Metabolic and epigenetic dysfunctions underlie the arrest of in vitro fertilized human embryos in a senescent-like state.

Around 60% of in vitro fertilized (IVF) human embryos irreversibly arrest before compaction between the 3- to 8-cell stage, posing a significant clinical problem. The mechanisms behind this arrest are unclear. Here, we show that the arrested embryos enter a senescent-like state, marked by cell cycle arrest, the down-regulation of ribosomes and histones and down-regulation of MYC and p53 activity. The arrested embryos can be divided into 3 types. Type I embryos fail to complete the maternal-zygotic transition, and Type II/III embryos have low levels of glycolysis and either high (Type II) or low (Type III) levels of oxidative phosphorylation. Treatment with the SIRT agonist resveratrol or nicotinamide riboside (NR) can partially rescue the arrested phenotype, which is accompanied by changes in metabolic activity. Overall, our data suggests metabolic and epigenetic dysfunctions underlie the arrest of human embryos.

Novel quantitative immunohistochemistry method using histone H3, family 3B as the internal reference standard for measuring human epidermal growth factor receptor 2 expression in breast cancer.

BACKGROUND: Immunohistochemistry (IHC) is an essential technique in surgical and clinical pathology for detecting diagnostic, prognostic, and predictive biomarkers for personalized cancer therapy. However, the lack of standardization and reference controls results in poor reproducibility, and a reliable tool for IHC quantification is urgently required. The objective of this study was to describe a novel approach in which H3F3B (histone H3, family 3B) can be used as an internal reference standard to quantify protein expression levels using IHC. METHODS: The authors enrolled 89 patients who had human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). They used a novel IHC-based assay to measure protein expression using H3F3B as the internal reference standard. H3F3B was uniformly expressed at the protein level in all tumor regions in cancer tissues. HER2 expression levels were measured with the H-score using HALO software. RESULTS: Kaplan-Meier analysis indicated that, among patients who had HER2-positive BC in The Cancer Genome Atlas data set and the authors' data set, the subgroup with low HER2 expression had a significantly better prognosis than the subgroup with high HER2 expression. Furthermore, the authors observed that HER2 expression levels were precisely evaluated using the proposed method, which can classify patients who are at higher risk of HER2-positive BC to receive trastuzumab-based adjuvant therapy. Dual-color IHC with H3F3B is an excellent tool for internal and external quality control of HER2 expression assays. CONCLUSIONS: The proposed IHC-based quantification method accurately assesses HER2 expression levels and provides insights for predicting clinical prognosis in patients with HER2-positive BC who receive trastuzumab-based adjuvant therapy.

In Situ Fabrication of Solvent-Free Solid Polymer Electrolytes for Wide-Temperature All-Solid-State Lithium Metal Batteries.

All-solid-state lithium metal batteries (ASSLMBs) have been regarded as promising candidates to settle the safety issues of liquid electrolytes for rechargeable lithium batteries. However, the currently reported gel polymer electrolytes still have flammable liquid solvents, thus leading to the potential safety hazard. Here, solvent-free deep eutectic solid polymer electrolytes (SPEs) are designed and fabricated via an in situ polymerization, which are composed of a poly(vinylidene fluoride-hexafluoropropylene) (PVDF-HFP) electrospun membrane, succinonitrile (SN), poly(ethylene glycol) diacrylate (PEGDA200, Mn = 200 g mol-1), lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), and lithium difluoro(oxalato)borate (LiDFOB). The deep eutectic solvent (DES) with SN/LiTFSI provides a superior room-temperature ionic conductivity, while the PEGDA200 precursor acts as cross-linking network to form SPEs under thermal initiation for free radical polymerization, and LiDFOB can form a stable solid electrolyte interface (SEI) layer. The PVDF-HFP electrospun membrane with a three-dimensional nanofibrous network structure for SN/PEGDA200/LiTFSI/LiDFOB SPEs exhibits a wide electrochemical stability window, high lithium-ion transference number, and good compatibility with the lithium metal anode. Furthermore, the obtained SPEs assembled with Li//LiMn0.6Fe0.4PO4, Li//LiFePO4, and Li//LiNi0.8Co0.1Mn0.1O2 asymmetric cells show excellent cycling performance and rate capability at a wide temperature. This strategy provides a promising path in designing high-energy-density ASSLMBs for practical application.

