WAV E3 ubiquitin ligases mediate degradation of IAA32/34 in the TMK1-mediated auxin signaling pathway during apical hook development.

Auxin regulates plant growth and development through downstream signaling pathways, including the best-known SCFTIR1/AFB-Aux/IAA-ARF pathway and several other less characterized "noncanonical" pathways. Recently, one SCFTIR1/AFB-independent noncanonical pathway, mediated by Transmembrane Kinase 1 (TMK1), was discovered through the analyses of its functions in Arabidopsis apical hook development. Asymmetric accumulation of auxin on the concave side of the apical hook triggers DAR1-catalyzed release of the C-terminal of TMK1, which migrates into the nucleus, where it phosphorylates and stabilizes IAA32/34 to inhibit cell elongation, which is essential for full apical hook formation. However, the molecular factors mediating IAA32/34 degradation have not been identified. Here, we show that proteins in the CYTOKININ INDUCED ROOT WAVING 1 (CKRW1)/WAVY GROWTH 3 (WAV3) subfamily act as E3 ubiquitin ligases to target IAA32/34 for ubiquitination and degradation, which is inhibited by TMK1c-mediated phosphorylation. This antagonistic interaction between TMK1c and CKRW1/WAV3 subfamily E3 ubiquitin ligases regulates IAA32/34 levels to control differential cell elongation along opposite sides of the apical hook.

Species-specific IL-1ß is an inflammatory sensor of Seneca Valley Virus 3C Protease.

Inflammasomes play pivotal roles in inflammation by processing and promoting the secretion of IL-1ß. Caspase-1 is involved in the maturation of IL-1ß and IL-18, while human caspase-4 specifically processes IL-18. Recent structural studies of caspase-4 bound to Pro-IL-18 reveal the molecular basis of Pro-IL-18 activation by caspase-4. However, the mechanism of caspase-1 processing of pro-IL-1ß and other IL-1ß-converting enzymes remains elusive. Here, we observed that swine Pro-IL-1ß (sPro-IL-1ß) exists as an oligomeric precursor unlike monomeric human Pro-IL-1ß (hPro-IL-1ß). Interestingly, Seneca Valley Virus (SVV) 3C protease cleaves sPro-IL-1ß to produce mature IL-1ß, while it cleaves hPro-IL-1ß but does not produce mature IL-1ß in a specific manner. When the inflammasome is blocked, SVV 3C continues to activate IL-1ß through direct cleavage in porcine alveolar macrophages (PAMs). Through molecular modeling and mutagenesis studies, we discovered that the pro-domain of sPro-IL-1ß serves as an 'exosite' with its hydrophobic residues docking into a positively charged 3C protease pocket, thereby directing the substrate to the active site. The cleavage of sPro-IL-1ß generates a monomeric and active form of IL-1ß, initiating the downstream signaling. Thus, these studies provide IL-1ß is an inflammatory sensor that directly detects viral protease through an independent pathway operating in parallel with host inflammasomes.

Genome balance and dosage effect drive allopolyploid formation in Brassica.

Polyploidy is a major evolutionary force that has shaped plant diversity. However, the various pathways toward polyploid formation and interploidy gene flow remain poorly understood. Here, we demonstrated that the immediate progeny of allotriploid AAC Brassica (obtained by crossing allotetraploid Brassica napus and diploid Brassica rapa) was predominantly aneuploids with ploidal levels ranging from near-triploidy to near-hexaploidy, and their chromosome numbers deviated from the theoretical distribution toward increasing chromosome numbers, suggesting that they underwent selection. Karyotype and phenotype analyses showed that aneuploid individuals containing fewer imbalanced chromosomes had higher viability and fertility. Within three generations of self-fertilization, allotriploids mainly developed into near or complete allotetraploids similar to B. napus via gradually increasing chromosome numbers and fertility, suggesting that allotriploids could act as a bridge in polyploid formation, with aneuploids as intermediates. Self-fertilized interploidy hybrids ultimately generated new allopolyploids carrying different chromosome combinations, which may create a reproductive barrier preventing allotetraploidy back to diploidy and promote gene flow from diploids to allotetraploids. These results suggest that the maintenance of a proper genome balance and dosage drove the recurrent conversion of allotriploids to allotetraploids, which may contribute to the formation and evolution of polyploids.

