Two-dimensional MoS2-enabled flexible rectenna for Wi-Fi-band wireless energy harvesting.

The mechanical and electronic properties of two-dimensional materials make them promising for use in flexible electronics1-3. Their atomic thickness and large-scale synthesis capability could enable the development of 'smart skin'1,3-5, which could transform ordinary objects into an intelligent distributed sensor network6. However, although many important components of such a distributed electronic system have already been demonstrated (for example, transistors, sensors and memory devices based on two-dimensional materials1,2,4,7), an efficient, flexible and always-on energy-harvesting solution, which is indispensable for self-powered systems, is still missing. Electromagnetic radiation from Wi-Fi systems operating at 2.4 and 5.9 gigahertz8 is becoming increasingly ubiquitous and would be ideal to harvest for powering future distributed electronics. However, the high frequencies used for Wi-Fi communications have remained elusive to radiofrequency harvesters (that is, rectennas) made of flexible semiconductors owing to their limited transport properties9-12. Here we demonstrate an atomically thin and flexible rectenna based on a MoS2 semiconducting-metallic-phase heterojunction with a cutoff frequency of 10 gigahertz, which represents an improvement in speed of roughly one order of magnitude compared with current state-of-the-art flexible rectifiers9-12. This flexible MoS2-based rectifier operates up to the X-band8 (8 to 12 gigahertz) and covers most of the unlicensed industrial, scientific and medical radio band, including the Wi-Fi channels. By integrating the ultrafast MoS2 rectifier with a flexible Wi-Fi-band antenna, we fabricate a fully flexible and integrated rectenna that achieves wireless energy harvesting of electromagnetic radiation in the Wi-Fi band with zero external bias (battery-free). Moreover, our MoS2 rectifier acts as a flexible mixer, realizing frequency conversion beyond 10 gigahertz. This work provides a universal energy-harvesting building block that can be integrated with various flexible electronic systems.

Vibrational Fermi Resonance in Atomically Thin Black Phosphorus.

Fermi resonance is a phenomenon involving the hybridization of two coincidentally quasi-degenerate states that is observed in the vibrational or electronic spectra of molecules. Despite numerous examples in molecular systems, vibrational Fermi resonances in dispersive semiconducting systems remain largely unexplored due to the rarity of occurrence. Here we report a vibrational Fermi resonance in atomically thin black phosphorus. The Fermi resonance arises via anharmonic mixing of a fundamental Raman mode and a Davydov component of an infrared mode, leading to a doublet with mixed character. The extent of Fermi coupling can be modulated by the application of external biaxial strain. The consequences of Fermi hybridization are revealed by electronic resonance effects in the thickness-dependent and excitation-wavelength-dependent Raman spectrum, which is predicted by ab initio hybrid functional simulations including excitonic interactions. This work reveals new insight into electron-phonon coupling in black phosphorus and demonstrates a novel method for modulating Fermi resonances in 2D semiconductors.

Observation of Three-State Nematicity and Domain Evolution in Atomically Thin Antiferromagnetic NiPS3.

Nickel phosphorus trisulfide (NiPS3), a van der Waals 2D antiferromagnet, has received significant interest for its intriguing properties in recent years. However, despite its fundamental importance in the physics of low-dimensional magnetism and promising potential for technological applications, the study of magnetic domains in NiPS3 down to an atomically thin state is still lacking. Here, we report the layer-dependent magnetic characteristics and magnetic domains in NiPS3 by employing linear dichroism spectroscopy, polarized microscopy, spin-correlated photoluminescence, and Raman spectroscopy. Our results reveal the existence of the paramagnetic-to-antiferromagnetic phase transition in bulk to bilayer NiPS3 and provide evidence of the role of stronger spin fluctuations in thin NiPS3. Furthermore, our study identifies three distinct antiferromagnetic domains within atomically thin NiPS3 and captures the thermally activated domain evolution. Our findings provide crucial insights for the development of antiferromagnetic spintronics and related technologies.

A derivative of tanshinone IIA and salviadione, 15a, inhibits inflammation and alleviates DSS-induced colitis in mice by direct binding and inhibition of RIPK2.

Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions primarily affecting the gastrointestinal tract. Previous studies established the role of the NF-κB signaling pathway in the development of IBDs, suggesting that anti-inflammatory therapies might offer a viable treatment strategy. Tanshinone IIA and salviadione, both derived from Salviae Miltiorrhizae Radix et Rhizoma, possess anti-inflammatory and anti-oxidative activities. A series of new compounds were synthesized by hybridizing salviadione with tanshinone. Among these compounds, 15a showed beneficial effects in LPS-induced acute lung injury and diabetes-induced renal injury mouse models. The current study explored the therapeutic efficacy of 15a using both acute and chronic colitis models and elucidated the underlying mechanisms. DSS-induced colitis models were established in mice, where acute colitis was treated with compound 15a (5 or 10 mg·kg-1·d-1) for 8 days, while chronic colitis mice received compound 15a (5 or 10 mg·kg-1·d-1, i.g.) during 2.5% DSS administration. The 15a treatment significantly alleviated DSS-induced pathological and inflammatory damages in both acute and chronic colitis mouse models. In mouse intestinal epithelial cell line MODE-K, pretreatment with compound 15a (5 or 10 µM) significantly suppressed LPS + L18-MDP-induced inflammatory responses. The receptor-interacting serine/threonine kinase 2 (RIPK2) was identified as a direct binding target of compound 15a using microarrays and recombinant human proteins. Moreover, 15a could directly bind to and inhibit the phosphorylation of RIPK2, leading to the suppression of the NF-κB and MAPK signaling pathways. Furthermore, LEU153 and VAL32 were identified within the KD domain of RIPK2 as critical amino residues for the binding of 15a. Briefly, the current findings demonstrate that compound 15a holds promise as a therapeutic agent for managing acute and chronic colitis.

Trajectory model to analyze the effect of multi-metal exposures on sperm parameters and sex hormones of the MARHCS cohort in China.

BACKGROUND: At present, several cross-sectional studies have found that exposure to metal/metalloid elements is closely associated with male reproduction. However, the long-term effects of metal exposure on male reproduction have not been explored. METHODS: In 2013, 796 volunteers were recruited, followed by first and second follow-ups in 2014 and 2015. Urine, semen, and blood samples were collected at each stage to examine urinary metal/metalloid levels, sperm parameters, and sex hormones. Initially, the latent class trajectory model (LCTM) was utilized to analyze the trajectories of urinary metals. Subsequently, the effects of urinary metal trajectories on semen parameters and sex hormones were examined using the linear mixed model. Finally, the impact of urinary metal trajectories on the classification of semen quality (normal or abnormal) was evaluated using the generalized linear mixed model. RESULTS: Among the 18 metals/metalloids studied, trajectories were formed by 6 of them (Li, Al, Fe, Zn, As, Rb). Further analysis using the linear mixed model and the generalized linear mixed model revealed that Li was negatively correlated with semen volume, and sperm motility (P < 0.05). The maximum-decreasing trajectory group had a detrimental effect on semen quality (OR = 1.75, 95%CI: 1.22, 2.53) compared to the minimum-stable trajectory group. Al showed negative associations with sperm concentration, total sperm count, and normal morphology (P < 0.05). Rb was positively associated with progressive motility (P < 0.05). The high-stable trajectory group exhibited a protective effect on semen quality (OR = 0.66, 95%CI: 0.49, 0.90) compared to the low-stable trajectory group. Additionally, Fe was observed to have a negative relationship with follicle-stimulating hormone (FSH) (P < 0.05), and Rb exhibited a negative correlation with progesterone (P) (P < 0.05). CONCLUSION: Our three-year cohort study provides new evidence that Li and Al have a negative impact on semen quality, whereas Rb is associated with beneficial effects. Additionally, Rb and Fe are endocrine disruptors of sex hormones.

Improving Strain-localized GaSe Single Photon Emitters with Electrical Doping.

Exciton localization through nanoscale strain has been used to create highly efficient single-photon emitters (SPEs) in 2D materials. However, the strong Coulomb interactions between excitons can lead to nonradiative recombination through exciton-exciton annihilation, negatively impacting SPE performance. Here, we investigate the effect of Coulomb interactions on the brightness, single photon purity, and operating temperatures of strain-localized GaSe SPEs by using electrostatic doping. By gating GaSe to the charge neutrality point, the exciton-exciton annihilation nonradiative pathway is suppressed, leading to ∼60% improvement of emission intensity and an enhancement of the single photon purity g(2)(0) from 0.55 to 0.28. The operating temperature also increased from 4.5 K to 85 K consequently. This research provides insight into many-body interactions in excitons confined by nanoscale strain and lays the groundwork for the optimization of SPEs for optoelectronics and quantum photonics.

Targeted local anesthesia: a novel slow-release Fe3O4-lidocaine-PLGA microsphere endowed with a magnetic targeting function.