Changes in retinal and choroidal thickness and vascular density in patients with systemic lupus erythematosus: Assessed by optical coherence tomography angiography.

OBJECTIVE: The aim was to investigate the changes in retinal and choroidal thickness and vascular density in patients with systemic lupus erythematosus (SLE) using optical coherence tomography angiography (OCTA). METHODS: Twenty-nine patients with SLE (29 eyes) and 25 control subjects (25 eyes) were enrolled. SLE activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Retinal thickness (RT), inner retinal thickness (IRT), outer retinal thickness (ORT), choroidal thickness (ChT), retinal superficial vascular density (SVD), retinal deep vascular density (DVD), choriocapillary vascular density (CCVD), foveal avascular zone (FAZ), superficial FAZ (sFAZ), and deep FAZ (dFAZ) were measured using OCTA. The retinal and choroidal thickness and vascular density between the control group and SLE group were compared. The relationships between SLEDAI scores and the retinal and choroidal thickness and vascular density in SLE group were analyzed. RESULTS: The SVD was significantly increased, and the DVD and CCVD were significantly decreased in the SLE group compared to the control group (p < .05). The results of receiver operating characteristic (ROC) showed that the area under the curve (AUC) values of SVD, DVD, and CCVD were 0.873, 0.729, and 0.727, indicating a high accuracy in discriminating patients with SLE from controls. Correlation analysis showed that the SLEDAI scores were positively correlated with dFAZ (r = 0.589, p = .001) and FAZ (r = 0.451, p = .018), and negatively correlated with DVD (r = -0.491, p = .009) and CCVD (r = -0.521, p = .005). CONCLUSIONS: DVD and CCVD were decreased in the SLE and might be related to the disease activity. SVD, DVD, and CCVD may hold promise in the discovery of biomarkers for diagnosing SLE.

Video-Based Identification and Prediction Techniques for Stable Vessel Trajectories in Bridge Areas.

In recent years, the global upswing in vessel-bridge collisions underscores the vital need for robust vessel track identification in accident prevention. Contemporary vessel trajectory identification strategies often integrate target detection with trajectory tracking algorithms, employing models like YOLO integrated with DeepSORT or Bytetrack algorithms. However, the accuracy of these methods relies on target detection outcomes and the imprecise boundary acquisition method results in erroneous vessel trajectory identification and tracking, leading to both false positives and missed detections. This paper introduces a novel vessel trajectory identification framework. The Co-tracker, a long-term sequence multi-feature-point tracking method, accurately tracks vessel trajectories by statistically calculating the translation and heading angle transformation of feature point clusters, mitigating the impact of inaccurate vessel target detection. Subsequently, vessel trajectories are predicted using a combination of Long Short-Term Memory (LSTM) and a Graph Attention Neural Network (GAT) to facilitate anomaly vessel trajectory warnings, ensuring precise predictions for vessel groups. Compared to prevalent algorithms like YOLO integrated with DeepSORT, our proposed method exhibits superior accuracy and captures crucial heading angle features. Importantly, it effectively mitigates the common issues of false positives and false negatives in detection and tracking tasks. Applied in the Three Rivers area of Ningbo, this research provides real-time vessel group trajectories and trajectory predictions. When the predicted trajectory suggests potential entry into a restricted zone, the system issues timely audiovisual warnings, enhancing real-time alert functionality. This framework markedly improves vessel traffic management efficiency, diminishes collision risks, and ensures secure navigation in multi-target and wide-area vessel scenarios.

