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In brief The appropriate growth and functions of Sertoli cells are crucial to testis development and spermatogenesis in mammals. This study reveals a novel mechanism of follicle-stimulating hormone in immature porcine Sertoli cell proliferation. Abstract Follicle-stimulating hormone (FSH) is a major Sertoli cell mitogen that binds to the FSH receptor. Sertoli cells are indispensable for testis development and spermatogenesis. However, the regulatory mechanisms of FSH in immature Sertoli cell proliferation have not been determined, particularly in domestic animals. In the present study, we identified the regulatory mechanisms of FSH during immature porcine Sertoli cell proliferation. Transcriptome analysis revealed 114 differentially expressed genes that were induced by FSH treatment, which contains 68 upregulated and 46 downregulated genes. These differentially expressed genes were enriched in multiple pathways, including the Ras signaling pathway. Knockdown of the CC-chemokine receptor 7 (CCR7) gene, which was upregulated by FSH, inhibited cell cycle progression by arresting cells in the G1 phase and reduced the cell proliferation and ERK1/2 phosphorylation. In addition, Kobe0065 inhibited Ras signaling in a similar manner as CCR7 knockdown. Furthermore, FSH abolished the effects of Ras signaling pathway inhibition and CCR7 knockdown. Collectively, FSH promotes immature porcine Sertoli cell proliferation by activating the CCR7/Ras-ERK signaling axis. Our results provide novel insights into the regulatory mechanism of FSH in porcine testis development and spermatogenesis by deciding the fate of immature porcine Sertoli cells.

A two-stage isothermal amplification method termed rolling cycle strand exchange amplification (RC-SEA) was established to accomplish ssRNA and dsDNA analysis using only one DNA polymerase in a single closed tube at a constant temperature.

SPRY4-IT1 (SPRY4 intronic transcript 1) is a long non-coding RNA (lncRNA) that has been identified as a novel oncogene in various cancers, including glioma. However, its function and underlying mechanism in glioma remain largely unclear. Here, we investigated the role of SPRY4-IT1 in the development of glioma and its underlying mechanism.Bioinformatics analysis and RT-qPCR assay were used to examine the expression of SPRY4-IT1 in glioma tissues. The CCK-8, EdU, and Xenograft tumor assays wereperformed to assess the proliferation effect of glioma cells. The tube forming assay and Chick Embryo Chorioallantoic Membrane (CAM) assay were conducted to detect the angiogenesis effect of HUVECs. RNA-sequencing, western blotting, RT-qPCR, ELISA, and IHC assays were employed to verify the regulatory mechanism of the SPRY4-IT1/ miR-101-3p/EZH2/VEGFA axis.Analysis of the TCGA dataset and data from our own cohort demonstrated that SPRY4-IT1 was overexpressed in patients with glioma, and high SPRY4-IT1 expression correlated with poor prognosis. In vitro and in vivo experiments showed that SPRY4-IT1 promoted the proliferation of glioma cells. RNA sequencing and Gene Ontology (GO) enrichment analysis indicated significant enrichment of angiogenesis. HUVEC tube forming assay and CAM assay confirmed that SPRY4-IT1 could induce angiogenesis of glioma cells in vitro and in vivo. Mechanistically, SPRY4-IT1 upregulated EZH2 expression by sponging miR-101-3p to induce VEGFA expression in glioma cells. Moreover, SPRY4-IT1 activated the VEGFR2/AKT/ERK1/2 pathway in HUVECs mediated by glioma cells. Rescue experiments further confirmed that SPRY4-IT1 promoted glioma cell proliferation and angiogenesis via the miR-101-3p/EZH2/VEGFA signaling axis.Our findings provide compelling evidence showing that SPRY4-IT1 upregulated EZH2 to induce VEGFA by sponging miR-101-3p, thereby achieving cell proliferation and angiogenesis in glioma. Therefore, targeting SPRY4-IT1/miR-101-3p/EZH2/VEGFA axis may improve the outcomes of patients with glioma.