PURPOSE: Lidocaine microspheres can prolong the analgesic time to 24-48 h, which still cannot meet the need of postoperative analgesia lasting more than 3 days. Therefore, we added Fe3O4 to the lidocaine microspheres and used an applied magnetic field to attract Fe3O4 to fix the microspheres around the target nerves, reducing the diffusion of magnetic lidocaine microspheres to the surrounding tissues and prolonging the analgesic time. METHODS: Fe3O4-lidocaine-PLGA microspheres were prepared by the complex-emulsion volatilization method to characterize and study the release properties in vitro. The neural anchoring properties and in vivo morphology of the drug were obtained by magnetic resonance imaging. The nerve blocking effect and analgesic effect of magnetic lidocaine microspheres were evaluated by animal experiments. RESULTS: The mean diameter of magnetically responsive lidocaine microspheres: 9.04 ± 3.23 µm. The encapsulation and drug loading of the microspheres were 46.18 ± 3.26% and 6.02 ± 1.87%, respectively. Magnetic resonance imaging showed good imaging of Fe3O4-Lidocain-PLGA microspheres, a drug-carrying model that slowed down the diffusion of the microspheres in the presence of an applied magnetic field. Animal experiments demonstrated that this preparation had a significantly prolonged nerve block, analgesic effect, and a nerve anchoring function. CONCLUSION: Magnetically responsive lidocaine microspheres can prolong analgesia by slowly releasing lidocaine, which can be immobilized around the nerve by a magnetic field on the body surface, avoiding premature diffusion of the microspheres to surrounding tissues and improving drug targeting.

π-Extension of a Multiple Resonance Core: Double Helical and Heptagon-Embedded Nanographenes.

Multiple resonance (MR) boron-nitrogen doped polycyclic aromatic hydrocarbons (BN-PAHs) have shown compelling thermally activated delayed fluorescence (TADF), surpassing those of their hydrocarbon analogues. However, the structural variety of π-extended BN-PAHs remains narrow. In this study, we synthesized three double helical BN-doped nanographenes (BN-NGs), 2 a-2 c, and three heptagon-embedded BN-NGs, 1 a-1 c, by π-extension of the MR core. During the formation of 2 a, a nanographene with one heptagon (1 a) was obtained, whereas further dehydrocyclization of the [6]helicene units within 2 b and 2 c led to heptagon structures, yielding other two BN-NGs containing double heptagons (1 b and 1 c). These BN-NGs (2 a-2 c and 1 a-1 c) showed pronounced redshifts of 100-190 nm compared to the parent MR core, while preserving the TADF characteristics and prolonging the delayed fluorescence lifetime to the millisecond level. Furthermore, the integration of a heptagon ring into 1 a-1 c expanded the conjugation, reduced the oxidation potentials, and yielded a more flexible framework compared to those of 2 a-2 c. The enantiomers of 2 a-2 c, 1 a, and 1 c were resolved and their chiroptical properties were studied. Notably, 1 a and 1 c exhibited increased chiroptical dissymmetry factors.

Helical Nanographenes Bearing Pentagon-Heptagon Pairs by Stepwise Dehydrocyclization.

The incorporation of pentagon-heptagon pairs into helical nanographenes lacks a facile synthetic route, and the impact of these pairs on chiroptical properties remains unclear. In this study, a method for the stepwise construction of pentagon-heptagon pairs in helical nanographenes by the dehydrogenation of [6]helicene units was developed. Three helical nanographenes containing pentagon-heptagon pairs were synthesized and characterized using this approach. A wide variation in the molecular geometries and photophysical properties of these helical nanographenes was observed, with changes in the helical length of these structures and the introduction of the pentagon-heptagon pairs. The embedded pentagon-heptagon pairs reduced the oxidation potential of the synthesized helical nanographenes. The high isomerization energy barriers enabled the chiral resolution of the helicene enantiomers. Chiroptical investigations revealed remarkably enhanced circularly polarized luminescence and luminescence dissymmetry factors with an increasing number of the pentagon-heptagon pairs.

FDX1 enhances endometriosis cell cuproptosis via G6PD-mediated redox homeostasis.

