Transgenerational increases in DNA methylation in Arabidopsis plants defective in active DNA demethylation.

Spontaneous gain or loss of DNA methylation occurs in plant and animal genomes, and DNA methylation changes can lead to meiotically stable epialleles that generate heritable phenotypic diversity. However, it is unclear whether transgenerational epigenetic stability may be regulated by any cellular factors. Here, we examined spontaneously occurring variations in DNA methylation in wild-type and ros1 mutant Arabidopsis plants that were propagated for ten generations from single-seed descent. We found that the ros1 mutant, which is defective in active DNA demethylation, showed an increased transgenerational epimutation rate. The ros1 mutation led to more spontaneously gained methylation than lost methylation at individual cytosines, compared to the wild type which had similar numbers of spontaneously gained and lost methylation cytosines. Consistently, transgenerational differentially methylated regions were also biased toward hypermethylation in the ros1 mutant. Our results reveal a genetic contribution of the ROS1 DNA demethylase to transgenerational epigenetic stability and suggest that ROS1 may have an unexpected surveillance function in preventing transgenerational DNA methylation increases.

Reciprocal Regulation of the TOR Kinase and ABA Receptor Balances Plant Growth and Stress Response.

As sessile organisms, plants must adapt to variations in the environment. Environmental stress triggers various responses, including growth inhibition, mediated by the plant hormone abscisic acid (ABA). The mechanisms that integrate stress responses with growth are poorly understood. Here, we discovered that the Target of Rapamycin (TOR) kinase phosphorylates PYL ABA receptors at a conserved serine residue to prevent activation of the stress response in unstressed plants. This phosphorylation disrupts PYL association with ABA and with PP2C phosphatase effectors, leading to inactivation of SnRK2 kinases. Under stress, ABA-activated SnRK2s phosphorylate Raptor, a component of the TOR complex, triggering TOR complex dissociation and inhibition. Thus, TOR signaling represses ABA signaling and stress responses in unstressed conditions, whereas ABA signaling represses TOR signaling and growth during times of stress. Plants utilize this conserved phospho-regulatory feedback mechanism to optimize the balance of growth and stress responses.

Efficient and stable acidic CO2 electrolysis to formic acid by a reservoir structure design.

Electrochemical synthesis of valuable chemicals and feedstocks through carbon dioxide (CO2) reduction in acidic electrolytes can surmount the considerable CO2 loss in alkaline and neutral conditions. However, achieving high productivity, while operating steadily in acidic electrolytes, remains a big challenge owing to the severe competing hydrogen evolution reaction. Here, we show that vertically grown bismuth nanosheets on a gas-diffusion layer can create numerous cavities as electrolyte reservoirs, which confine in situ-generated hydroxide and potassium ions and limit inward proton diffusion, producing locally alkaline environments. Based on this design, we achieve formic acid Faradaic efficiency of 96.3% and partial current density of 471 mA cm-2 at pH 2. When operated in a slim continuous-flow electrolyzer, the system exhibits a full-cell formic acid energy efficiency of 40% and a single pass carbon efficiency of 79% and performs steadily over 50 h. We further demonstrate the production of pure formic acid aqueous solution with a concentration of 4.2 weight %.

Human papillomavirus (HPV) DNA methylation changes in HPV-associated head and neck cancer.

Despite the rising incidence, currently, there are no early detection methods for HPV-driven HNC (HPV-HNC). Cervical cancer studies suggest that HPV DNA methylation changes can be used as a biomarker to discriminate cancer patients from HPV-infected individuals. As such, this study was designed to establish a protocol to evaluate DNA methylation changes in HPV late genes and long control region (LCR) in saliva samples of HPV-HNC patients and HPV-positive controls. Higher methylation levels were detected in HPV late genes (L1 and L2) in both tumour and saliva samples of HPV-HNC patients compared with HPV-positive controls. Moreover, methylation patterns between tumours and corresponding saliva samples were observed to have a strong correlation (Passing-Bablok regression analysis; τ = 0.7483, P < 0.0001). Considering the differences between HNC and controls in methylation levels in late genes, and considering primer amplification efficiencies, 13 CpG sites located at L1 and L2 genes were selected for further evaluation. A total of 18 HNC saliva samples and 10 control saliva samples were assessed for the methylation levels in the selected sites. From the CpG sites evaluated statistically significant differences were identified for CpG sites at L2-CpG 6 (P = 0.0004), L1-CpG 3 (P = 0.0144), L1-CpG 2 (P = 0.0395) and L2-CpG 19 (P = 0.0455). Our pilot data indicate that higher levels of DNA methylation in HPV late genes are indicative of HPV-HNC risk, and it is a potential supplementary biomarker for salivary HPV detection-based HPV-HNC screening.