Nucleic acid amplification tests (NAATs) have become an attractive approach for pathogen detection, and obtaining high-quality nucleic acid extracts from biological samples plays a critical role in ensuring accurate NAATs. In this work, we established an elution-free magnetic bead (MB)-based method by introducing polyethylene-polypropylene glycol (PEPPG) F68 in lysis buffer and using NaOH solution instead of alcohols as the washing buffer for rapid nucleic acid extraction from multiple types of biological samples, including nasopharyngeal swabs, serum, milk, and pork, which bypassed the nucleic acid elution step and allowed the nucleic acid/MB composite to be directly used as the template for amplification reactions. The entire extraction process was able to be completed in approximately 7 min. Even though the nucleic acid/MB composite could not be used for quantitative real-time PCR (qPCR) assays, this elution-free MB-based method significantly improved the sensitivity of the loop-mediated isothermal amplification (LAMP) assay. The sensitivity of the quantitative real-time LAMP (qLAMP) assays combined with this elution-free MB-based method showed an improvement of one to three orders of magnitude compared with qLAMP or qPCR assays combined with the traditional MB-based method. In addition to manual operation, like the traditional MB-based method, this universal, rapid, and facile nucleic acid extraction method also has potential for integration into automated robotic processing, making it particularly suitable for the establishment of an analysis platform for ultrafast and sensitive pathogen detection in various biological samples both in centralized laboratories and at remote sites.

The potential role of brassinosteroid (BR) and abscisic acid (ABA) against cold stress in plants separately has been made with much effort. However, the connection between BR and ABA in response to cold stress is less clear. Herein, the potential involvement of ABA in BR-induced cold resistance in grapevines was investigated by contrasting the different responses among ABA, BR, and the combination of BR and NDGA (an inhibitor of endogenous ABA biosynthesis) treatments under cold stress. Results showed BR and ABA foliar application alone increased the chlorophyll fluorescence parameters, regulated the antioxidant system, and alleviated oxidative damage induced by low temperature stress. Interestingly, NDGA blocked the BR-induced cold resistance by increasing reactive oxygen species content and reducing antioxidant enzyme activity. Transcriptomic analysis suggested that exposure to cold stress resulted in very different patterns of gene expression and enriched pathway responses. Among them, genes from the ERF transcription factors were observed to be up-regulated both BR and ABA treatment, calcium-binding protein genes were up-regulated only under BR treatment alone, xyloglucosyl transferase genes were up-regulated only under ABA treatment. Overall, we concluded that ABA was involved in BR-induced cold resistance in grapevines, but there was also a different candidate pathway between ABA and BR treatments under cold stress.

Non-alcoholic fatty liver disease (NAFLD) has increasingly become a serious public health problem. There is growing evidence that nonylphenol (NP) exposure may cause steatosis, but the underlying mechanism is not fully understood. Curcumin (CUR) improves NAFLD-related lipid metabolism disorders and oxidative stress, but its preventive and therapeutic effects on NP-induced steatosis have not been reported. The objective of this investigation was to determine the capability and potential mechanism of NP to induce steatosis

Calcium/calmodulin-dependent protein kinase (CaMK), a key downstream target protein in the Ca2+ signaling pathway of eukaryotes, plays an important regulatory role in the growth, development and pathogenicity of plant fungi. Three AaCaMKs (AaCaMK1, AaCaMK2 and AaCaMK3) with conserved PKC_like superfamily domains, ATP binding sites and ACT sites have been cloned from Alternaria alternata, However, their regulatory mechanism in A. alternata remains unclear. In this study, the function of the AaCaMKs in the development, infection structure differentiation and pathogenicity of A. alternata was elucidated through targeted gene disruption. The single disruption of AaCaMKs had no impact on the vegetative growth and spore morphology but significantly influenced hyphae growth, sporulation, biomass accumulation and melanin biosynthesis. Further expression analysis revealed that the AaCaMKs were up-regulated during the infection structure differentiation of A. alternata on hydrophobic and pear wax substrates. In vitro and in vivo analysis further revealed that the deletion of a single AaCaMKs gene significantly reduced the A. alternata conidial germination, appressorium formation and infection hyphae formation. In addition, pharmacological analysis confirmed that the CaMK specific inhibitor, KN93, inhibited conidial germination and appressorium formation in A. alternata. Meanwhile, the AaCaMKs genes deficiency significantly reduced the A. alternata pathogenicity. These results demonstrate that AaCaMKs regulate the development, infection structure differentiation and pathogenicity of A. alternata and provide potential targets for new effective fungicides.

Tremendous attention has been paid on high efficiency, readily available and stability of electrocatalysts. Herein, we ingenious report a one-step reaction strategy synthesis of CoFe/CP grown on three-dimensional (3D) nanoarray carbon paper (CP) containing non-precious metals for oxygen evolution reaction (OER) with low-cost and unique hierarchical porous structure. This amorphous CoFe/CP hybrid exhibits commendable electrocatalytic performance in the OER process, requiring only overpotential of 278 mV to achieve 10 mAcm−2 in 1.0 M KOH solution and a lower Tafel slope of 49.12 mVdec-1. In addition, this sample shows a long-term durability even at 200 mAcm−2 without obvious decay, which attributes to peculiar multistage graded nano structure and the change of composition at the interface of CP. Therefore, the remarkable OER activity can provide a new strategy to construct potential candidates, which will replace the state-of-the-art precious metals for OER in the future.

