Oxidation-reduction process of Arabidopsis thaliana roots induced by bisphenol compounds based on RNA-seq analysis.

Bisphenol compounds (BPs) have various industrial uses and can enter the environment through various sources. To evaluate the ecotoxicity of BPs and identify potential gene candidates involved in the plant toxicity, Arabidopsis thaliana was exposed to bisphenol A (BPA), BPB, BPE, BPF, and BPS at 1, 3, 10 mg/L for a duration of 14 days, and their growth status were monitored. At day 14, roots and leaves were collected for internal BPs exposure concentration detection, RNA-seq (only roots), and morphological observations. As shown in the results, exposure to BPs significantly disturbed root elongation, exhibiting a trend of stimulation at low concentration and inhibition at high concentration. Additionally, BPs exhibited pronounced generation of reactive oxygen species, while none of the pollutants caused significant changes in root morphology. Internal exposure concentration analysis indicated that BPs tended to accumulate in the roots, with BPS exhibiting the highest level of accumulation. The results of RNA-seq indicated that the shared 211 differently expressed genes (DEGs) of these 5 exposure groups were enriched in defense response, generation of precursor metabolites, response to organic substance, response to oxygen-containing, response to hormone, oxidation-reduction process and so on. Regarding unique DEGs in each group, BPS was mainly associated with the redox pathway, BPB primarily influenced seed germination, and BPA, BPE and BPF were primarily involved in metabolic signaling pathways. Our results provide new insights for BPs induced adverse effects on Arabidopsis thaliana and suggest that the ecological risks associated with BPA alternatives cannot be ignored.

Environmental colloid behaviors of humic acid - Cadmium nanoparticles in aquatic environments.

Humic acid (HA), a principal constituent of natural organic matter (NOM), manifests ubiquitously across diverse ecosystems and can significantly influence the environmental behaviors of Cd(II) in aquatic systems. Previous studies on NOM-Cd(II) interactions have primarily focused on the immobilization of Cd(II) solids, but little is known about the colloidal stability of organically complexed Cd(II) particles in the environment. In this study, we investigated the formation of HA-Cd(II) colloids and quantified their aggregation, stability, and transport behaviors in a saturated porous media representative of typical subsurface conditions. Results from batch experiments indicated that the relative quantity of HA-Cd(II) colloids increased with increasing C/Cd molar ratio and that the carboxyl functional groups of HA dominated the stability of HA-Cd(II) colloids. The results of correlation analysis between particle size, critical aggregation concentration (CCC), and zeta potential indicated that both Derjaguin-Landau-Verwey-Overbeek (DLVO) and non-DLVO interactions contributed to the enhanced colloidal stability of HA-Cd(II) colloids. Column results further confirmed that the stable HA-Cd(II) colloid can transport fast in a saturated media composed of clean sand. Together, this study provides new knowledge of the colloidal behaviors of NOM-Cd(II) nanoparticles, which is important for better understanding the ultimate cycling of Cd(II) in aquatic systems.

Single-atom Barium Promoter Enormously Enhanced Non-noble Metal Catalyst for Ammonia Decomposition.

As a well-established topic, single-atom catalyst has drawn growing interest for its high utilization of metal. However, researchers prefer to develop various active metals with single-atom form, the intrinsic roles of single-atom promoters are usually underrated, which are significant in boosting reaction activity. In this work, Ba single atoms were in situ prepared in the Co-Ba/Y2O3 catalyst with crystallized BaCO3 as the precursor under the ammonia decomposition reaction condition. The optimized Co-Ba/Y2O3 catalyst achieves extremely high H2 production rate of 138.3 mmolH2·gcat-1·min-1 at very low temperature (500 °C, GHSV = 840,000 mL·g-1·h-1) and Co-Ba/Y2O3 exhibits excellent durability during the 350 h test, which realizes the highest activity among all non-noble catalysts, and reaches or even exceeds numerous reported Ru-based catalysts. Both Y2O3 and Co demonstrate positive interactions with Ba, which significantly facilitates the dispersion of Ba species at high temperatures (≥ 600 °C). Ba single atoms significantly enhance the charge density of Co and form additionally active Co-O-Ba-Y2O3 interfacial sites, which alleviates hydrogen poisoning and decreases the reaction barrier of the N-H bond activation of *NH. The exploration of atomically dispersed promoters is groundbreaking in heterogeneous catalysis, which opens up a whole new domain of catalytic material.