Homocysteine concentration in coronary artery disease and severity of coronary lesions.

Our previous study reckons that the impact of the rs1801133 variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) on coronary artery disease (CAD) is possibly mediated by cardiometabolic disorder. This study is performed to verify this hypothesis. Four hundred and thirty CAD patients and 216 CAD-free individuals were enrolled in this case-control study. The rs1801133 variant was genotyped by PCR-RFLP. Severity of coronary lesions was evaluated by number of stenotic coronary vessels and extent of coronary stenosis. The rs1801133 T allele significantly increased homocysteine levels in patients with CAD and CAD-free individuals. Individuals with the T allele of rs1801133 had an increased risk of developing CAD. In contrast, individuals with the TT genotype of rs1801133 were at high risk of multiple vessel lesions. The carriers of CT genotype had higher levels of systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP), and lower levels of apolipoprotein A1 (APOA1) than those with CC genotype in male patients with CAD. The receiver operating characteristic (ROC) curve and precision-recall (PR) curve indicated that hyperhomocysteinemia was sensitive to predict the severity of CAD. Multivariate logistic regression revealed that homocysteine, rs1801133, age, smoking, weight, body mass index (BMI), lipoprotein(a) [Lp(a)], and hs-CRP were independent risk factors for CAD. The increased risk of CAD and severity of coronary lesions associated with rs1801133 in the Chinese Han population were attributed, at least partly, to high homocysteine levels. Hyperhomocysteinemia had a high predictive value for severe CAD or multiple vessel lesions.

Rhizobacterium-derived diacetyl modulates plant immunity in a phosphate-dependent manner.

Plants establish mutualistic associations with beneficial microbes while deploying the immune system to defend against pathogenic ones. Little is known about the interplay between mutualism and immunity and the mediator molecules enabling such crosstalk. Here, we show that plants respond differentially to a volatile bacterial compound through integral modulation of the immune system and the phosphate-starvation response (PSR) system, resulting in either mutualism or immunity. We found that exposure of Arabidopsis thaliana to a known plant growth-promoting rhizobacterium can unexpectedly have either beneficial or deleterious effects to plants. The beneficial-to-deleterious transition is dependent on availability of phosphate to the plants and is mediated by diacetyl, a bacterial volatile compound. Under phosphate-sufficient conditions, diacetyl partially suppresses plant production of reactive oxygen species (ROS) and enhances symbiont colonization without compromising disease resistance. Under phosphate-deficient conditions, diacetyl enhances phytohormone-mediated immunity and consequently causes plant hyper-sensitivity to phosphate deficiency. Therefore, diacetyl affects the type of relation between plant hosts and certain rhizobacteria in a way that depends on the plant's phosphate-starvation response system and phytohormone-mediated immunity.

Fluid shear stress regulates the survival of circulating tumor cells via nuclear expansion.

Distant metastasis mainly occurs through hematogenous dissemination, where suspended circulating tumor cells (CTCs) experience a considerable level of fluid shear stress. We recently reported that shear flow induced substantial apoptosis of CTCs, although a small subpopulation could still persist. However, how suspended tumor cells survive in shear flow remains poorly understood. This study finds that fluid shear stress eliminates the majority of suspended CTCs and increases nuclear size, whereas it has no effect on the viability of adherent tumor cells and decreases their nuclear size. Shear flow promotes histone acetylation in suspended tumor cells, the inhibition of which using one drug suppresses shear-induced nuclear expansion, suggesting that shear stress might increase nuclear size through histone acetylation. Suppressing histone acetylation-mediated nuclear expansion enhances shear-induced apoptosis of CTCs. These findings suggest that suspended tumor cells respond to shear stress through histone acetylation-mediated nuclear expansion, which protects CTCs from shear-induced destruction. Our study elucidates a unique mechanism underlying the mechanotransduction of suspended CTCs to shear flow, which might hold therapeutic promise for CTC eradication.