Stiffness-Based Evaluation of Hinge Joints in Prefabricated Assembled Multi-Girder Bridges under Operational Conditions.

Presently, the prevailing approaches to assessing hinge joint damage predominantly rely on predefined damage indicators or updating finite element models (FEMs). However, these methods possess certain limitations. The damage indicator method requires high-quality monitoring data and demonstrates variable sensitivities of distinct indicators to damage. On the other hand, the FEM approach mandates a convoluted FEM update procedure. Hinge joint damage represents a major kind of defect in prefabricated assembled multi-girder bridges (AMGBs). Therefore, effective damage detection methods are imperative to identify the damage state of hinge joints. To this end, a stiffness-based method for the performance evaluation of hinge joints of AMGBs is proposed in this paper. The proposed method estimates hinge joint stiffness by solving the characteristic equations of the multi-beam system. In addition, this study introduces a method for determining baseline joint stiffness using design data and FEM. Subsequently, a comprehensive evaluation framework for hinge joints is formulated, coupling a finite element model with the baseline stiffness, thereby introducing a damage indicator rooted in stiffness ratios. To verify the effectiveness of the proposed method, strain and displacement correlations are analyzed using actual bridge monitoring data, and articulation joint stiffness is identified. The results underscore the capability of the proposed method to accurately pinpoint the location and extent of hinge joint damage.

Reduced plasma coagulation factor XIII in patients with acute leukemia in remission during consolidation chemotherapy cycles.

Acute leukemia (AL) is a malignancy from hematologic stem cells (HSC). Consolidation with intensive chemotherapy is required after induced remission and repeatedly causes treatment-related bleeding that is usually attributed to chemotherapy-induced thrombocytopenia (CIT). However, our previous study demonstrated that severe deficiency of plasma coagulation factor XIII (pFXIII) also participated in the bleeding of CIT in AL. However, the relationship between pFXIII deficiency and consolidation chemotherapy was unknown. Here, we observed the concentration of pFXIII in patients with AL before and after consolidation chemotherapy and reevaluated the correlation to bleeding in myelosuppression. Thus, we found that the concentration of pFXIII before chemotherapy in all patients was markedly lower than in the control data and was further decreased by chemotherapy, related to bleeding in myelosuppression. These findings indicated that chemotherapy-induced pFXIII deficiency should be of concern and explored in depth.

The role of self-esteem and emotion regulation in the associations between childhood trauma and mental health in adulthood: a moderated mediation model.

BACKGROUND: High levels of childhood trauma (CT) have been observed in adults with mental health problems. Herein, we investigated whether self-esteem (SE) and emotion regulation strategies (cognitive reappraisal (CR) and expressive suppression (ES)) affect the association between CT and mental health in adulthood, including depression and anxiety symptoms. METHODS: We performed a cross-sectional study of 6057 individuals (39.99% women, median age = 34 y), recruited across China via the internet, who completed the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Childhood Trauma Questionnaire (CTQ), Self-esteem Scale (SES), and Emotion Regulation Questionnaire (ERQ). Multivariate linear regression analysis and bias-corrected percentile bootstrap methodologies were used to assess the mediating effect of SE, and hierarchical regression analysis and subgroup approach were performed to examine the moderating effects of emotion regulation strategies. RESULTS: After controlling for age and sex, we found that (1) SE mediated the associations between CT and depression symptoms in adulthood (indirect effect = 0.05, 95% confidence interval [CI]: 0.04-0.05, 36.2% mediated), and CT and anxiety symptoms in adulthood (indirect effect = 0.03, 95% CI: 0.03-0.04, 32.0% mediated); (2) CR moderated the association between CT and SE; and (3) ES moderated the association between of CT and mental health in adulthood via SE, and such that both the CT-SE and SE-mental health pathways were stronger when ES is high rather than low, resulting the indirect effect was stronger for high ES than for low ES. CONCLUSIONS: These findings suggested that SE plays a partially mediating role in the association between CT and mental health in adulthood. Furthermore, ES aggravated the negative effect of CT on mental health in adulthood via SE. Interventions such as emotional expression training may help reduce the detrimental effects of CT on mental health. TRIAL REGISTRATION: The study was registered on http://www.chictr.org.cn/index.aspx and the registration number was ChiCTR2200059155.

