Weakening warming on spring freeze-thaw cycle caused greening Earth's third pole.

The Tibetan Plateau, recognized as Earth's third pole and among the most responsive regions to climate shifts, profoundly influences regional and even global hydrological processes. Here, we discerned a significant weakening in the influence of temperature on the initiation of surface freeze-thaw cycle (the Start of Thawing, SOT), which can be ascribed to a multitude of climatic variables, with radiation emerging as the most pivotal factor. Additionally, we showed that the diminishing impact of warming on SOT yields amplified soil moisture within the root zone. This, in turn, fosters a greening third pole with increased leaf area index and solar-induced chlorophyll fluorescence. We further showed that current Earth system models failed to reproduce the linkage between weakened sensitivity and productivity under various shared socioeconomic pathways. Our findings highlight the dynamic shifts characterizing the influence of climate warming on spring freeze-thaw process and underscore the profound ecological implications of these changes in the context of future climate scenarios.

Flagellimonas halotolerans sp. nov., a novel bacterium isolated from the South China Sea.

Two Gram-stain-negative strains, designed SYSU M86414T and SYSU M84420, were isolated from marine sediment samples of the South China Sea (Sansha City, Hainan Province, PR China). These strains were aerobic and could grow at pH 6.0-8.0 (optimum, pH 7.0), 4-37 °C (optimum, 28 °C), and in the presence of 0-10 % NaCl (w/v; optimum 3 %). The predominant respiratory menaquinone of strains SYSU M86414T and SYSU M84420 was MK-6. The primary cellular polar lipid was phosphatidylethanolamine. The major cellular fatty acids (>10 %) in both strains were iso-C15 : 0, iso-C15 : 1 G, and iso-C17 : 0 3-OH. The DNA G+C content of strains SYSU M86414T and SYSU M84420 were both 42.10 mol%. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that these novel strains belonged to the genus Flagellimonas and strain SYSU M86414T showed the highest 16S rRNA gene sequence similarity to Flagellimonas marinaquae JCM 11811T (98.83 %), followed by Flagellimonas aurea BC31-1-A7T (98.62 %), while strain SYSU M84420 had highest 16S rRNA gene sequence similarity to F. marinaquae JCM 11811T (98.76 %) and F. aurea BC31-1-A7T (98.55 %). Based on the results of polyphasic analyses, strains SYSU M86414T and SYSU M84420 should be considered to represent a novel species of the genus Flagellimonas, for which the name Flagellimonas halotolerans sp. nov. is proposed. The type strain of the proposed novel isolate is SYSU M86414T (=GDMCC 1.3806T=KCTC 102040T).

Distinct Assembly Processes Structure Planktonic Bacterial Communities Among Near- and Offshore Ecosystems in the Yangtze River Estuary.

The estuarine system functions as natural filters due to its ability to facilitate material transformation, planktonic bacteria play a crucial role in the cycling of complex nutrients and pollutants within estuaries, and understanding the community composition and assembly therein is crucial for comprehending bacterial ecology within estuaries. Despite extensive investigations into the composition and community assembly of two bacterial fractions (free-living, FLB; particle-attached, PAB), the process by which bacterioplankton communities in these two habitats assemble in the nearshore and offshore zones of estuarine ecosystems remains poorly understood. In this study, we conducted sampling in the Yangtze River Estuary (YRE) to investigate potential variations in the composition and community assembly of FLB and PAB in nearshore and offshore regions. We collected 90 samples of surface, middle, and bottom water from 16 sampling stations and performed 16S rRNA gene amplicon analysis along with environmental factor measurements. The results unveiled that the nearshore communities demonstrated significantly greater species richness and Chao1 indices compared to the offshore communities. In contrast, the nearshore communities had lower values of Shannon and Simpson indices. When compared to the FLB, the PAB exhibit a higher level of biodiversity and abundance. However, no distinct alpha and beta diversity differences were observed between the bottom, middle, and surface water layers. The community assembly analysis indicated that nearshore communities are predominantly shaped by deterministic processes, particularly due to heterogeneous selection of PAB; In contrast, offshore communities are governed more by stochastic processes, largely due to homogenizing dispersal of FLB. Consequently, the findings of this study demonstrate that nearshore and PAB communities exhibit higher levels of species diversity, while stochastic and deterministic processes exert distinct influences on communities among near- and offshore regions. This study further sheds new light on our understanding of the mechanisms governing bacterial communities in estuarine ecosystems.

