeping soil temperature at 50 °C, and adding 7 % microbial decomposer MD to chopped tomato cuttings.

Comparative Analysis of Nutritional Quality, Serum Biochemical Indices, and Visceral Peritoneum of Grass Carp (Ctenopharyngodon idellus) Fed with Two Distinct Aquaculture Systems.

This study scrutinized the nutritional quality and serum biochemical indices of grass carp (Ctenopharyngodon idellus) cultivated in traditional pond intercropping (TPI) and in-pond raceway system (IPRS) aquaculture setups. The findings showed that the TPI group exhibited a superior water-holding capacity, while the IPRS showcased heightened crude lipid content and levels of textural properties such as springiness. Moreover, significant differences emerged in the fatty acid profiles, with the TPI group manifesting higher total polyunsaturated fatty acids (ΣPUFAs), EPA, DHA, and Σn-3, while the IPRS group exhibited elevated total saturated fatty acids (ΣSFAs). In terms of amino acids, valine and histidine levels were notably higher in the IPRS group, whereas lysine levels were reduced. Volatile compound analysis revealed significant variations, with the IPRS group containing more volatile substances with a better aroma, resulting in a better odor. The IPRS group performed better in serum biochemistry analysis. Additionally, grass carp in the IPRS group displayed an improved structure and greater coverage area of the visceral peritoneum, appearing lighter in color compared to the TPI group. TPI mainly influences nutritional elements; IPRSs primarily affect muscle texture, serum biochemistry, and overall health. This study aims to fill the gap in quality comparison research and provide an important scientific basis.

A new method to analysis synthetic acetic acid to vinegar: Hydrogen isotope ratio at the methyl site of acetic acid in vinegar by GC-IRMS.

Acetic acid is the key organic substance used to verify the authenticity of vinegar. A new method for precisely determining acetic acid δDCH3 in vinegar via gas chromatography -pyrolytic-stable isotope ratio mass spectrometry (GC-P-IRMS) was established. The δDCH3 values were obtained via calibration with a series of standards. The optimised method demonstrated a repeatability standard deviation within 3 ‰. The standard deviation of accuracy of the new method compared with that of the SNIF-NMR method was within 2.6 ‰. The synthetic acetic acid δDCH3 values was -136.7 ‰ ± 29.6 ‰, and the δDCH3 value of acetic acid in vinegar was -414.9 ‰ ± 40.5 ‰, with significant isotopic distribution characteristics. This methodology serves as a supplementary method for measuring the δDCH3 value of acetic acid in vinegar. It has advantages over other methods in terms of time, sensitivity and operability. And provides a new idea for solving the problem of analyzing substances in the presence of exchangeable groups.

Nanoarchitectonics of Bimetallic Cu-/Co-Doped Nitrogen-Carbon Nanozyme-Functionalized Hydrogel with NIR-Responsive Phototherapy for Synergistic Mitigation of Drug-Resistant Bacterial Infections.

Superbug infections and transmission have become major challenges in the contemporary medical field. The development of novel antibacterial strategies to efficiently treat bacterial infections and conquer the problem of antimicrobial resistance (AMR) is extremely important. In this paper, a bimetallic CuCo-doped nitrogen-carbon nanozyme-functionalized hydrogel (CuCo/NC-HG) has been successfully constructed. It exhibits photoresponsive-enhanced enzymatic effects under near-infrared (NIR) irradiation (808 nm) with strong peroxidase (POD)-like and oxidase (OXD)-like activities. Upon NIR irradiation, CuCo/NC-HG possesses photodynamic activity for producing singlet oxygen(1O2), and it also has a high photothermal conversion effect, which not only facilitates the elimination of bacteria but also improves the efficiency of reactive oxygen species (ROS) production and accelerates the consumption of GSH. CuCo/NC-HG shows a lower hemolytic rate and better cytocompatibility than CuCo/NC and possesses a positive charge and macroporous skeleton for restricting negatively charged bacteria in the range of ROS destruction, strengthening the antibacterial efficiency. Comparatively, CuCo/NC and CuCo/NC-HG have stronger bactericidal ability against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AmprE. coli) through destroying the cell membranes with a negligible occurrence of AMR. More importantly, CuCo/NC-HG plus NIR irradiation can exhibit satisfactory bactericidal performance in the absence of H2O2, avoiding the toxicity from high-concentration H2O2. In vivo evaluation has been conducted using a mouse wound infection model and histological analyses, and the results show that CuCo/NC-HG upon NIR irradiation can efficiently suppress bacterial infections and promote wound healing, without causing inflammation and tissue adhesions.