Cuproptosis is a new form of programmed cell death, which is associated with the mitochondrial TCA (tricarboxylic acid) cycle. But the functions of cuproptosis in endometriosis progression are still unknown. Here, we find that cuproptosis suppresses the growth of endometriosis cells and the growth of ectopic endometrial tissues in a mouse model. FDX1 as a key regulator in cuproptosis pathway could promote cuproptosis in endometriosis cells. Interestingly, FDX1 interacts with G6PD, and reduces its protein stability, which predominantly affects the cellular redox-regulating systems. Then, the reduced G6PD activity enhances cuproptosis via down-regulating NADPH and GSH levels. Collectively, our study demonstrates that FDX1 mediates cuproptosis in endometriosis via G6PD pathway, resulting in repression of endometriosis cell proliferation and metastasis.

Sperm telomere length is associated with sperm nuclear DNA integrity and mitochondrial DNA abnormalities among healthy male college students in Chongqing, China.

STUDY QUESTION: Is sperm telomere length (STL) associated with sperm nuclear DNA damage and mitochondrial DNA abnormalities? SUMMARY ANSWER: Sperm telomere length is related to sperm nuclear DNA integrity and mitochondrial DNA abnormalities in healthy young college students. WHAT IS KNOWN ALREADY: Many studies have revealed the correlations between sperm genetic alterations in both the nucleus and mitochondria and sperm functionality, however, the possible associations between the telomere, an important component of chromosome, and conventional indicators of mitochondrial DNA and nuclear DNA changes have not been investigated. STUDY DESIGN, SIZE, DURATION: A prospective cohort study, Male Reproductive Health in Chongqing College Students (MARHCS), was conducted from June 2013 to June 2015. We pooled data collected from the follow-up study in 2014 and a total of 444 participants were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: STL was measured by quantitative (Q)-PCR. Sperm nuclear DNA integrity was determined using sperm chromatin structure assay (SCSA) and comet assay. Mitochondrial DNA damage was assessed by mitochondrial DNA copy number (mtDNAcn) evaluated with Q-PCR, and mtDNA integrity was determined with long PCR. MAIN RESULTS AND THE ROLE OF CHANCE: The univariable-linear regression analysis revealed that STL was significantly positively correlated with markers of sperm nuclear DNA damage including the DNA fragmentation index (DFI) and comet parameters (the percentage of DNA in the tail, tail length, comet length, and tail moment). Additionally, STL was also significantly positively correlated with mtDNAcn and significantly negatively correlated with mtDNA integrity. After adjustment for potential confounders, these relationships remained appreciable. Moreover, we investigated potential effects of biometric factors, including age, parental age at conception, and BMI on STL and found that STL was increased with paternal age at conception. LIMITATIONS, REASONS FOR CAUTION: A mechanistic explanation of the correlation between STL, sperm nuclear DNA integrity, and mtDNA abnormalities cannot be provided with a cross-sectional study design, so well-designed longitudinal studies are still necessary. In addition, a single semen samples were provided and were not all obtained at the same time point, which may increase the intraindividual bias in this study. WIDER IMPLICATIONS OF THE FINDINGS: The findings extend the literature including assessment of mitochondrial dysfunction, sperm nuclear DNA damage, and telomere length and provide new insights into the relevance of STL in male reproduction. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (No. 82073590), the National Natural Science Foundation of China (No. 81903363), the National Natural Science Foundation of China (No. 82130097), and the National Key R&D Program of China (2022YFC2702900). The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

TERT transcription and translocation into mitochondria regulate benzo[a]pyrene/BPDE-induced senescence and mitochondrial damage in mouse spermatocytes.

Telomere and mitochondria may be the targets of Benzo[a]pyrene (BaP) -induced male reproductive damage, and further elucidation of the toxic molecular mechanisms is necessary. In this study, we used in vivo and in vitro exposure models to explore the molecular mechanisms of TERT regulation in BaP-induced telomere and mitochondrial damage in spermatocytes. The results showed that the treatment of benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), the active metabolite of BaP, caused telomere dysfunction in mouse spermatocyte-derived GC-2 cells, resulting in S-phase arrest and increased senescence-associated secretory phenotype (SASP). These effects were significantly alleviated by telomerase agonist (ABG) pretreatment in GC-2 cells. SIRT1, FOXO3a, or c-MYC overexpressing GC-2 cell models were established to demonstrate that BPDE inhibited TERT transcriptional expression through the SIRT1/FOXO3a/c-MYC pathway, leading to telomere dysfunction. We also observed that BPDE induced mitochondrial compromise, including complex I damage, accompanied by reduced mitochondrial TERT expression. Based on this, we constructed wild-type TERT-overexpressing (OE-TERTwt) and mitochondria targeting TERT-overexpressing (OE-TERTmst) GC-2 cell models and found that OE-TERTmst GC-2 cells improved mitochondrial function better than OE-TERTwt GC-2 cells. Finally, ICR mice were given BaP by intragastric administration for 35 days, which verified the results of the in vitro study. The results shown that BaP exposure can lead to spermatogenesis disturbance, which is related to the telomere and mitochondrial damage in spermatocytes. In conclusion, our results suggest that BPDE causes telomere and mitochondrial damage in spermatocytes by inhibiting TERT transcription and mitochondrial TERT expression. This study elucidates the molecular mechanism of male reproductive toxicity due to environmental pollutant BaP, and also provides a new perspective for the exploration of interventions and protective measures against male reproductive damage by BaP.