Spatio-temporal variations of energy carbon emissions in Xinjiang based on DMSP-OLS and NPP-VIIRS nighttime light remote sensing data.

With the rapid economic development of Xinjiang Uygur Autonomous Region (Xinjiang), energy consumption became the primary source of carbon emissions. The growth trend in energy consumption and coal-dominated energy structure are unlikely to change significantly in the short term, meaning that carbon emissions are expected to continue rising. To clarify the changes in energy-related carbon emissions in Xinjiang over the past 15 years, this paper integrates DMSP/OLS and NPP/VIIRS data to generate long-term nighttime light remote sensing data from 2005 to 2020. The data is used to analyze the distribution characteristics of carbon emissions, spatial autocorrelation, frequency of changes, and the standard deviation ellipse. The results show that: (1) From 2005 to 2020, the total carbon emissions in Xinjiang continued to grow, with noticeable urban additions although the growth rate fluctuated. In spatial distribution, non-carbon emission areas were mainly located in the northwest; low-carbon emission areas mostly small and medium-sized towns; and high-carbon emission areas were concentrated around the provincial capital and urban agglomerations. (2) There were significant regional differences in carbon emissions, with clear spatial clustering of energy consumption. The clustering stabilized, showing distinct "high-high" and "low-low" patterns. (3) Carbon emissions in central urban areas remained stable, while higher frequencies of change were seen in the peripheral areas of provincial capitals and key cities. The center of carbon emissions shifted towards southeast but later showed a trend of moving northwest. (4) Temporal and spatial variations in carbon emissions were closely linked to energy consumption intensity, population size, and economic growth. These findings provided a basis for formulating differentiated carbon emission targets and strategies, optimizing energy structures, and promoting industrial transformation to achieve low-carbon economic development in Xinjiang.

Lower-dose vs high-dose oral bisphenol S action of lipid metabolism in liver of male SD rat via mediating different SREBP isoforms.

Bisphenol S (BPS) is commonly used for the industrial production of thermal paper, polycarbonate plastics, epoxy resins and other materials. Studies have reported that BPS can lead to triglyceride (TAG) or/and cholesterol (CHO) accumulation in the liver in zebrafish and mice, but the reasons for the different types of lipids that accumulate in the liver following BPS exposure are unclear. Here, the influences of lower-dose (10 mg/kg body weight/day) and high-dose (50 mg/kg body weight/day) BPS exposure to male SD rats on the accumulation of different lipids in the liver were explored. The results indicated that BPS treatment increased the levels of acetyl-CoA and glycogen in the liver. A lower dose of BPS upregulated the mRNA and protein expression levels of sterol regulatory element-binding protein 1 (srebp1), which is involved in the de novo synthesis of TAG in the liver, thus promoting the synthesis of glycerides (diacetylglyceride and TAG). However, a higher dose of BPS induced CHO accumulation, but inhibited the mRNA expression of genes (i.e., srebp2, hmgcr and hmgcs) involved in the de novo synthesis of CHO in the liver. Excessive accumulation of glycerides and CHO led to destruction of the physiological structure of rat liver, causing disorders in liver function. Our data provide new insight into the different mechanisms by which glyceride and CHO accumulate in the liver after BPS exposure.

Direct cleavage of C=O double bond in CO2 by the subnano MoOx surface on Mo2N.

Compared to H2-assisted activation mode, the direct dissociation of CO2 into carbonyl (*CO) with a simplified reaction route is advantageous for CO2-related synthetic processes and catalyst upgrading, while the stable C = O double bond makes it very challenging. Herein, we construct a subnano MoO3 layer on the surface of Mo2N, which provides a dynamically changing surface of MoO3↔MoOx (x < 3) for catalyzing CO2 hydrogenation. Rich oxygen vacancies on the subnano MoOx surface with a high electron donating capacity served as a scissor to directly shear the C = O double bond of CO2 to form CO at a high rate. The O atoms leached in CO2 dissociation are removed timely by H2 to regenerate active oxygen vacancies. Owing to the greatly enhanced dissociative activation of CO2, this MoOx/Mo2N catalyst without any supported active metals shows excellent performance for catalyzing CO2 hydrogenation to CO. The construction of highly disordered defective surface on heterostructures paves a new pathway for molecule activation.