Diversity, abundance, and expression of proteorhodopsin genes in the northern South China Sea.

Proteorhodopsins have been suggested as an important strategy among phototrophs to capture solar energy in marine environments. The goals of this study was to investigate the diversity of proteorhodopsin genes and to explore their abundance, distribution, and expression in the coastal surface waters of the northern South China Sea, one of the largest marginal seas of the western North Pacific Ocean. Using 21 metagenomes, we recovered proteorhodopsin genes from a wide range of prokaryotic taxa, and chlorophyll a contributed significantly to the community composition of proteorhodopsin-containing microbes. Most proteorhodopsin sequences were predicted to encode green light-absorbing proton pumps and green light-absorbing proteorhodopsin genes were more abundant than blue-absorbing ones. The variations in the conserved residues involved in ion pumping and several uncharacterized proteorhodopsins were observed. The gene abundance pattern of proteorhodopsin types were significantly influenced by the levels of total organic carbon and soluble reactive phosphorus. Gene expression analysis confirmed the importance of proteorhodopsin-based phototrophy and revealed different expressional patterns among major phyla. In tandem, we screened 2295 metagenome-assembled genomes to describe the taxonomic distribution of proteorhodopsins. Bacteroidota are the key lineages encoding proteorhodopsins, but proteorhodopsins were predicated from members of Proteobacteria, Marinisomatota, Myxococcota, Verrucomicrobiota and Thermoplasmatota. Our study expanded the diversity of proteorhodopsins and improve our understanding on the significance of proteorhodopsin-mediated phototrophy in the marine ecosystem.

Enhanced Electron Transport in Nonconjugated Radical Oligomers Occurs by Tunneling.

Incorporating temperature- and air-stable organic radical species into molecular designs is a potentially advantageous means of controlling the properties of electronic materials. However, we still lack a complete understanding of the structure-property relationships of organic radical species at the molecular level. In this work, the charge transport properties of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) radical-containing nonconjugated molecules are studied using single-molecule charge transport experiments and molecular modeling. Importantly, the TEMPO pendant groups promote temperature-independent molecular charge transport in the tunneling region relative to the quenched and closed-shell phenyl pendant groups. Results from molecular modeling show that the TEMPO radicals interact with the gold metal electrodes near the interface to facilitate a high-conductance conformation. Overall, the large enhancement of charge transport by incorporation of open-shell species into a single nonconjugated molecular component opens exciting avenues for implementing molecular engineering in the development of next-generation electronic devices based on novel nonconjugated radical materials.

Research progress on multiple cell death pathways of podocytes in diabetic kidney disease.

Diabetic kidney disease (DKD) is the main cause of end-stage renal disease, and its clinical manifestations are progressive proteinuria, decreased glomerular filtration rate, and renal failure. The injury and death of glomerular podocytes are the keys to DKD. Currently, a variety of cell death modes have been identified in podocytes, including apoptosis, autophagy, endoplasmic reticulum (ER) stress, pyroptosis, necroptosis, ferroptosis, mitotic catastrophe, etc. The signaling pathways leading to these cell death processes are interconnected and can be activated simultaneously or in parallel. They are essential for cell survival and death that determine the fate of cells. With the deepening of the research on the mechanism of cell death, more and more researchers have devoted their attention to the underlying pathologic research and the drug therapy research of DKD. In this paper, we discussed the podocyte physiologic role and DKD processes. We also provide an overview of the types and specific mechanisms involved in each type of cell death in DKD, as well as related targeted therapy methods and drugs are reviewed. In the last part we discuss the complexity and potential crosstalk between various modes of cell death, which will help improve the understanding of podocyte death and lay a foundation for new and ideal targeted therapy strategies for DKD treatment in the future.

Ultrasensitive Homogeneous Detection of PCSK9 and Efficacy Monitoring of the PCSK9 Inhibitor Based on Proximity Hybridization-Dependent Chemiluminescence Imaging Immunoassay.

