Gradient Graphene Spiral Sponges for Efficient Solar Evaporation and Zero Liquid Discharge Desalination with Directional Salt Crystallization.

Solar desalination is a promising strategy to utilize solar energy to purify saline water. However, the accumulation of salt on the solar evaporator surface severely reduces light absorption and evaporation performance. Herein, a simple and eco-friendly method to fabricate a 3D gradient graphene spiral sponge (GGS sponge) is presented that enables high-rate solar evaporation and zero liquid discharge (ZLD) desalination of high-salinity brine. The spiral structure of the GGS sponge enhances energy recovery, while the gradient network structures facilitate radial brine transport and directional salt crystallization, which cooperate to endow the sponge with superior solar evaporation (6.5 kg m-2  h-1 for 20 wt.% brine), efficient salt collection (1.5 kg m-2  h-1 for 20 wt.% brine), ZLD desalination, and long-term durability (continuous 144 h in 20 wt.% brine). Moreover, the GGS sponge shows an ultrahigh freshwater production rate of 3.1 kg m-2  h-1 during the outdoor desalination tests. A continuous desalination-irrigation system based on the GGS sponge for crop growth, which has the potential for self-sustainable agriculture in remote areas is demonstrated. This work introduces a novel evaporator design and also provides insight into the structural principles for designing next-generation solar desalination devices that are salt-tolerant and highly efficient.

SEM Electron-Beam-Induced Ultrathin Carbon Deposition Layer on Cu Substrate: Improved Dry Oxidation Protection Performance than CVD Single Layer Graphene.

An amorphous carbon deposition layer (CDL) with nanoscale thickness induced by scanning electron microscope (SEM) electron beam is studied as a carbon-based protective layer on copper (Cu). CDL is prepared by inducing the deposition of pollutants or hydrocarbons in the cavity of SEM through electron beam irradiation (EBI). Wrinkles and cracks will not form and the interfacial spacing of CDL/Cu is smaller than Graphene/Cu (Gr/Cu). The thickness and coverage of the interfacial oxide layer of CDL/Cu are all smaller than that of the Gr/Cu after the same oxidation conditions. Characterization of Raman mapping also demonstrates that CDL shows better oxidation inhibition effects than graphene. The structure of CDL is determined to be C = C and C = O, CH3 - and C-O can be loaded vertically on CDL. Density functional theory (DFT) is employed for demonstrating the smaller interfacial gap of CDL/Cu, less wrinkles and cracks and larger adsorbing energy of water/oxygen compared with Gr/Cu. Molecular dynamic (MD) simulation also indicates that the diffusion of water or oxygen into CDL/Cu is more difficult and the oxidation of Cu covered by CDL is well suppressed. This work provides a new approach for the study of carbon-based antioxidant materials on Cu.

Comparing the effectiveness of extracorporeal shockwave therapy and myofascial release therapy in chronic pelvic pain syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome is a highly prevalent syndrome. Previous studies showed that extracorporeal shockwave therapy and myofascial release therapy could improve the quality of life in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Theoretically, combined therapy with extracorporeal shockwave therapy and myofascial release therapy will likely have significant advantages in treating CP/CPPS. We, therefore, present a protocol for conducting a well-designed randomized controlled trial to compare the efficacy and safety of each therapy. METHODS: The proposed study will be a three-group randomized control trial (RCT) design that includes 150 participants from Zhongda Hospital Affiliated to Southeast University, with equal allocation of participants to the three intervention groups. The study duration will be 8 weeks, which includes a 4-week treatment period and a 4-week follow-up period. The primary outcome will be the changes in surface electromyography (sEMG) assessment and National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). The secondary outcomes will include the changes in three-dimensional quantification, shear wave elastography (SWE), and sympathetic skin response (SSR) testing. Assessments will be conducted before the intervention (T0), before the 5th intervention (T1), immediately after the 8th intervention (T2), and the 4th week after the end of the 8th intervention (T3). DISCUSSION: This trial will compare the differences in efficacy between single extracorporeal shockwave therapy, single myofascial release therapy, and combined therapy to select the most appropriate treatment option for patients with CP/CPPS. The possible pathogenesis of CP/CPPS would also be analyzed by comparing the intercorrelation between each objective and subjective measurement (NIH-CPSI score, sEMG, SWE, SSR). TRIAL REGISTRATION: The name of the registry: Extracorporeal Shockwave and Myofascial Release Therapy in Chronic Pelvic Pain Syndrome. REGISTRATION NUMBER: NCT05659199. Date of registration: December 2022.