Integrated immunogenomic analyses of single-cell and bulk profiling construct a T cell-related signature for predicting prognosis and treatment response in osteosarcoma.

PURPOSES: T cells play a crucial role as regulators of anti-tumor activity within the tumor microenvironment (TME) and are closely associated with the progression of osteosarcoma (OS). Nevertheless, the specific role of T cell-related genes (TCRGs) in the pathogenesis of OS remains unclear. METHODS: First, we processed single-cell RNA sequencing (scRNA-seq) data of OS from the public databases and performed cell annotation. We identified highly variable genes in each cell type using the "FindAllMarkers" function, explored the distribution of different clusters, and investigated inter-cellular communication patterns via the "CellChat" framework. Then, we used multivariate Cox analysis to construct a TCRG and developed a nomogram to predict survival probabilities for OS patients. Finally, we validated the aforementioned results using various cell lines and investigated the immune cell infiltration, expression of immune checkpoints, chemotherapy sensitivity, and the efficacy of targeted therapies across different risk groups. RESULTS: From the scRNA-seq data, we identified 3,000 highly variable genes, presented the top 10 genes, and validated the expression of core genes across different cell lines.Moreover, our analysis delved into interactions between T cells and other cell types. Our analyses constructed a predictive T cell-related signature (TCRS) that incorporated these prognostic TCRGs, showing a clear prognostic separation between the high-risk and low-risk OS patient groups in multiple cohorts. Survival analysis indicated better outcomes for patients classified in the high-risk group. The low-risk group exhibited elevated levels of CD4 memory resting T cells, contrasting with the higher levels of macrophage M0 observed in the high-risk group via the CIBERSORT algorithm. Furthermore, we observed that the low-risk group exhibitedAQ1 significant up-regulation of immune checkpoint genes (ICGs) and lower Tumour Immune Dysfunction and Exclusion (TIDE) scores, suggesting that they may be suitable for immunotherapy. Conversely, the high-risk group appeared more responsive to chemotherapy and targeted therapies, according to our drug sensitivity analysis. CONCLUSION: In conclusion, our study identified TCRGs, constructed and validated a TCRS for OS, and assessed immune response and drug sensitivity in different risk groups of OS patients. These findings provide novel insights into personalized treatment strategies for OS, potentially guiding more effective therapeutic interventions.

Molecular mechanism of proteolytic cleavage-dependent activation of CadC-mediated response to acid in E. coli.

Colonizing in the gastrointestinal tract, Escherichia coli confronts diverse acidic challenges and evolves intricate acid resistance strategies for its survival. The lysine-mediated decarboxylation (Cad) system, featuring lysine decarboxylase CadA, lysine/cadaverine antiporter CadB, and transcriptional activator CadC, plays a crucial role in E. coli's adaptation to moderate acidic stress. While the activation of the one-component system CadC and subsequent upregulation of cadBA operon in response to acid and lysine presence have been proposed, the molecular mechanisms governing the transition of CadC from an inactive to an active state remain elusive. Under neutral conditions, CadC is inhibited by forming a complex with lysine-specific permease LysP, stabilized in this inactive state by a disulfide bond. Our study unveils that, in an acidic environment, the disulfide bond in CadC is reduced by the disulfide bond isomerase DsbC, exposing R184 to periplasmic proteases, namely DegQ and DegP. Cleavage at R184 by DegQ and DegP generates an active N-terminal DNA-binding domain of CadC, which binds to the cadBA promoter, resulting in the upregulated transcription of the cadA and cadB genes. Upon activation, CadA decarboxylates lysine, producing cadaverine, subsequently transported extracellularly by CadB. We propose that accumulating cadaverine gradually binds to the CadC pH-sensing domain, preventing cleavage and activation of CadC as a feedback mechanism. The identification of DegP, DegQ, and DsbC completes a comprehensive roadmap for the activation and regulation of the Cad system in response to moderate acidic stress in E. coli.