Accurate quantification of proprotein convertase subtilisin/kexin type 9 (PCSK9) in serum before and after the medication is helpful in grasping the evolution of PCSK9-related disease and evaluating the efficacy of PCSK9 inhibitors. Conventional approaches for PCSK9 quantification suffered from complicated operations and low sensitivity. By integrating stimuli-responsive mesoporous silica nanoparticles, dual-recognition proximity hybridization, and T7 exonuclease-assisted recycling amplification, a novel homogeneous chemiluminescence (CL) imaging approach was proposed for ultrasensitive and convenient immunoassay of PCSK9. Owing to the intelligent design and signal amplification property, the whole assay was conducted without separation and rinsing, significantly simplifying the procedure and eliminating the errors associated with the professional operation; meanwhile, it showed linear ranges over 5 orders of magnitude and detection limit as low as 0.7 pg mL-1. Parallel testing was allowed due to the imaging readout, which brought a maximum throughput of 26 tests h-1. The proposed CL approach was applied to analyze PCSK9 from hyperlipidemia mice before and after the intervention of the PCSK9 inhibitor. Serum PCSK9 levels in the model group and the intervention group could be distinguished efficiently. The results were reliable compared to commercial immunoassay results and histopathologic findings. Thus, it could facilitate the monitoring of the serum PCSK9 level and the lipid-lowering effect of the PCSK9 inhibitor, showing promising potential in bioanalysis and pharmaceuticals.

Dose-dependent long-distance movement of microRNA399 duplex regulates phosphate homeostasis in Arabidopsis.

MicroRNA399 (miR399), a phosphate (Pi) starvation-induced long-distance signal, is first produced in shoots and moves to roots to suppress PHO2 encoding a ubiquitin conjugase, leading to enhanced Pi uptake and root-to-shoot translocation. However, the molecular mechanism underlying miR399 long-distance movement remains elusive. Hypocotyl grafting with various Arabidopsis mutants or transgenic lines expressing artificial miR399f was employed. The movement of miR399 across graft junction and the rootstock PHO2 transcript and scion Pi levels were analyzed to elucidate the potential factors involved. Our results showed that miR399f precursors are cell-autonomous and mature miR399f movement is independent of its biogenesis, sequence context, and length (21 or 22 nucleotides). Expressing viral silencing suppressor P19 in the root stele or blocking unloading in the root phloem pore pericycle (PPP) antagonized its silencing effect, suggesting that the miR399f/miR399f* duplex is a mobile entity unloaded through PPP. Notably, the scion miR399f level positively correlates with its amount translocated to rootstocks, implying dose-dependent movement. This study uncovers the molecular basis underlying the miR399-mediated long-distance silencing in coordinating shoot Pi demand with Pi acquisition and translocation activities in the roots.

The start of frozen dates over northern permafrost regions with the changing climate.

The soil freeze-thaw cycle in the permafrost regions has a significant impact on regional surface energy and water balance. Although increasing efforts have been made to understand the responses of spring thawing to climate change, the mechanisms controlling the global interannual variability of the start date of permafrost frozen (SOF) remain unclear. Using long-term SOF from the combinations of multiple satellite microwave sensors between 1979 and 2020, and analytical techniques, including partial correlation, ridge regression, path analysis, and machine learning, we explored the responses of SOF to multiple climate change factors, including warming (surface and air temperature), start date of permafrost thawing (SOT), soil properties (soil temperature and volume of water), and the snow depth water equivalent (SDWE). Overall, climate warming exhibited the maximum control on SOF, but SOT in spring was also an important driver of SOF variability; among the 65.9% significant SOT and SOF correlations, 79.3% were positive, indicating an overall earlier thawing would contribute to an earlier frozen in winter. The machine learning analysis also suggested that apart from warming, SOT ranked as the second most important determinant of SOF. Therefore, we identified the mechanism responsible for the SOT-SOF relationship using the SEM analysis, which revealed that soil temperature change exhibited the maximum effect on this relationship, irrespective of the permafrost type. Finally, we analyzed the temporal changes in these responses using the moving window approach and found increased effect of soil warming on SOF. In conclusion, these results provide important insights into understanding and predicting SOF variations with future climate change.

Ectobacillus ponti sp. nov., a novel bacterium isolated from Pearl River Estuary.