Homogeneous nano-CeO2 coated on LiMn2O4 powder has been successfully prepared via a facile solid-state approach. Our work demonstrates that surface modification of LiMn2O4 sintered at 450 °C shows a high initial discharge of 137.7 mAh·g−1 and superior capacity retention with 95.86%, which is much higher that of the pristine LiMn2O4. In addition, CeO2@LMO-450 has excellent rate performance especially at elevated performance, probably due to the faster Li+ transportation and the improvement of the electrical conductivity by nano-CeO2 layer. When cycled at 0.2 C between 3.0 and 4.3 V at 60 °C, CeO2@LMO-450 shows discharge capacity of 116.1 mAh·g−1 after 60 cycles with a capacity retention of 88.36%, which is two times more than that of pristine LiMn2O4. The improvement of the electrochemical performance of LiMn2O4 by nano-CeO2 layer surface modification can suppress the dissolution reaction of manganese ions, even at elevated temperature, and clearly improve the cyclability of spinel LiMn2O4.

Glioblastoma has high recurrence, while the sensitivity of recurrent glioblastoma to chemotherapy is lower than that of primary glioblastoma. Moreover, there is no standardized treatment for recurrent glioblastoma. Unfortunately, the biological mechanism of recurrent glioblastoma is still unclear, and there are few related studies. We compared the phenotypes of clinical glioblastoma specimens, in-vitro cultured glioma stem-like cells (GSCs) and patient-derived xenograft tumor (PDX) models to explore the molecular genetic characteristics of primary and recurrent glioblastoma from the same patient. In vitro, SU5-2, GSCs derived from recurrent glioblastoma specimens, had stronger proliferative activity and self-renewal ability. Meanwhile, SU5-2 was more resistant to temozolomide and invasive than SU5-1, which derived from primary glioblastoma specimens. Further analysis of the expression of costimulatory molecules showed that the expression of B7-H1, B7-H2 and B7-H3 of SU5-2 were upregulated. In vivo, Kaplan-Meier survival curve analysis showed that the median survival of the recurrent PDX group was worse. The results of gene detection in vitro, PDX model and clinical samples were consistent. Our results showed that the GSCs based on glioblastoma specimens and the PDX models could replicate the main molecular genetic characteristics of original tumors, which provided a reliable experimental platform for both tumor translation kinds of research and screening of molecular therapeutic targets.

Purpose This study aimed to analyze the growth of preterm infants after birth regarding weight, length, and head circumference (HC) and determine the risk factors affecting their catch-up growth. Methods Anthropometric data and clinical information from 288 preterm infants were collected. Z-scores were calculated using the World Health Organization Anthro software. Logistic regression analysis assessed the risk factors for catch-up growth in preterm births. Results The percentage of preterm infants with z-scores

Di(2-ethyl-hexyl) phthalate (DEHP), an environmental endocrine disruptor, can destroy the sperm genomic integrity and impairs spermatogenesis. N6-methyladenosine (m6A) is involved in the cellular effects of DEHP. However, the genotoxic effect of DEHP on spermatocytes and the possible role of m6A in this process remain unclear. This study demonstrated that m6A alleviates DEHP genotoxicity in GC-2 cells. In DEHP-treated mice, DNA double-strand breaks (DSBs) were induced in the testis and spermatocytes. To further explore the molecular mechanism of DEHP genotoxicity on spermatocytes, GC-2 cells were exposed to DEHP. DEHP produced distinct genotoxicity and caused DSBs, which led to the inhibition of DNA synthesis and cell cycle arrest. The DNA damage response (DDR) was initiated to repair the DSBs induced by environmentally relevant levels of DEHP (100 μM and 200 μM). During this process, METTL3 upregulated m6A, which facilitated the DDR via stabilizing the DNA damage repair factors (Rad51 and Xrcc5) mRNA to maintain the pro-survival state. Moreover, Mettl3 knockdown partially inhibited DDR. Interestingly, high-dose DEHP (400 μM and 600 μM) directly induced apoptosis rather than the pro-survival state. Altogether: METTL3-mediated m6A participates in maintaining the pro-survival state by upregulating DDR, providing guidance for mitigating the genotoxicity of environment-related level DEHP exposure.