Xylooligosaccharide interferes with the cell cycle and reduces the antibiotic tolerance of avian pathogenic Escherichia coli by associating with its potential antimetabolic actions.

This study aimed to probe if xylooligosaccharide (XOS) could act as an antimetabolite to impact the cell cycle and antibiotic tolerance of avian pathogenic Escherichia coli (APEC). We firstly measured the bacteriostasis of XOS against APEC O78 and its effect on the growth of APEC O78 growing on different medium. Afterwards, the effects of XOS on xylose operon activation along with the cell cycle and antibiotic tolerance of APEC O78 were analyzed. The results showed that XOS caused no inhibitory circle against APEC O78 and did not affect (P > 0.05) the growth of APEC O78 growing on LB medium. Besides, APEC O78 was unable to grow on M9 medium (carbon-free) added with XOS. However, XOS exerted a similar role as xylose in increasing (P < 0.05) the expression of certain xylose operon genes including xylose isomerase (XylA)-encoding gene (xylA) and xylose-binding periplasmic protein (XylF)-encoding gene (xylF) in APEC O78. The molecular docking simulation revealed that the major monomer components (xylobiose, xylotriose and xylotetraose) of XOS had stable binding potentials to both XylA and XylF proteins of E. coli, as supported by the low binding free energy and the formation of considerable hydrogen bonds between them. The subsequent analysis showed that XOS altered certain cell cycle-related genes expression, especially elevated (P < 0.05) nrdB expression and decreased ihfB expression to a degree. Moreover, XOS played a similar role as 2-deoxy-glucose (a glucose analogue serving as a typical antimetabolite) in lowering (P < 0.05) the number of ampicillin-tolerant APEC O78. Collectively, XOS had no direct bacteriostasis against APEC and could not be metabolized/utilized by APEC O78. However, it might become an analogue of xylose and then activate xylose transport- and metabolism-related proteins in APEC O78, thus functioning as a potential antimetabolite and exerting antimetabolic actions. This could at least partially interpret the observed roles of XOS in interfering with the cell cycle and diminishing the antibiotic tolerance of APEC O78. The above findings expand the knowledges about the functions of XOS and provide a basis for exploring novel strategies to reduce the antibiotic tolerance of APEC.

Antibacterial activity and mechanism of Stevia extract against antibiotic-resistant Escherichia coli by interfering with the permeability of the cell wall and the membrane.

Natural plant-derived compounds with broad-spectrum antimicrobial activity have become an effective strategy against multidrug-resistant bacteria. The present study was designed to compare the antibacterial activity of six chlorogenic acid (CA) isomers extracted from stevia and investigated the underlying antibacterial mechanisms involved. The results indicated that isochlorogenic acid C (ICAC) exhibited the strongest antibacterial activity against the tested bacteria, especially E. coli, at a 2 mg/mL minimum inhibitory concentration (MIC) and 8 mg/mL minimum bactericidal concentration (MBC). At the MBC, ICAC inhibited 72.66% of the clinical multidrug-resistant strains. Scanning electron microscopy (SEM) revealed that ICAC induced considerable morphological alterations in E. coli ATCC25922 and C4E2. The significant increase in the activity of extracellular alkaline phosphatase (AKP) indicated that ICAC damages the permeability of the bacterial cell wall. Additionally, the intracellular membrane (IM) permeability and the content of lipopolysaccharide (LPS), a main component of the outer membrane (OM), were determined. The significant decrease in LPS content and increased leakage of intracellular proteins and K+ from E. coli indicated that ICAC could induce the exfoliation of OM and disrupt IM permeability, resulting in the loss of barrier function. The uptake of propidium iodide (PI), a compromised cell membrane nucleic acid stain, and confocal laser scanning microscopy (CLSM) further demonstrated that ICAC disrupted IM integrity. Moreover, the bactericidal effect and damage to bacterial microstructural function occurred in a dose-dependent manner. These data demonstrate that ICAC has excellent antibacterial activity and is a promising approach for overcoming the antibiotic resistance of pathogenic bacteria.