A Gram-staining-positive, aerobic, motile, and rod-shaped strain, designated SYSU M60031T, was isolated from a Pearl River Estuary sediment sample, Guangzhou, Guangdong, China. The isolate could grow at pH 5.0-8.0 (optimum, pH 7.0), 25-37 °C (optimum, 28 °C) and in the presence of 0-1 % (w/v) NaCl (optimum, 0 %). The predominant respiratory menaquinone of SYSU M60031T was MK-7. The cellular polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminophospholipid, and one unidentified aminolipid. The major fatty acids (>10 % of total) were iso-C14 : 0, iso-C15 : 0, anteiso-C15 : 0, iso-C16 : 0, and C16 : 0. The genomic DNA G+C content was 51.2 %. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that strain SYSU M60031T belonged to the genus Ectobacillus and showed the highest sequence similarity to Ectobacillus funiculus NAF001T (96.16%), followed by Ectobacillus antri SYSU K30001T (95.08 %). Based on the phenotypic, genotypic, and phylogenetic data, strain SYSU M60031T should be considered to represent a novel species of the genus Ectobacillus, for which the name Ectobacillus ponti sp. nov. is proposed. The type strain of the proposed novel isolate is SYSU M60031T (=CGMCC 1.19243T =NBRC 115614T).

Cereibacter flavus sp. nov., a novel member of the family Rhodobacteraceae isolated from seawater of the South China Sea and reclassification of Rhodobacter alkalitolerans as Cereibacter alkalitolerans comb. nov.

A Gram-stain-negative, aerobic, motile, ovoid-shaped and yellow-coloured strain, designated SYSU M79828T, was isolated from seawater collected from the South China Sea. Growth of this strain was observed at 4-37 °C (optimum, 28 °C), pH 6.0-8.0 (optimum, pH 7.0) and with 0-6% NaCl (optimum, 3.0 %, w/v). The respiratory quinone was found to be Q-10. Major fatty acid constituents were C18 : 1 ω7c/C18 : 1 ω6c, C18 : 1 ω7c11-methyl and C18 : 0 (>5 % of total). The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, phosphoglycolipid, two unidentified phospholipid, one unidentified lipid and an unidentified glycolipid. The genomic DNA G+C content was 64.5 mol%. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that strain SYSU M79828T belonged to the genus Cereibacter and had the highest sequences similarity to 'Rhodobacter xinxiangensis' TJ48T (98.41 %). Based on 16S rRNA gene phylogeny, physiological and chemotaxonomic characterizations, we consider that strain SYSU M79828T represents a novel species of the genus Cereibacter, for which the name Cereibacter flavus sp. nov. is proposed. The type strain is SYSU M79828T (=GDMCC 1.3803T=KCTC 92893T). In addition, according to the results of phylogenetic analysis and similar taxonomic characteristics, we propose that Rhodobacter alkalitolerans should be reclassified as Cereibacter alkalitolerans comb. nov.

S1PR1 attenuates pulmonary fibrosis by inhibiting EndMT and improving endothelial barrier function.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic fatal disease of unknown etiology. Its pathological manifestations include excessive proliferation and activation of fibroblasts and deposition of extracellular matrix. Endothelial cell-mesenchymal transformation (EndMT), a novel mechanism that generates fibroblast during IPF, is responsible for fibroblast-like phenotypic changes and activation of fibroblasts into hypersecretory cells. However, the exact mechanism behind EndMT-derived fibroblasts and activation is uncertain. Here, we investigated the role of sphingosine 1-phosphate receptor 1 (S1PR1) in EndMT-driven pulmonary fibrosis. METHODS: We treated C57BL/6 mice with bleomycin (BLM) in vivo and pulmonary microvascular endothelial cells with TGF-ß1 in vitro. Western blot, flow cytometry, and immunofluorescence were used to detect the expression of S1PR1 in endothelial cells. To evaluate the effect of S1PR1 on EndMT and endothelial barrier and its role in lung fibrosis and related signaling pathways, S1PR1 agonist and antagonist were used in vitro and in vivo. RESULTS: Endothelial S1PR1 protein expression was downregulated in both in vitro and in vivo models of pulmonary fibrosis induced by TGF-ß1 and BLM, respectively. Downregulation of S1PR1 resulted in EndMT, indicated by decreased expression of endothelial markers CD31 and VE-cadherin, increased expression of mesenchymal markers α-SMA and nuclear transcription factor Snail, and disruption of the endothelial barrier. Further mechanistic studies found that stimulation of S1PR1 inhibited TGF-ß1-mediated activation of the Smad2/3 and RhoA/ROCK1 pathways. Moreover, stimulation of S1PR1 attenuated Smad2/3 and RhoA/ROCK1 pathway-mediated damage to endothelial barrier function. CONCLUSIONS: Endothelial S1PR1 provides protection against pulmonary fibrosis by inhibiting EndMT and attenuating endothelial barrier damage. Accordingly, S1PR1 may be a potential therapeutic target in progressive IPF.