Anti-inflammatory, cardioprotective effect of gypenoside against isoproterenol-induced cardiac remodeling in rats via alteration of inflammation and gut microbiota.

BACKGROUND: Myocardial infarction (MI), commonly referred to as a heart attack, occurs when the blood flow to a portion of the heart is blocked, causing damage to the heart muscle. In this study, we scrutinized the cardioprotective effect of gypenoside against the isoproterenol (ISO)-induced myocardial injury (MI) in the rats. METHODS: Wistar rats were divided into four groups as follow: normal, gypenoside (10 mg/kg), ISO control, and ISO control treated with the gypenoside (2.5, 5, and 10 mg/kg). Various parameters were estimated such as infract size, hemodynamic, inflammatory, antioxidant, cardiac, cytokines, and apoptotic markers. We also estimated the gut microbiota in the faces of the experimental rats. Finally, heart tissue histopathology performed. RESULT: Dose-dependent treatment of gypenoside significantly (P < 0.001) reduced the infracted size along with suppression of the heart weight and heart ratio along with enhance the body weight. Gypenoside treatment considerably altered the level of cardiac parameters, cardiac membrane stabilizing enzyme, hemodynamic parameters, antioxidant, lipid parameters, hepatic parameters, renal parameters, inflammatory cytokines, and mediators. Gypenoside significantly (P < 0.001) suppressed the level of apoptotic markers such as caspase-3, caspase-6, and caspase-9. Gypenoside significantly (P < 0.001) altered the relative abundance of unclassified bacteria, Tenericutes, Candidatus_Saccharibacteria, Verrucomicrobia, Actinobacteria, Bacteroidetes, Firmicutes and suppressed the ratio of F/B. CONCLUSION: Gypenoside acts as a protective phytoconstituents against the ISO-induced myocardial infraction in the rats via alteration of gut microbiota, inflammatory, and oxidative stress.

Construction of Built-In Electric Field in TiO2@Ti2O3 Core-Shell Heterojunctions toward Optimized Photocatalytic Performance.

A series of Ti2O3@TiO2 core-shell heterojunction composite photocatalysts with different internal electric fields were synthesized using simple heat treatment methods. The synthesized Ti2O3@TiO2 core-shell heterojunction composites were characterized by means of SEM, XRD, PL, UV-Vis, BET, SPV, TEM and other related analytical techniques. Tetracycline (TC) was used as the degradation target to evaluate the photocatalytic performance of the synthesized Ti2O3@TiO2 core-shell heterojunction composites. The relevant test results show that the photocatalytic performance of the optimized materials has been significantly enhanced compared to Ti2O3, while the photocatalytic degradation rate has increased from 28% to 70.1%. After verification via several different testing and characterization techniques, the excellent catalytic performance is attributed to the efficient separation efficiency of the photogenerated charge carriers derived from the built-in electric field formed between Ti2O3 and TiO2. When the recombination of electrons and holes is occupied, more charges are generated to reach the surface of the photocatalyst, thereby improving the photocatalytic degradation efficiency. Thus, this work provides a universal strategy to enhance the photocatalytic performance of Ti2O3 by coupling it with TiO2 to build an internal electric field.

Adversarial Spatiotemporal Contrastive Learning for Electrocardiogram Signals.

Extracting invariant representations in unlabeled electrocardiogram (ECG) signals is a challenge for deep neural networks (DNNs). Contrastive learning is a promising method for unsupervised learning. However, it should improve its robustness to noise and learn the spatiotemporal and semantic representations of categories, just like cardiologists. This article proposes a patient-level adversarial spatiotemporal contrastive learning (ASTCL) framework, which includes ECG augmentations, an adversarial module, and a spatiotemporal contrastive module. Based on the ECG noise attributes, two distinct but effective ECG augmentations, ECG noise enhancement, and ECG noise denoising, are introduced. These methods are beneficial for ASTCL to enhance the robustness of the DNN to noise. This article proposes a self-supervised task to increase the antiperturbation ability. This task is represented as a game between the discriminator and encoder in the adversarial module, which pulls the extracted representations into the shared distribution between the positive pairs to discard the perturbation representations and learn the invariant representations. The spatiotemporal contrastive module combines spatiotemporal prediction and patient discrimination to learn the spatiotemporal and semantic representations of categories. To learn category representations effectively, this article only uses patient-level positive pairs and alternately uses the predictor and the stop-gradient to avoid model collapse. To verify the effectiveness of the proposed method, various groups of experiments are conducted on four ECG benchmark datasets and one clinical dataset compared with the state-of-the-art methods. Experimental results showed that the proposed method outperforms the state-of-the-art methods.