The overexpression of the switchgrass (Panicum virgatum L.) genes PvTOC1-N or PvLHY-K affects circadian rhythm and hormone metabolism in transgenic Arabidopsis seedlings.

Switchgrass (Panicum virgatum L.) is a perennial C4 warm-season grass known for its high-biomass yield and wide environmental adaptability, making it an ideal bioenergy crop. Despite its potential, switchgrass seedlings grow slowly, often losing out to weeds in field conditions and producing limited biomass in the first year of planting. Furthermore, during the reproductive growth stage, the above-ground biomass rapidly increases in lignin content, creating a significant saccharification barrier. Previous studies have identified rhythm-related genes TOC1 and LHY as crucial to the slow seedling development in switchgrass, yet the precise regulatory functions of these genes remain largely unexplored. In this study, the genes TOC1 and LHY were characterized within the tetraploid genome of switchgrass. Gene expression analysis revealed that PvTOC1 and PvLHY exhibit circadian patterns under normal growth conditions, with opposing expression levels over time. PvTOC1 genes were predominantly expressed in florets, vascular bundles, and seeds, while PvLHY genes showed higher expression in stems, leaf sheaths, and nodes. Overexpression of PvTOC1 from the N chromosome group (PvTOC1-N) or PvLHY from the K chromosome group (PvLHY-K) in Arabidopsis thaliana led to alterations in circadian rhythm and hormone metabolism, resulting in shorter roots, delayed flowering, and decreased resistance to oxidative stress. These transgenic lines exhibited reduced sensitivity to hormones and hormone inhibitors, and displayed altered gene expression in the biosynthesis and signal transduction pathways of abscisic acid (ABA), gibberellin (GA), 3-indoleacetic acid (IAA), and strigolactone (SL). These findings highlight roles of PvTOC1-N and PvLHY-K in plant development and offer a theoretical foundation for genetic improvements in switchgrass and other crops.

The Effect of Temperature and Humidity on Yellow Tea Volatile Compounds during Yellowing Process.

Yellowing is the key processing technology of yellow tea, and environmental conditions have a significant impact on the yellowing process. In this study, volatile compounds of the yellowing process under different environmental conditions were analyzed by GC-MS. Results showed that a total of 75 volatile compounds were identified. A partial least squares discriminant analysis (PLS-DA) determined that 42 of them were differential compounds, including 12 hydrocarbons, 8 ketones, 8 aldehydes, 6 alcohols, and 8 other compounds, and compared the contents of differential compounds under the conditions of 40 °C with 90% humidity, 50 °C with 50% humidity, and 30 °C with 70% humidity, then analyzed the variation patterns of hydrocarbons under different yellowing environmental conditions. A 40 °C with 90% humidity treatment reduced the content of more hydrocarbons and increased the aldehydes. The content of 3-hexen-1-ol was higher when treated at 50 °C with 50% humidity and was consistent with the results of sensory evaluation. This study could provide a theoretical basis for future research on the aroma of yellow tea.

Effects of Different Levels of Green Tea Powder on Performance, Antioxidant Activity, Egg Mass, Quality, and Cecal Microflora of Chickens.

This study was conducted to investigate the effects of different levels of Green Tea Powder on the performance, egg quality, serum immune and antioxidant indices, and cecal microflora of 300-day-old Chishui black-bone chickens during the peak laying period. A total of 360 Chishui black-bone chickens were selected as the experimental animals. They were randomly allocated into four groups: the control group (CON), trial group I (T1), trial group II (T2), and trial group III (T3), each group with six replicates and 15 hens in each replicate. The control group was fed a basal diet, and the experimental groups were fed a basal diet supplemented with 0.8%, 1.6%, and 2.4% Green Tea Powder, respectively. The accommodation period was 14 d, and the experimental period was 60 d. The statistical software SPSS was used to perform a one-way analysis of variance (ANOVA) on the experimental data, and Duncan's method was used to perform multiple comparisons among groups. The results showed the following: compared with those of the control group, the average daily gain of the laying hens significantly decreased in the 1.6% Green Tea Powder group (p < 0.05); adding Green Tea Powder significantly reduced the content of malondialdehyde in the serum (p < 0.05), and the addition of 0.8% tea leaves significantly increased the immunoglobulin M and immunoglobulin A contents (p < 0.05); the egg yolk weight, eggshell thickness, eggshell strength, and yolk color of the laying hens significantly decreased in the 1.6% Green Tea Powder group (p < 0.05), and the addition of Green Tea Powder at the level of 2.4% significantly increased the percentage of umami, essential, and total amino acids (p < 0.05); and the structure of intestinal microorganisms was improved, and the abundance of Bacteroidetes and Bacteroidaceae significantly increased, while the abundance of Firmicutes and Lachnospiraceae significantly decreased (p < 0.05).

