Preparation and Characterization of Chloroprene Latexes Modified with Vinyl-POSS.

Water-based chloroprene latex is a solvent-free, environmentally friendly adhesive. Currently, its market demand is growing rapidly. However, there are problems such as a lack of heat resistance and poor mechanical properties, which limit its application. The introduction of vinyl-POSS (OVS) into the resin structure can effectively improve the thermal stability of chloroprene adhesives. In this paper, modified waterborne chloroprene latex was prepared by copolymerization of methyl methacrylate and OVS with chloroprene latex. The results showed that vinyl-POSS was successfully grafted onto the main chain of the waterborne chloroprene latex, and the modified waterborne chloroprene latex had good storage stability. With the increase in vinyl-POSS, the tensile strength of the chloroprene latex firstly increased and then decreased, the tensile property (peel strength of 20.2 kgf) was maintained well at a high temperature (100 °C), and the thermal stability of the chloroprene latex was improved. When the addition amount was 4%, the comprehensive mechanical properties were their best. This study provides a new idea for the construction of a new and efficient waterborne chloroprene latex system and provides more fields for the practical application of waterborne chloroprene latex. This newly developed vinyl-POSS modified chloroprene latex has great application potential for use in home furniture, bags, and seat cushions.

Exploring urinary modified nucleosides as biomarkers for diabetic retinopathy: Development and validation of a ultra performance liquid chromatography-tandem mass spectrometry method.

The dynamic modification of RNA plays a crucial role in biological regulation and is strongly linked to human disease development and progression. Notably, modified nucleosides in urine have shown promising potential as early diagnostic biomarkers for various conditions. In this study, we developed and validated a rapid, sensitive, and accurate UPLC-MS/MS method for quantifying eight types of modified nucleosides (N1-methyladenosine (m1A), N6-methyladenosine (m6A), 5-methyluridine (m5U), 5-taurinomethyl-2-thiouridine (τm5s2U), 5-methylcytidine (m5C), 2'-O-methylcytidine (Cm), N1-methylguanosine (m1G), and N7-methylguanosine (m7G) in human urine. Using the method, we measured the urinary concentrations of m1A, m6A, m5U, τm5s2U, m5C, Cm, m1G, and m7G in a total of 21 control individuals and 23 patients diagnosed with diabetic retinopathy (DR). Cm levels showed promise as a diagnostic marker for diabetic retinopathy (DR), with a significant value (P < 0.01) and an AUC of 0.735. Other modified nucleosides also exhibited significant differences within specific subpopulations. As non-proliferative diabetic retinopathy (NPDR) signifies the latent early stage of diabetic retinopathy, we developed a multivariate linear model that integrates patients' sex, age, height, and urinary concentration of modified nucleosides which aims to predict and differentiate between healthy individuals, NPDR patients, and proliferative diabetic retinopathy (PDR) patients. Encouragingly, the model achieved satisfactory accuracy rates: healthy (81%), NPDR (75%), and PDR (80%). Our findings provide valuable insights into the development of an early, cost-effective, and noninvasive diagnostic approach for diabetic retinopathy.

Walnut Protein Peptides Ameliorate DSS-Induced Ulcerative Colitis Damage in Mice: An in Silico Analysis and in Vivo Investigation.

Walnut (Juglans regia L.) is a food with food-medicine homology, whose derived protein peptides have been shown to have anti-inflammatory activity in vitro. However, the effects and mechanisms of walnut protein peptides on ulcerative colitis (UC) in vivo have not been systematically and thoroughly investigated. In this study, we applied virtual screening and network pharmacology screening of bioactive peptides to obtain three novel WPPs (SHTLP, HYNLN, and LGTYP) that may alleviate UC through TLR4-MAPK signaling. In vivo studies have shown that WPPs improve intestinal mucosal barrier dysfunction and reduce inflammation by inhibiting activation of the TLR4-MAPK pathway. In addition, WPPs restore intestinal microbial homeostasis by reducing harmful bacteria (Helicobacter and Bacteroides) and increasing the relative abundance of beneficial bacteria (Candidatus_Saccharimonas). Our study showed that the WPPs obtained by virtual screening were effective in ameliorating colitis, which has important implications for future screening of bioactive peptides from medicinal food homologues as drugs or dietary supplements.

Mechanisms of Rapid Bactericidal and Anti-Biofilm Alpha-Mangostin In Vitro Activity against Staphylococcus aureus.