Increased plasma expression of a disintegrin and metalloproteinase with thrombospondin motifs like 4 in patients with idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) can result in right heart failure. We aimed to evaluate the plasma protein levels of a disintegrin and metalloproteinase with thrombospondin motifs like 4 (ADAMTSL4) and its relationship with IPAH and CTEPH. Plasma ADAMTSL4 protein levels were measured using proteomics analysis in eight patients with IPAH and nine healthy controls. ADAMTSL4 levels in pulmonary tissues were assessed using bioinformatics tools. Protein expression of ADAMTSL4 in platelet-derived growth factor (PDGF)-BB-treated primary rat pulmonary arterial smooth muscle cells (PASMCs) was detected by Western blot. Plasma ADAMTSL4 concentrations were measured in 45 patients (15 with IPAH and 30 with CTEPH) using enzyme-linked immunosorbent assay (ELISA). Correlation between ADAMTSL4 levels and clinical parameters was evaluated. In patients with IPAH, the plasma levels of ADAMTSL4 protein were significantly higher than those in healthy controls (flod change [FC] 1.85, p < 0.05), and mRNA expression levels were significantly elevated (log FC 0.66, p < 0.05). The protein expression of ADAMTSL4 was significantly increased in PDGF-BB-treated PASMCs compared to that in the control grAoup (p < 0.05). Plasma ADAMTSL4 protein levels in patients with IPAH (4.71 ± 0.73 ng/mL, p < 0.01) and CTEPH (4.22 ± 0.66 ng/mL, p < 0.01) were higher than in healthy controls (3.01 ± 0.46 ng/mL). Plasma ADAMATL4 protein levels had a cutoff value of 3.55 ng/mL based on the receiver operator characteristic curve and were positively correlated with mean pulmonary artery pressure (mPAP) (r = 0.305, p < 0.05). In patients with IPAH and CTEPH, elevated plasma ADAMTSL4 levels were positively associated with mPAP.

RcSPL1-RcTAF15b regulates the flowering time of rose (Rosa chinensis).

Rose (Rosa chinensis), which is an economically valuable floral species worldwide, has three types, namely once-flowering (OF), occasional or re-blooming (OR), and recurrent or continuous flowering (CF). However, the mechanism underlying the effect of the age pathway on the duration of the CF or OF juvenile phase is largely unknown. In this study, we observed that the RcSPL1 transcript levels were substantially upregulated during the floral development period in CF and OF plants. Additionally, accumulation of RcSPL1 protein was controlled by rch-miR156. The ectopic expression of RcSPL1 in Arabidopsis thaliana accelerated the vegetative phase transition and flowering. Furthermore, the transient overexpression of RcSPL1 in rose plants accelerated flowering, whereas silencing of RcSPL1 had the opposite phenotype. Accordingly, the transcription levels of floral meristem identity genes (APETALA1, FRUITFULL, and LEAFY) were significantly affected by the changes in RcSPL1 expression. RcTAF15b protein, which is an autonomous pathway protein, was revealed to interact with RcSPL1. The silencing and overexpression of RcTAF15b in rose plants led to delayed and accelerated flowering, respectively. Collectively, the study findings imply that RcSPL1-RcTAF15b modulates the flowering time of rose plants.

Scutebarbatine A induces ROS-mediated DNA damage and apoptosis in breast cancer cells by modulating MAPK and EGFR/Akt signaling pathway.