Cardiotoxicity induced by fluoropyrimidine drugs in the treatment of gastrointestinal tumors.

In this editorial, we review the article published in World J Gastrointest Oncol 2019, 11: 1031-1042. We specifically focus on the occurrence, clinical characteristics, and risk factors of fluoropyrimidine drug-related cardiotoxicity in patients with gastrointestinal tumors. Despite significant advancements in diagnostic and therapeutic techniques that have reduced mortality rates associated with digestive system tumors, the incidence and mortality rates of treatment-related cardiotoxicity have been increasing, severely impacting the survival and prognosis of cancer patients. Fluoropyrimidine drugs are widely used as antimetabolites in the treatment of malignant tumors, including gastrointestinal tumors, and they represent the second largest class of drugs associated with cardiotoxicity. However, there is often a lack of awareness or understanding regarding their cardiotoxic effects and associated risks.

Cytochrome P450 CitCYP97B modulates carotenoid accumulation diversity by hydroxylating ß-cryptoxanthin in Citrus.

Carotenoids in plant foods provide health benefits by functioning as provitamin A. One of the vital provitamin A carotenoids, ß-cryptoxanthin, is typically plentiful in citrus fruit. However, little is known about the genetic basis of ß-cryptoxanthin accumulation in citrus. Here, we performed a widely targeted metabolomic analysis of 65 major carotenoids and carotenoid derivatives to characterize carotenoid accumulation in Citrus and determine the taxonomic profile of ß-cryptoxanthin. We used data from 81 newly sequenced representative accessions and 69 previously sequenced Citrus cultivars to reveal the genetic basis of ß-cryptoxanthin accumulation through a genome-wide association study. We identified a causal gene, CitCYP97B, which encodes a cytochrome P450 protein whose substrate and metabolic pathways in land plants were undetermined. We subsequently demonstrated that CitCYP97B functions as a novel monooxygenase that specifically hydroxylates the ß-ring of ß-cryptoxanthin in a heterologous expression system. In planta experiments provided further evidence that CitCYP97B negatively regulates ß-cryptoxanthin content. Using the sequenced Citrus accessions, we found that two critical structural cis-element variations contribute to increased expression of CitCYP97B, thereby altering ß-cryptoxanthin accumulation in fruit. Hybridization/introgression appear to have contributed to the prevalence of two cis-element variations in different Citrus types during citrus evolution. Overall, these findings extend our understanding of the regulation and diversity of carotenoid metabolism in fruit crops and provide a genetic target for production of ß-cryptoxanthin-biofortified products.

Evidence that co-existing cadmium and microplastics have an antagonistic effect on greenhouse gas emissions from paddy field soils.

Accumulation of microplastics (MPs) and cadmium (Cd) are ubiquitous in paddy soil. However, the combined effects of MPs and Cd on physiochemical and microbial mechanisms in soils and the attendant implications for greenhouse gas (GHG) emissions, remain largely unknown. Here, we evaluated the influence of polylactic acid (PLA) and polyethylene (PE) MPs on GHG emissions from Cd-contaminated paddy soil using a microcosm experiment under waterlogged and drained conditions. The results showed that PLA significantly increased CH4 and N2O emission fluxes and hence the global warming potential (GWP) of waterlogged soil. Soils treated with MPs+Cd showed significantly reduced GWP compared to those treated only with MPs suggesting that, irrespective of attendant consequences, Cd could alleviate N2O emissions in the presence of MPs. Conversely, the presence of MPs in Cd-contaminated soils tended to alleviate the bioavailability of Cd. Based on a structural equation model analysis, both the MPs-derived dissolved organic matter and the soil bioavailable Cd affected indirectly on soil GHG emissions through their direct influencing on microbial abundance (e.g., Firmicutes, Nitrospirota bacteria). These findings provide new insights into the assessment of GHG emissions and soil/cereal security in response to MPs and Cd coexistence that behaved antagonistically with respect to adverse ecological effects in paddy systems.

A rapid method for the determination of stable hydrogen isotope ratios of acetic acid in vinegar.

