Extending laser wavelengths to 1630†nm in centimeter-scale Er-phosphate fiber.

The spectral bandwidth of Er-doped fibers limits their lasing wavelength at longer wave band. Here, to the best of our knowledge, we report a broad emission band (1420‒1680 nm) of Er3+ and demonstrate for the first time an Er-phosphate fiber, which supports laser oscillation at the extended wavelengths of 1627 nm and 1630 nm, with the output powers and slope efficiencies of 44 mW/12.5% and 16.5 mW/5.6%, respectively, pumped at 1480 nm. To the best of our knowledge, these are the highest output powers and slope efficiencies at 1627 nm and 1630 nm from an Er3+-doped all-fiber configuration.

Comparison Of Observation-Based And Model-Based Identification Of Alert Concentrations From Concentration-Expression Data.

MOTIVATION: An important goal of concentration-response studies in toxicology is to determine an 'alert' concentration where a critical level of the response variable is exceeded. In a classical observation-based approach, only measured concentrations are considered as potential alert concentrations. Alternatively, a parametric curve is fitted to the data that describes the relationship between concentration and response. For a prespecified effect level, both an absolute estimate of the alert concentration and an estimate of the lowest concentration where the effect level is exceeded significantly are of interest. RESULTS: In a simulation study for gene expression data, we compared the observation-based and the model-based approach for both absolute and significant exceedance of the prespecified effect level. Results show that, compared to the observation-based approach, the model-based approach overestimates the true alert concentration less often and more frequently leads to a valid estimate, especially for genes with large variance. AVAILABILITY AND IMPLEMENTATION: The code used for the simulation studies is available via the GitHub repository: https://github.com/FKappenberg/Paper-IdentificationAlertConcentrations. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Sympatric genetic divergence between early- and late-season weedy rice populations.

Sympatric genetic divergence is the most appealing and controversial pattern in the theory of ecological speciation. Examples that support sympatric genetic divergence in plant species are extremely rare. Solid evidence of sympatric genetic divergence will provide deep insights for revealing the underlying mechanisms of ecological speciation. We analysed the total genomic DNA sequences of 120 weedy rice (WR; Oryza sativa f. spontanea) plants, representing three WR population pairs separately from three early- and late-season rice fields, in comparison with those of the co-occurring rice cultivars and other rice materials. We detected substantial genetic divergence within the pairs of the sympatric early- and late-season WR populations, although genetic divergence was unevenly distributed across the genomes. Restricted gene flow was determined between the sympatric WR populations, resulting in their distinct genetic structures. We also detected relatively low genetic diversity that was likely to be associated with stronger selection in early-season WR populations. Our findings provide strong evidence for sympatric genetic divergence between the WR populations in the same fields but in different seasons. We conclude that temporal isolation plays an important role in creating genetic divergence between sympatric populations/species in plants.

Surface design of g-C3N4 quantum dot-decorated TiO2(001) to enhance the photodegradation of indoor formaldehyde by experimental and theoretical investigation.

Formaldehyde (CHOH), a common volatile organic compound, causes many adverse effects on human health. The highly exposed TiO2(001) facet possesses a high photodegradation efficiency of CHOH due to its excellent ability to trap photogenerated holes and high density of surface unsaturated Ti atoms (Ti5c) to bind CHOH. However, the rapid recombination of photoinduced electron-hole pairs of TiO2(001) limits the photodegradation efficiency. We adopted a strategy of decorating TiO2(001) with g-C3N4 quantum dots (QDs), exploiting the quantum effect of g-C3N4QDs and their combined staggered band structure. This decoration improves the photocatalytic activity of TiO2(001). Moreover, the chemical configuration of g-C3N4QDs/TiO2(001) and the combination mode between the g-C3N4QDs and TiO2(001) support were explored in detail using high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), and density functional theory (DFT) calculations. Following the physiochemical characteristic results, the transport mechanism of photoinduced carriers was further analyzed by ultraviolet photoelectron spectroscopy (UPS), electron paramagnetic resonance (EPR), and Heyd-Scuseria-Ernzerh (HSE) exchange-correlation functional calculations. Finally, the performance and reaction mechanism of the photodegradation of CHOH by TiO2(001) and g-C3N4QDs/TiO2(001) were thoroughly investigated. The results show that the g-C3N4QDs were composed of an N-defect tri-s-triazine supported by TiO2(001) via a strong C-O-Ti chemical bond, which accelerated the separation of photoinduced carriers through a Z-scheme route. The photodegradation and mineralization efficiencies of CHOH were significantly promoted by 30% and 60% for g-C3N4QDs/TiO2(001) compared with those of TiO2(001). The photodegradation mechanism proceeded as CHOH - dioxymethylene - formate - carbonate - CO2. This study provides a surface engineering means to design highly active modified TiO2 for CHOH photodegradation.

