P3N-PIPO but not P3 is the avirulence determinant in melon carrying the Wmr resistance against watermelon mosaic virus, although they contain a common genetic determinant.

Viruses employ a series of diverse translational strategies to expand their coding capacity, which produces viral proteins with common domains and entangles virus-host interactions. P3N-PIPO, which is a transcriptional slippage product from the P3 cistron, is a potyviral protein dedicated to intercellular movement. Here, we show that P3N-PIPO from watermelon mosaic virus (WMV) triggers cell death when transiently expressed in Cucumis melo accession PI 414723 carrying the Wmr resistance gene. Surprisingly, expression of the P3N domain, shared by both P3N-PIPO and P3, can alone induce cell death, whereas expression of P3 fails to activate cell death in PI 414723. Confocal microscopy analysis revealed that P3N-PIPO targets plasmodesmata (PD) and P3N associates with PD, while P3 localizes in endoplasmic reticulum in melon cells. We also found that mutations in residues L35, L38, P41, and I43 of the P3N domain individually disrupt the cell death induced by P3N-PIPO, but do not affect the PD localization of P3N-PIPO. Furthermore, WMV mutants with L35A or I43A can systemically infect PI 414723 plants. These key residues guide us to discover some WMV isolates potentially breaking the Wmr resistance. Through searching the NCBI database, we discovered some WMV isolates with variations in these key sites, and one naturally occurring I43V variation enables WMV to systemically infect PI 414723 plants. Taken together, these results demonstrate that P3N-PIPO, but not P3, is the avirulence determinant recognized by Wmr, although the shared N terminal P3N domain can alone trigger cell death.IMPORTANCEThis work reveals a novel viral avirulence (Avr) gene recognized by a resistance (R) gene. This novel viral Avr gene is special because it is a transcriptional slippage product from another virus gene, which means that their encoding proteins share the common N-terminal domain but have distinct C-terminal domains. Amazingly, we found that it is the common N-terminal domain that determines the Avr-R recognition, but only one of the viral proteins can be recognized by the R protein to induce cell death. Next, we found that these two viral proteins target different subcellular compartments. In addition, we discovered some virus isolates with variations in the common N-terminal domain and one naturally occurring variation that enables the virus to overcome the resistance. These results show how viral proteins with common domains interact with a host resistance protein and provide new evidence for the arms race between plants and viruses.

Sub-micron pixel polarization-sensitive photodetector based on silicon nanowire.

Silicon nanowire is a potential candidate to be used as polarization-sensitive material, but the relative mechanism of polarization response must be carried out. Herein, a sub-micron metal-single silicon nanowire-metal photodetector exhibits polarization-sensitive characteristics with an anisotropic photocurrent ratio of 1.59 at 780 nm, an excellent responsivity of 24.58 mA/W, and a high detectivity of 8.88 × 109 Jones at 980 nm. The underlying principle of optical anisotropy in silicon nanowire is attributed to resonance enhancement verified by polarizing light microscopy and simulation. Furthermore, Stokes parameter measurements and imaging are all demonstrated by detecting the characteristics of linearly polarized light and imaging the polarizer array, respectively. Given the maturity of silicon processing, the sub-micron linearly polarized light detection proposed in this study lays the groundwork for achieving highly integrated, simplified processes, and cost-effective on-chip polarization-sensitive optical chips in the future.

Laparoscopic Versus Open Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review and Meta-Analysis of Propensity-Score Matched Studies.

BACKGROUND: The effectiveness of laparoscopic nephroureterectomy (LNU) vs open nephroureterectomy (ONU) for upper tract urothelial carcinoma (UTUC) is unclear. METHODS: We conducted a meta-analysis of studies based on propensity score-matched cohorts to compare the surgical and oncological outcomes of LNU and ONU in UTUC patients. A literature search was conducted on PubMed, Embase, and Cochrane Library until July 12, 2023. The Newcastle-Ottawa Scale was utilized to assess the quality of eligible studies. Measurements of surgical and oncological outcomes were extracted and pooled including mean difference (MD), risk ratio (RR), hazard ratios (HR), and 95% confidence intervals (CI). RESULTS: Five high-quality retrospective studies were included, totaling 6422 patients; 2080 (32.4%) underwent LNU, and 4342 (67.6%) underwent ONU. With respect to surgical outcomes, patients in the LNU group experienced less estimated blood loss and had shorter hospital stay than those in the ONU group, but there was no significant difference in complication rates and operation time. In regard to oncological outcomes, there were no significant differences between the LNU and ONU groups in 3-year overall survival (OS) and cancer-specific survival (CSS). However, 3-year intravesical recurrence free survival (IVRFS) was worse in the LNU group compared to the ONU group. CONCLUSION: LNU was associated with less estimated blood loss and shorter hospital stays than ONU, but there were no differences in OS and CSS between the surgical modalities. Nonetheless, LNU might result in poorer IVRFS than ONU.