Alpha-mangostin (α-mangostin) was discovered as a potent natural product against Gram-positive bacteria, whereas the underlying molecular mechanisms are still unclear. This study indicated that α-mangostin (at 4 × MIC) rapidly killed Staphylococcus aureus planktonic cells more effectively (at least 2-log10 CFU/ml) than daptomycin, vancomycin and linezolid at 1 and 3 h in the time-killing test. Interestingly, this study also found that a high concentration of α-mangostin (≥4×MIC) significantly reduced established biofilms of S. aureus. There were 58 single nucleotide polymorphisms (SNPs) in α-mangostin nonsensitive S. aureus isolates by whole-genome sequencing, of which 35 SNPs were located on both sides of the sarT gene and 10 SNPs in the sarT gene. A total of 147 proteins with a different abundance were determined by proteomics analysis, of which 91 proteins increased, whereas 56 proteins decreased. The abundance of regulatory proteins SarX and SarZ increased. In contrast, the abundance of SarT and IcaB was significantly reduced (they belonged to SarA family and ica system, associated with the biofilm formation of S. aureus). The abundance of cell membrane proteins VraF and DltC was augmented, but the abundance of cell membrane protein UgtP remarkably decreased. Propidium iodide and DiBaC4(3) staining assay revealed that the fluorescence intensities of DNA and the cell membrane were elevated in the α-mangostin treated S. aureus isolates. In conclusion, this study reveals that α-mangostin was effective against S. aureus planktonic cells by targeting cell membranes. The anti-biofilm effect of α-mangostin may be through inhibiting the function of SarT and IcaB.

Reduced genetic diversity and restricted gene flow of broadcast-spawning coral Galaxea fascicularis in the South China Sea reveals potential degradation under environmental change.

Under the dual effects of climate change and anthropogenic activities, coral reefs in the South China Sea (SCS) are at serious risk of degradation. Galaxea fascicularis is a widely distributed species in the SCS, and the study of its genetics, survival, and adaptability is conducive to further understanding the future characteristics of coral reefs in the SCS. In this study, 146 G. fascicularis samples were selected from 9 survey stations across 12 latitudes in the SCS, and 8 pairs of microsatellite markers were used to characterize their genetic diversity and structure. The results showed moderate genetic diversity index values (Ar = 3.444-4.147, He = 0.634-0.782, Ho = 0.367-0.586). The AMOVA results and pairwise FST values showed a moderate level of genetic differentiation (ΦST = 0.119, P < 0.05) among G. fascicularis populations in the SCS, whereas its genetic structure showed high genetic differentiation (FST = 0.062-0.225) among relatively high-latitude populations (n = 3) and low genetic differentiation (FST = 0.012-0.064) in low-latitude populations (n = 6). The living environment of relatively high-latitude populations is disturbed by high-intensity human activities, leading to the specialization of local populations. Mantel test results showed a significant positive correlation between genetic differentiation among G. fascicularis populations and sea surface temperature (SST) variance (R2 = 0.4885; Mantel test, p = 0.010 < 0.05) in addition to geographical distance (R2 = 0.1134; Mantel, test p = 0.040 < 0.05), indicating that SST and geographical isolation were primary factors affecting the genetic structure of this species in the SCS. The lower genetic diversity and limited gene flow of G. fascicularis indicate limited genetic adaptation, and corresponding vulnerability may be more pronounced under future environmental changes. These findings provide a theoretical basis for the conservation and restoration of coral reefs in the SCS.

A Droplet Method for Synthesis of Multiclass Ultrathin Metal Halides.

2D metal halides have attracted increasing research attention in recent years; however, it is still challenging to synthesize them via liquid-phase methods. Here it is demonstrated that a droplet method is simple and efficient for the synthesis of multiclass 2D metal halides, including trivalent (BiI3 , SbI3 ), divalent (SnI2 , GeI2 ), and monovalent (CuI) ones. In particular, 2D SbI3 is first experimentally achieved, of which the thinnest thickness is ≈6 nm. The nucleation and growth of these metal halide nanosheets are mainly determined by the supersaturation of precursor solutions that are dynamically varying during the solution evaporation. After solution drying, the nanosheets can fall on the surface of many different substrates, which further enables the feasible fabrication of related heterostructures and devices. With SbI3 /WSe2 being a good demonstration, the photoluminescence intensity and photo responsivity of WSe2 is obviously enhanced after interfacing with SbI3 . The work opens a new pathway for 2D metal halides toward widespread investigation and applications.