Screening drug effects in patient-derived cancer cells links organoid responses to genome alterations.

Cancer drug screening in patient-derived cells holds great promise for personalized oncology and drug discovery but lacks standardization. Whether cells are cultured as conventional monolayer or advanced, matrix-dependent organoid cultures influences drug effects and thereby drug selection and clinical success. To precisely compare drug profiles in differently cultured primary cells, we developed DeathPro, an automated microscopy-based assay to resolve drug-induced cell death and proliferation inhibition. Using DeathPro, we screened cells from ovarian cancer patients in monolayer or organoid culture with clinically relevant drugs. Drug-induced growth arrest and efficacy of cytostatic drugs differed between the two culture systems. Interestingly, drug effects in organoids were more diverse and had lower therapeutic potential. Genomic analysis revealed novel links between drug sensitivity and DNA repair deficiency in organoids that were undetectable in monolayers. Thus, our results highlight the dependency of cytostatic drugs and pharmacogenomic associations on culture systems, and guide culture selection for drug tests.

Prediction of liver toxicity and mode of action using metabolomics in vitro in HepG2 cells.

Liver toxicity is a leading systemic toxicity of drugs and chemicals demanding more human-relevant, high throughput, cost effective in vitro solutions. In addition to contributing to animal welfare, in vitro techniques facilitate exploring and understanding the molecular mechanisms underlying toxicity. New 'omics technologies can provide comprehensive information on the toxicological mode of action of compounds, as well as quantitative information about the multi-parametric metabolic response of cellular systems in normal and patho-physiological conditions. Here, we combined mass-spectroscopy metabolomics with an in vitro liver toxicity model. Metabolite profiles of HepG2 cells treated with 35 test substances resulted in 1114 cell supernatants and 3556 intracellular samples analyzed by metabolomics. Control samples showed relative standard deviations of about 10-15%, while the technical replicates were at 5-10%. Importantly, this procedure revealed concentration-response effects and patterns of metabolome changes that are consistent for different liver toxicity mechanisms (liver enzyme induction/inhibition, liver toxicity and peroxisome proliferation). Our findings provide evidence that identifying organ toxicity can be achieved in a robust, reliable, human-relevant system, representing a non-animal alternative for systemic toxicology.

Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures.

Bosentan is well known to induce cholestatic liver toxicity in humans. The present study was set up to characterize the hepatotoxic effects of this drug at the transcriptomic, proteomic, and metabolomic levels. For this purpose, human hepatoma-derived HepaRG cells were exposed to a number of concentrations of bosentan during different periods of time. Bosentan was found to functionally and transcriptionally suppress the bile salt export pump as well as to alter bile acid levels. Pathway analysis of both transcriptomics and proteomics data identified cholestasis as a major toxicological event. Transcriptomics results further showed several gene changes related to the activation of the nuclear farnesoid X receptor. Induction of oxidative stress and inflammation were also observed. Metabolomics analysis indicated changes in the abundance of specific endogenous metabolites related to mitochondrial impairment. The outcome of this study may assist in the further optimization of adverse outcome pathway constructs that mechanistically describe the processes involved in cholestatic liver injury.

Reduced weed seed shattering by silencing a cultivated rice gene: strategic mitigation for escaped transgenes.