Dysregulation of microRNAs in metal-induced angiogenesis and carcinogenesis.

MicroRNAs (miRNAs) are small endogenous non-coding RNAs that regulate cancer initiation, development, angiogenesis, and therapeutic resistance. Metal exposure widely occurs through air, water, soil, food, and industrial contaminants. Hundreds of millions of people may have metal exposure associated with toxicity, serious health problems, and cancer occurrence. Metal exposure is found to induce oxidative stress, DNA damage and repair, and activation of multiple signaling pathways. However, molecular mechanisms of metal-induced carcinogenesis remain to be elucidated. Recent studies demonstrated that the exposure of metals such as arsenic, hexavalent chromium, cadmium, and nickel caused dysregulation of microRNAs that are implicated to play an important role in cell transformation, tumor growth and angiogenesis. This review focuses on the recent studies that show metal-induced miRNA dysregulation and underlined mechanisms in cell malignant transformation, angiogenesis and tumor growth.

A tobacco ringspot virus-based vector system for gene and microRNA function studies in cucurbits.

Cucurbits are economically important crops worldwide. The genomic data of many cucurbits are now available. However, functional analyses of cucurbit genes and noncoding RNAs have been impeded because genetic transformation is difficult for many cucurbitaceous plants. Here, we developed a set of tobacco ringspot virus (TRSV)-based vectors for gene and microRNA (miRNA) function studies in cucurbits. A TRSV-based expression vector could simultaneously express GREEN FLUORESCENT PROTEIN (GFP) and heterologous viral suppressors of RNA silencing in TRSV-infected plants, while a TRSV-based gene silencing vector could knock down endogenous genes exemplified by PHYTOENE DESATURASE (PDS) in Cucumis melo, Citrullus lanatus, Cucumis sativus, and Nicotiana benthamiana plants. We also developed a TRSV-based miRNA silencing vector to dissect the functions of endogenous miRNAs. Four representative miRNAs, namely, miR159, miR166, miR172, and miR319, from different cucurbits were inserted into the TRSV vector using a short tandem target mimic strategy and induced characteristic phenotypes in TRSV-miRNA-infected plants. This TRSV-based vector system will facilitate functional genomic studies in cucurbits.

Regulation of OsPIL15 on rice quality.

The phytochrome-interacting factor-like gene OsPIL15 negatively regulates grain size and 1000-grain weight, but its regulatory effect on rice quality traits is unknown. Here, knock-down, knock-out, and over-expression of OsPIL15 transgenic rice lines were used to investigate the effects of OsPIL15 on rice yield and quality traits. The results showed that knock-down or knock-out of OsPIL15 increased grain length and width, chalkiness, amylose content, glutenin and globulin content, and total protein content but reduced amylopectin content, total starch content, prolamin and albumin content, and gel consistency. Over-expression of OsPIL15 showed the opposite results, except for the reduction of prolamin content. Although OsPIL15 changed the grain size and weight, it had no effect on grain length/width ratio, brown rice rate, and milled rice rate. KEGG pathway enrichment analysis of differentially expressed genes between transgenic lines and wild type showed that OsPIL15 mainly regulated genes related to ribosome, metabolic pathways, and biosynthesis of secondary metabolites. Gene expression analysis showed that RNAi transgenic lines decreased OsCIN2 and OsSUS1 expression and increased OsGBSSI, OsSSI, OsAPGL2, and OsAPGL3 expression level, while over-expression of OsPIL15 increased OsCIN2, OsSUS1, OsSUS6, and OsSSI and decreased OsSSIIa, OsSSIIc, and OsAPGL2 expression level. These results revealed that OsPIL15 plays an important role in rice grain development. In addition to grain shape, OsPIL15 also regulates chalkiness, starch content, protein content, and gel consistency. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01311-x.