Scutebarbatine A (SBT-A), a diterpenoid alkaloid, has exerted cytotoxicity on hepatocellular carcinoma cells in our previous works. Here, the antitumor activity of SBT-A in breast cancer cells and the underlying mechanism were explored. The anti-proliferative effect of SBT-A was measured by trypan blue staining, 5-ethynyl-2'-deoxyuridine (EdU) incorporation and colony formation assay. DNA double-strand breaks (DSBs) were evaluated by observing the nuclear focus formation of γ-H2AX. Cell cycle distribution was assessed by flow cytometry. Apoptosis was determined by a TUNEL assay. Intracellular reactive oxygen species (ROS) generation and superoxide production were measured with 2', 7'-dichlorofluorescein diacetate (DCFH-DA) and dihydroethidium (DHE) staining, respectively. The results indicated that SBT-A showed a dose-dependent cytotoxic effect against breast cancer cells while revealing less toxicity toward MCF-10A breast epithelial cells. Moreover, SBT-A remarkably induced DNA damage, cell cycle arrest and apoptosis in both MDA-MB-231 and MCF-7 cells. SBT-A treatment increased the levels of ROS and cytosolic superoxide production. Pretreatment with N-acetyl cysteine (NAC), a ROS scavenger, was sufficient to block viability reduction, DNA damage, apoptosis and endoplasmic reticulum (ER) stress caused by SBT-A. By exposure to SBT-A, the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) was upregulated, while the phosphorylation of extracellular signal-regulated kinase (ERK) was downregulated. In addition, SBT-A inhibited the EGFR signaling pathway by decreasing EGFR expression and phosphorylation of Akt and p70S6K. As mentioned above, SBT-A has a potent inhibitory effect on breast cancer cells through induction of DNA damage, apoptosis and ER stress via ROS generation and modulation of MAPK and EGFR/Akt signaling pathway.

Nanoscale characterization of the heterogeneous interfacial oxidation layer of graphene/Cu based on a SEM electron beam induced reduction effect.

Characterization of the interfacial oxidation layer of graphene/metal is a challenging task using conventional spectroscopy techniques because interfacial oxidation is heterogeneous at the nanoscale underneath the graphene. Here we developed a feasible method for nanoscale characterization of the interfacial oxidation layer of graphene/Cu (Gr/Cu) based on scanning electron microscopy (SEM) electron beam irradiation (EBI) induced reduction of interfacial oxides (SEM EBI-RIO method) at room temperature. The change in the thickness and coverage of the interfacial Cu oxide layer induced by EBI is responsible for the observed contrast reversal or change in SEM images of a targeted area with a width down to 200 nm in the EBI time scale of seconds to minutes. This method offers the capability of mapping heterogeneous interfacial oxidation of Gr/Cu with sub-100 nm spatial resolution and determining the range of thickness (1-5 nm) of the interfacial oxide layer. The SEM EBI-RIO method will be a powerful method to complement X-ray photoelectron spectroscopy (XPS), Raman microscopy, and high resolution transmission electron microscopy (HRTEM) for characterization of the interfacial oxidation layer of 2D materials and devices.

Baicalin regulates TLR4/IκBα/NFκB signaling pathway to alleviate inflammation in Doxorubicin related cardiotoxicity.

Cancers and the toxic and side effects of their treatment have always been a major problem for human beings. Doxorubicin (DOX) is one of the classical anthracycline antineoplastic drugs, but it can cause different degrees of heart damage and even serious heart failure. The incidence of myocardial toxicity increased significantly when the cumulative dose of the drug was more than 550 mg/m2, and the relevant mechanism was related to the inflammatory reaction, reactive oxygen species and the apoptosis of cardiomyocytes in the myocardium. Relevant studies have shown that baicalein (Ba) can inhibit NFκB-related inflammatory signaling pathway protects cardiac function, but whether it can inhibit DOX induced cardiotoxicity has not been reported. Therefore, in animal studies, we explored the effects of doxorubicin and baicalein on cardiac function, TLR4/IκBα/NFκB signaling pathway and related inflammatory indicators in rats. In cell experiments, by silencing or overexpressing TLR4, we explored whether baicalein could achieve anti-inflammatory effect through regulating TLR4/IκBα/NFκB signaling pathway and ultimately inhibit doxorubicin induced cardiotoxicity.

Silencing of SlMYB50 affects tolerance to drought and salt stress in tomato.