Transgene flow form a genetically engineered (GE) crop to its wild relatives may result in unwanted environmental consequences. Mitigating transgenes via introducing a gene that is disadvantageous to wild relatives but beneficial to crops, and is tightly-linked with the target transgenes, may provide a promising solution to limit the spread of transgenes in wild/weedy populations. Here we demonstrate a novel system with significantly reduced seed shattering in crop-weed hybrid descendants by partially silenced expression of the seed-shattering gene SH4 in cultivated rice, using artificial microRNA and antisense RNA techniques. Accordingly, fewer seeds were found in the soil of the field plots where transgenic hybrid lineages were grown. However, no differences in productivity-related traits were detected between GE and non-GE cultivated rice. To silence seed-shattering genes provides a useful strategy to reduce the potential environmental impacts caused by transgene flow from commercial GE rice to weedy rice, in addition to the control of weedy rice.

Investigations on the dose-response relationship of combined exposure to low doses of three anti-androgens in Wistar rats.

The current investigation examines whether combined exposure to three anti-androgens (flutamide, prochloraz, vinclozolin) result in interference with endocrine homeostasis when applied at very low dose levels, and whether the results of combined exposure are more pronounced than to the individual compounds. A pre-post-natal in vivo study design was chosen with more parameters than regulatory testing protocols require (additional endpoints addressing hormone levels, morphology and histopathological examinations). Dose levels were chosen to represent the lowest observed adverse effect level (LOAEL), the no observed adverse effect level (NOAEL), and the acceptable daily intake for each individual substance. Anti-androgenic changes were observable at the effect level (LOAEL) but not at lower exposures. Nipple/areola counts appeared to be a sensitive measure of effect, in addition to male sex organ weights at sexual maturation, and finally gross findings. The results indicate the absence of evidence for effects at low or very low dose levels. No (adverse) effects were seen at the NOAEL dose. A non-monotonic dose-response relationship was not evident. Combined exposure at LOAEL level resulted in enhanced responses for anogenital index, number of areolas/nipples, delayed preputial separation and reduced ventral prostate weight in comparison to the individual compounds.

Statistical strategies for averaging EC50 from multiple dose-response experiments.

In most dose-response studies, repeated experiments are conducted to determine the EC50 value for a chemical, requiring averaging EC50 estimates from a series of experiments. Two statistical strategies, the mixed-effect modeling and the meta-analysis approach, can be applied to estimate average behavior of EC50 values over all experiments by considering the variabilities within and among experiments. We investigated these two strategies in two common cases of multiple dose-response experiments in (a) complete and explicit dose-response relationships are observed in all experiments and in (b) only in a subset of experiments. In case (a), the meta-analysis strategy is a simple and robust method to average EC50 estimates. In case (b), all experimental data sets can be first screened using the dose-response screening plot, which allows visualization and comparison of multiple dose-response experimental results. As long as more than three experiments provide information about complete dose-response relationships, the experiments that cover incomplete relationships can be excluded from the meta-analysis strategy of averaging EC50 estimates. If there are only two experiments containing complete dose-response information, the mixed-effects model approach is suggested. We subsequently provided a web application for non-statisticians to implement the proposed meta-analysis strategy of averaging EC50 estimates from multiple dose-response experiments.

Summarizing EC50 estimates from multiple dose-response experiments: a comparison of a meta-analysis strategy to a mixed-effects model approach.

Dose-response studies are performed to investigate the potency of a compound. EC50 is the concentration of the compound that gives half-maximal response. Dose-response data are typically evaluated by using a log-logistic model that includes EC50 as one of the model parameters. Often, more than one experiment is carried out to determine the EC50 value for a compound, requiring summarization of EC50 estimates from a series of experiments. In this context, mixed-effects models are designed to estimate the average behavior of EC50 values over all experiments by considering the variabilities within and among experiments simultaneously. However, fitting nonlinear mixed-effects models is more complicated than in a linear situation, and convergence problems are often encountered. An alternative strategy is the application of a meta-analysis approach, which combines EC50 estimates obtained from separate log-logistic model fitting. These two proposed strategies to summarize EC50 estimates from multiple experiments are compared in a simulation study and real data example. We conclude that the meta-analysis strategy is a simple and robust method to summarize EC50 estimates from multiple experiments, especially suited in the case of a small number of experiments.