Interfacial Effects of Nanostructured Doubly Reentrant Surfaces on the Evolution of Local Concentration and Fluid Flow in an Evaporating Droplet.

Surface modification, such as bioinspired nanostructured doubly reentrant surfaces that have presented superhydrophobic wettability even under low-surface-tension liquid, is a very promising technology for controlling droplet dynamics, heat transfer, and evaporation. In this article, we investigate the interfacial effects of nanostructured doubly reentrant surfaces on the flow behaviors and local concentration evolution during the evaporation of an ethanol/water multicomponent droplet. Using particle image velocimetry (PIV) and novel aggregate-induced emission-based (AIE) techniques, the flow patterns and local concentration distributions on both hydrophobic and nanostructured doubly reentrant surfaces were probed and compared. It is found that in addition to the established Marangoni flow-dominated stage, transition stage, and buoyancy-induced flow-dominated stage, a new transition stage and a rolling stage for the nanostructured doubly reentrant surface are detected in the late evaporation period. Differences in the local concentration distribution evolution occur depending on the hydrophobicity of the surface on which the droplet is placed. For the hydrophobic surface, a nonuniform local concentration distribution exists consistently, with a high water fraction in a shell-shaped region near the liquid-air interface and a secondary concentration gradient within this shell-shaped region. The concentration distribution on the nanostructured doubly reentrant surface evolves in a more complex manner, with a strip-shaped region of high water fraction forming in the intermediate stage and then reorganized by rolling flow in the late stage. Finally, theoretical analysis combining PIV and AIE visualization results reveals that the variations in droplet concentration distributions on surfaces with different hydrophobicities exert a significant impact on evaporative behaviors. These behaviors, in turn, affect the evolution of the local concentration distribution.

Deinococcus rhizophilus sp.nov., isolated from rhizosphere soil.

A spherical, pink, aerobic, Gram-stain-positive bacterial strain (MIMF12T) was isolated from rhizosphere soil collected in the Inner Mongolia Autonomous Region, PR China. Cellular growth of the strain was observed at pH 6.0-8.0 (optimum, pH 7.0), at 20-37 °C (optimum, 28 °C) and with 0-1 % (w/v) NaCl (optimum, 0 %). Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain MIMF12T was most closely related to Deinococcus terrestris SDU3-2T with a similarity value of 96.0 %. The respiratory quinone was menaquinone 8, the major fatty acids were C15 : 1 ω6c and C17 : 1 ω8c, and the major polar lipids were composed of two aminophospholipids, one phospholipid and four unidentified lipids. The G+C content of the genomic DNA was 70.1 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain MIMF12T and the closest related type strain SDU3-2T were 88.1 and 52.1 %, respectively. The discovery that MIMF12T differs not only from validly named species in the genus Deinococcus, but also from currently unnamed species in the GDTB, gives us new insights into the genus. Based on phenotypic, chemotaxonomic and phylogenetic characteristics, strain MIMF12T represents a novel species of the genus Deinococcus, for which the name Deinococcus rhizophilus sp. nov. is proposed. The type strain is MIMF12T (=CGMCC 1.61579T=KCTC 43572T).

Photoredox Synthesis of Silicon-Containing Isoindolin-1-ones and Deuterated Analogues Through Hydrosilylation and Deuterium-silylation.

An efficient, practical, and metal-free protocol for the synthesis of silicon-containing isoindolin-1-ones and deuterated analogues via the synergistic combination of an organic photoredox and hydrogen atom transfer process is described. This strategy features mild reaction conditions, high atom economy, and excellent functional group compatibility, delivering a myriad of structurally diverse and valuable products with good to excellent yields.

Terrihabitans rhizophilus sp. nov., isolated from the rhizosphere soil of plant in temperate semi-arid steppe.