Alsobacter ponti sp. nov., a novel denitrification and sulfate reduction bacterium isolated from Pearl River sediment.

A Gram-staining negative, aerobic, motile, and short rods strain, designated SYSU M60028T, was isolated from a Pearl River sediment sample in Guangzhou, Guangdong, China. The isolate could be able to grow at pH 6.0-8.0 (optimum, pH 7.0), 25-37 °C (optimum, 28 °C) and in the presence of 0-2% (w/v) NaCl (optimum, 0% NaCl). The cellular polar lipids of this strain were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, one unidentified aminolipid and three unidentified lipids. The respiratory quinone of SYSU M60028T was found to be Q-10. The major fatty acids (> 5% of total) were summed feature 8, C16:0, and C18:1 ω7c 11-methy1. The genomic DNA G + C content was 69.9%. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that strain SYSU M60028T belonged to the genus Alsobacter and had the highest sequences similarities to Alsobacter metallidurans SK200a-9T (96.87%) and Alsobacter soli SH9T (96.87%). Based on the phenotypic, genotypic, and phylogenetic data, strain SYSU M0028T should be considered to represent a novel species of the genus Alsobacter, for which the name Alsobacter ponti sp. nov. is proposed. The type strain is SYSU M60028T (= CGMCC 1.19341T = KCTC 92046T).

Comparative transcriptome analysis reveals the function of SlPRE2 in multiple phytohormones biosynthesis, signal transduction and stomatal development in tomato.

KEY MESSAGE: Transcriptomic, physiological, and qRT-PCR analysis revealed the potential mechanism by which SlPRE2 regulates plant growth and stomatal size via multiple phytohormone pathways in tomato. Paclobutrazol resistance proteins (PREs) are atypical members of the basic/helix-loop-helix (bHLH) transcription factor family that regulate plant morphology, cell size, pigment metabolism and abiotic stress in response to different phytohormones. However, little is known about the network regulatory mechanisms of PREs in plant growth and development in tomato. In this study, the function and mechanism of SlPRE2 in tomato plant growth and development were investigated. The quantitative RT-PCR results showed that the expression of SlPRE2 was regulated by multiple phytohormones and abiotic stresses. It showed light-repressed expression during the photoperiod. The RNA-seq results revealed that SlPRE2 regulated many genes involved in photosynthesis, chlorophyll metabolism, phytohormone metabolism and signaling, and carbohydrate metabolism, suggesting the role of SlPRE2 in gibberellin, brassinosteroid, auxin, cytokinin, abscisic acid and salicylic acid regulated plant development processes. Moreover, SlPRE2 overexpression plants showed widely opened stomata in young leaves, and four genes involved in stomatal development showed altered expression. Overall, the results demonstrated the mechanism by which SlPRE2 regulates phytohormone and stress responses and revealed the function of SlPRE2 in stomatal development in tomato. These findings provide useful clues for understanding the molecular mechanisms of SlPRE2-regulated plant growth and development in tomato.

Stratified analysis of clinical pregnancy outcomes of sequential embryo transfer in frozen embryo transfer cycles based on different factors: a retrospective study.