Breast cancer is one of the most common malignant tumors in women. The existence of multiple breast cancer subtypes often leads to chemotherapy failure or the development of drug resistance. In recent years, photodynamic therapy has been proven to enhance the sensitivity of tumors to chemotherapeutic drugs. Porphyrin-based metal-organic framework (MOF) materials could simultaneously be used as carriers for chemotherapy and photosensitizers in photodynamic therapy. In this paper, doxorubicin hydrochloride (DOX) was loaded in porphyrin MOFs, and the mechanism of the synergistic effect of the DOX carriers and photodynamic therapy on breast cancer was investigated. In vitro and in vivo experiments have shown that MOFs could prolong the residence time of DOX in tumor tissues and promote the endocytosis of DOX by tumor cells. In addition, adjuvant treatment with photodynamic therapy can promote breast cancer tumors to resensitize to DOX and synergistically enhance the chemotherapy effect of DOX. Therefore, this study can provide effective development ideas for reversing drug resistance during breast cancer chemotherapy and improving the therapeutic effect of chemotherapy on breast cancer.

According to the immune inflammation theory of Alzheimer’s disease (AD), triptolide (TP) is a potential drug for the treatment of AD, but it distributed widely in vivo resulting in the multi-organ toxicity. In order to improve the efficacy and reduce the toxicity of TP, stealth brain-targeting TP nanoliposomes (Lf-TP-PL) were prepared with polyethyleneglycol (PEG)-modified and lactoferrin (Lf) as the brain-targeting head group. Compared with TP solution (TP-S), common TP nanoliposomes (TP-CL) and PEG-modified TP nanoliposomes (TP-PL), the effect of Lf-TP-PL on the growth of PC12 cells inductively damaged by Aβ1-42, as the model in vitro AD cells, was studied. The effects of Lf-TP-PL on the behavioral ability of AD model mice were evaluated by Morris water maze test. The results showed that compared with TP-S, TP-CL, and TP-PL, Lf-TP-PL had stronger abilities to repair the PC12 cells inductively damaged by Aβ1-42, and could mitigate spatial memory deficit of AD model mice in a better way. Lf-TP-PL is a potential nanomedicine for AD treatment.

Bone morphogenetic protein 9 (BMP9) is a recently discovered cytokine mainly secreted by the liver and is a member of the transforming growth factor β (TGF-β) superfamily. In recent years, an increasing number of studies have shown that BMP9 is associated with liver diseases, including nonalcoholic fatty liver disease (NAFLD), liver fibrosis and hepatocellular carcinoma (HCC), and BMP9 signaling may play dual roles in liver diseases. In this review, we mainly summarized and discussed the roles and potential mechanisms of BMP9 signaling in NAFLD, liver fibrosis and HCC. Specifically, this article will provide a better understanding of BMP9 signaling and new clues for the treatment of liver diseases.

Aims Calmodulin (CaM), acts as a kind of multifunctional Ca2+ sensing protein, which is ubiquitous in fungi, is highly conserved across eukaryotes and is involved in the regulation of a range of physiological processes, including morphogenesis, reproduction and secondary metabolites biosynthesis. Our aim was to understand the characteristics and functions of AaCaM in Alternaria alternata, the causal agent of pear black spot. Methods and results A 450 bp cDNA sequence of AaCaM gene of A. alternata was cloned by the PCR homology method. Sequence analysis showed that this protein encoded by AaCaM was a stable hydrophilic protein and had a high similarity to Neurospora crassa (CAA50271.1) and other fungi. RT-qPCR analysis determined that AaCaM was differentially upregulated during infection structural differentiation of A. alternata both on hydrophobic and pear wax extract-coated surface, with a 3.37-fold upregulation during the hydrophobic induced appressorium formation period (6 h) and a 1.46-fold upregulation during the infection hyphae formation period (8 h) following pear wax induction. Pharmaceutical analysis showed that the CaM-specific inhibitor, trifluoperazine (TFP), inhibited spore germination and appressorium formation, and affected toxins and melanin biosynthesis in A. alternata. Conclusions AaCaM plays an important role in regulating infection structure differentiation and secondary metabolism of A. alternata. Significance and impact of study Our study provides a theoretical basis for further in-depth investigation of the specific role of AaCaM in the calcium signalling pathway underlying hydrophobic and pear wax-induced infection structure differentiation and pathogenicity of A. alternata.