Cinacalcet exhibits rapid bactericidal and efficient anti-biofilm activities against multidrug-resistant Gram-positive pathogens.

Infections caused by Gram-positive bacteria pose a serious threat to global public health. Drug resistance, dormant persister cells, and biofilm formation are the key challenges affecting the efficacy of antibiotics against Gram-positive bacterial infections. In this study, cinacalcet exhibited good inhibitory activity against multidrug-resistant Gram-positive bacteria, with minimum inhibitory concentrations (MICs) ranging from 3.13 µg/mL to 25 µg/mL. Cinacalcet displayed more rapid and stronger bactericidal activity against planktonic and persister cells of Staphylococcus aureus and Enterococcus faecalis compared with the antibiotics vancomycin or ampicillin, as well as potent inhibition and eradication of mature biofilms of methicillin-resistant S. aureus (MRSA) and linezolid-resistant E. faecalis (LRE). In addition, the robust antibacterial activity was demonstrated in vivo by a pneumonia infection model and a biofilm formation and deep-seated infection model. Collectively, these findings indicate that cinacalcet may be a promising new candidate antibiotic to combat infections caused by multidrug-resistant Gram-positive pathogens.

miR­151a­5p promotes the proliferation and metastasis of colorectal carcinoma cells by targeting AGMAT.

Colorectal carcinoma (CRC) is one of the most common types of digestive cancer. It has been reported that the ectopic expression of microRNAs (miRs) plays a critical role in the occurrence and progression of CRC. In addition, it has also been suggested that miR­151a­5p may serve as a useful biomarker for the early detection and treatment of different types of cancer and particularly CRC. However, the specific effects and underlying mechanisms of miR­151a­5p in CRC remain elusive. The results of the current study demonstrated that miR­151a­5p was upregulated in CRC cell lines and clinical tissues derived from patients with CRC. Functionally, the results showed that miR­151a­5p significantly promoted CRC cell proliferation, migration and invasion. Additionally, dual luciferase reporter assays verified that agmatinase (AGMAT) was a direct target of miR­151a­5p and it was positively associated with miR­151a­5p expression. Mechanistically, miR­151a­5p could enhance the epithelial­mesenchymal transition of CRC cells. Taken together, the results of the current study revealed a novel molecular mechanism indicating that the miR­151a­5p/AGMAT axis could serve a crucial role in the regulation of CRC and could therefore be considered as a potential therapeutic strategy for CRC.

Thickness-dependent excitonic properties of WSe2/FePS3 van der Waals heterostructures.

van der Waals heterostructures (vdWHs), with their flexible combination of various two-dimensional (2D) materials, are continuously revealing new physics and functionalities. 2D magnetic materials have recently become a focus due to their fascinating electronic and spintronic properties. However, there has rarely been any investigation of the optical properties of 2D magnetic materials-based heterostructures. Herein, we construct a new WSe2/FePS3 heterostructure, in which WSe2 works as a "sensor" to visualize the thickness-dependent properties of FePS3. As characterized by photoluminescence (PL) spectra, whether under or on top of the FePS3, the PL intensity of the monolayer WSe2 is strongly quenched. The quenching effect becomes more obvious as the FePS3 thickness increases. This is because of the efficient charge transfer process occurring at the WSe2/FePS3 interface with type II band alignment, which is faster for thicker FePS3, as is evident from transient absorption measurements. The thickness-dependent charge transfer process and corresponding excitonic properties are further revealed in low-temperature photoluminescence spectra of WSe2/FePS3 heterostructures. Our results show that the thickness of 2D magnetic materials can work as an experimental tuning knob to manipulate the optical performance of conventional 2D semiconductors, endowing van der Waals heterostructures with more unexpected properties and functionalities.

Boosting the Sensitivity of WSe2 Phototransistor via Janus Interfaces with 2D Perovskite and Ferroelectric Layers.