RATIONALE: Vinegar is an everyday condiment made from fermented grains or fruits. It contains acetic acid which is the main organic material produced by fermentation. Vinegar suffers from the authenticity problem of exogenous adulteration due to the indistinguishability of low-cost chemical sources of synthetic acetic acid from acetic acid produced by fermentation. It is necessary to establish a simple and rapid measurement technique. METHODS: Determination was according to the total acid content of vinegar diluted with acetone to a certain concentration. Online separation and determination of acetic acid δD in vinegar were carried out using gas chromatography-pyrolysis-isotope ratio mass spectrometry. RESULTS: An HP-Plot/U column was selected for online separation of acetic acid and water with molecular sieve characteristics. At the same time, combined with the instrument blowback function to remove water. Dilute solvent acetone was treated with a molecular sieve to remove trace water. The reproducibility of this method is less than 3‰. The long-term stability is within a reasonable error range. The accuracy correlation coefficient is greater than 0.99. The δD values of acetic acid in vinegar (-264.5 ± 20.3‰) and from chemical sources (-30.5 ± 90.8‰) were obtained. CONCLUSIONS: A rapid method was developed for identification of different sources of acetic acid. These different sources of acetic acid exhibited significant hydrogen isotope distribution characteristics. Additionally, it was observed that the carboxyl hydrogen of acetic acid exhibited facile exchange with water. In future investigations, we aim to mitigate this interference.

Effect of biochar on biochemical properties of saline soil and growth of rice.

To amend physical properties of coastal saline soil for rice production, six biochar treatments (0, 0.5, 1, 2, 4 and 6 kg biochar per m2 soil) were set up as CK, T1, T2, T3, T4 and T5, respectively and their effect on the biochemical properties of coastal saline soil and rice growth characteristics were evaluated in a barrel planting experiment. The results showed that compared with CK (with no biochar added), the soil EC of T1 and T2-T5 was reduced by 11.5 %, but increased by 8.8-62.9 %, respectively. The available potassium and organic matter contents of T1-T5 increased ranging from 3.7-10.2 % to 8.0-46.8 %, respectively. With the increase of the biochar amount, the urease activity of soil in the 0-10 cm deep soil showed an increasing trend by 194.8-744.6 % with T1-T5, compared with that of the CK treatment. The activity of alkaline phosphatase in soil increased first and then decreased, and its increment with T1-T5 was between 28.2 and 64.8 % in comparison with that of CK. With more biochar added to soil, the leaf dry weight, root dry weight, total dry matter mass, total root length, single panicle quality and weight per 100 grains showed a trend of increase first and then decrease. The highest incremental values of all measurements were obtained with T1 by 21.8 %, 23.9 %, 13.8 %, 33.9 %, 30.8 % and 11.6 % respectively, compared with those with CK. However, adding biochar in soil demonstrated insignificant effect on the weight of single panicle, panicle length, stem thickness, tillers, setting rate, soil hydrolyzable nitrogen, available phosphorus content, rice protein, amylose, and taste quality among all treatments. In summary, the application of 0.5 kg m-2 biochar can improve the biochemical properties of saline soil and therefore increase rice yield.

Innovations in chemical degradation technologies for the removal of micro/nano-plastics in water: A comprehensive review.

Micro/nanoplastics (M/NPs) in water have raised global concern due to their potential environmental risks. To reestablish a M/NPs free world, enormous attempts have been made toward employing chemical technologies for their removal in water. This review comprehensively summarizes the advances in chemical degradation approaches for M/NPs elimination. It details and discusses promising techniques, including photo-based technologies, Fenton-based reaction, electrochemical oxidation, and novel micro/nanomotors approaches. Subsequently, critical influence factors, such as properties of M/NPs and operating factors, are analyzed in this review specifically. Finally, it concludes by addressing the current challenges and future perspectives in chemical degradation. This review will provide guidance for scientists to further explore novel strategies and develop feasible chemical methods for the improved control and remediation of M/NPs in the future.

Exogenous Chemicals Used to Alleviate or Salvage Plants under Flooding/Waterlogging Stress: Their Biochemical Effects and Perspectives.

Plant flooding/waterlogging stress (FWS) can be a threat to food security worldwide due to climate change. To mitigate its potential devastation, numerous exogenous chemicals (ECs) have been used to demonstrate their effectiveness on alleviating FWS for the last 20 years. This review has summarized the most recent findings on use of various ECs as either nutrients or regulatory substances on crop plants under FWS and their roles involved in improving root respiration of seedlings, optimizing nutritional status, synthesizing osmotic regulators, enhancing the activity of antioxidant enzymes, adjusting phytohormone levels, maintaining photosynthetic systems, and activating flood-tolerance related gene expressions. The effect of ESs on alleviating plants under FWS proves to be beneficial and useful but rather limited unless they are applied on appropriate crops, at the right time, and with optimized methods. Further research should be focused on use of ESs in field settings and on their potential synergetic effect for more FWS tolerance.