OBJECTIVE: To explore the effect of sequential embryo transfer (ET) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycle and the indications of sequential transfer. METHODS: A total of 1440 FET cycles were enrolled in this retrospective study, of which 1080 patients received conventional ET and 360 patients received sequential ET. Further stratified analysis was performed according to the number of previous failed cycles, the number of embryos transferred and the stage of blastocyst (day 5 or 6, denoted D5 or D6) transferred. Comparison of pregnancy rates, implantation rate, miscarriage rate and multiple pregnancy rate among the groups of patients. RESULTS: The clinical pregnancy rate and implantation rate of the sequential ET group were higher than those of the conventional ET group (P < 0.01); however, there was no statistical difference in multiple pregnancy rate and miscarriage rate (P > 0.05). In sequential transfer, the number of transferred embryos (2 or 3) and the stage of transferred blastocysts (D5 or D6) had no effect on clinical pregnancy rate, implantation rate, multiple pregnancy rate and miscarriage rate (P > 0.05). In patients with three or more previous failure cycles, the sequential ET group showed higher clinical pregnancy rate and implantation rate (P > 0.05). CONCLUSIONS: Compared with conventional ET in FET cycle, sequential ET strategy could significantly improve the clinical pregnancy rate and implantation rate. In sequential transfer, patients with three embryos transferred don't have higher pregnancy rate and implantation rate. Besides, sequential transfer is more suitable for patients with repeated implantation failures (RIF), and increase the utilization rate of D6 blastocysts.

Novel Antioxidant Peptides from Pearl Shell Meat Hydrolysate and Their Antioxidant Activity Mechanism.

Free radicals are associated with aging and many diseases. Antioxidant peptides with good antioxidant activity and absorbability are one of the hotspots in antioxidant researches. In our study, pearl shell (Pinctada martensii) meat hydrolysate was purified, and after identification by proteomics, six novel antioxidant peptides SPSSS, SGTAV, TGVAS, GGSIT, NSVAA, and GGSLT were screened by bioinformatics analysis. The antioxidant peptides exhibited good cellular antioxidant activity (CAA) and the CAA of SGTAV (EC50: 0.009 mg/mL) and SPSSS (EC50: 0.027 mg/mL) were better than that of positive control GSH (EC50: 0.030 mg/mL). In the AAPH-induced oxidative damage models, the antioxidant peptides significantly increased the viability of HepG2 cells, and the cell viability of SGTAV, SPSSS, and NAVAA were significantly restored from 79.41% to 107.43% and from 101.09% and 100.09%, respectively. In terms of antioxidant mechanism by molecular docking, SGTAV, SPSSS, and NAVAA could tightly bind to free radicals (DPPH and ABTS), antioxidant enzymes (CAT and SOD), and antioxidant channel protein (Keap1), suggesting that the antioxidant peptides had multiple antioxidant activities and had structure-activity linkages. This study suggests that the antioxidant peptides above are expected to become new natural materials for functional food industries, which contribute to the high-value applications of pearl shell meat.

Transitions in patterns of caregiver involvement before and during the COVID-19 pandemic: A latent transition analysis.

This retrospective study investigated transitions in patterns of caregiver involvement before and during COVID-19 and their antecedents and consequences. A total of 504 young children (age: M ± SD = 49.92 ± 4.30 months) and their primary caregivers were recruited from the junior classes of 10 preschools in Zhengzhou City, Henan Province, China. Latent profile analysis identified three profiles characterized by (1) high levels of caregiver involvement (HCI), (2) average levels of caregiver involvement (ACI), and (3) low levels of caregiver involvement (LCI). Latent transition analysis showed that caregivers who belonged to the HCI or LCI latent status before COVID-19 tended to transition to the ACI latent status during COVID-19. Higher levels of caregiver depression contributed to a higher probability of transitioning from the HCI to the ACI latent status, while higher levels of household chaos predicted a higher probability of transitioning from the HCI to the ACI latent status and a lower probability of transitioning from the LCI to the ACI latent status. Finally, the transitions in patterns of caregiver involvement were associated with young children's approaches to learning during the pandemic.

Mepanipyrim induces visual developmental toxicity and vision-guided behavioral alteration in zebrafish larvae.