ROS and miRNA Dysregulation in Ovarian Cancer Development, Angiogenesis and Therapeutic Resistance.

The diverse repertoires of cellular mechanisms that progress certain cancer types are being uncovered by recent research and leading to more effective treatment options. Ovarian cancer (OC) is among the most difficult cancers to treat. OC has limited treatment options, especially for patients diagnosed with late-stage OC. The dysregulation of miRNAs in OC plays a significant role in tumorigenesis through the alteration of a multitude of molecular processes. The development of OC can also be due to the utilization of endogenously derived reactive oxygen species (ROS) by activating signaling pathways such as PI3K/AKT and MAPK. Both miRNAs and ROS are involved in regulating OC angiogenesis through mediating multiple angiogenic factors such as hypoxia-induced factor (HIF-1) and vascular endothelial growth factor (VEGF). The NAPDH oxidase subunit NOX4 plays an important role in inducing endogenous ROS production in OC. This review will discuss several important miRNAs, NOX4, and ROS, which contribute to therapeutic resistance in OC, highlighting the effective therapeutic potential of OC through these mechanisms.

TBX15/miR-152/KIF2C pathway regulates breast cancer doxorubicin resistance via promoting PKM2 ubiquitination.

BACKGROUND: Chemoresistance is a critical risk problem for breast cancer treatment. However, mechanisms by which chemoresistance arises remains to be elucidated. The expression of T-box transcription factor 15 (TBX-15) was found downregulated in some cancer tissues. However, role and mechanism of TBX15 in breast cancer chemoresistance is unknown. Here we aimed to identify the effects and mechanisms of TBX15 in doxorubicin resistance in breast cancer. METHODS: As measures of Drug sensitivity analysis, MTT and IC50 assays were used in DOX-resistant breast cancer cells. ECAR and OCR assays were used to analyze the glycolysis level, while Immunoblotting and Immunofluorescence assays were used to analyze the autophagy levels in vitro. By using online prediction software, luciferase reporter assays, co-Immunoprecipitation, Western blotting analysis and experimental animals models, we further elucidated the mechanisms. RESULTS: We found TBX15 expression levels were decreased in Doxorubicin (DOX)-resistant breast cancer cells. Overexpression of TBX15 reversed the DOX resistance by inducing microRNA-152 (miR-152) expression. We found that KIF2C levels were highly expressed in DOX-resistant breast cancer tissues and cells, and KIF2C was a potential target of miR-152. TBX15 and miR-152 overexpression suppressed autophagy and glycolysis in breast cancer cells, while KIF2C overexpression reversed the process. Overexpression of KIF2C increased DOX resistance in cancer cells. Furthermore, KIF2C directly binds with PKM2 for inducing the DOX resistance. KIF2C can prevent the ubiquitination of PKM2 and increase its protein stability. In addition, we further identified that Domain-2 of KIF2C played a major role in the binding with PKM2 and preventing PKM2 ubiquitination, which enhanced DOX resistance by promoting autophagy and glycolysis. CONCLUSIONS: Our data identify a new mechanism by which TBX15 abolishes DOX chemoresistance in breast cancer, and suggest that TBX15/miR-152/KIF2C axis is a novel signaling pathway for mediating DOX resistance in breast cancer through regulating PKM2 ubiquitination and decreasing PKM2 stability. This finding suggests new therapeutic target and/or novel strategy development for cancer treatment to overcome drug resistance in the future.

Surface Triple Junctions Govern the Strength of a Nanoscale Solid.