Involvement of Arabidopsis Acyl Carrier Protein 1 in PAMP-Triggered Immunity.

Plant fatty acids (FAs) and lipids are essential in storing energy and act as structural components for cell membranes and signaling molecules for plant growth and stress responses. Acyl carrier proteins (ACPs) are small acidic proteins that covalently bind the fatty acyl intermediates during the elongation of FAs. The Arabidopsis thaliana ACP family has eight members. Through reverse genetic, molecular, and biochemical approaches, we have discovered that ACP1 localizes to the chloroplast and limits the magnitude of pattern-triggered immunity (PTI) against the bacterial pathogen Pseudomonas syringae pv. tomato. Mutant acp1 plants have reduced levels of linolenic acid (18:3), which is the primary precursor for biosynthesis of the phytohormone jasmonic acid (JA), and a corresponding decrease in the abundance of JA. Consistent with the known antagonistic relationship between JA and salicylic acid (SA), acp1 mutant plants also accumulate a higher level of SA and display corresponding shifts in JA- and SA-regulated transcriptional outputs. Moreover, methyl JA and linolenic acid treatments cause an apparently enhanced decrease of resistance against P. syringae pv. tomato in acp1 mutants than that in WT plants. The ability of ACP1 to prevent this hormone imbalance likely underlies its negative impact on PTI in plant defense. Thus, ACP1 links FA metabolism to stress hormone homeostasis to be negatively involved in PTI in Arabidopsis plant defense. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

First Report of Trichoderma crassum Causing Leaf Spot on Tomato (Solanum lycopersicum cv. M82) in Ohio.

Trichoderma is a genus of wood-decaying fungi generally found in soil (Druzhinina and Kubicek 2005). Trichoderma crassum was confirmed to be a sister species to T. virens according to the molecular sequencing results (Chaverri et al. 2003). A foliar disease with ~70% incidence on Solanum lycopersicum was observed in a greenhouse at The Ohio State University (40°0'8'' north latitude, 83°1'36'' west longitude), Columbus, United States, in December 2021. On average up to 60% of the leaves per two-month-old tomato plant were infected. Initially, the dark-grey color and irregular spots appeared at the leaf tips. As the disease progressed, the yellow necrotic lesions were observed surrounding the preformed disease spots. Finally, the infected leaves appeared curled and wilted as a whole. The leaf fragments from three tomato plants 40 inches apart were cut from the diseased lesions and surface sterilized with 75% ethanol (30 seconds) and 1% NaOCl (60 seconds), subsequently rinsed with sterilized deionized water three times. Nine pieces of the sterilized leaf tissues were then placed on the PDA plates at 28℃ in the dark and incubated in one incubator for 4 days. The pure cultures of five isolates were acquired and examined with a light microscope. The fungus from all the isolates changed from white to dark green with the radial pattern and profuse sporulation on the PDA. The produced round conidia were observed under a light microscope (Fig S1). The DNA was extracted from two representative isolates which showed the same morphology. The internal transcribed spacer (ITS) region and a conserved fungal rRNA region were amplified using the primers ITS1/ITS4 (5'-TCCGTAGGTGAACCTGCGG-3' and 5'-TCCTCCGCTTATTGATATGC-3') (White et al. 1990) and SR6f/SR7r (5'-TGTTACGACTTTTACTT-3' and 5'-AGTTAAAAAGCTCGTAGTTG-3') (Hirose et al. 2012), respectively. The PCR products were further sequenced by Sanger sequencing (Table S1). Based on the BLAST results through NCBI website, the ITS sequences of the two isolates were 99% (566/572) and 98% (558/572) identical to Trichoderma crassum DAOM 164916 (EU280067). Their SR sequences both showed 99% (290/293; 289/293) identity to the same strain. The phylogenetic tree was also created with the sequences of ITS region by MEGA software (version 11) (Fig S2). Therefore, the fungus was identified as Trichoderma crassum based on its morphological characteristics (green conidia), Sanger sequencing results, and phylogenetic tree. To complete Koch's postulates, the 5-mm-diameter fungal agar discs of 7-day-old pure cultures were used for the inoculation on 18 healthy leaves of six tomato cv. M82 plants with two-month-old. The sterile pure PDA discs of the equal size were used for the mock inoculation as a comparison. Fungal plug method was chosen in this study because it had been widely applied to characterization of the fungal pathogens causing leaf spot disease (Pornsuriya et al. 2020; Yang et al. 2021). Five days later, the same symptom as those that occurred on the previously naturally infected tomato plants were observed on all the inoculated leaves (Fig S3A). However, there were no symptoms on the leaves with the mock inoculation. The fungus re-isolated from the symptomatic leaves showed the consistent morphology (dark-green color with radial sporulation) with the original isolates (Fig S3B). Thus, Trichoderma crassum was verified as the causal agent of the foliar disease on Solanum lycopersicum cv. M82 in our greenhouse. To our knowledge, it is the first report of Trichoderma crassum leading to the leaf spot and wilt on tomato in Ohio. The identification of the causal agent lays the groundwork for the development of necessary disease management techniques. We acknowledge the funding support from CFAES Internal Grants Program 2021009.