Modulation of heteromeric glycine receptor function through high concentration clustering.

Ion channels are targeted by many drugs for treating neurological, musculoskeletal, renal and other diseases. These drugs bind to and alter the function of individual channels to achieve desired therapeutic effects. However, many ion channels function in high concentration clusters in their native environment. It is unclear if and how clustering modulates ion channel function. Human heteromeric glycine receptors (GlyRs) are the major inhibitory neurotransmitter receptors in the spinal cord and are active targets for developing chronic pain medications. We show that the α2ß heteromeric GlyR assembles with the master postsynaptic scaffolding gephyrin (GPHN) into micron-sized clustered at the plasma membrane after heterologous expression. The inhibitory trans- synaptic adhesion protein neuroligin-2 (NL2) further increases both the cluster sizes and GlyR concentration. The apparent glycine affinity increases monotonically as a function of GlyR concentration but not with cluster size. We also show that ligand re-binding to adjacent GlyRs alters kinetics but not chemical equilibrium. A positively charged N- terminus sequence of the GlyR ß subunit was further identified essential for glycine affinity modulation through clustering. Taken together, we propose a mechanism where clustering enhances local electrostatic potential, which in turn concentrates ions and ligands, modulating the function of GlyR. This mechanism is likely universal across ion channel clusters found ubiquitously in biology and provides new perspectives in possible pharmaceutical development.

Weaker neuroligin 2 - neurexin 1ß interaction tethers membranes and signal synaptogenesis through clustering.

Single-pass transmembrane proteins neuroligin (NL) and neurexin (NRX) constitute a pair of synaptic adhesion molecules (SAMs) that are essential for the formation of functional synapses. Binding affinities vary by ∼ 1000 folds between arrays of NL and NRX subtypes, which contribute to chemical and spatial specificities. Current structures are obtained with truncated extracellular domains of NL and NRX and are limited to the higher-affinity NL1/4-NRX complexes. How NL-NRX interaction leads to functional synapses remains unknown. Here we report structures of full-length NL2 alone, and in complex with NRX1ß in several conformations, which has the lowest affinity among major NL-NRX subtypes. We show how conformational flexibilities may help in adapting local membrane geometry, and reveal mechanisms underlying variations in NL-NRX affinities modulation. We further show that, despite lower affinity, NL2-NRX1ß interaction alone is capable of tethering different lipid membranes in total reconstitution, and that NL2 and NRX1ß cluster at inter-cellular junctions without the need of other synaptic components. In addition, NL2 combines with the master post-synaptic scaffolding protein gephyrin and clusters neurotransmitter receptors at cellular membrane. These findings suggest dual roles of NL2 - NRX1ß interaction - both as mechanical tether, and as signaling receptors, to ensure correct spatial and chemical coordination between two cells to generate function synapses.

Rapid Construction of Liquid-like Surfaces via Single-Cycle Polymer Brush Grafting for Enhanced Antifouling in Microfluidic Systems.

Liquid-like surfaces have demonstrated immense potential in their ability to resist cell adhesion, a critical requirement for numerous applications across various domains. However, the conventional methodologies for preparing liquid-like surfaces often entail a complex multi-step polymer brush modification process, which is not only time-consuming but also presents significant challenges. In this work, we developed a single-cycle polymer brush modification strategy to build liquid-like surfaces by leveraging high-molecular-weight bis(3-aminopropyl)-terminated polydimethylsiloxane, which significantly simplifies the preparation process. The resultant liquid-like surface is endowed with exceptional slipperiness, effectively inhibiting bacterial colonization and diminishing the adherence of platelets. Moreover, it offers promising implications for reducing the dependency on anticoagulants in microfluidic systems constructed from PDMS, all while sustaining its antithrombotic attributes.