A bacterial strain PJ23T was isolated from the rhizosphere soil of Elymus dahuricus Turcz. sampled from a temperate semi-arid steppe in the northern of Inner Mongolia Autonomous Region, China. The strain is Gram-stain-negative, aerobic, light-pink, short rod-shaped, and non-spore-forming. Cell growth could be observed at 4-29℃ (optimal at 24℃), pH 6.0-8.6 (optimal at 8.0) and in the presence of 0-5.0% (w/v) NaCl (optimal at 2.5%). The major cellular fatty acids of strain PJ23T were Summed feature 8 (C18:1 ω6c and/or C18:1 ω7c) (39.42%) and C16:0 (9.60%). The polar lipids were phosphatidylcholine, two unidentified glycolipids, one unidentified aminophospholipid, and two other unidentified polar lipids. The major respiratory quinone was ubiquinone-10. Phylogeny analysis based on 16S rRNA gene sequences retrieved from the genomes showed that, the strain was closely related to the species Terrihabitans soli IZ6T and Flaviflagellibacter deserti SYSU D60017T, with the sequence similarities of 96.79% and 96.15%, respectively. The G + C content was 65.23 mol% calculated on draft genome sequencing. Between the strains PJ23T and Terrihabitans soli IZ6T, the average nucleotide identity (ANI), amino acid identity (AAI) and digital DNA-DNA hybridization (dDDH) was 73.39%,71.12% and 15.7%, these values were lower than the proposed and generally accepted species boundaries of ANI, AAI and dDDH, respectively. Based on phenotypic, chemotaxonomic, and phylogenetic characteristics, strain PJ23T represents a novel species of Terrihabitans, for which the name Terrihabitans rhizophilus sp. nov. is proposed. The type strain is PJ23T (= KCTC 92977 T = CGMCC 1.61577 T).

Roseihalotalea indica gen. nov., sp. nov., a halophilic Bacteroidetes from mesopelagic Southwest Indian Ocean with higher carbohydrate metabolic potential.

The pink-colored and strictly aerobic bacterium strain, designated as TK19036T, was isolated from mesopelagic layer of the Southwest Indian Ocean. This novel isolate can grow at 10-45 °C (optimum, 30 °C), pH 6.0-8.0 (optimum, pH 7.0), and 2-14% NaCl concentrations (w/v) (optimum, 6%). The predominant respiratory quinone was Menaquinone-7. Major polar lipid profiles contained two aminolipids, aminophospholipid, two glycolipids, phosphatidylethanolamine, and three unknown polar lipids. The preponderant cellular fatty acids were iso-C15:0, C16:1 ω5c and iso-C17:0 3-OH. Phylogenetic analyses based on 16S rRNA gene sequence uncovered that the strain TK19036T pertained to the family Catalinimonadaceae under phylum Bacteroidota, and formed a distinct lineage with the closed species Tunicatimonas pelagia NBRC 107804T. The up-to-bacteria-core gene phylogenetic trees also demonstrated a deep and novel branch formed by the strain TK19036T within the family Catalinimonadaceae. Based on chemotaxonomic, phylogenetic and genomic features presented above, strain TK19036T represents a novel species from a novel genus of the family Catalinimonadaceae, for which the name Roseihalotalea indica gen. nov. sp. nov. is proposed. The type strain is TK19036T (= CGMCC 1.18940T = NBRC 116371T).

Paediatric hypertrophic cardiomyopathy secondary to Danon disease.

Danon disease is a rare X-linked disorder caused by deficiency of the lysosome-associated membrane protein-2. We report a case of hypertrophic obstructive cardiomyopathy secondary to a novel mutation in the lysosome-associated membrane protein-2 gene in a 10-year-old male adolescent. We performed a modified extended Morrow procedure to minimise the risk of death and improve the patient's quality of life. The patient did not have exertional dyspnoea, and auscultation did not reveal a cardiac murmur at 1-year follow-up.

Profiling salivary miRNA expression levels in Fanconi anemia patients - a pilot study.