Overexpression of plant chitin receptors in wheat confers broad-spectrum resistance to fungal diseases.

Wheat (Triticum aestivum L.) is a globally staple crop vulnerable to various fungal diseases, significantly impacting its yield. Plant cell surface receptors play a crucial role in recognizing pathogen-associated molecular patterns (PAMPs) and activating PAMP-triggered immunity, boosting resistance against a wide range of plant diseases. Although the role of plant chitin receptor CERK1 in immune recognition and defense has been established in Arabidopsis and rice, its function and potential agricultural applications in enhancing resistance to crop diseases remain largely unexplored. Here, we identify and characterize TaCERK1 in Triticeae crop wheat, uncovering its involvement in chitin recognition, immune regulation, and resistance to fungal diseases. By a comparative analysis of CERK1 homologs in Arabidopsis and monocot crops, we demonstrate that AtCERK1 in Arabidopsis elicits the most robust immune response. Moreover, we show that overexpressing TaCERK1 and AtCERK1 in wheat confers resistance to multiple fungal diseases, including Fusarium head blight, stripe rust, and powdery mildew. Notably, transgenic wheat lines with moderately expressed AtCERK1 display superior disease resistance and heightened immune responses without adversely affecting growth and yield, compared to TaCERK1 overexpression transgenics. Our findings highlight the significance of plant chitin receptors across diverse plant species and suggest potential strategies for bolstering crop resistance against broad-spectrum diseases in agricultural production through the utilization of plant immune receptors.

Landscape Heterogeneity Explains the Genetic Differentiation of a Forest Bird across the Sino-Himalayan Mountains.

Mountains are the world's most important centers of biodiversity. The Sino-Himalayan Mountains are global biodiversity hotspot due to their extremely high species richness and endemicity. Ample research investigated the impact of the Qinghai-Tibet Plateau uplift and Quaternary glaciations in driving species diversification in plants and animals across the Sino-Himalayan Mountains. However, little is known about the role of landscape heterogeneity and other environmental features in driving diversification in this region. We utilized whole genomes and phenotypic data in combination with landscape genetic approaches to investigate population structure, demography, and genetic diversity in a forest songbird species native to the Sino-Himalayan Mountains, the red-billed leiothrix (Leiothrix lutea). We identified 5 phylogeographic clades, including 1 in the East of China, 1 in Yunnan, and 3 in Tibet, roughly consistent with differences in song and plumage coloration but incongruent with traditional subspecies boundaries. Isolation-by-resistance model best explained population differentiation within L. lutea, with extensive secondary contact after allopatric isolation leading to admixture among clades. Ecological niche modeling indicated relative stability in the extent of suitable distribution areas of the species across Quaternary glacial cycles. Our results underscore the importance of mountains in the diversification of this species, given that most of the distinct genetic clades are concentrated in a relatively small area in the Sino-Himalayan Mountain region, while a single shallow clade populates vast lower-lying areas to the east. This study highlights the crucial role of landscape heterogeneity in promoting differentiation and provides a deep genomic perspective on the mechanisms through which diversity hotspots form.

Species-specific cleavage of cGAS by picornavirus protease 3C disrupts mitochondria DNA-mediated immune sensing.