The complete mitochondrial genome of Pontederia crassipes: using HiFi reads to investigate genome recombination and gene transfer from chloroplast genome.

Water hyacinth (Pontederia crassipes Mart.) is a monocotyledonous aquatic plant renowned for its rapid growth, extensive proliferation, biological invasiveness, and ecological resilience to variations in pH, nutrients, and temperature. The International Union for Conservation of Nature (IUCN) has listed P. crassipes among the top 100 invasive species. However, comprehensive genomic information, particularly concerning its mitochondrial genome (mitogenome), remains surprisingly limited. In this study, the complete mitogenome of P. crassipes was analyzed using bioinformatics approaches. The mitogenome is 399,263 bp long and contains 38 protein-coding genes (PCGs), 24 tRNA genes, and 3 rRNA genes. Sequence analysis revealed that the complete mitogenome of the species contains 3,289 dispersed repeats, and 765 RNA editing sites in protein-coding genes. The P. crassipes mitogenome possessed un-conserved structures, including extensive sequence transfer between its chloroplasts and mitochondria. Our study on the mitogenome of P. crassipes offers critical insights into its evolutionary patterns and phylogenetic relationships with related taxa. This research enhances our understanding of this invasive species, known for its significant biomass and rapid overgrowth in aquatic environments.

Highly Bioactive MXene-M2-Exosome Nanocomposites Promote Angiogenic Diabetic Wound Repair through Reconstructing High Glucose-Derived Immune Inhibition.

The repair of diabetic wounds remains challenging, primarily due to the high-glucose-derived immune inhibition which often leads to the excessive inflammatory response, impaired angiogenesis, and heightened susceptibility to infection. However, the means to reduce the immunosuppression and regulate the conversion of M2 phenotype macrophages under a high-glucose microenvironment using advanced biomaterials for diabetic wounds are not yet fully understood. Herein, we report two-dimensional carbide (MXene)-M2 macrophage exosome (Exo) nanohybrids (FM-Exo) for promoting diabetic wound repair by overcoming the high-glucose-derived immune inhibition. FM-Exo showed the sustained release of M2 macrophage-derived exosomes (M2-Exo) up to 7 days and exhibited broad-spectrum antibacterial activity. In the high-glucose microenvironment, relative to the single Exo, FM-Exo could significantly induce the optimized M2a/M2c polarization ratio of macrophages by activating the PI3K/Akt signaling pathway, promoting the proliferation, migration of fibroblasts, and angiogenic ability of endothelial cells. In the diabetic full-thickness wound model, FM-Exo effectively regulated the polarization status of macrophages and promoted their transition to the M2 phenotype, thereby inhibiting inflammation, promoting angiogenesis through VEGF secretion, and improving proper collagen deposition. As a result, the healing process was accelerated, leading to a better healing outcome with reduced scarring. Therefore, this study introduced a promising approach to address diabetic wounds by developing bioactive nanomaterials to regulate immune inhibition in a high-glucose environment.

Primulapingbaensis (Primulaceae), a new species from Guizhou, China.

Primulapingbaensis Na Zhang, X.Q.Jiang & Z.K.Wu, a new species of Primulaceae from Gaofeng Mountain of Pingba county, Guizhou, China, is described and illustrated. Morphological evidence supports P.pingbaensis as a member of P.sect.Petiolares on account of scape elongating, pedicels conspicuously thickening in fruit, and its capsule cracking irregularly round the top and crumbling away. Amongst the members of subsect. Davidii, the new species is characterized by having a uniquely smooth leaf blade due to inconspicuously raised veinlets and homostylous flowers with the style usually extending beyond the anthers. The distribution, phenology and conservation status of the new species are also provided.

Rediscovery of Primulabrachystoma (Primulaceae), a rare species endemic to Gaoligong Mountain of Chinese-Burma frontier.