Surface triple junctions (STJs), i.e., the termination lines of grain boundaries at solid surface, are the common line defects in polycrystalline materials. Compared with planar defects such as grain boundaries and surfaces, STJ lines are usually overlooked in a material's strengthening although abundant atoms may reside at STJs in many nanomaterials. In this study, by in situ compression of coarse-grained and nanocrystalline nanoporous gold samples in an electrochemical environment, the effect of STJs on the strength of nanoporous gold was successfully decoupled from grain-boundary and surface effects. We found that the strength of nanoporous gold became sensitive to STJ modification when ligament size was decreased to below ∼100 nm, indicating that STJs started to influence ligament strength at sub-100 nm scale. This STJ effect was associated with the emission of dislocations from STJs during plastic deformation. Our findings strongly suggest that the structure and chemistry at STJs should be considered in understanding the mechanical response of sub-100 nm scale materials.

Transition from Homogeneous to Localized Deformation in Nanoporous Gold.

We report a transition from homogeneous deformation to localized densification for nanoporous gold (NPG) under compression, with its solid fraction (φ) increasing to above ∼1/3. Results obtained herein suggest that this transition is inverted compared to that of conventional porous materials. Consequently, under compression, the low-density NPGs with φ<1/3 showed evident strain hardening, whereas a stress plateau was observed for high-density NPGs with φ>1/3, which is contrary to the established notions for conventional porous materials. The ligament pinch-offs and bending-dominated structures are responsible for the homogeneous deformation of low-density NPGs. For high-density NPGs, the compression- or tension-dominated structure enables the collective strain bursts in nanoligaments, resulting in localized densification and stress plateau in their compression curves. In addition to the nanosize effect, the surface-diffusion-mediated topology evolution and the large-scale crystal-lattice coherency arising from the large grain size are also decisive to the mechanical response of dealloyed NPGs, which might be universal for self-organized nanonetwork materials.

The Zinc-Sensing Receptor GPR39 in Physiology and as a Pharmacological Target.

The G-protein coupled receptor GPR39 is abundantly expressed in various tissues and can be activated by changes in extracellular Zn2+ in physiological concentrations. Previously, genetically modified rodent models have been able to shed some light on the physiological functions of GPR39, and more recently the utilization of novel synthetic agonists has led to the unraveling of several new functions in the variety of tissues GPR39 is expressed. Indeed, GPR39 seems to be involved in many important metabolic and endocrine functions, but also to play a part in inflammation, cardiovascular diseases, saliva secretion, bone formation, male fertility, addictive and depression disorders and cancer. These new discoveries offer opportunities for the development of novel therapeutic approaches against many diseases where efficient therapeutics are still lacking. This review focuses on Zn2+ as an endogenous ligand as well as on the novel synthetic agonists of GPR39, placing special emphasis on the recently discovered physiological functions and discusses their pharmacological potential.

Differential expression profiling of lncRNAs related to Epstein-Barr virus infection in the epithelial cells.

Epstein-Barr virus (EBV) is a prevalent γ-herpesvirus associated with a variety of cancers, including epithelial nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC). Long noncoding RNAs (lncRNAs) are emerging as powerful regulators that have demonstrated to play crucial roles in cancer development. In this approach, based on genome-wide RNA sequencing, we examined the lncRNA expression profiles in four EBV genome-infected and EBV-negative 293 cells. A series of lncRNAs were found to be dysregulated in a comparative analysis. Then, eight typical lncRNAs were selected for validation of expression levels by real-time quantitative polymerase chain reaction and were detected in EBV-positive or EBV-negative GC and NPC cells. The differential expression patterns of the eight lncRNAs for validation were fundamentally identical to those revealed in RNA sequencing. Particularly, the differential expression of these lncRNAs in GC and NPC cells indicated their possible roles in EBV infection and tumorigenesis. In addition, a predicted lncRNA-microRNA-messenger RNA network suggested their potential interactions. This study reveals the first lncRNAome related to EBV infection in the epithelial cells and provides novel clues for the study of viral role in epithelial cancers through the interaction between EBV and host lncRNAs.

Arsenic-induced metabolic shift triggered by the loss of miR-199a-5p through Sp1-dependent DNA methylation.