High salinity and drought stresses often cause plants to produce ROS, including hydrogen peroxide (H2O2) and superoxide (O2-), which interfere with plant growth and affect crop yield. The transcription factors of the MYB family are involved in responses to biotic and abiotic stresses. Here, we isolated the R2R3-MYB transcription factor gene SlMYB50 and found that silencing of SlMYB50 increased resistance to PEG 6000, mannitol and salt. In addition, the resistance of transgenic tomatoes increased under high salt and drought stress. After stress treatment, the relative water content, chlorophyll content (critical for carbon fixation) and root vitality of the SlMYB50-RNAi lines were higher than those of the wild-type (WT). The opposite was true the water loss rate, relative conductivity, and MDA (as a sign of cell wall disruption). Under drought stress conditions, SlMYB50-silenced lines exhibited less H2O2 and less O2- accumulation, as well as higher CAT enzyme activity, than were exhibited by the WT. Notably, after stress treatment, the expression levels of chlorophyll-synthesis-related, flavonoid-synthesis-related, carotenoid-related, antioxidant-enzyme-related and ABA-biosynthesis-related genes were all upregulated in SlMYB50-silenced lines compared to those of WT. A dual-luciferase reporter system was used to verify that SlMYB50 could bind to the CHS1 promoter. In summary, this study identified essential roles for SlMYB50 in regulating drought and salt tolerance.

TIPE2 protects cardiomyocytes from ischemia-reperfusion-induced apoptosis by decreasing cell autophagy via the mTORC1 signaling pathway.

In cardiac ischemia-reperfusion (I/R), autophagy of hyperactivated cardiomyocytes degrades normal proteins and organelles, destroys cells and causes irreversible cell death. The present study aimed to determine the molecular mechanism through which TNF-α-induced protein 8-like protein 2 (TIPE2) regulates cardiomyocyte apoptosis via autophagy in I/R. The results revealed that the number of apoptotic cells and the protein expression levels of TIPE2 in the heart tissue of I/R model mice were significantly increased. In vitro, the overexpression of TIPE2 decreased oxygen glucose deprivation (OGD)-induced autophagy, apoptosis and activation of the mTOR complex 1 (mTORC1) signaling pathway in H9c2 cells. Treatment with the mTORC1 inhibitor not only inhibited the TIPE2-activated mTORC1 signaling pathway, but also increased OGD-induced autophagy and apoptosis of H9c2 cells. In conclusion, the results of the present study revealed that TIPE2 may protect cardiomyocytes from I/R-induced apoptosis by decreasing cell autophagy via the mTORC1 signaling pathway.

m6A Regulator-Based Exosomal Gene Methylation Modification Patterns Identify Distinct Microenvironment Characterization and Predict Immunotherapeutic Responses in Colon Cancer.

Recent studies have highlighted the biological significance of exosomes and m6A modifications in immunity. Nonetheless, it remains unclear whether the m6A modification gene in exosomes of body fluid has potential roles in the tumor microenvironment (TME). Herein, we identified three different m6A-related exosomal gene modification patterns based on 59 m6A-related exosomal genes, which instructed distinguishing characteristics of TME in colon cancer (CC). We demonstrated that these patterns could predict the stage of tumor inflammation, subtypes, genetic variation, and patient prognosis. Furthermore, we developed a scoring mode-m6A-related exosomal gene score (MREGS)-by detecting the level of m6A modification in exosomes to classify immune phenotypes. Low MREGS, characterized by prominent survival and immune activation, was linked to a better response to anti-PDL1 immunotherapy. In contrast, the higher MREGS group displayed remarkable stromal activation, high activity of innate immunocytes, and a lower survival rate. Hence, this work provides a novel approach for evaluating TME cell infiltration in colon cancer and guiding more effective immunotherapy strategies.

Inhibition of the m6A reader IGF2BP2 as a strategy against T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignant leukemia with extremely limited treatment for relapsed patients. N6-methyladenosine (m6A) reader insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) participates in the initiation and growth of cancers by communicating with various targets. Here, we found IGF2BP2 was highly expressed in T-ALL. Gain and loss of IGF2BP2 demonstrated IGF2BP2 was essential for T-ALL cell proliferation in vitro and loss of IGF2BP2 prolonged animal survival in a human T-ALL xenograft model. Mechanistically, IGF2BP2 directly bound to T-ALL oncogene NOTCH1 via an m6A dependent manner. Furthermore, we identified a small-molecule IGF2BP2 inhibitor JX5 and treatment of T-ALL with JX5 showed similar functions as knockdown of IGF2BP2. These findings not only shed light on the role of IGF2BP2 in T-ALL, but also provide an alternative γ­Secretase inhibitors (GSI) therapy to treat T-ALL.