Arabidopsis Plasma Membrane ATPase AHA5 Is Negatively Involved in PAMP-Triggered Immunity.

Plants evolve a prompt and robust immune system to defend themselves against pathogen infections. Pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) is the first battle layer activated upon the PAMP's perception, which leads to multiple defense responses. The plasma membrane (PM) H+-ATPases are the primary ion pumps to create and maintain the cellular membrane potential that is critical for various essential biological processes, including plant growth, development, and defense. This study discovered that the PM H+-ATPase AHA5 is negatively involved in Arabidopsis PTI against the virulent pathogen Pseudomonas syringae pvr. tomato (Pto) DC3000 infection. The aha5 mutant plants caused the reduced stomata opening upon the Pto infection, which was associated with the salicylic acid (SA) pathway. In addition, the aha5 mutant plants caused the increased levels of callose deposition, defense-related gene expression, and SA accumulation. Our results also indicate that the PM H+-ATPase activity of AHA5 probably mediates the coupling of H2O2 generation and the apoplast alkalization in PTI responses. Moreover, AHA5 was found to interact with a vital defense regulator, RPM1-interacting protein 4 (RIN4), in vitro and in vivo, which might also be critical for its function in PTI. In summary, our studies show that AHA5 functions as a novel and critical component that is negatively involved in PTI by coordinating different defense responses during the Arabidopsis-Pto DC3000 interaction.

Genome Sequence Resource of Bacillus sp. RRD69, a Beneficial Bacterial Endophyte Isolated from Switchgrass Plants.

We report here the genome sequence of Bacillus sp. RRD69, a plant-growth-promoting bacterial endophyte isolated from switchgrass plants grown on a reclaimed coal-mining site in Kentucky. RRD69 is predicted to contain 3,758 protein-coding genes, with a genome size of 3.715 Mbp and a 41.41% GC content.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

CDC26 is a key factor in human oocyte aging.