Inorganic arsenic is an environmental carcinogen that poses a major global public health risk. A high percentage of drinking water from wells in the U.S. contains higher-than-normal levels of arsenic, suggesting an increased risk of arsenic-induced deleterious effects. In addition to primary preventive measures, therapeutic strategies need to effectively address and integrate multiple molecular mechanisms underlying arsenic-induced carcinogenesis. We previously showed that the loss of miR-199a-5p in arsenic-transformed cells is pivotal to promote arsenic-induced angiogenesis and tumor growth in lung epithelial cells. In this study, we further showed that subacute or chronic exposure to arsenic diminished miR-199a-5p levels largely due to DNA methylation, which was achieved by increased DNA methyltransferase-1 (DNMT1) activity, mediated by the formation of specific protein 1 (Sp1)/DNMT1 complex. In addition to the DNA hypermethylation, arsenic exposure also repressed miR-199a transcription through a transcriptional repressor Sp1. We further identified an association between miR-199a-5p repression and the arsenic-mediated energy metabolic shift, as reflected by mitochondria defects and a switch to glycolysis, in which a glycolytic enzyme pyruvate kinase 2 (PKM2) was a functional target of miR-199a-5p. Taken together, the repression of miR-199a-5p through both Sp1-dependent DNA methylation and Sp1 transcriptional repression promotes an arsenic-mediated metabolic shift from mitochondria respiration to aerobic glycolysis via PKM2.

Suppression of miR-143 contributes to overexpression of IL-6, HIF-1α and NF-κB p65 in Cr(VI)-induced human exposure and tumor growth.

Hexavalent chromium [Cr(VI)] is a known occupational and environmental contaminant and carcinogen, but new mechanisms of Cr(VI)-induced carcinogenesis remain to be elucidated. In this study, we found that expression of miR-143 is decreased, whereas that of Interleukin 6 (IL-6) is increased in blood samples of Cr(VI)-exposing workers compared with corresponding unexposed workers. In addition, IL-6 was increased in human bronchial epithelial cells (BEAS-Cr) exposed to Cr(VI) compared with unexposed BEAS-2B cells. To further investigate the mechanisms by which Cr(VI) promotes these changes, we assessed the effects of miR-143 on gene expression and found that miR-143 suppressed expression of IL-6, HIF-1α and NF-κB p65, and that inhibiting miR-143 promoted expression of IL-6, HIF-1α and NF-κB p65. Interestingly, IL-6 regulated expression of HIF-1α, and HIF-1α transcriptionally regulated expression of IL-6. Experiments in animals showed that miR-143 inhibited tumor growth and angiogenesis by regulating IL-6/HIF-1α and downstream signaling pathways in vivo. These outcomes support the hypothesis that the miR-143/IL-6/HIF-1α pathway functions to regulate Cr(VI)-induced carcinogenesis.

Encapsulating Pt Nanoparticles through Transforming Fe3O4 into MIL-100(Fe) for Well-Defined Fe3O4@Pt@MIL-100(Fe) Core-Shell Heterostructures with Promoting Catalytic Activity.

Metal-organic framework (MOF)-based magnetic Pt catalyst Fe3O4@Pt@MIL-100(Fe) core-shell heterostructures were prepared through transforming Fe3O4 into MIL-100(Fe) in benzene-1,3,5-tricarboxylic acid solution along with encapsulating the Pt nanoparticles successively adsorbed onto the surface of the Fe3O4 nanosphere and the continuously forming surfaces of the growing MIL-100(Fe) crystals. This method circumvented the obstacles, controlling the formation of metal nanoparticles (MNPs) inside MOFs or regulating growth of MOFs around the MNPs, for preparing an MNP-MOF composite catalyst. The obtained well-defined Fe3O4@Pt@MIL-100(Fe) core-shell heterostructure was shown promoting catalytic activity on the reduction of 4-nitrophenol due to the synergistic effect between the Pt nanoparticles and the MIL-100(Fe) shell and recycling convenience due to the rapid separation of the Fe3O4 core under an external magnetic field.

Estrogen-induced miR-196a elevation promotes tumor growth and metastasis via targeting SPRED1 in breast cancer.