The rare Primulabrachystoma W.W.Sm. is an endemic species confined to Gaoligong mountain of Chinese-Burma frontier, which has been rediscovered from the same region after nearly 100 years. In total, 11 specimens from Gaoligong Mountain have been found in the herbaria worldwide, since its first collection in 1920 by Farrer, Reginald John. Previously, this species was described as homostylous but our finding shows the species also exhibited heterostyly. A complete description of the species, the distribution, morphological comparison and identification key from closely related species are provided here. An assessment of its conservation status suggests that the species is 'Endangered' (EN).

Peptidome analysis reveals critical roles for peptides in a rat model of intestinal ischemia/reperfusion injury.

Intestinal ischemia/reperfusion injury (IIRI) has the potential to be life threatening and is associated with significant morbidity and serious damage to distant sites in the body on account of disruption of the intestinal mucosal barrier. In the present study, we have explored this line of research by comparing and identifying peptides that originated from the intestinal segments of IIRI model rats by using liquid chromatography-mass spectrometry (LC-MS). We also analyzed the basic characteristics, cleavage patterns, and functional domains of differentially expressed peptides (DEPs) between the IIRI model rats and control (sham-operated) rats and identified bioactive peptides that are potentially associated with ischemia reperfusion injury. We also performed bioinformatics analyses in order to identify the biological roles of the DEPs based on their precursor proteins. Enrichment analysis demonstrated the role of several DEPs in impairment of the intestinal mucosal barrier caused by IIRI. Based on the results of comprehensive ingenuity pathway analysis, we identified the DEPs that were significantly correlated with IIRI. We identified a candidate precursor protein (Actg2) and seven of its peptides, and we found that Actg2-6 had a more significant difference in its expression, a longer half-life, and better lipophilicity, hydrophobicity, and stability than the other candidate Actg2 peptides examined. Furthermore, we observed that Actg2-6 might play critical roles in the protection of the intestinal mucosal barrier during IIRI. In summary, our study provides a better understanding of the peptidomics profile of IIRI, and the results indicate that Actg2-6 could be a useful target in the treatment of IIRI.

MDL-800, the SIRT6 Activator, Suppresses Inflammation via the NF-κB Pathway and Promotes Angiogenesis to Accelerate Cutaneous Wound Healing in Mice.

Sirtuin 6 (SIRT6) is an NAD+-dependent deacetylase belonging to the sirtuin family. It has been shown to participate in wound healing and some inflammation-related disorders. However, the effect of MDL-800, a highly efficient and selective SIRT6 activator, on wound healing and inflammation has not been reported. Therefore, this study investigated whether MDL-800 confers anti-inflammatory effects and promotes wound healing and uncovered the molecular mechanisms involved. This was achieved using mouse models of full-thickness wounds. Results showed that MDL-800 significantly downregulated inflammation by attenuating the release of inflammatory mediators and improved collagen deposition and neovascularization of wounds, thereby accelerating cutaneous wound healing. Furthermore, MDL-800 significantly downregulated expression levels of TNF-α and IL-6 in the dorsal skin tissue of mice via the NF-κB pathway. These results demonstrated that MDL-800 exerted anti-inflammatory and prohealing effects, indicating that the SIRT6/NF-κB/IκB signaling pathway may play an important role in wound healing.

Reducing Seed Shattering in Weedy Rice by Editing SH4 and qSH1 Genes: Implications in Environmental Biosafety and Weed Control through Transgene Mitigation.

Mitigating the function of acquired transgenes in crop wild/weedy relatives can provide an ideal strategy to reduce the possible undesired environmental impacts of pollen-mediated transgene flow from genetically engineered (GE) crops. To explore a transgene mitigation system in rice, we edited the seed-shattering genes, SH4 and qSH1, using a weedy rice line ("C9") that originally had strong seed shattering. We also analyzed seed size-related traits, the total genomic transcriptomic data, and RT-qPCR expression of the SH4 or qSH1 gene-edited and SH4/qSH1 gene-edited weedy rice lines. Substantially reduced seed shattering was observed in all gene-edited weedy rice lines. The single gene-edited weedy rice lines, either the SH4 or qSH1 gene, did not show a consistent reduction in their seed size-related traits. In addition, reduced seed shattering was closely linked with the weakness and absence of abscission layers and reduced abscisic acid (ABA). Additionally, the genes closely associated with ABA biosynthesis and signaling transduction, as well as cell-wall hydrolysis, were downregulated in all gene-edited weedy rice lines. These findings facilitate our deep insights into the underlying mechanisms of reduced seed shattering in plants in the rice genus Oryza. In addition, such a mitigating technology also has practical applications for reducing the potential adverse environmental impacts caused by transgene flow and for managing the infestation of weedy rice by acquiring the mitigator from GE rice cultivars through natural gene flow.

