PSAT1 Promotes Metastasis via p-AKT/SP1/ITGA2 Axis in Estrogen Receptor-Negative Breast Cancer Cell.

BACKGROUND: Accumulating evidence indicates that PSAT1 not only reprogrammed metabolic function but also exhibits "moonlighting" functions in promoting tumor malignancy. However, the underlying molecular mechanisms of PSAT1 promoting ER-negative breast cancer cell migration need further investigation. METHODS: Briefly, the PSAT1 and ITGA2 expression in cells and tissues was detected using qRT-PCR, immunofluorescence staining and western blot assay. The effect of PSAT1 and ITGA2 was verified both in vitro and in vivo. RNA-seq analysis explored a series of differently expressed genes. The regulation between SP1 and ITGA2 was investigated by ChIP analysis. RESULTS: We reported PSAT1 was highly expressed in ER-breast cancer tissues and tumor cells and positively correlated with metastasis. Moreover, RNA-seq analysis explored a series of differently expressed genes, including ITGA2, in PSAT1 overexpressed cells. Mechanistically, PSAT1 facilitated breast cancer metastasis via the p-AKT/SP1/ITGA2 axis. We further elucidated that PSAT1 promoted the entry of SP1 into the nucleus through the upregulation of p-AKT and confirmed ITGA2 is a target of SP1. In addition, enhanced cell migration was remarkably reversed by ITGA2 depletion or p-AKT inhibitor treatment. CONCLUSION: This study clarified the mechanism of PSAT1 in promoting ER-negative breast cancer metastasis, which may provide mechanistic clues for attenuating breast cancer metastasis.

Enhanced Efficiency and Stability of Inverted CsPbI2Br Perovskite Solar Cells via Fluorinated Organic Ammonium Salt Surface Passivation.

All-inorganic perovskite solar cells (PSCs) have recently received increasing attention due to their outstanding thermal stability. However, the performance of these devices, especially for the devices with a p-i-n structure, is still inferior to that of the typical organic-inorganic counterparts. In this study, we introduce phenylammonium iodides with different side groups on the surface of the CsPbI2Br perovskite film and investigate their passivation effects. Our studies indicate that the 4-trifluoromethyl phenylammonium iodide (CFPA) molecule with the -CF3 side group effectively decreases the trap density of the perovskite film by forming interactions with the undercoordinated Pb2+ ions and significantly inhibits the nonradiative recombination in the derived PSC, leading to an enhanced open-circuit voltage (Voc) from 0.96 to 1.10 V after passivation. Also, the CFPA post-treatment enables better energy-level alignment between the conduction band minimum of CsPbI2Br perovskite and [6,6]-phenyl C61 butyric acid methyl ester, thereby enhancing the charge extraction from the perovskite to the charge transport layer. These combined benefits result in a significant enhancement of the power conversion efficiency from 11.22 to 14.37% for inverted CsPbI2Br PSCs. The device without encapsulation exhibits a degradation of only ≈4% after 1992 h in a N2 glovebox.

Enhanced metabolic ability enabled wild panicgrass (Panicum miliaceum L. var. ruderale kit.) resistance to ALS inhibitor herbicide.

Wild panicgrass (Panicum miliaceum L. var. ruderale kit.) is an annual grass weed that primarily occurs in maize fields. Nicosulfuron is a widely used selective herbicide that effectively controls gramineous weeds in maize fields. However, owing to its long-term and extensive application, the control of P. miliaceum has been substantially reduced. The objective of this study was to determine the resistance pattern to ALS inhibitors in P. miliaceum and investigate the underlying resistance mechanisms. These are important for guiding the prevention and eradication of resistant weeds. Whole plant bioassays showed P. miliaceum had evolved high levels of resistance to nicosulfuron and multiple resistance to atrazine and mesotrione. The ALS gene sequence results indicated the absence of mutations in the resistant population. Additionally, there was no significant difference found in the inhibition rate of the ALS enzyme activity (I50) between the resistant and sensitive populations. Following the application of malathion the resistant P. miliaceum population became more sensitive to nicosulfuron. At 96 h after application of nicosulfuron, glutathione-S-transferase activity in the resistant population was significantly higher than that in the susceptible population. The study reveals that the main cause of resistance to ALS inhibitor herbicide in P. miliaceum is likely increased metabolism of herbicides. These findings may assist in devising effective strategies for preventing and eliminating resistant P. miliaceum.