The overarching goal of this study is to predict the risk of developing oral squamous cell carcinoma (OSCC) in Fanconi anemia (FA) patients. We have compared the microRNA (miRNA, miR) expression levels in saliva samples from FA patients (n = 50) who are at a low-moderate and/or high risk of developing OSCC to saliva samples from healthy controls (n = 16). The miRNA expression levels in saliva samples were quantified using qPCR. We observed that miR-744, miR-150-5P, and miR-146B-5P had the best discriminatory capacity between FA patients and controls, with an area under the curve (AUC) of 94.0%, 92.9% and 85.3%, respectively. Our data suggest that miR-1, miR-146B-5P, miR-150-5P, miR-155-5P, and miR-744 could be used as panel to predict the risk of developing OSCC in FA patients, with a 89.3% sensitivity and a 68.2% specificity (AUC = 81.5%). Our preliminary data support the notion that the expression levels of salivary miRNAs have the potential to predict the risk of developing OSCC in FA patients and in the future may reduce deaths associated with OSCC.

In vivo evaluation of T-Scan in quantifying occlusal contact.

BACKGROUND: The T-scan system has been used previously to analyse occlusion, but the quantitative analysis of occlusal contact by T-Scan system has yet to be reported. OBJECTIVES: To evaluate the reliability and validity of T-Scan system for quantitatively measuring occlusal contact area and occlusal contact number. METHODS: Twenty-two individuals with normal occlusion, 11 men and 11 women, were recruited for the study. Two occlusal analysis methods, including silicone transmission analysis method (STA) and T-Scan occlusion analysis method (TSO), were used to make quantitative analysis to measure occlusal contact area (OCA) and occlusal contact number (OCN). A test-retest check was performed with an interval of 2 weeks. The values of intraclass correlation coefficients (ICC) between test-retest of each method were calculated for reliability evaluation. Pearson correlations analysis, paired t-tests, regression analysis and Bland-Altman analysis were performed for validity evaluation. RESULTS: The ICC values of STA were greater than those of TSO for OCA while for OCN, ICC values of TSO were greater than STA. The higher OCA and OCN values were found in TSO compared with STA. Pearson's correlation coefficient indicated strong relations between TSO and STA (0.730-0.812) for OCA, while good relations between then (0.569-0.583) for OCN. Paired t-test showed a significant difference between the OCA and OCN values between TSO and STA. Bland-Altman analysis showed good agreement between OCA and OCN values of TSO and STA both in men and women. Regression analysis identified a linear correlation between OCA values obtained from these two methods. CONCLUSIONS: T-Scan method showed strong reliability for measuring OCA and OCN quantitatively. Strong correlations were found between OCA values from TSO and STA method, but the validity of TSO for measuring OCN needs to be promoted. CLINICAL SIGNIFICANCE: T-Scan system demonstrates good potential in quantitative analysis of occlusion, which will expand its clinical application.

A Portable Electrochemical Dopamine Detector Using a Fish Scale-Derived Graphitized Carbon-Modified Screen-Printed Carbon Electrode.

In this paper, a highly conductive alkali-activated graphitized carbon (a-GC) was prepared using tilapia fish scales as precursors through enzymolysis, activation and pyrolytic carbonization methods. The prepared a-GC was modified on the surface of a screen-printed carbon electrode to construct a flexible portable electrochemical sensing platform, which was applied to the differential pulse voltametric detection of dopamine (DA) using a U-disk electrochemical workstation combined with a smart phone and Bluetooth. The prepared a-GC possesses good electrical conductivity, a large specific surface area and abundant active sites, which are beneficial for the electrooxidation of DA molecules and result in excellent sensitivity and high selectivity for DA analysis. Under the optimal conditions, the oxidation peak current of DA increased gradually, with its concentrations in the range from 1.0 µmol/L to 1000.0 µmol/L, with the detection limit as low as 0.25 µmol/L (3S/N). The proposed sensor was further applied to the determination of DA in human sweat samples, with satisfactory results, which provided an opportunity for developing noninvasive early diagnosis and nursing equipment.

Ultrasound-Triggered In Situ Photon Emission for Noninvasive Optogenetics.