Hybrid systems have recently attracted increasing attention, which combine the special attributes of each constitute and create interesting functionalities through multiple heterointerface interactions. Here, we design a two-dimensional (2D) hybrid phototransistor utilizing Janus-interface engineering, in which the WSe2 channel combines light-sensitive perovskite and spontaneously polarized ferroelectrics, achieving collective ultrasensitive detection performance. The top perovskite (BA2(MA)3Pb4I13) layer can absorb the light efficiently and provide generous photoexcited holes to WSe2. WSe2 exhibit p-type semiconducting states of different degrees due to the selective light-operated doping effect, which also enables the ultrahigh photocurrent of the device. The bottom ferroelectric (Hf0.5Zr0.5O2) layer dramatically decreases the dark current, which should be attributed to the ferroelectric polarization assisted charge trapping effect and improved gate control. As a whole, our phototransistors show excellent photoelectric performances across the ultraviolet to near-infrared range (360-1050 nm), including an ultrahigh ON/OFF current ratio > 109 and low noise-equivalent power of 1.3 fW/Hz1/2, all of which are highly competitive in 2D semiconductor-based optoelectronic devices. In particular, the devices show excellent weak light detection ability, where the distinguishable photoswitching signal is obtained even under a record-low light intensity down to 1.6 nW/cm2, while showing a high responsivity of 2.3 × 105 A/W and a specific detectivity of 4.1 × 1014 Jones. Our work demonstrates that Janus-interface design makes the upper and lower interfaces complement each other for the joint advancement into high-performance optoelectronic applications, providing a picture to realize the integrated engineering on carrier dynamics by light irradiation, electric field, interfacial trapping, and band alignment.

Synthesis and Properties of Cationic Core-Shell Fluorinated Polyurethane Acrylate.

Vinyl-capped cationic waterborne polyurethane (CWPU) was prepared using isophorone diisocyanate (IPDI), polycarbonate diol (PCDL), N-methyldiethanolamine (MDEA), and trimethylolpropane (TMP) as raw materials and hydroxyethyl methacrylate (HEMA) as a capping agent. Then, a crosslinked FPUA composite emulsion with polyurethane (PU) as the shell and fluorinated acrylate (PA) as the core was prepared by core-shell emulsion polymerization with CWPU as the seed emulsion, together with dodecafluoroheptyl methacrylate (DFMA), diacetone acrylamide (DAAM), and methyl methacrylate (MMA). The effects of the core-shell ratio of PA/PU on the surface properties, mechanical properties, and heat resistance of FPUA emulsions and films were investigated. The results showed that when w(PA) = 30~50%, the stability of FPUA emulsion was the highest, and the particles showed a core-shell structure with bright and dark intersections under TEM. When w(PA) = 30%, the tensile strength reached 23.35 ± 0.08 MPa. When w(PA) = 50%, the fluorine content on the surface of the coating film was 14.75% and the contact angle was as high as 98.5°, which showed good hydrophobicity; the surface flatness of the film was observed under AFM. It is found that the tensile strength of the film increases and then decreases with the increase in the core-shell ratio and the heat resistance of the FPUA film is gradually increased. The FPUA film has excellent properties such as good impact resistance, high flexibility, high adhesion, and corrosion resistance.

Synthesis and Characterization of Pressure-Sensitive Adhesives Based on a Naphthyl Curing Agent.

The incorporation of a naphthyl curing agent (NCA) can enhance the thermal stability of pressure-sensitive adhesives (PSAs). In this study, a PSA matrix was synthesized using a solution polymerization process and consisted of butyl acrylate, acrylic acid, and an ethyl acrylate within an acrylic copolymer. Benzoyl peroxide was used as an initiator during the synthesis. To facilitate the UV curing of the solvent-borne PSAs, glycidyl methacrylate was added to introduce unsaturated carbon double bonds. The resulting UV-curable acrylic PSA tapes exhibited longer holding times at high temperatures (150 °C) compared to uncross-linked PSA tapes, without leaving any residues on the substrate surface. The thermal stability of the PSA was further enhanced by adding more NCA and increasing the UV dosage. This may be attributed to the formation of cross-linking networks within the polymer matrix at higher doses. The researchers successfully balanced the adhesion performance and thermal stability by modifying the amount of NCA and UV radiation, despite the peel strength declining and the holding duration shortening. This research also investigated the effects of cross-linking density on gel content, molecular weight, glass transition temperature, and other properties of the PSAs.

Evaluation of Cell-Free DNA-Based Next-Generation Sequencing for Identifying Pathogens in Bacteremia Patients.