Glioblastoma multiforme (GBM) is the most invasive malignant central nervous system tumor with poor prognosis. Nicardipine, a dihydropyridine calcium channel antagonist, has been used as an adjuvant to enhance sensitivity to chemotherapeutic drugs. However, whether glioma stem cells (GSCs) can be sensitized to chemotherapy via combined treatment with temozolomide (TMZ) and nicardipine is unclear. In this study, surgical specimen derived GSCs SU4 and SU5 were applied to explore the sensitization effect of nicardipine on temozolomide against GSCs, and further explore the relevant molecular mechanisms. Our results showed that nicardipine can enhance the toxic effect of temozolomide against GSCs, promote apoptosis of GSCs, and inhibit autophagy of GSCs. The relevant mechanisms were related to activation of mTOR, and selective inhibition of mTOR by rapamycin could weaken the sensitization of nicardipine to temozolomide, which suggest that nicardipine can be applied as an adjuvant to inhibit autophagy in GSCs, and enhance apoptosis-promoting effect of temozolomide in GSCs as well. Nicardipine can inhibit autophagy by activating expression of mTOR, thus play tumor inhibition roles both in vitro and in vivo. Repurposing of nicardipine can help to improving therapeutic effect of TMZ against GBM, which deserves further clinical investigations.

Pressure sensors for living organisms can monitor both the movement behavior of the organism and pressure changes of the organ, and they have vast perspectives for the health management information platform and disease diagnostics/treatment through the micropressure changes of organs. Although pressure sensors have been widely integrated with e-skin or other wearable systems for health monitoring, they have not been approved for comprehensive surveillance and monitoring of living organisms due to their unsatisfied sensing performance. To solve the problem, here, we introduce a novel structural design strategy to manufacture reduced graphene oxide-polypyrrole aerogel-based microfibers with a typical coaxial heterogeneous structure, which significantly enhances the sensitivity, resolution, and stability of the derived pressure microsensors. The as-fabricated pressure microsensors exhibit ultrahigh sensitivities of 12.84, 18.27, and 4.46 kPa-1 in the pressure ranges of 0-20, 20-40, and 40-65 Pa, respectively, high resolution (0.2 Pa), and good stability in 450 cycles. Furthermore, the microsensor is applied to detect the movement behavior and organic micropressure changes for mice and serves as a platform for monitoring micropressure for the integrative diagnosis both in vivo and in vitro of organisms.

There has been a surge of interest in applying quantitative approaches to stylistics in recent decades. These researches can be roughly divided into two branches, i.e., quantitative or computationa...

Ammonia (NH3) is an important chemical substance widely used in agriculture, pharmaceuticals, and industry. Nitrogen makes up 78% of the atmosphere, which is also the main raw material for the production of ammonia. However, due to the strong bond energy of NN, cracking the triple bond between nitrogen and nitrogen is the most important step in the nitrogen reduction reaction (NRR). Two-dimensional layered materials have been widely explored due to their large specific surface area and tunable electronic structure, such as graphene, black phosphorus, and MXenes. To achieve the targeted design of a new type of nitrogen reduction electrocatalyst, relevant theoretical calculations must be done before the experiment. However, it is far from enough to rely on the two-dimensional layered material; thus, it is necessary to compound itself, or prepare its related derivatives.

Single-modality tumor therapy confronts many challenges, such as incomplete tumor ablation, tumor metastasis, and limited tumor tissue penetration. Combination therapy simultaneously achieves deep drug delivery to fully exert synergistic effects and has received increasing attention. Herein, based on the excellent efficacy of anti-angiogenesis therapy combined with chemotherapy and the specific size of the poly-amidoamine dendrimer (PAMAM), we developed a pH-triggered size-converted nano-drug delivery system to co-deliver fruquintinib (FRU) and doxorubicin (DOX). This study used cyclic Arg-Gly-Asp (cRGD) as the target, pH-responsive liposomes (PRLs), and PAMAM as the drug carrier. The FRU and DOX-loaded small-particle-size complex polyamide-amine-doxorubicin (PD) was encapsulated into PRLs with the target to construct a size-converted nano-drug delivery system, PRL-PD/FRU-cRGD. This nanoparticle (∼120 nm) actively targeted tumor tissues and used the acidic microenvironment outside tumor cells to release FRU and small-particle-size complex PD (∼15 nm), enabling the conversion of large-size nanoparticles to small-size nanoparticles and resulting in efficient tumor accumulation. In addition, the released PD could realize the deep delivery of DOX, showing efficient deep tumor penetration and further enhancing the tumor-suppressing effect. The results of in vivo and in vitro experiments showed that PRL-PD/FRU-cRGD exhibited the excellent synergistic effects of anti-angiogenesis therapy combined with chemotherapy and effectively inhibited tumor cell proliferation and metastasis, thereby achieving efficient tumor therapy. Thus, PRL-PD/FRU-cRGD shows great potential for combined tumor therapy.