STUDY QUESTION: Is CDC26 a key factor in human oocyte aging? SUMMARY ANSWER: The lack of CDC26 disrupts the oocytes maturation process, leading to oocyte aging, but these defects could be partially rescued by overexpression of the CDC26 protein. WHAT IS KNOWN ALREADY: Age-related oocyte aging is the main cause of female fertility decline. In mammalian oocytes, aberrant meiosis can cause chromosomal abnormalities that might lead to infertility and developmental disorders. CDC26 participates in the meiosis process. STUDY DESIGN, SIZE, DURATION: Differential gene expression in young and old women oocytes were screened by single-cell RNA-seq technology, and the functions of differentially genes were verified on mouse oocytes. Finally, transfection technology was used to evaluate the effect of a differentially expressed gene in rescuing human oocyte from aging. PARTICIPANTS/MATERIALS, SETTING, METHODS: Discarded human oocytes were collected for single-cell RNA-seq, q-PCR and immunocytochemical analyses to screen for and identify differential gene expression. Female KM mice oocytes were collected for IVM of oocytes, q-PCR and immunocytochemical analyses to delineate the relationships between oocyte aging and differential gene expression. Additionally, recombinant lentiviral vectors encoding CDC26 were transfected into the germinal vesicle oocytes of older women, to investigate the effects of the CDC26 gene expression on oocyte development. MAIN RESULTS AND THE ROLE OF CHANCE: Many genes were found to be differentially expressed in the oocytes of young versus old patients via RNA-seq technology. CDC26 mRNA and protein levels in aged oocytes were severely decreased, when compared with the levels observed in young oocytes. Moreover, aged oocytes lacking CDC26 were more prone to aneuploidy. These defects in aged oocytes could be partially rescued by overexpression of the CDC26 protein. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Our study delineated key steps in the oocyte aging process by identifying the key role of CDC26 in the progression of oocyte maturation. Future studies are required to address whether other signaling pathways play a role in regulating oocyte maturation via CDC26 and which genes are the direct molecular targets of CDC26. WIDER IMPLICATIONS OF THE FINDINGS: Our results using in vitro systems for both mouse and human oocyte maturation provide a proof of principle that CDC26 may represent a novel therapeutic approach against maternal aging-related spindle and chromosomal abnormalities. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the National Natural Science Foundation of China (81571442 and 81170571), the outstanding Talent Project of Shanghai Municipal Commission of Health (XBR2011067) and Clinical Research and Cultivation Project in Shanghai Municipal Hospitals (SHDC12019X32). The authors declare no conflict of interest.

Is there a relationship between psoriasis and hepatitis C? A meta-analysis and bioinformatics investigation.

BACKGROUND: The relationship between psoriasis and hepatitis C was previously controversial, so our purpose is to investigate this connection. METHODS: We conducted a systematic review of the case-control, cross-sectional and cohort studies examining the association between psoriasis and hepatitis C in PubMed, EMBASE and Cochrane library databases and investigated the overlapping genes between psoriasis targets and hepatitis C targets using bioinformatics analysis. Based on overlapping genes and hub nodes, we also constructed the protein-protein interaction (PPI) network and module respectively, followed by the pathway enrichment analysis. RESULTS: We included 11 publications that reported a total of 11 studies (8 cross-sectional and 3 case-control). The case-control and cross-sectional studies included 25,047 psoriasis patients and 4,091,631 controls in total. Psoriasis was associated with a significant increase of prevalent hepatitis C (OR 1.72; 95% confidence interval [CI] (1.17-2.52)). A total of 389 significant genes were common to both hepatitis C and psoriasis, which mainly involved IL6, TNF, IL10, ALB, STAT3 and CXCL8. The module and pathway enrichment analyses showed that the common genes had the potential to influence varieties of biological pathways, including the inflammatory response, cytokine activity, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, which play an important role in the pathogenesis of hepatitis C and psoriasis. CONCLUSION: Patients with psoriasis display increased prevalence of hepatitis C and the basic related mechanisms between hepatitis C and psoriasis had been preliminarily clarified.

Over-expression of RALYL suppresses the progression of ovarian clear cell carcinoma through inhibiting MAPK and CDH1 signaling pathways.