Bioinspired Glycopeptide Hydrogel Reestablishing Bone Homeostasis through Mediating Osteoclasts and Osteogenesis in Periodontitis Treatment.

Irreversible alveolar bone resorption is one of the important clinical manifestations of periodontitis, which is initiated by a plaque biofilm and exacerbated by the imbalance of osteoclast activity and osteogenesis, affecting a patient's masticatory function and resulting in a high recurrence rate of periodontitis. Herein, to reestablish bone homeostasis in periodontitis, a minocycline hydrochloride (MH)-loaded glycopeptide hydrogel (MH/GRWgel) is fabricated to mediate alveolar bone absorption through sequential antibacterial and RANKL-blocking activities. GRWgel shows an ECM-like fibrous and porous microstructure serving as a scaffold for cell proliferation and differentiation and holds the merits including injectability, self-healing properties, and good biocompatibility. After injection in situ, MH is released rapidly from the hydrogel in the early stage, demonstrating a potent antimicrobial effect to combat the biofilm in the deep periodontal pocket. Moreover, MH/GRWgel exhibits a high specific binding efficiency with RANKL to suppress osteoclast maturation by shielding the RANKL/RANK interaction and enhancing osteogenic differentiation, thereby synergistically regulating bone homeostasis. In the rat periodontitis model, MH/GRWgel significantly curtails periodontitis progression through antimicrobial activity, inhibition of alveolar bone resorption, and promotion of bone regeneration, which is superior to the treatment of a commercial gel. These findings suggest that MH/GRWgel with superiority in regulating bone homeostasis provides a promising therapeutic strategy for periodontitis.

SARS-CoV-2 N protein coordinates viral particle assembly through multiple domains.

Increasing evidence suggests that mutations in the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may enhance viral replication by modulating the assembly process. However, the mechanisms governing the selective packaging of viral genomic RNA by the N protein, along with the assembly and budding processes, remain poorly understood. Utilizing a virus-like particles (VLPs) system, we have identified that the C-terminal domain (CTD) of the N protein is essential for its interaction with the membrane (M) protein during budding, crucial for binding and packaging genomic RNA. Notably, the isolated CTD lacks M protein interaction capacity and budding ability. Yet, upon fusion with the N-terminal domain (NTD) or the linker region (LKR), the resulting NTD/CTD and LKR/CTD acquire RNA-dependent interactions with the M protein and acquire budding capabilities. Furthermore, the presence of the C-tail is vital for efficient genomic RNA encapsidation by the N protein, possibly regulated by interactions with the M protein. Remarkably, the NTD of the N protein appears dispensable for virus particle assembly, offering the virus adaptive advantages. The emergence of N* (NΔN209) in the SARS-CoV-2 B.1.1 lineage corroborates our findings and hints at the potential evolution of a more streamlined N protein by the SARS-CoV-2 virus to facilitate the assembly process. Comparable observations have been noted with the N proteins of SARS-CoV and HCoV-OC43 viruses. In essence, these findings propose that ß-coronaviruses may augment their replication by fine-tuning the assembly process.IMPORTANCEAs a highly transmissible zoonotic virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve. Adaptive mutations in the nucleocapsid (N) protein highlight the critical role of N protein-based assembly in the virus's replication and evolutionary dynamics. However, the precise molecular mechanisms of N protein-mediated viral assembly remain inadequately understood. Our study elucidates the intricate interactions between the N protein, membrane (M) protein, and genomic RNA, revealing a C-terminal domain (CTD)-based assembly mechanism common among ß-coronaviruses. The appearance of the N* variant within the SARS-CoV-2 B.1.1 lineage supports our conclusion that the N-terminal domain (NTD) of the N protein is not essential for viral assembly. This work not only enhances our understanding of coronavirus assembly mechanisms but also provides new insights for developing antiviral drugs targeting these conserved processes.