Correlation between 25-Hydroxyvitamin D, sFlt-1, PLGF, and Hypertension in Pregnancy.

Gestational hypertension is a common disease in clinical practice, which does great harm to the mother and infant. The purpose of this study was to investigate the relationship between 25-hydroxyvitamin D, sFlt-1, and PLGF and hypertensive disorder complicating pregnancy. Specimen preparation: after delivery or placental caesarean section, in order to avoid calcification and necrosis in the middle of the placenta, an area of about 1.5 cm × 1.5 cm × 1.5 cm should be separated immediately. After dehydration, use a Citadel 2000 dryer to dry it and place it in a block of saline for xylene immunohistochemical staining. Statistical processing was performed according to the proportion of positive cells in each part and the depth of staining. Placental tissue collection and treatment: within 20 minutes after the delivery of the placenta, two pieces of the placental tissue (about 1.0 cm × 1.0 cm × 1.0 cm) were taken from the central zone of the placental maternal surface without obvious bleeding and calcification. They were rinsed repeatedly in normal saline, fixed in 10% neutral formaldehyde solution for 24 hours, dehydrated using an automatic dehydrator, and embedded in paraffin for detection. Before the study, 20 ml of distilled water was added to the sample to stand for 20 minutes; the Cobas E610 immunoanalyzer was turned on, and sFlt-1 and PLGF (placental growth factor) were selected. The serum 25-hydroxyvitamin D level of pregnant women was detected in the fasting state at 24-28 weeks of gestation, and the best collection time was 8 : 00-11 : 00 in the morning. 5 ml of the whole blood sample without anticoagulant was collected and stored at 0-4°C in a cold storage and dark environment. The serum was obtained by high-speed centrifugation within 24 hours after collection. The method is suitable for the quantitative determination of 25-OH-vitamin D in human serum. In the hypertensive pregnancy group, the level of 25-hydroxyvitamin D was 18.44 ± 3.48 ng/ml, and the sFlt-1/PLGF level was highest at 0-5 weeks followed by 5-10 weeks, 10-15 weeks, and 15-20 weeks. This study provides new ideas and experimental clues for the prevention and treatment of pre-eclampsia.

Increased Longevity and Dormancy of Soil-Buried Seeds from Advanced Crop-Wild Rice Hybrids Overexpressing the EPSPS Transgene.

Estimating the fitness effect conferred by a transgene introgressed into populations of wild relative species from a genetically engineered (GE) crop plays an important role in assessing the potential environmental risks caused by transgene flow. Such estimation has essentially focused on the survival and fecundity-related characteristics measured above the ground, but with little attention to the fate of GE seeds shattered in the soil seed banks after maturation. To explore the survival and longevity of GE seeds in soil, we examined the germination behaviors of crop-wild hybrid seeds (F4-F6) from the lineages of a GE herbicide-tolerant rice (Oryzasativa) line that contains an endogenous EPSPS transgene hybridized with two wild O. rufipogon populations after the seeds were buried in soil. The results showed significantly increased germination of the GE crop-wild hybrid seeds after soil burial, compared with that of the non-GE hybrid seeds. Additionally, the proportion of dormant seeds and the content of the growth hormone auxin (indole-3-acetic acid, IAA) in the GE crop-wild hybrid seeds significantly increased. Evidently, the EPSPS transgene enhances the survival and longevity of GE crop-wild rice seeds in the soil seed banks. The enhanced survival and longevity of the GE hybrid seeds is likely associated with the increases in seed dormancy and auxin (IAA) by overexpressing the rice endogenous EPSPS transgene. Thus, the fate of GE seeds in the soil seed banks should be earnestly considered when assessing the environmental risks caused by transgene flow.