Background: The molecular mechanism in the progression of ovarian clear cell carcinoma (OCCC) remains unclear. Objective: This study aimed to investigate the potential function of RAYLY in OCCC. Methods: To validate RAYLY expression, immunohistochemistry, quantitative real-time PCR and western blotting were performed in OCCC tissues and the cell lines of OCCC and epithelial ovarian carcinoma (EOC). Subsequently, the biological effects of RALYL were evaluated through colony formation, and cell proliferation, migration and invasion assays. Finally, RNA-sequencing and gene set enrichment analysis (GSEA) were conducted to explore potential mechanism of RALYL in OCCC. Results: In our study, RALYL was significantly down-regulated in a majority of OCCC tissues compared to adjacent non-tumorous tissues, and OCCC cells had a lower expression level of RALYL than that of EOC cells. OCCC patients with high RALYL expression had a better pathological stage and prognosis. In vitro, over-expression of RALYL inhibited cell proliferation, migration and invasion in OCCC. GSEA analysis and western blot indicated an enrichment of MAPK and CDH1 signaling pathways in OCCC cells without RALYL over-expression. Conclusions: RALYL played an important role in the progression of OCCC, and might serve as a potential prognostic biomarker and novel therapeutic target for OCCC.

Sulfur-centered hemi-bond radicals as active intermediates in S-DNA phosphorothioate oxidation.

Phosphorothioate (PS) modifications naturally appear in bacteria and archaea genome and are widely used as antisense strategy in gene therapy. But the chemical effects of PS introduction as a redox active site into DNA (S-DNA) is still poorly understood. Herein, we perform time-resolved spectroscopy to examine the underlying mechanisms and dynamics of the PS oxidation by potent radicals in free model, in dinucleotide, and in S-oligomer. The crucial sulphur-centered hemi-bonded intermediates -P-S∴S-P- were observed and found to play critical roles leading to the stable adducts of -P-S-S-P-, which are backbone DNA lesion products. Moreover, the oxidation of the PS moiety in dinucleotides d[GPSG], d[APSA], d[GPSA], d[APSG] and in S-oligomers was monitored in real-time, showing that PS oxidation can compete with adenine but not with guanine. Significantly, hole transfer process from A+• to PS and concomitant -P-S∴S-P- formation was observed, demonstrating the base-to-backbone hole transfer unique to S-DNA, which is different from the normally adopted backbone-to-base hole transfer in native DNA. These findings reveal the distinct backbone lesion pathway brought by the PS modification and also imply an alternative -P-S∴S-P-/-P-S-S-P- pathway accounting for the interesting protective role of PS as an oxidation sacrifice in bacterial genome.

Evaluation of a Small-Molecule Compound, N-Acetylcysteine, for the Management of Bacterial Spot of Tomato Caused by Copper-Resistant Xanthomonas perforans.

Bacterial spot caused by Xanthomonas spp. is one of the major diseases in tomato. Xanthomonas perforans is the main pathogen of bacterial spot on tomato in Florida. Currently, application of copper fungicides is the primary measure used to manage this disease. However, the development of copper resistance in X. perforans and accumulation of copper in the environment are major concerns for excessive use of copper-based products in agriculture. Due to its antibacterial properties and low environmental impact, N-acetylcysteine (NAC), a small molecule commonly used in medicine for human bacterial diseases, has been studied in agriculture for the control of plant bacterial pathogens, including X. citri and Xylella fastidiosa. This study evaluated the effect of NAC alone and in combination with copper on a copper-resistant X. perforans strain in vitro and its ability to control bacterial spot of tomato under greenhouse and field conditions. In vitro, the minimum inhibitory concentration of NAC against the X. perforans strain was 2,048 mg liter-1. NAC increased sensitivity of the copper-resistant X. perforans to copper in vitro when application of NAC was followed by copper application after 6 h. In greenhouse assays, NAC applied alone or in combination with copper significantly (P < 0.05) reduced the disease severity of bacterial spot on tomato compared with the untreated control. NAC at 100 mg liter-1 + copper at 300 mg liter-1 consistently exhibited synergistic effects against bacterial spot. In the field trials, NAC at 1,000 mg liter-1 + copper at 150 mg liter-1 significantly reduced disease severity compared with the untreated control. Results from this study demonstrated that NAC significantly reduced the disease severity of bacterial spot of tomato and enhanced the efficacy of copper against copper-resistant X. perforans, indicating that NAC could be applied for the effective management of bacterial spot of tomato.