BACKGROUND: Estrogen plays a critical role in breast cancer (BC) progression through estrogen receptor (ER)-mediated gene regulation. Emerging studies suggest that the malignant progress of BC cells is influenced by the cross talk between microRNAs (miRNAs) and ER-α signaling. However, the mechanism and functional linkage between estrogen and miRNAs remain unclear. METHODS: The expression levels of miR-196a and SPRED1 in BC were tested by qRT-PCR in 46 paired BC and adjacent tissues and by the GEO datasets. The role of miR-196a in estrogen-induced BC development was examined by CCK-8 assay, wound healing assay, Matrigel invasion assay and tumorigenicity assay in nude mice. The binding site of ER-α in miR-196a promoter region was analyzed by ChIP-seq, ChIP assay and luciferase reporter assay. The potential targets of miR-196a in BC cells were explored using the luciferase reporter assay and western blot analysis, and the correlation between miR-196a and SPRED1 was analyzed by Spearman's correlation analysis in BC specimens and GEO dataset. TCGA BRCA data was used to characterize the ESR1 signatures according to MSigDB gene set. RESULTS: The expression levels of miR-196a were higher in ER-positive (ER+) breast tumors compared to ER-negative (ER-) tumor tissue samples. Besides, miR-196a was involved in estrogen-induced BC cell proliferation, migration and invasion. Notably, the up-regulation of miR-196a was mediated by a direct interaction with estrogen receptor α (ER-α) but not estrogen receptor ß (ER-ß) in its promoter region, and miR-196a expression levels were positively correlated to ER-α signature scores. Furthermore, SPRED1 was a new direct target of miR-196a which participated in miR-196a-promoted BC development and was suppressed by ligand-activated ER-α signal pathway. Finally, forced expression of miR-196a induced tumor growth of MCF7 cells, while inhibition of miR-196a significantly suppressed the tumor progress in vivo. CONCLUSIONS: Overall, the identification of estrogen/miR-196a/SPRED1 cascade will shed light on new molecular mechanism of estrogen signaling in BC development and therapy.

Unprecedented Fluorescent Dinuclear CoII and ZnII Coordination Compounds with a Symmetric Bis(salamo)-Like Tetraoxime.

Two unprecedented homometallic CoII and ZnII coordination compounds, [M2(L)(OCH3)][M2(L)(OAc)] (MII = CoII (1) and ZnII (2)), with a novel symmetric bis(salamo)-like tetraoxime ligand H3L were synthesized and characterized by elemental analyses, infrafred (IR), ultraviolet⁻visible spectroscopy (UV-Vis), fluorescent spectra and single-crystal X-ray diffraction analyses. The unit cell of the two coordination compounds contains two crystallographically and chemically independent dinuclear coordination compounds. In the two coordination compounds, three metal ions are five-coordinated, formed two square pyramidal and a trigonal bipyramidal geometries, and the other metal ion is a hexacoordinate octahedral configuration. In addition, the coordination compound 1 forms a 3D supramolecular structure, and the coordination compound 2 forms a 0D dimer structure by the inter-molecular hydrogen bond interactions. Meanwhile, the fluorescence spectra of the coordination compounds 1 and 2 were also measured and discussed.

Synthesis and Fluorescence Properties of a New Heterotrinuclear Co(II)-Ce(III)Complex Constructed from a bis(salamo)-Type Tetraoxime Ligand.

[Co2(L)Ce(OAc)3(CH3CH2OH)]·1.5CH3OH∙0.5CH2Cl2, a heterotrinuclear Co(II)-Ce(III) bis(salamo)-type complex with a symmetric bi(salamo)-type ligand H4L and an acyclic naphthalenediol moiety, was designed, synthesized and characterized by elemental analyses, FT-IR, UV-Vis and fluorescence spectroscopy and X-ray crystallography. The X-ray crystallographic investigation revealed the heterotrinuclear complex consisted of two Co(II) atoms, one Ce(III) atom, one (L)4‒ unit, three µ2-acetate ions, one coordinated ethanol molecule, one and half crystallization methanol molecule and half crystallization dichloromethane molecule. Two Co(II) atoms located in the N2O2 coordination spheres, are both hexacoordinated, with slightly distorted octahedral geometries. The Ce(III) atom is nine-coordinated and located in the O6 cavity possesses a single square antiprismatic geometry. In addition, supramolecular interactions exist in the Co(II)-Ce(III) complex. Two infinite 2D supramolecular structures are built via intermolecular O-H···O, C-H···O and C-H···π interactions, respectively.