Ultrasound-guided serratus anterior plane block to prevent neurocognitive impairment in elderly patients after thoracoscopic lobectomy: protocol for a single-centre, double-blind, randomised controlled trial.

INTRODUCTION: Postoperative neurocognitive dysfunction (PND), including postoperative delirium (POD), is a common complication in elderly patients after major surgeries, often leading to poor postoperative recovery. Although the pathological mechanism underlying PND is still unclear, postoperative pain is strongly associated with the development of PND. The ultrasound-guided serratus anterior plane block (SAPB) has been reported to relieve postoperative pain in thoracic surgery. Therefore, this prospective trial hypothesises that SAPB may reduce the incidence of PND in the elderly undergoing thoracoscopic lobectomy. METHODS AND ANALYSIS: This study is designed as a single-centre, double-blind, randomised controlled clinical trial. A total of 256 elderly patients scheduled to undergo thoracoscopic lobectomy at Shanghai Pulmonary Hospital will be randomly assigned to general anaesthesia group or SAPB group. The primary outcome is the incidence of PND 7 days postoperatively or before discharge from hospital. The secondary outcomes include the occurrence of POD, the postoperative pain scores, Quality of Recovery at 1-2 days postoperatively and incidence of PND at 3 months postoperatively. The levels of fasting blood glucose in peripheral blood will be examined before and 1-2 days postoperatively. ETHICS AND DISSEMINATION: The trial has been approved by the Clinical Research Ethics Committee of Shanghai Pulmonary Hospital (identifier: K20-290). All participants will be required to provide written informed consent before any protocol-specific procedures. Findings will be disseminated in a peer-reviewed journal and in national and/or international meetings to guide future practice. TRIAL REGISTRATION NUMBER: ChiCTR2100052633.

Circular RNA hsa_circ_0001846 facilitates the malignant behaviors of pancreatic cancer by sponging miR-204-3p and upregulating KRAS expression.

Pancreatic cancer (PC) is mainly derived from the exocrine pancreatic ductal epithelial cells, and it is strongly aggressive malignant tumor. Due to its insidious onset and the lack of effective diagnostic biomarkers, PC currently remains one of the main causes of cancer-related mortality worldwide. Recent studies have found that hsa_circ_0001846 is involved in the progression of multiple cancers and has the potential to become biomarkers, but its function and mechanism in PC remains unclear. We found by qRT-PCR experiments that hsa_circ_0001846 was upregulated in PC cells and tissues, while circBase, Sanger sequencing, agarose gel electrophoresis and FISH experiments identified the splicing site, ring structure and cellular localization of hsa_circ_0001846. Various functional experiments by using the construction of small interfering RNA targeting hsa_circ_0001846 and overexpression plasmid demonstrated that hsa_circ_0001846 promoted the proliferation, migration and invasion of PC cells. Moreover, the tumor weight and volume of nude mice were significantly reduced after the stable knockdown of hsa_circ_0001846. In the mechanism exploration, RNA pull-down experiments and dual-luciferase experiments helped us to determine that hsa_circ_0001846 regulated the KRAS expression by sponging miR-204-3p in PC, thus playing a pro-cancer role. In this study, the effect of miR-204-3p on PC was also explored for the first time, and we found that knockdown of miR-204-3p reversed the tumor suppressive effect caused by silencing hsa_circ_0001846, and silencing KRAS also rescued the pro-cancer effect caused by overexpression of hsa_circ_0001846. In conclusion, our study revealed the pro-cancer role of hsa_circ_0001846 in PC, and for the first time identified the mechanism that hsa_circ_0001846 regulated KRAS by sponging miR-204-3p to promote PC progression and had the potential to become a cancer biomarker.

CT target scanning in the diagnosis of solid pseudopapillary tumor of the pancreas.