All-Weather Thermal Simulation Methods for Concrete Maglev Bridge Based on Structural and Meteorological Monitoring Data.

Thermal energy exchange induces non-uniform temperature distribution on the concrete bridge structures, leading to variation of static and dynamic properties of structural systems. The finite element method can facilitate thermal simulation and predict the structural temperature distribution based on heat flow theories. Previous studies mainly focused on the daytime with sunny weather, and the effects of solar shadow distribution were not fully considered or even ignored. In this paper, a systematic all-weather thermal simulation method was proposed to investigate the temperature distributions of concrete maglev bridges. The solar shadow distribution on the bridge surface could be accurately simulated to determine the solar radiation-imposed range. A meteorological station and some thermocouples were installed on a real concrete maglev bridge to obtain the real-time structural temperatures and environmental conditions. Its temperature distribution is also simulated using the proposed method within the 27 monitoring days in Summer. Results show that the simulated structural temperature matches well with the measured results under various weather conditions, except that of the east structural surface. Moreover, the simulation method acquired a higher accuracy under overcast or rainy weather due to weaker solar radiation effects. Both the numerical results and experimental records illustrated that direct solar radiation dominates the thermal energy exchange under sunny or cloudy conditions. The proposed methodology for temperature field simulation is oriented by all-weather prediction of structural temperature, which is reliable for concrete bridge structures with the help of accurate measurement of real-time solar radiation.

Transmission of dynamic supercoiling in linear and multi-way branched DNAs and its regulation revealed by a fluorescent G-quadruplex torsion sensor.

DNA supercoiling is an important regulator of gene activity. The transmission of transcription-generated supercoiling wave along a DNA helix provides a way for a gene being transcribed to communicate with and regulate its neighboring genes. Currently, the dynamic behavior of supercoiling transmission remains unclear owing to the lack of a suitable tool for detecting the dynamics of supercoiling transmission. In this work, we established a torsion sensor that quantitatively monitors supercoiling transmission in real time in DNA. Using this sensor, we studied the transmission of transcriptionally generated negative supercoiling in linear and multi-way DNA duplexes. We found that transcription-generated dynamic supercoiling not only transmits along linear DNA duplex but also equally diverges at and proceeds through multi-way DNA junctions. We also show that such a process is regulated by DNA-protein interactions and non-canonical DNA structures in the path of supercoiling transmission. These results imply a transcription-coupled mechanism of dynamic supercoiling-mediated intra- and inter-chromosomal signal transduction pathway and their regulation in DNA.

Visual crowding in driving.

Visual crowding-the deleterious influence of nearby objects on object recognition-is considered to be a major bottleneck for object recognition in cluttered environments. Although crowding has been studied for decades with static and artificial stimuli, it is still unclear how crowding operates when viewing natural dynamic scenes in real-life situations. For example, driving is a frequent and potentially fatal real-life situation where crowding may play a critical role. In order to investigate the role of crowding in this kind of situation, we presented observers with naturalistic driving videos and recorded their eye movements while they performed a simulated driving task. We found that the saccade localization on pedestrians was impacted by visual clutter, in a manner consistent with the diagnostic criteria of crowding (Bouma's rule of thumb, flanker similarity tuning, and the radial-tangential anisotropy). In order to further confirm that altered saccadic localization is a behavioral consequence of crowding, we also showed that crowding occurs in the recognition of cluttered pedestrians in a more conventional crowding paradigm. We asked participants to discriminate the gender of pedestrians in static video frames and found that the altered saccadic localization correlated with the degree of crowding of the saccade targets. Taken together, our results provide strong evidence that crowding impacts both recognition and goal-directed actions in natural driving situations.