Rapid detection of bloodstream pathogens would greatly facilitate clinicians to make precise antimicrobial treatment in patients with bacteremia. In this study, 114 plasma samples were collected from patients with identified or suspected bacteremia, and pathogens were detected by the conventional blood culture (BC) and cell-free DNA metagenomics next-generation sequencing (cfDNA mNGS). The present study indicated that 76% (38/50) of positive conventional blood culture (BC+ group) patients were positively detected by cfDNA mNGS, and only 4% were mismatched between cfDNA mNGS and conventional bacteria culture. Pathogens in 32.8% of suspected bacteremia patients with negative conventional blood culture (BC- group) were determined accurately by cfDNA mNGS combined with analyzing the patients' clinical manifestations. Escherichia coli and Klebsiella pneumoniae were the most detected pathogens in identified bacteremia patients by cfDNA mNGS. 76.2% (16/21) of E. coli and 92.3% (12/13) of K. pneumoniae in bacteremia patients were identified by conventional blood cultures that were also detected by cfDNA mNGS. This study demonstrated that genomic coverage of E. coli and K. pneumoniae were more often detected in BC+ group patients and genomic coverage of Acinetobacter johnsonii and Paucibacter sp. KCTC 42545 was more often detected in BC- group patients. In conclusion, cfDNA mNGS could rapidly and precisely provide an alternative detection method for the diagnosis of bacteremia.

20S-ginsenoside Rg3 inhibits the biofilm formation and haemolytic activity of Staphylococcus aureus by inhibiting the SaeR/SaeS two-component system.

Introduction. Staphylococcus aureus is a major cause of chronic diseases and biofilm formation is a contributing factor. 20S-ginsenoside Rg3 (Rg3) is a natural product extracted from the traditional Chinese medicine red ginseng.Gap statement. The effects of Rg3 on biofilm formation and haemolytic activity as well as its antibacterial mechanism against S. aureus have not been reported.Aim. This study aimed to investigate the effects of Rg3 on biofilm formation and haemolytic activity as well as its antibacterial action against clinical S. aureus isolates.Methodology. The effect of Rg3 on biofilm formation of clinical S. aureus isolates was studied by crystal violet staining. Haemolytic activity analysis was carried out. Furthermore, the influence of Rg3 on the proteome profile of S. aureus was studied by quantitative proteomics to clarify the mechanism underlying its antibacterial action and further verified by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR).Results. Rg3 significantly inhibited biofilm formation and haemolytic activity in clinical S. aureus isolates. A total of 63 with >1.5-fold changes in expression were identified, including 34 upregulated proteins and 29 downregulated proteins. Based on bioinformatics analysis, the expression of several virulence factors and biofilm-related proteins, containing CopZ, CspA, SasG, SaeR/SaeS two-component system and SaeR/SaeS-regulated proteins, including leukocidin-like protein 2, immunoglobulin-binding protein G (Sbi) and fibrinogen-binding protein, in the S. aureus of the Rg3-treated group was downregulated. RT-qPCR confirmed that Rg3 inhibited the regulation of SaeR/SaeS and decreased the transcriptional levels of the biofilm-related genes CopZ, CspA and SasG.Conclusions. Rg3 reduces the formation of biofilm by reducing cell adhesion and aggregation. Further, Rg3 can inhibit the SaeR/SaeS two-component system, which acts as a crucial signal transduction system for the anti-virulence activity of Rg3 against clinical S. aureus isolates.

Transcriptome sequencing of hepatocellular carcinoma uncovers multiple types of dysregulated ncRNAs.