Optogenetics has revolutionized neuroscience understanding by allowing spatiotemporal control over cell-type specific neurons in neural circuits. However, the sluggish development of noninvasive photon delivery in the brain has limited the clinical application of optogenetics. Focused ultrasound (FUS)-derived mechanoluminescence has emerged as a promising tool for in situ photon emission, but there is not yet a biocompatible liquid-phase mechanoluminescence system for spatiotemporal optogenetics. To achieve noninvasive optogenetics with a high temporal resolution and desirable biocompatibility, we have developed liposome (Lipo@IR780/L012) nanoparticles for FUS-triggered mechanoluminescence in brain photon delivery. Synchronized and stable blue light emission was generated in solution under FUS irradiation due to the cascade reactions in liposomes. In vitro tests revealed that Lipo@IR780/L012 could be triggered by FUS for light emission at different stimulation frequencies, resulting in activation of opsin-expressing spiking HEK cells under the FUS irradiation. In vivo optogenetic stimulation further demonstrated that motor cortex neurons could be noninvasively and reversibly activated under the repetitive FUS irradiation after intravenous injection of lipid nanoparticles to achieve limb movements.

Quinine-Fabricated Surface-Enhanced Raman Spectroscopy Chiral Sensing Platform Enables Simultaneous Enantioselective Discrimination and Identification of Aliphatic Amino Acids.

Due to low optical activity and structural simplicity, synchronous chiral discrimination and identification of aliphatic amino acids (AAs) are still challenging yet demanding. Herein, we developed a novel surface-enhanced Raman spectroscopy (SERS)-based chiral discrimination-sensing platform for aliphatic AAs, in which l- and d-enantiomers are able to discriminately bind with quinine to generate distinct differences in the SERS vibrational modes. Meanwhile, the plasmonic sub-nanometer gaps supported by the rigid quinine enable the maximization of SERS signal enhancement to reveal feeble signals, allowing for simultaneously acquiring the structural specificity and enantioselectivity of aliphatic amino acid enantiomers in a single SERS spectrum. Different kinds of chiral aliphatic AAs were successfully identified by using this sensing platform, demonstrating its potential and practicality in recognizing chiral aliphatic molecules.

Corner cube retroreflector with a spiral phase structure generating annular far-field diffraction pattern.

The importance of the far-field diffraction pattern (FFDP) for retroreflectors lies in its ability to describe the performance of retroreflectors commonly used for positioning or measurement in optical systems. We proposed a new, to the best of our knowledge, retroreflector structure integrating a metal-coated corner cube retroreflector (CCR) and a spiral phase plate (SPP) to produce an annular FFDP. We analyzed the propagation characteristics of the light beam traveling through this combination and described the mechanism underlying the generation of an annular FFDP. We developed a simulation program to calculate the far-field pattern for various critical parameters of the spiral phase CCR and experimentally demonstrated its annular FFDP.

Model containing sarcopenia and visceral adiposity can better predict the prognosis of hepatocellular carcinoma: a multicenter study.

AIM: This study aimed to explore whether the addition of sarcopenia and visceral adiposity could improve the accuracy of model predicting progression-free survival (PFS) in hepatocellular carcinoma (HCC). METHODS: In total, 394 patients with HCC from five hospitals were divided into the training and external validation datasets. Patients were initially treated by liver resection or transarterial chemoembolization. We evaluated adipose and skeletal muscle using preoperative computed tomography imaging and then constructed three predictive models, including metabolic (ModelMA), clinical-imaging (ModelCI), and combined (ModelMA-CI) models. Their discrimination, calibration, and decision curves were compared, to identify the best model. Nomogram and subgroup analysis was performed for the best model. RESULTS: ModelMA-CI containing sarcopenia and visceral adiposity had good discrimination and calibrations (integrate area under the curve for PFS was 0.708 in the training dataset and 0.706 in the validation dataset). ModelMA-CI had better accuracy than ModelCI and ModelMA. The performance of ModelMA-CI was not affected by treatments or disease stages. The high-risk subgroup (scored > 198) had a significantly shorter PFS (p < 0.001) and poorer OS (p < 0.001). CONCLUSIONS: The addition of sarcopenia and visceral adiposity improved accuracy in predicting PFS in HCC, which may provide additional insights in prognosis for HCC in subsequent studies.