Licochalcone B induces DNA damage, cell cycle arrest, apoptosis, and enhances TRAIL sensitivity in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a highly fatal disease recognized as a growing global health crisis. Traditional Chinese herbal medicines have been used to treat patients with cancer for many years in China. This study investigated the effects of licochalcone B (LCB), a flavonoid compound isolated from the root of Glycyrrhiza uralensis Fisch., on cell proliferation, DNA damage and TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in HCC cells. Our results showed that LCB inhibited cell proliferation and induced DNA damage, cell cycle arrest and apoptosis. Treatment with LCB significantly inhibited the Akt/mTOR pathway and activated endoplasmic reticulum (ER) stress and mitogen-activated protein kinase (MAPK) signaling pathway. Moreover, combined treatment with LCB and TRAIL yielded evident enhancements in the viability reduction and apoptosis. LCB upregulated death receptor 4 (DR4) and death receptor 5 (DR5) protein in a concentration- and time-dependent manner. The knockdown of DR5 significantly suppressed TRAIL-induced cleavage of PARP, which was enhanced by LCB. Treatment with an extracellular-regulated kinase (ERK) inhibitor (PD98059) or c-Jun N-terminal kinase (JNK) inhibitor (SP600125) markedly reduced the LCB-induced upregulation of DR5 expression and attenuated LCB-mediated TRAIL sensitization. In summary, LCB exhibits cytotoxic activity through modulation of the Akt/mTOR, ER stress and MAPK pathways in HCC cells and effectively enhances TRAIL sensitivity through the upregulation of DR5 expression in ERK- and JNK-dependent manner. Combination therapy with LCB and TRAIL may be an alternative treatment strategy for HCC.

Deacetylation of YAP1 Promotes the Resistance to Chemo- and Targeted Therapy in FLT3-ITD+ AML Cells.

The FLT3-ITD mutation occurs in about 30% of acute myeloid leukemia (AML) and is associated with poor prognosis. However, FLT3 inhibitors are only partially effective and prone to acquired resistance. Here, we identified Yes-associated protein 1 (YAP1) as a tumor suppressor in FLT3-ITD+ AML. YAP1 inactivation conferred FLT3-ITD+ AML cell resistance to chemo- and targeted therapy. Mass spectrometric assay revealed that DNA damage repair gene poly (ADP-ribose) polymerase 1 (PARP1) might be the downstream of YAP1, and the pro-proliferative effect by YAP1 knockdown was partly reversed via PARP1 inhibitor. Importantly, histone deacetylase 10 (HDAC10) contributed to decreased YAP1 acetylation levels through histone H3 lysine 27 (H3K27) acetylation, leading to the reduced nuclear accumulation of YAP1. Selective HDAC10 inhibitor chidamide or HDAC10 knockdown activated YAP1, enhanced DNA damage, and significantly attenuated FLT3-ITD+ AML cell resistance. In addition, combination chidamide with FLT3 inhibitors or chemotherapy agents synergistically inhibited growth and increased apoptosis of FLT3-ITD+ AML cell lines and acquired resistant cells from the relapse FLT3-ITD+ AML patients. These findings demonstrate that the HDAC10-YAP1-PARP1 axis maintains FLT3-ITD+ AML cells and targeting this axis might improve clinical outcomes in FLT3-ITD+ AML patients.

Chemerin Regulates the Proliferation and Migration of Pulmonary Arterial Smooth Muscle Cells via the ERK1/2 Signaling Pathway.

Pulmonary arterial hypertension (PAH) is an incurable disease with high mortality. Chemerin has been found to be associated with pulmonary hypertension (PH). However, the specific role of chemerin in mediating PH development remains unclear. This study aimed to elucidate the regulatory effects and the underlying mechanism of chemerin on PH and to investigate the expression levels of chemerin protein in plasma in PAH patients. In vivo, two animal models of PH were established in rats by monocrotaline (MCT) injection and hypoxia. We found that the expression levels of chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), were significantly upregulated in the lungs of PH rats. Primary cultured pulmonary arterial smooth muscle cells [(PASMCs) (isolated from pulmonary arteries of normal healthy rats)] were exposed to hypoxia or treated with recombinant human chemerin, we found that CMKLR1 expression was upregulated in PASMCs in response to hypoxia or chemerin stimulation, whereas the exogenous chemerin significantly promoted the migration and proliferation of PASMCs. Notably, the regulatory effects of chemerin on PASMCs were blunted by PD98059 (a selective ERK1/2 inhibitor). Using enzyme linked immunosorbent assay (ELISA), we found that the protein level of chemerin was also markedly increased in plasma from idiopathic pulmonary arterial hypertension (IPAH) patients compared to that from healthy controls. Moreover, the diagnostic value of chemerin expression in IPAH patients was determined through receiver operating characteristic (ROC) curve analysis and the result revealed that area under ROC curve (AUC) for plasma chemerin was 0.949. Taken together, these results suggest that chemerin exacerbates PH progression by promoting the proliferation and migration of PASMCs via the ERK1/2 signaling pathway, and chemerin is associated with pulmonary hypertension.