Transcriptome profiling of hepatocellular carcinoma (HCC) by next-generation sequencing (NGS) technology has been broadly performed by previous studies, which facilitate our understanding of the molecular mechanisms of HCC formation, progression, and metastasis. However, few studies jointly analyze multiple types of noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and micro-RNAs (miRNAs), and further uncover their implications in HCC. In this study, we observed that the circRNA cZRANB1 and lncRNA DUXAP10 were not only significantly upregulated in tumor tissues, but also higher expressed in blood exosomes of HCC as compared with healthy donors. From the analysis of subclass-associated dysregulated ncRNAs, we observed that DLX6-AS1, an antisense RNA of DLX6, and the sense gene DLX6 were highly expressed in S1, a subclass with a more invasive/disseminative phenotype. High correlation between DLX6-AS1 and DLX6 suggested that DLX6-AS1 may function via promoting the transcription of DLX6. Integrative analysis uncovers circRNA-miRNA, lncRNA-miRNA, and competing endogenous RNA networks (ceRNAs). Specifically, cZRANB1, LINC00501, CTD-2008L17.2, and SLC7A11-AS1 may function as ceRNAs that regulate mRNAs by competing the shared miRNAs. Further prognostic analysis demonstrated that the dysregulated ncRNAs had the potential to predict HCC patients' overall survival. In summary, we identified some novel circRNAs and miRNAs, and dysregulated ncRNAs that could participate in HCC tumorigenesis and progression by inducing transcription of their neighboring genes, increasing their derived miRNAs, or acting as miRNA sponges. Moreover, our systematic analysis provides not only rich data resources for related researchers, but also new insights into the molecular basis of how different ncRNAs coordinately or antagonistically participate in the pathogenesis process of diseases.

Agmatinase facilitates the tumorigenesis of pancreatic adenocarcinoma through the TGFß/Smad pathway.

Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Due to the lack of typical symptoms and difficulties in early diagnosis, PAAD has a high mortality rate. Therefore, it is essential to identify novel specific biomarkers for the application of targeted therapies. A previous study suggested that agmatinase (AGMAT) may fulfill important roles in tumor progression; however, these roles and the underlying mechanisms of AGMAT involvement in PAAD have yet to be thoroughly investigated. To address this shortcoming, in the present study the expression and prognostic significance of AGMAT were analyzed via several bioinformatics databases. Gain- and loss-of-function experiments were subsequently performed to observe the impact of AGMAT on the proliferation and metastasis of PAAD cells via Cell Counting Kit 8 (CCK-8) assay, colony formation assay, and cell migration and invasion assays in vitro. In order to probe the mechanisms involved, western blot assays were performed. AGMAT was found to be overexpressed in PAAD, and it was positively associated with a poor prognosis. Stable overexpression of AGMAT was found to lead to a marked increase in cell proliferation and metastasis through activation of the transforming growth factor-ß (TGFß)/Smad pathway, and via enhancing epithelial-mesenchymal transition (EMT). In conclusion, the results of the present study suggest that AGMAT may be an oncogene, and a pivotal mechanism has been uncovered in which AGMAT facilitates the progression of PAAD tumorigenesis through the TGFß/Smad pathway.

Multiple Colletotrichum species commonly exhibit focal effector accumulation in a biotrophic interface at the primary invasion sites in their host plants.

Fungal plant pathogens deploy a suite of secreted proteins, called effectors, to facilitate successful infection. Several fungal pathogens have been reported to secrete and accumulate their effector proteins in the host-pathogen interfacial spaces. Previously, we reported that the strain 104-T of the cucurbit anthracnose pathogen Colletotrichum orbiculare secretes and accumulates mCherry-tagged effectors along with the formation of ring-shaped fluorescence signals beneath the appressoria. However, it was unclear whether these effector accumulation patterns occur in other C. orbiculare isolates and other species belonging to the Colletotrichum genus. Here, we investigated the effector localization during host infection of C. orbiculare MAFF306589, C. trifolii MAFF305078, which infects alfalfa, and C. higginsianum MAFF305635, which infects Brassicaceae plants. We generated effector-reporter lines of each species, which constitutively expressed mCherry-tagged CoDN3 effector (CoDN3:mCherry). Immunoblotting analysis of the liquid culture fluids of the generated lines detected CoDN3:mCherry, which confirmed secretion of CoDN3:mCherry by fungal cells. Via inoculation assays in the corresponding host plants, we detected ring-shaped CoDN3:mCherry fluorescence around the appressorial invasion sites in all tested reporter lines. These results suggest that pathogens in the Colletotrichum genus have evolutionarily conserved the trait of effector secretion in the infection stage irrespective of differences in their hosts.

Comparative transient expression analyses on two conserved effectors of Colletotrichum orbiculare reveal their distinct cell death-inducing activities between Nicotiana benthamiana and melon.