Investigation of resistance mechanisms to fomesafen in Ipomoea nil from China.

Recently, the herbicide fomesafen has frequently failed to control the troublesome weed Ipomoea nil in soybean fields in Liaoning Province, China. Hence, we collected 10 suspected resistant populations and evaluated their sensitivity to fomesafen. The results revealed various degrees of Ipomoea nil resistance to fomesafen, with a resistance index of 2.88 to 22.43; the highest value occurred in the LN3 population. Therefore, the mechanisms of the resistance in LN3 to fomesafen were explored. After fomesafen treatment, the expression levels of InPPX1 and InPPX2 genes were 4.19- and 9.29-fold higher, respectively, in LN3 than those in the susceptible (LN1) population. However, mutations and copy number variations were not detected between the two populations. Additionally, malathion pretreatment reduced the dose necessary to halve the growth rate of LN3 by 58%. Liquid chromatography with tandem mass spectrometry demonstrated that metabolism of fomesafen was significantly suppressed by malathion. Moreover, LN3 displayed increased reactive oxygen species scavenging capacity, which was represented by higher superoxide dismutase and peroxidase activities after fomesafen application than those in LN1. An orthogonal partial least squares-discriminant analysis revealed that the high resistance in LN3 could be attributed mainly to enhanced metabolism. Fortunately, the fomesafen-resistant I. nil remained sensitive to 2,4-D-ethylhexylester and bentazon, providing methods for its control.

Role of cuproptosis in understanding diseases.

Cell death is involved in a wide range of physiological and pathological processes. Recently, the term "cuproptosis" was coined to describe a novel type of cell death. This type of cell death, characterized by copper accumulation and proteotoxic stress, is a copper-dependent manner of death. Despite the progress achieved toward a better understanding of cuproptosis, mechanisms and related signaling pathways in physiology and pathology across various diseases remain to be proved. This mini review summarizes current research on cuproptosis and diseases, providing insights into prospective clinical therapies via targeting cuproptosis.

Mutation at the 197 site and P450-mediated metabolic resistance are involved in bensulfuron-methyl resistance in Sagittaria trifolia.

Sagittaria trifolia control is threatened by the emergence of resistance to acetolactate synthase (ALS)-inhibiting herbicides. Hence, we systematically uncovered the molecular mechanism of resistance to the main herbicide (bensulfuron-methyl) in Liaoning Province from target-site and non-target-site resistance perspectives. The suspected resistant population (TR-1) exhibited high-level resistance. A new amino acid substitution (Pro-197-Ala) in resistant Sagittaria trifolia for ALS was detected, and the molecular docking results showed that the spatial structure of ALS changed significantly after the substitution, manifested by an increase in the number of contacted amino acid residues and the disappearance of hydrogen bonds. Dose-response test of transgenic Arabidopsis thaliana further demonstrated that the Pro-197-Ala substitution conferred bensulfuron-methyl resistance. The assays found that the sensitivity of the ALS enzyme in TR-1 to this herbicide was decreased in vitro; and this population had developed resistance to other types of ALS-inhibiting herbicides. Furthermore, the resistance of TR-1 to bensulfuron-methyl was significantly alleviated after co-treatment with a P450-inhibitor (malathion). TR-1 metabolized bensulfuron-methyl significantly faster than sensitive population (TS-1) did, but this gap was narrowed after malathion treatment. Overall, the resistance of Sagittaria trifolia to bensulfuron-methyl was derived from the mutation of the target-site gene and the enhancement of the P450s-mediated detoxification metabolism.

Increase in glutathione S-transferase activity and antioxidant damage ability drive resistance to bensulfuron-methyl in Sagittaria trifolia.