OBJECTIVE: To discuss the value of computed tomography (CT) iterative reconstruction technique combined with target scanning in the diagnosis of solid pseudopapillary tumor of the pancreas (SPTP). METHODS: The clinical information and CT examination data of 27 patients with SPTP were retrospectively analyzed, and the general condition and CT performance of the patients were observed. The CT image reconstruction algorithm of all patients used iterative reconstruction technique combined with the application of target scanning technique. RESULTS: A total of 27 patients were included in this study, including 6 males and 21 females, aged 14-72 years with a mean age of 39.6 ± 13.6 years. SPTP was more common in young and middle-aged females, with a low level of tumor markers, dominated by cystic-solid tumors. The combination of CT iterative reconstruction technology and targeted scanning revealed the following: the capsule of SPTP was clear and complete, where calcifications were visible, solid components were progressively enhanced, and rare pancreatic and bile duct dilation was seen. Tumors were cystic-solid in 18 of 27 patients with SPTP, of which the solid components showed isodensity or slightly low-density, with calcifications. The solid components and cyst walls were mildly enhanced during the arterial phase, and were progressively enhanced during the parenchymal phase, portal vein phase, and delayed phase, with their enhancement degree lower than that of normal pancreatic parenchyma, and pancreatic and bile duct dilation was rare. There were no statistical differences in tumor location, morphology, growth pattern, integrity of capsule, cystic or solid, calcifications, and enhancement features between the male group and the female group (P > 0.05). CONCLUSION: The iterative reconstruction combined with target scanning clearly displayed the CT features of tumors, helping the diagnosis and clinical treatment of the disease.

Melatonin Alleviates Acute Respiratory Distress Syndrome by Inhibiting Alveolar Macrophage NLRP3 Inflammasomes Through the ROS/HIF-1α/GLUT1 Pathway.

Sepsis-induced acute respiratory distress syndrome (ARDS) is a devastating clinically severe respiratory disorder, and no effective therapy is available. Melatonin (MEL), an endogenous neurohormone, has shown great promise in alleviating sepsis-induced ARDS, but the underlying molecular mechanism remains unclear. Using a lipopolysaccharide (LPS)-treated mouse alveolar macrophage cell line (MH-S) model, we found that MEL significantly inhibited NOD-like receptor protein 3 (NLRP3) inflammasome activation in LPS-treated macrophages, whereas this inhibitory effect of MEL was weakened in MH-S cells transfected with glucose transporter 1 (GLUT1) overexpressing lentivirus. Further experiments showed that MEL downregulated GLUT1 via inhibition of hypoxia-inducible factor 1 (HIF-1α). Notably, hydrogen peroxide (H2O2), a donor of reactive oxygen species (ROS), significantly increased the level of intracellular ROS and inhibited the regulatory effect of MEL on the HIF-1α/GLUT1 pathway. Interestingly, the protective effect of MEL was attenuated after the knockdown of melatonin receptor 1A (MT1) in MH-S cells. We also confirmed in vivo that MEL effectively downregulated the HIF-1α/GLUT1/NLRP3 pathway in the lung tissue of LPS-treated mice, as well as significantly ameliorated LPS-induced lung injury and improved survival in mice. Collectively, these findings revealed that MEL regulates the activation of the ROS/HIF-1α/GLUT1/NLRP3 pathway in alveolar macrophages via the MT1 receptor, further alleviating sepsis-induced ARDS.

Cu2+@metal-organic framework-derived amphiphilic sandwich catalysts for enhanced hydrogenation selectivity of ketenes at the oil-water interface.

Selective catalysis has always been an essential process for manufacturing various fine chemicals, such as food additives, pharmaceuticals and perfumes. Practically, pure target products are difficult to obtain even after complex purification procedures during industrial production. The development of a cost-effective, highly chemoselective and long-life catalyst may be an attractive solution, but such a catalyst is elusive. Herein, a novel class of amphiphilic N-doped carbon (NC), featuring graphitic carbon (GC) and highly dispersed Cu@Co NPs, was fabricated via simple calcination of a Cu2+-doped bimetallic metal-organic framework (MOF) precusor directly. Compared with monometallic Co@GC/NC, the side reaction of CO bond hydrogenation is obviously restrained, and thus, pure target product can be systematically obtained by Cu@Co@GC/NC, highlighting the high selectivity of Cu. More importantly, an amphiphilic characteristic in Cu@Co@GC/NC is a significant knob to integrate organic substrates with water very well. This amphiphilic material shows great potential as a field-deployable pathway for dispersible metal catalysts in organic systems.

ELK3 Targeting AEG1 Promotes Migration and Invasion of Ovarian Cancer Cells under Hypoxia.