Combined toxic effects of polystyrene microplastic and benzophenone-4 on the bioaccumulation, feeding, growth, and reproduction of Daphniamagna.

The potential toxicity of microplastics (MPs) and UV filter Benzophenone-4 (BP4) to aquatic organisms has caused widespread concern among the public. However, the combined effects of MPs and BP4 on aquatic organisms are not well understood. This study sought to examine the combined impacts of 10 µg/L BP4, 1 mg/L Polystyrene (PS, 10 µm), and a mixture of both on the feeding, behavior, growth, and reproduction of Daphnia magna (D. magna) over a period of 21 days. The results showed that the combined exposure led to a reciprocal facilitation of bioaccumulation, along with a decrease in the second antenna beats frequency in D. magna. While the co-exposure did not change the body size or growth rate of D. magna, it did affect their feeding efficiency, leading to a decrease in Chlorella ingestion within a 24-h period. Furthermore, there was a high occurrence of malformations in two generations of D. magna exposed to BP4 and PS. The combined exposure also negatively affected reproductive parameters, such as the cumulative number of neonates and the days of first brood, suggesting a decline in overall reproductive success possibly due to feeding inhibition, with available energy potentially being redistributed between reproduction and growth in the daphnids. Co-exposure to BP4 and PS also led to elevated levels of Reactive Oxygen Species (ROS), Malonydialdehyde (MDA), and Glutathione (GSH) levels, as well as mRNA levels related to reproduction, growth, and detoxification in D. magna. Overall, this study delved into the consequences of BP4 and PS on bioaccumulation, feeding, behavior, growth, and reproduction, demonstrating that simultaneous exposure to BP4 and PS could pose a synergistic ecological hazard, potentially threatening aquatic organisms. These findings are critical and should be taken into account for accurate environmental risk assessments.

Intensity Modulated Carbon Ion Radiation Therapy Using Pencil Beam Scanning Technology for Patients With Unresectable Sacrococcygeal Chordoma.

Purpose: To investigate the safety and efficacy of intensity modulated carbon ion radiation therapy (IM-CIRT) using pencil beam scanning technology for patients with unresectable sacrococcygeal chordoma (SC). Methods and Materials: A total of 35 patients with unresectable SC were retrospectively analyzed, including 54.3% (19/35) recurrent cases. In 68.6% (24/35) cases, tumor was located in S2 or above, and all cases were treated with hypofractionated IM-CIRT. The median dose was 70.4 Gy (range, 69-80 Gy) (relative biologic effectiveness) in 16 fractions (range, 16-23 fractions), typically delivered over 5 fractions per week. Results: The 3-year overall survival, cause-specific survival, progression-free survival, locoregional progression-free survival, and distant metastasis-free survival rates with a median follow-up time of 42 months (range, 12-91 months) for the entire cohort were 93.2%, 96.3%, 61.8%, 80%, and 77.3%, respectively. Multivariate analysis revealed that gross tumor volume (hazard ratio, 3.807; 95% CI, 1.044-13.887; P = .043) was the only significant prognostic factor for progression-free survival and the dose for the gross tumor volume ≥70.4 Gy (relative biologic effectiveness) was relevant with significantly better locoregional progression-free survival (hazard ratio, 0.190; 95% CI, 0.038-0.940; P = .042). No significant prognostic factor for overall survival, cause-specific survival, and distant metastasis-free survival and no severe (ie, grade ≥3) acute toxicity were identified. Severe late toxicities occurred in 3 patients (8.57%): pain (1 patient), motor neuropathy (1 patient), and skin ulcer (1 patient). Furthermore, no severe toxicity related to urinary function or defecation was observed following IM-CIRT. Pain grades improved or remained unchanged in 85.7% of patients. Conclusions: IM-CIRT produced acceptable 3-year outcomes without substantial late adverse effects, especially urinary and anorectal complications for SC, and did not appear to increase pain. IM-CIRT at high doses using hypofractionated radiation therapy may improve outcomes for local control and seems to be feasible even for postoperative recurrent SC.