CmrA, as transcription factor for regulating DHN-melanin synthesis, controls melanin synthesis gene expression, and also regulate growth, development, stress response and virulence of plant fungi. However, little is known about the roles of CmrA on infection structure formation, penetration and pathogenicity of pear fungal Alternaria alternata. Here, we identified cmrA gene in A. alternata and assigned as AacmrA, sequence alignment and phylogenetic analysis revealed that AacmrA is highly conserved among fungi and encoded protein contain two Cys2His2 zinc finger motifs and one Zn(II)2Cys6 zinc cluster protein motif. ΔAacmrA severely decreased melanin production and DHN melanin synthesis related genes expression. Deletion of AacmrA impaired the morphology of spore and hyphae. Spore germination and appressorium formation induced by hydrophobicity surfaces and fruit wax significantly decreased in ΔAacmrA mutant. ΔAacmrA mutants were more sensitive than the wild type to osmotic stress and cell wall inhibitors, especially more sensitive to oxidative stress. In addition, lesion diameter of pear fruit wound inoculated with the ΔAacmrA mutant was reduced by 40.8% compared with the wild type 12 d after inoculation. All findings of this study suggested that AacmrA is required for melanin biosynthesis, infection structure formation, and pathogenicity in A. alternata.

Nonylphenol (NP) is one of the most toxic and ubiquitously present endocrine disrupting compounds. Numerous studies have shown that NP exposure induces liver injury, but the interactions between epigenetic factors and necroptosis in this context have not been examined. In this study, rats received daily NP administration (15, 45, and 135 mg/kg/day) via oral gavage over a 28-day period. The upregulation of lncRNA PVT1 was associated with the elevated expression of necroptosis-related proteins (ZBP1, RIPK3, MLKL, and p-MLKL). Moreover, similar effects were also observed after NP exposure in BRL-3A cells. LncRNA PVT1 was predominantly expressed in the nucleus, and ASO was chosen to knock down lncRNA PVT1 in BRL-3A cells. Experimental techniques such as RNA immunoprecipitation, chromatin immunoprecipitation, and co-immunoprecipitation were used to verify direct binding interactions among lncRNA PVT1, EZH2, DNMT1, and ZBP1. The evidence obtained indicated that lncRNA PVT1 could bind to DNMT1 via EZH2 and increase methylation at the ZBP1 promoter, thereby promoting necroptosis. Meanwhile, the demethylation of the highly expressed gene TET1 also promoted ZBP1 upregulation, inducing necroptosis. Taken together, these findings provide valuable insights into the potential molecular mechanisms underlying liver injury in response to NP exposure. Hence, they lay a mechanistic foundation for the evaluation of NP biosafety.

To establish successful infections in host plants, pathogenic fungi must sense and respond to an array of stresses, such as oxidative stress. In this study, we systematically analyzed the effects of 30 mM H2O2 treatment on reactive oxygen species (ROS) metabolism in Alternaria alternata. Results showed that 30 mM H2O2 treatment lead to increased O2− generation rate and H2O2 content, and simultaneously, increased the activities and transcript levels of NADPH oxidase (NOX). The activities and gene expression levels of enzymes related with ascorbic acid-glutathione cycle (AsA-GSH cycle) and thioredoxin systems, including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), ascorbate peroxidase (AXP) and thioredoxin (TrxR), were remarkably enhanced by 30 mM H2O2 stress treatment. Additionally, 30 mM H2O2 treatment decreased the glutathione (GSH) content, whereas it increased the amount of oxidized glutathione (GSSG), dehydroascorbate (DHA) and ascorbic acid (AsA). These results revealed that cellular responses are required for oxidative stress tolerance of the necrotrophic fungus A. alternata.

To establish successful infections in host plants, pathogenic fungi must sense and respond to an array of stresses, such as oxidative stress. In this study, we systematically analyzed the effects of 30 mM H

To investigate functional connectivity (FC) changes in end-stage renal disease (ESRD) patients with and without cognitive impairment (CI) by using resting-state functional magnetic resonance imaging (rs-fMRI). Twenty-three ESRD patients with CI, 22 ESRD patients with non-CI (NCI) and 23 matched healthy controls (HC) were included. Rs-fMRI scans were performed in all subjects. Full-range, long-range, and short-range FC defined voxel-wise based degree centrality (DC) and seed based FC were computed and contrasted among the groups. Compared with HC, the DC value of short functional connectivity (SFC), in ESRD patients have increased on the left supramarginal gyrus, while it reduced on the left insula and right postcentral gyrus in CI and decreased on the right precentral gyrus in NCI. Compared with NCI, the DC value of LFC in CI increased on the left fusiform gyrus, while the DC value of short functional connectivity (SFC) increased on the left middle orbital gyrus. In the seed-based FC analyses, the CI showed significantly decreased FC between the left insula and bilateral middle temporal gyrus, between the left fusiform gyrus and the right hippocampus, and between the left postcentral gyrus and the right parahippocampus compared to HC; the CI showed significantly increased FC between the left precuneus and the left fusiform gyrus, between the left postcentral gyrus and the right precuneus compared with NCI. Positive correlations were found between DC values on the right superior frontal gyrus and LDL and BDST, and between MoCA and the DC values on the left insula and the left postcentral gyrus. The altered degree centrality may serve as early biomarkers for CI in ESRD patients.