The AP2/ERF transcription factor SlERF.F5 functions in leaf senescence in tomato.

KEY MESSAGE: Our results confirmed that SlERF.F5 can directly regulate the promoter activity of ACS6 and interact with SlMYC2 to regulate tomato leaf senescence. The process of plant senescence is complex and highly coordinated, and is regulated by many endogenous and environmental signals. Ethylene and jasmonic acid are well-known senescence inducers, but their molecular mechanisms for inducing leaf senescence have not been fully elucidated. Here, we isolated an ETHYLENE RESPONSE FACTOR F5 (SlERF.F5) from tomato. Silencing of SlERF.F5 causes accelerated senescence induced by age, darkness, ethylene, and jasmonic acid. However, overexpression of SlERF.F5 would not promote senescence. Moreover, SlERF.F5 can regulate the promoter activity of ACS6 in vitro and in vivo. Suppression of SlERF.F5 resulted in increased sensitivity to ethylene and jasmonic acid, decreased accumulation of chlorophyll content, and inhibited the expression of chlorophyll- and light response-related genes. Compared with the wild type, the qRT-PCR analysis showed the expression levels of genes related to the ethylene biosynthesis pathway and the jasmonic acid signaling pathway in SlERF.F5-RNAi lines increased. Yeast two-hybrid experiments showed that SlERF.F5 and SlMYC2 (a transcription factor downstream of the JA receptor) can interact physically, thereby mediating the role of SlERF.F5 in jasmonic acid-induced leaf senescence. Collectively, our research provides new insights into how ethylene and jasmonic acid promote leaf senescence in tomato.

Cardioprotective Effect of Gossypin Against Myocardial Ischemic/Reperfusion in Rats via Alteration of Oxidative Stress, Inflammation and Gut Microbiota.

Background: Myocardial ischemic/reperfusion (I/R) injury is a key prognostic factor after the myocardial infarction. However, at the time of reperfusion, the myocardial tissue has undergone for the necrosis and initiated the induction of oxidative stress and inflammation. The current study was to scrutinize the cardioprotective effect of gossypin against ISO-induced I/R injury in myocardial tissue and explore the possible underlying mechanism. Methods: Sprague Dawley (SD) was used in the current protocol and ISO was used for induction the I/R in rat. The rats were divided into different groups and received the oral administration of gossypin treatment before the reperfusion. The body weight, heart weight and heart body weight ratio were estimated. The antioxidant, cardiac injury parameters, inflammatory cytokines, inflammatory mediators, gut microbiota and lipid parameters were estimated. At the end, heart tissue histopathological study was carried out. Results: ISO-induced I/R rats received the gossypin treatment significantly (P < 0.001) enhanced the body weight and decreased the heart weight, along with suppressed the infarct size. Gossypin treatment significantly (P < 0.001) reduced the level of heart parameters, such as creatinine kinase-MB (CK-MB), lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin I (CTn-I) and cardiac troponin T (CTn-T) in the serum. Gossypin treatment significantly (P < 0.001) altered the cardiac function, hepatic, antioxidant, inflammatory cytokines and inflammatory mediators. Gossypin significantly (P < 0.001) suppressed the MMP-2 and MMP-9 in ISO-induced I/R rats. Gossypin treatment considerably alleviated the gut dysbiosis through altered Firmicutes to Bacteroidetes (F/B) ratio and also maintained the relative abundance of Butyricicoccus, Clostridium IV, Akkermansia, Roseburia and Clostridium XIVs. Conclusion: Based on result, we can conclude that gossypin is an alternative drug for the treatment of ISO-induced I/R in rats via alteration of oxidative stress, inflammatory reaction and gut microbiota.