A hepatocyte differentiation model reveals two subtypes of liver cancer with different oncofetal properties and therapeutic targets.

Clinical observation of the association between cancer aggressiveness and embryonic development stage implies the importance of developmental signals in cancer initiation and therapeutic resistance. However, the dynamic gene expression during organogenesis and the master oncofetal drivers are still unclear, which impeded the efficient elimination of poor prognostic tumors, including human hepatocellular carcinoma (HCC). In this study, human embryonic stem cells were induced to differentiate into adult hepatocytes along hepatic lineages to mimic liver development in vitro. Combining transcriptomic data from liver cancer patients with the hepatocyte differentiation model, the active genes derived from different hepatic developmental stages and the tumor tissues were selected. Bioinformatic analysis followed by experimental assays was used to validate the tumor subtype-specific oncofetal signatures and potential therapeutic values. Hierarchical clustering analysis revealed the existence of two subtypes of liver cancer with different oncofetal properties. The gene signatures and their clinical significance were further validated in an independent clinical cohort and The Cancer Genome Atlas database. Upstream activator analysis and functional screening further identified E2F1 and SMAD3 as master transcriptional regulators. Small-molecule inhibitors specifically targeting the oncofetal drivers extensively down-regulated subtype-specific developmental signaling and inhibited tumorigenicity. Liver cancer cells and primary HCC tumors with different oncofetal properties also showed selective vulnerability to their specific inhibitors. Further precise targeting of the tumor initiating steps and driving events according to subtype-specific biomarkers might eliminate tumor progression and provide novel therapeutic strategy.

Buchwald-Hartwig coupled conjugated microporous polymer for efficient removal COVID-19 antiviral drug famciclovir from waters: Adsorption behavior and mechanism.

The consumption of famciclovir (FCV) has been increased dramatically since the outbreak of coronavirus in 2019, and the pollution and harm of FCV in waters are concerned. Here, by utilizing aryl halides on 2, 4, 6-tris(4-bromophenyl)- 1, 3, 5-triazine (BPT) and primary amine groups on benzidine (BZ), a novel conjugated microporous polymer, namely BPT-BZ-CMP, was synthesized by Buchwald-Hartwig coupling reaction and applied in the removal of FCV from aqueous solution firstly. The synthesized BPT-BZ-CMP were characterized by various methods, including FTIR, SEM, BET, and Zeta-potential. Due to the micropore structure and high specific surface area, it took only 30 min for BPT-BZ-CMP to adsorb FCV to reach an equilibrium, and the maximum adsorption capacity was 347.8 mg·g-1. The Liu and pseudo-second-order kinetic models properly fit the adsorption equilibrium and kinetic data, respectively. The adsorption process was a spontaneous process, and the hydrogen bonding, π-π interaction and C-H···π interaction enhanced the adsorption of FCV on BPT-BZ-CMP. BPT-BZ-CMP maintained a good adsorption capacity after four consecutive adsorption-desorption cycle experiments. This study confirmed the potential of BPT-BZ-CMP as efficient sorbent to remove FCV from aqueous solutions.

M6 A demethylase fat mass and obesity-associated protein regulates cisplatin resistance of gastric cancer by modulating autophagy activation through ULK1.

Drug resistance is an important factor for treatment failure of gastric cancer. N6 -methyladenosine (m6 A) is the predominant mRNA internal modification in eukaryotes. The roles of m6 A modification in drug resistance of gastric cancer remains unclear. In the present study, the m6 A methylated RNA level was significantly decreased while the expression of m6 A demethylase fat mass and obesity-associated protein (FTO) was obviously elevated in cisplatin-resistant (SGC-7901/DDP) gastric cancer cells. Knockdown of FTO reversed cisplatin resistance of SGC-7901/DDP cells both in vitro and in vivo, which was attributed to the inhibition of Unc-51-like kinase 1 (ULK1)-mediated autophagy. Mechanistically, ULK1 expression was regulated in an FTO-m6 A-dependent and YTHDF2-mediated manner. Collectively, our findings indicate that the FTO/ULK1 axis exerts crucial roles in cisplatin resistance of gastric cancer.