Recent studies have confirmed that both cancer-associated bone marrow mesenchymal stem cells (BM-MSCs, MSCs) and glioma stem-like cells (GSCs) contribute to malignant progression of gliomas through their mutual interactions within the tumor microenvironment. However, the exact ways and relevant mechanisms involved in the actions of GSCs and MSCs within the glioma microenvironment are not fully understood. Using a dual-color fluorescence tracing model, our studies revealed that GSCs are able to spontaneously fuse with MSCs, yielding GSC/MSC fusion cells, which exhibited markedly enhanced proliferation and invasiveness. MiR-146b-5p was downregulated in the GSC/MSC fusion cells, and its overexpression suppressed proliferation, migration and invasion by the fusion cells. SMARCA5, which is highly expressed in high-grade gliomas, was a direct downstream target of miR-146b-5p in the GSC/MSC fusion cells. miR-146b-5p inhibited SMARCA5 expression and inactivated a TGF-β pathway, thereby decreasing GSC/MSC fusion cell proliferation, migration and invasion. Collectively, these findings demonstrate that miR-146b-5p suppresses the malignant phenotype of GSC/MSC fusion cells in the glioma microenvironment by targeting a SMARCA5-regulated TGF-β pathway.

A highly sensitive photoelectrochemical (PEC) sensing platform was constructed for Hg2+ determination based on the Schottky heterojunction between an emerging 2D material Ti3C2TX MXene and a promising semiconductor material BiVO4. Through simply spin-coating the single-layer Ti3C2TX onto the surface of BiVO4 film, the modified electrode exhibited significantly enhanced PEC activity. However, the boost in photocurrent could be noticeably suppressed due to the consumption of hole-scavenging agents (reduced glutathione) by the added Hg2+. Owing to the selective decrease in the photocurrent with the addition of Hg2+, the PEC sensor based on BiVO4/Ti3C2TX displayed a wide linear range from 1 pM to 2 nM with the limit of detection down to 1 pM. Moreover, the PEC sensor also exhibited satisfactory accuracy and repeatability in practical sample water, the Yangtze River water, demonstrating the great potential for monitoring heavy metal ions in natural water resources.

Developing highly active and stable Pt-free electrocatalysts to reduce the overpotential of hydrogen evolution reaction (HER) is of great significance for future energy technologies. In this study,...

In order to find a clean, efficient and sustainable new energy source that can replace fossil fuels, hydrogen energy is considered to be the most ideal choice. Electrocatalytic oxygen evolution plays a vital role in the development of hydrogen energy, promotes the research of new electrocatalysts, and is dedicated to find materials with high electrocatalytic efficiency. This article discusses in detail the major developments in OER electrocatalysts, including recently reported metal and non-metal based materials. Metal-based catalysts, although having the advantages of high catalytic activity, have disadvantages such as poor stability and low selectivity, which hinder the further application of such materials. Non-metallic based materials avoid such disadvantages and exhibit very substantial performance in overall water decomposition. This review provides useful knowledge of a well-designed OER electrocatalyst and a possible strategy for OER/HER dual-function catalytic performance for future development. Keywords: Oxygen evolution reaction (OER), Electrocatalyst, Metal-based electrocatalysts, Carbon-based electrocatalysts, Black phosphorous (BP)

Photothermal conversion in the near-infrared (NIR) wavelengths, wherein light energy is converted into heat energy, has attracted great interest and developed rapidly in recent years for its wide applications in health care, flexible electronics, energy and environmental fields. However, the photothermal temperature, as one of the most important parameters in the NIR photothermal conversion, still has not been effectively studied. Herein, we successfully achieved ultrahigh photothermal temperatures in a graphene/conducting polymer system. The surface temperature of the prepared free-standing reduced graphene oxide/polypyrrole (rGO/PPy) foam can be as high as 380 °C with 808 nm NIR irradiation at 2.6 W cm−2, and the surface temperature of the rGO/PPy film on the polydimethylsiloxane (PDMS) substrate can be as high as 310 °C under the same conditions. The photothermal energy has been used for burning, thermopolymerization, alloying reactions and thermal decomposition reactions, providing new directions for photothermal conversion beyond photothermal therapy and energy utilization.