Mepanipyrim, an anilinopyrimidine fungicide, has been extensively used to prevent fungal diseases in fruit culture. Currently, research on mepanipyrim-induced toxicity in organisms is still very scarce, especially visual developmental toxicity. Here, zebrafish larvae were employed to investigate mepanipyrim-induced visual developmental toxicity. Intense light and monochromatic light stimuli-evoked escape experiments were used to investigate vision-guided behaviors. Meanwhile, transcriptomic sequencing and real-time quantitative PCR assays were applied to assess the potential mechanisms of mepanipyrim-induced visual developmental toxicity and vision-guided behavioral alteration. Our results showed that mepanipyrim exposure could induce retinal impairment and vision-guided behavioral alteration in larval zebrafish. In addition, the grk1b gene of the phototransduction signaling pathway was found to be a potential aryl hydrocarbon receptor (AhR)-regulated gene. Mepanipyrim-induced visual developmental toxicity was potentially related to the AhR signaling pathway. Furthermore, mepanipyrim-induced behavioral alteration was guided by the visual function, and the effects of mepanipyrim on long and middle wavelength light-sensitive opsins may be the main cause of vision-guided behavioral alteration. Our results provide insights into understanding the relationship between visual development and vision-guided behaviors induced by mepanipyrim exposure.

Efficient Intermolecular Charge Transport in π-Stacked Pyridinium Dimers Using Cucurbit[8]uril Supramolecular Complexes.

Intermolecular charge transport through π-conjugated molecules plays an essential role in biochemical redox processes and energy storage applications. In this work, we observe highly efficient intermolecular charge transport upon dimerization of pyridinium molecules in the cavity of a synthetic host (cucurbit[8]uril, CB[8]). Stable, homoternary complexes are formed between pyridinium molecules and CB[8] with high binding affinity, resulting in an offset stacked geometry of two pyridiniums inside the host cavity. The charge transport properties of free and dimerized pyridiniums are characterized using a scanning tunneling microscope-break junction (STM-BJ) technique. Our results show that π-stacked pyridinium dimers exhibit comparable molecular conductance to isolated, single pyridinium molecules, despite a longer transport pathway and a switch from intra- to intermolecular charge transport. Control experiments using a CB[8] homologue (cucurbit[7]uril, CB[7]) show that the synthetic host primarily serves to facilitate dimer formation and plays a minimal role on molecular conductance. Molecular modeling using density functional theory (DFT) reveals that pyridinium molecules are planarized upon dimerization inside the host cavity, which facilitates charge transport. In addition, the π-stacked pyridinium dimers possess large intermolecular LUMO-LUMO couplings, leading to enhanced intermolecular charge transport. Overall, this work demonstrates that supramolecular assembly can be used to control intermolecular charge transport in π-stacked molecules.

Identification and characterization of MKK6 and AP-1 in Anodonta woodiana reveal their potential roles in the host defense response against bacterial challenge.

Mitogen-activated protein kinase kinase 6 (MKK6) and activator protein-1 (AP-1) are two of the essential regulatory proteins in the p38 mitogen-activated protein kinase (MAPK) pathway, which participates in the innate immune response to bacterial infections. In this study, molluscan MKK6 (AwMKK6) and AP-1 (AwAP-1) genes were cloned and identified from Anodonta woodiana. The open reading frame (ORF) of AwMKK6 encodes for a putative polypeptide sequence of 345 amino acids containing a conserved serine/threonine protein kinase (S_TKc) domain, a SVAKT motif and a DVD domain. AwAP-1 consists of 294 amino acids including a typical nuclear localization signal (NLS), a Jun domain and a basic region leucine zipper (BRLZ) domain. Quantitative real-time PCR analysis showed that both AwMKK6 and AwAP-1 were widely expressed in all selected tissues of A. woodiana and their transcript levels in hemocytes were significantly upregulated when challenged with Aeromonas hydrophila and lipopolysaccharide (LPS). Additionally, the signaling molecules of the AwMKK6/AwAP-1 pathway including AwTLR4, AwMyD88, AwTRAF6, AwMEKK1, AwMEKK4, AwASK1, AwTAK1 and Awp38 mRNA expression showed a stronger responsiveness to LPS challenge in hemocytes of A. woodiana. RNA interference (RNAi) experiments indicated that the silencing of AwMKK6 or AwAP-1 could decrease the mRNA expression levels of immune effectors (AwTNF, AwLYZ and AwDefense). Subcellular localization studies suggested that AwMKK6 and AwAP-1 were distributed throughout the cells and nucleus, respectively, and their overexpression could significantly enhance the transcriptional activities of AP-1-Luc in HEK293T cells. These findings suggest that MKK6 and AP-1 play a major role in the host defense response to bacterial injection, which may make contributions to a better understanding of the immune function of the p38 MAPK pathway in mollusks.