Colletotrichum orbiculare infects cucurbits, such as cucumber and melon (Cucumis melo), as well as the model Solanaceae plant Nicotiana benthamiana, by secreting an arsenal of effectors that suppress the immunity of these distinct plants. Two conserved effectors of C. orbiculare, called NLP1 and NIS1, induce cell death responses in N. benthamiana, but it is unclear whether they exhibit the same activity in Cucurbitaceae plants. In this study, we established a new Agrobacterium-mediated transient expression system to investigate the cell death-inducing activity of NLP1 and NIS1 in melon. NLP1 strongly induced cell death in melon but, in contrast to the effects seen in N. benthamiana, mutations either in the heptapeptide motif or in the putative glycosylinositol phosphorylceramide-binding site did not cancel its cell death-inducing activity in melon. Furthermore, NLP1 lacking the signal peptide caused cell death in melon but not in N. benthamiana. Study of the transient expression of NIS1 also revealed that, unlike in N. benthamiana, NIS1 did not induce cell death in melon. In contrast, NIS1 suppressed flg22-induced reactive oxygen species generation in melon, as seen in N. benthamiana. These findings indicate distinct cell death-inducing activities of NLP1 and NIS1 in these two plant species that C. orbiculare infects.

FUBP1 mediates the growth and metastasis through TGFß/Smad signaling in pancreatic adenocarcinoma.

Recent studies have reported that the expression levels of far upstream element­binding protein 1 (FUBP1) were upregulated and served a crucial role in several types of cancer. However, the underlying molecular mechanisms and clinical significance of FUBP1 in pancreatic adenocarcinoma (PAAD) remain unclear. The present study aimed to determine the expression levels of FUBP1 in patients with PAAD and subsequently investigated the biological functions and mechanisms of FUBP1 using in vitro assays. FUBP1 expression levels and survival outcomes in patients with PAAD were analyzed using The Cancer Genome Atlas and starBase databases. Reverse transcription­quantitative PCR was used to analyze the mRNA expression levels of FUBP1 in PAAD and adjacent normal tissues. In addition, the expression of FUBP1 was knocked down with small interfering RNA and overexpressed using FUBP1­overexpressed plasmids, and the effects on biological functions, including cell proliferation, migration and invasion, were investigated. Western blotting and immunofluorescence assays were used to determine the role of FUBP1 in epithelial­mesenchymal transition (EMT). The results of the present study revealed that the expression levels of FUBP1 were upregulated in PAAD tissues compared with adjacent normal tissues and the upregulated expression was significantly associated with poor survival. The knockdown of FUBP1 expression significantly inhibited the proliferative, migratory and invasive abilities of the PAAD PaTu8988 cell line, while the overexpression of FUBP1 promoted cell proliferation, migration and invasion in the PAAD SW1990 cell line. Furthermore, the knockdown of FUBP1 downregulated the expression levels of EMT­related markers, including N­cadherin, ß­catenin and vimentin, while the expression levels of E­cadherin were upregulated. The knockdown of FUBP1 was also revealed to regulate the TGFß/Smad signaling cascade by downregulating phosphorylated­Smad2/3 and TGFß1 expression levels. Conversely, the overexpression of FUBP1 reversed these effects. In conclusion, the findings of the present study indicated that FUBP1 may be a potential oncogene that mediates the EMT of PAAD via TGFß/Smad signaling. These data suggested that FUBP1 may represent a potential biomarker for the diagnosis of PAAD or a target for the treatment of patients with PAAD.

A potent and selective small molecule inhibitor of myoferlin attenuates colorectal cancer progression.

As a pivotal vesicular trafficking protein, Myoferlin (MYOF) has become an attractive target for cancer therapy. However, the roles of MYOF in colorectal cancer invasion remain enigmatic, and MYOF-targeted therapy in this malignancy has not been explored. In the present study, we provided the first functional evidence that MYOF promoted the cell invasion of colorectal cancer. Furthermore, we identified a novel small molecule inhibitor of MYOF (named YQ456) that showed high binding affinity to MYOF (KD  = 37 nM) and excellent anti-invasion capability (IC50  = 110 nM). YQ456 was reported for the first time to interfere with the interactions between MYOF and Ras-associated binding (Rab) proteins at low nanomolar levels. This interference disrupted several vesicle trafficking processes, including lysosomal degradation, exosome secretion, and mitochondrial dynamics. Further, YQ456 exhibited excellent inhibitory effects on the growth and invasiveness of colorectal cancer. As the first attempt, the anticancer efficacy of YQ456 in the patient-derived xenograft (PDX) mouse model indicated that targeting MYOF may serve as a novel and practical therapeutic approach for colorectal cancer.