Aims: Cardiac lipotoxicity is the common consequence of lipid metabolism disorders in cardiomyocytes during development of heart failure (HF). Adenosine 5′monophosphate-activated protein kinase (AMPK) acts as an energy sensor and has a beneficial effect in reducing lipotoxicity. Notoginsenoside R1 (NGR1) is extracted from the traditional Chinese medicine Panax notoginseng (Burkill) F.H.Chen (P. notoginseng) and has definite cardioprotective effects. However, whether NGR1 can attenuate HF by mitigating lipotoxicity has not been elucidated yet. This study aimed to explore whether NGR1 plays a protective role against HF by ameliorating cardiac lipotoxicity via the AMPK pathway.Methods: In this study, HF mice model was established by left anterior descending (LAD) ligation. palmitic acid (PA) stimulated H9C2 cell model was applied to clarify the effects and potential mechanism of NGR1 on lipotoxicity. In vivo, NGR1 (7.14 mg/kg/days) and positive drug (simvastatin: 2.9 mg/kg/days) were orally administered for 14 days. Echocardiography was applied to assess heart functions. Lipid levels were measured by Enzyme-linked immunosorbent assay (ELISA) and key proteins in the AMPK pathway were detected by western blots. In vitro, NGR1 (40 μmol/L) or Compound C (an inhibitor of AMPK, 10 μmol/L) was co-cultured with PA stimulation for 24 h in H9C2 cells. CCK-8 assay was used to detect cell viability. Key lipotoxicity-related proteins were detected by western blots and the LipidTOX™ neutral lipid stains were used to assess lipid accumulation. In addition, Apoptosis was assessed by Hoechst/PI staining.Results: NGR1 could significantly improve the cardiac function and myocardial injury in mice with HF and up-regulate the expression of p-AMPK. Impressively, NGR1 inhibited the synthesis of diacylglycerol (DAG) and ceramide and promoted fatty acid oxidation (FAO) in vivo. Moreover, NGR1 significantly promoted expression of CPT-1A, the key enzyme in FAO pathway, and down-regulated the expression of GPAT and SPT, which were the key enzymes catalyzing production of DAG and ceramide. In vitro experiments showed that NGR1 could significantly attenuate lipid accumulation in PA-induced H9C2 cells and the Hoechst/PI staining results showed that NGR1 ameliorated lipotoxicity-induced apoptosis in PA-stimulated H9C2 cell model. Furthermore, co-treatment with inhibitor of AMPK abrogated the protective effects of NGR1. The regulative effects of NGR1 on lipid metabolism were also reversed by AMPK inhibitor.Conclusion: NGR1 could significantly improve the heart function of mice with HF and reduce cardiac lipotoxicity. The cardio-protective effects of NGR1 are mediated by the activation of AMPK pathway.

Spliced X‑box binding protein 1 (XBP1s) has been reported to participate in the pathogenesis of numerous types of cancer; however, whether XBP1s plays a role in lung cancer remains to be elucidated. In the present study, bioinformatics analysis was performed to determine the mRNA expression level of XBP1 in lung cancer and adjacent normal tissues. Gene Ontology terms, pathway enrichment and Pearson's correlation analysis were performed to investigate the possible mechanism involved. Western blot and reverse transcription‑quantitative PCR were performed to quantify the protein and mRNA expression level of target proteins, respectively. Small interfering RNA or overexpression plasmid were used to knockdown or overexpress the expression level of XBP1s. EdU staining, colony formation, Cell Counting Kit‑8, Transwell and wound healing assays, and flow cytometry were performed to detect the proliferation, colony forming ability, cell viability, migration and invasion ability, and the apoptosis rate. The results showed that the mRNA and protein expression level of XBP1 was higher in tumor tissues compared with that in adjacent normal tissues using data from the TIMER2.0, ONCOMINE and UALCAN online databases. In addition, the mRNA expression level of XBP1 was also associated with clinical features, including age, smoking habit, individual cancer stage and nodal metastasis status. In the

The synergy of chemotherapy and antiangiogenesis therapy is a new strategy for cancer treatment. In this paper, a well-developed core-shell nanoparticle loaded with gambogic acid (GA), heparin (HP), and the immunoadjuvant cytosine-phosphate-guanine oligonucleotide (CpG ODN), called GHC NP, was constructed to treat hepatocellular carcinoma. GHC NPs with liver targeting activity can effectively inhibit tumor cell proliferation and angiogenesis. With the delivery of nanocarriers and the assistance of GA and HP, the GHC NPs can more effectively upregulate cytotoxic T cell (CTL) levels, promote helper T cell (Th cell) differentiation, and induce Th1 immune responses in long-term treatment compared with single CpG ODN. This synergistically enhanced immunotherapy might have universal application in cancer treatments.