Ovarian cancer (OC) is one of the most common tumors in female reproductive organs with a five-year survival rate of less than 45%. Metastasis is a crucial contributor to OC development. ETS transcription factor (ELK3), as a transcriptional factor, have been involved in multiple tumor development. However, its role in OC remains elusive. In this study, we observed high expression of ELK3 and AEG1 in human OC tissues. OVCAR-3 and SKOV3 cells were treated with hypoxia to mimic tumor microenvironment in vivo. We found that the expression of ELK3 was significantly increased in cells under hypoxia compared with normoxia. ELK3 knockdown inhibited cell migration and invasion abilities under hypoxia. Moreover, ELK3 knockdown decreased ß-catenin expression and inhibited the activation of Wnt/ß-catenin pathway in SKOV3 cells under hypoxia. Astrocyte-elevated gene-1 (AEG1) has been reported to promote OC progression. Our results showed that the mRNA level of AEG1 was decreased when ELK3 knockdown under hypoxia. Dural luciferase assay confirmed that ELK3 bound to gene AEG1 promoter (-2005-+15) and enhanced its transcriptional activity under hypoxia. Overexpression of AEG1 increased the migration and invasion abilities of SKOV3 cell with ELK3 knockdown. In the absence of ELK3, the activation of ß-catenin was recovered by AEG1 overexpression. To sum up, we conclude that ELK3 promotes AEG1 expression by binding to its promoter. ELK3 could promote migration and invasion of OC cells by targeting AEG1, which provides a potential basis for therapeutic approaches to OC.

Heavy metal stress in plants: Ways to alleviate with exogenous substances.

Accumulation and enrichment of excessive heavy metals due to industrialization and modernization not only devastate our ecosystem, but also pose a threat to the global vegetation, especially crops. To improve plant resilience against heavy metal stress (HMS), numerous exogenous substances (ESs) have been tried as the alleviating agents. After a careful and thorough review of over 150 recently published literature, 93 reported ESs and their corresponding effects on alleviating HMS, we propose that 7 underlying mechanisms of ESs be categorized in plants for: 1) improving the capacity of the antioxidant system, 2) inducing the synthesis of osmoregulatory substances, 3) enhancing the photochemical system, 4) detouring the accumulation and migration of heavy metals, 5) regulating the secretion of endogenous hormones, 6) modulating gene expressions, and 7) participating in microbe-involved regulations. Recent research advances strongly indicate that ESs have proven to be effective in mitigating a potential negative impact of HMS on crops and other plants, but not enough to ultimately solve the devastating problem associated with excessive heavy metals. Therefore, much more research should be focused and carried out to eliminate HMS for the sustainable agriculture and clean environmental through minimizing towards prohibiting heavy metals from entering our ecosystem, phytodetoxicating polluted landscapes, retrieving heavy metals from detoxicating plants or crop, breeding for more tolerant cultivars for both high yield and tolerance against HMS, and seeking synergetic effect of multiply ESs on HMS alleviation in our feature researches.

New insights into the degradation mechanism and risk assessment of HFPO-DA by advanced oxidation processes based on activated persulfate in aqueous solutions.

Hexafluoropropylene oxide dimer acid (HFPO-DA) is widely used as a substitute for perfluorooctanoic acid (PFOA). HFPO-DA exhibits high water solubility and low adsorption potential, conferring significant fluidity in aquatic environments. Given that the toxicity of HFPO-DA is similar to PFOA, it is necessary to control its content in aquatic environments. Electrochemical and thermally-activated persulfates have been successfully used to degrade HFPO-DA, but UV-activated persulfates cannot degrade the compound. Given that research on degradation mechanisms is still incomplete and lacks kinetic research, the mechanism and kinetic calculations of oxidative degradation were studied in detail using DFT calculations. And the toxicity of HFPO-DA degradation intermediates and products was evaluated to reveal the feasibility of using advanced oxidation process (AOP) technology based on persulfate to degrade HFPO-DA in wastewater. The results showed that the committed step of HFPO-DA degradation was initiated by the electron transfer reaction of SO4•- radicals. This reaction is not spontaneous at room temperature and requires sufficient electrical or thermal energy to be absorbed from the external environment. The perfluoroalcohol produced during this reaction can subsequently undergo four possible reactions: H atom abstraction from alcohol groups by an OH radical; H atom abstraction by SO4•-; direct HF removal; and HF removal with water as the catalyst. The final degradation products of HFPO-DA mainly include CO2, CF3CF2COOH, CF3COOH, FCOOH and HF, which has been identified through previous experimental analysis. Ecotoxicity assessment indicates that degradation does not produce highly toxic intermediates, and that the final products are non-toxic, supporting the feasibility of persulfate-based AOP technologies.