Weeds tend to develop resistance to herbicides with time. Understanding the resistance mechanisms evolved by weeds would help manage weed infestation. Sagittaria trifolia, a paddy weed found in the rice fields of Liaoning, China, has developed resistance to bensulfuron-methyl, causing severe yield losses in rice. This study deciphers the underlying mechanisms in terms of non-target-site resistance toward bensulfuron-methyl. We compared the ability of glutathione S-transferase (GST) mediated detoxification metabolism and reactive oxygen species (ROS) scavenging between sensitive (NHS) and resistant (NHR) populations of S. trifolia. The resistance ratio of NHR was 210; but the ratio was significantly decreased after GST-inhibitor treatment (44.9). This indicated that a GST-mediated enhancement of detoxification metabolism stimulated the development of resistance. Similarly, higher GST activity was observed in NHR; but the activity equaled that of NHS after GST-inhibitor treatment. However, treatment with the GST-inhibitor did not completely reverse bensulfuron-methyl resistance in NHR, indicating that additional factors contributed to herbicide resistance in these plants. We observed a rapid increase in H2O2 and malondialdehyde accumulation in the case of NHS after bensulfuron-methyl application, whereas those of NHR remained relatively stable, implying that NHR exhibited higher ROS-scavenging capacity under herbicide stress. Further, NHR showed higher glutathione and ascorbic acid contents and higher activities of glutathione reductase and dehydrogenase reductase, all of which contribute towards herbicide resistance in these plants. Our results indicate that GST-mediated detoxification metabolism of bensulfuron-methyl and ROS scavenging capacity contributed to the development of resistance in S. trifolia.

Reduced Immunity Regulator MAVS Contributes to Non-Hypertrophic Cardiac Dysfunction by Disturbing Energy Metabolism and Mitochondrial Homeostasis.

Cardiac dysfunction is manifested as decline of cardiac systolic function, and multiple cardiovascular diseases (CVDs) can develop cardiac insufficiency. Mitochondrial antiviral signaling (MAVS) is known as an innate immune regulator involved in viral infectious diseases and autoimmune diseases, whereas its role in the heart remains obscure. The alteration of MAVS was analyzed in animal models with non-hypertrophic and hypertrophic cardiac dysfunction. Then, MAVS-deficient mice were generated to examine the heart function, mitochondrial status and energy metabolism. In vitro, CRISPR/Cas9-based gene editing was used to delete MAVS in H9C2 cell lines and the phenotypes of mitochondria and energy metabolism were evaluated. Here we observed reduced MAVS expression in cardiac tissue from several non-hypertrophic cardiac dysfunction models, contrasting to the enhanced MAVS in hypertrophic heart. Furthermore, we examined the heart function in mice with partial or total MAVS deficiency and found spontaneously developed cardiac pump dysfunction and cardiac dilation as assessed by echocardiography parameters. Metabonomic results suggested MAVS deletion probably promoted cardiac dysfunction by disturbing energy metabolism, especially lipid metabolism. Disordered and mitochondrial homeostasis induced by mitochondrial oxidative stress and mitophagy impairment also advanced the progression of cardiac dysfunction of mice without MAVS. Knockout of MAVS using CRISPR/Cas9 in cardiomyocytes damaged mitochondrial structure and function, as well as increased mitochondrial ROS production. Therefore, reduced MAVS contributed to the pathogenesis of non-hypertrophic cardiac dysfunction, which reveals a link between a key regulator of immunity (MAVS) and heart function.

P450s mediated enhanced herbicide metabolism involved in the thifensulfuron-methyl resistance in Ipomoea purpurea L.

Ipomea purpurea (L.) Roth. reduces dry land crop yield and quality in Northeast China, especially in Liaoning Province. Frequent use of thifensulfuron-methyl in recent years has resulted in herbicide resistance in I. purpurea. We evaluated resistance levels of I. purpurea to thifensulfuron-methyl, an acetolactate synthase (ALS) inhibitor, in Liaoning Province and further investigated the resistance mechanisms. The results showed that 15 populations of I. purpurea have evolved up to 5.81-34.44-fold resistance to thifensulfuron-methyl, compared to the susceptible population (S), among which LN3 was the most resistant. DNA sequencing of the ALS gene in susceptible and resistant populations did not reveal any target site mutations that could be associated with resistance to thifensulfuron-methyl in I. purpurea. Additionally, no significant difference was detected between the in vitro ALS activity of LN3 and S. The GR50 of LN3 decreased sharply by 47% when malathion (a P450 inhibitor) was applied with thifensulfuron-methyl. Absorption of thifensulfuron-methyl by LN3 was equal to that of S; however, LN3 metabolized the herbicide significantly faster. This was repressed after the inhibition of P450s activity. Collectively, our results confirmed that I. purpurea in Liaoning Province has developed resistance to thifensulfuron-methyl and implied that the resistance was conferred by the increase in detoxification mediated by P450s. Furthermore, LN3 was sensitive to fluroxypyr, which can be used as an alternative to control I. purpurea.