Associations between isoflavone exposure and reproductive damage in adult males: evidence from human and model system studies†.

It is controversial whether exposure to isoflavones exerts male reproductive toxicity. The aim of this study was to investigate whether isoflavone exposure during adulthood could have deleterious impacts on male reproductive health by the cross-sectional study, animal experiments, and in vitro tests. In the cross-sectional study, we observed that urinary isoflavones were not significantly associated with semen quality including sperm concentrations, sperm count, progressive motility, and total motility, respectively. However, negative associations were found between plasma testosterone and urinary Σisoflavones, genistein, glycitein, and dihydrodaidzein. In the animal experiments, serum and intratesticular testosterone levels were decreased in mice exposed to several dosages of genistein. Genistein administration caused upregulation of estrogen receptor alpha and downregulation of cytochrome P45017A1 protein levels in testes of mice. In vitro tests showed that genistein caused a concentration-dependent inhibition of testosterone production by TM3 Leydig cells. Elevated protein expression of estrogen receptor alpha and decreased messenger RNA/protein level of cytochrome P45017A1 were also observed in genistein-treated cells. Protein level of cytochrome P45017A1 and testosterone concentration were significantly restored in the estrogen receptor alpha small interferring RNA-transfected cells, compared to cells that treated with genistein alone. The results demonstrate that exposure to isoflavones during adulthood may be associated with alterations of reproductive hormones. Particularly, genistein, which inhibits testosterone biosynthesis through upregulation of estrogen receptor alpha in Leydig cells of mice, might induce the disruption of testosterone production in human. The present study provides novel perspective into potential targets for male reproductive compromise induced by isoflavone exposure.

Spin-induced linear polarization of photoluminescence in antiferromagnetic van der Waals crystals.

Antiferromagnets are promising components for spintronics due to their terahertz resonance, multilevel states and absence of stray fields. However, the zero net magnetic moment of antiferromagnets makes the detection of the antiferromagnetic order and the investigation of fundamental spin properties notoriously difficult. Here, we report an optical detection of Néel vector orientation through an ultra-sharp photoluminescence in the van der Waals antiferromagnet NiPS3 from bulk to atomically thin flakes. The strong correlation between spin flipping and electric dipole oscillator results in a linear polarization of the sharp emission, which aligns perpendicular to the spin orientation in the crystal. By applying an in-plane magnetic field, we achieve manipulation of the photoluminescence polarization. This correlation between emitted photons and spins in layered magnets provides routes for investigating magneto-optics in two-dimensional materials, and hence opens a path for developing opto-spintronic devices and antiferromagnet-based quantum information technologies.

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.

Association between GNAQ Gene DNA Methylation and Vascular Recurrence in Patients with Acute Ischemic Stroke or Transient Ischemic Attack.

PURPOSE: We aimed to assess whether the aberrant methylation of GNAQ gene, which may involve in the clopidogrel resistance (CR), was associated with a higher risk of recurrent ischemic events in clopidogrel-treated acute ischemic stroke or transient ischemic attack (TIA) patients. METHODS: This is a nested case-control study, 152 clopidogrel-treated acute ischemic stroke or TIA patients that were propensity-matched were included in the final analysis, including 36 patients with vascular recurrence set as cases. Methylation levels of GNAQ gene were identified with MassARRAY EpiTYPER assays. Univariate and multivariate logistic regression analyses were conducted to explore the predictive value of CpG units for recurrent ischemic events within 1 year.Mediation analysis was performed to assess the role of CR in describing the effect of GNAQ methylation on recurrent ischemic events. RESULTS: A total of 16 differentially methylated CpG units were identified. Multivariate logistic analysis indicated that the average methylation of CpG 32-39 of GNAQ was associated with a significantly higher risk of ischemic events (p < 0.001). When transformed into dichotomous variables with the receiver operating characteristic curve, hypomethylation (<0.31) of CpG 32-39 of GNAQ significantly increased the risk of vascular recurrence (odds ratio 73.82, 95% confidence interval 20.33-268.01). The mediation effect of CR for recurrent ischemic events was not identified. CONCLUSIONS: Hypomethylation of CpG 32-39 of GANQ gene was associated with a higher risk of ischemic events for clopidogrel-treated acute ischemic stroke or TIA patients. Further studies were warranted to explain the possible mechanism.