RNA viruses cause numerous infectious diseases in humans and animals. The crosstalk between RNA viruses and the innate DNA sensing pathways attracts increasing attention. Recent studies showed that the cGAS-STING pathway plays an important role in restricting RNA viruses via mitochondria DNA (mtDNA) mediated activation. However, the mechanisms of cGAS mediated innate immune evasion by RNA viruses remain unknown. Here, we report that seneca valley virus (SVV) protease 3C disrupts mtDNA mediated innate immune sensing by cleaving porcine cGAS (pcGAS) in a species-specific manner. Mechanistically, a W/Q motif within the N-terminal domain of pcGAS is a unique cleavage site recognized by SVV 3C. Three conserved catalytic residues of SVV 3C cooperatively contribute to the cleavage of pcGAS, but not human cGAS (hcGAS) or mouse cGAS (mcGAS). Additionally, upon SVV infection and poly(dA:dT) transfection, pcGAS and SVV 3C colocalizes in the cells. Furthermore, SVV 3C disrupts pcGAS-mediated DNA binding, cGAMP synthesis and interferon induction by specifically cleaving pcGAS. This work uncovers a novel mechanism by which the viral protease cleaves the DNA sensor cGAS to evade innate immune response, suggesting a new antiviral approach against picornaviruses.

Complex evolutionary patterns within the tubulin gene family of ciliates, unicellular eukaryotes with diverse microtubular structures.

BACKGROUND: Tubulins are major components of the eukaryotic cytoskeletons that are crucial in many cellular processes. Ciliated protists comprise one of the oldest eukaryotic lineages possessing cilia over their cell surface and assembling many diverse microtubular structures. As such, ciliates are excellent model organisms to clarify the origin and evolution of tubulins in the early stages of eukaryote evolution. Nonetheless, the evolutionary history of the tubulin subfamilies within and among ciliate classes is unclear. RESULTS: We analyzed the evolutionary pattern of ciliate tubulin gene family based on genomes/transcriptomes of 60 species covering 10 ciliate classes. Results showed: (1) Six tubulin subfamilies (α_Tub, ß_Tub, γ_Tub, δ_Tub, ε_Tub, and ζ_Tub) originated from the last eukaryotic common ancestor (LECA) were observed within ciliates. Among them, α_Tub, ß_Tub, and γ_Tub were present in all ciliate species, while δ_Tub, ε_Tub, and ζ_Tub might be independently lost in some species. (2) The evolutionary history of the tubulin subfamilies varied. Evolutionary history of ciliate γ_Tub, δ_Tub, ε_Tub, and ζ_Tub showed a certain degree of consistency with the phylogeny of species after the divergence of ciliate classes, while the evolutionary history of ciliate α_Tub and ß_Tub varied among different classes. (3) Ciliate α- and ß-tubulin isoforms could be classified into an "ancestral group" present in LECA and a "divergent group" containing only ciliate sequences. Alveolata-specific expansion events probably occurred within the "ancestral group" of α_Tub and ß_Tub. The "divergent group" might be important for ciliate morphological differentiation and wide environmental adaptability. (4) Expansion events of the tubulin gene family appeared to be consistent with whole genome duplication (WGD) events in some degree. More Paramecium-specific tubulin expansions were detected than Tetrahymena-specific ones. Compared to other Paramecium species, the Paramecium aurelia complex underwent a more recent WGD which might have experienced more tubulin expansion events. CONCLUSIONS: Evolutionary history among different tubulin gene subfamilies seemed to vary within ciliated protists. And the complex evolutionary patterns of tubulins among different ciliate classes might drive functional diversification. Our investigation provided meaningful information for understanding the evolution of tubulin gene family in the early stages of eukaryote evolution.

Self S-RNase inhibits ABF-LRX signaling to arrest pollen tube growth to achieve self-incompatibility in pear.

Gametophytic self-incompatibility (GSI) has been widely studied in flowering plants, but studies of the mechanisms underlying pollen tube growth arrest by self S-RNase in GSI species are limited. In the present study, two leucine-rich repeat extensin genes in pear (Pyrus bretschneideri), PbLRXA2.1 and PbLRXA2.2, were identified based on transcriptome and quantitative real-time PCR analyses. The expression levels of these two LRX genes were significantly higher in the pollen grains and pollen tubes of the self-compatible cultivar 'Jinzhui' (harboring a spontaneous bud mutation) than in those of the self-incompatible cultivar 'Yali'. Both PbLRXA2.1 and PbLRXA2.2 stimulated pollen tube growth and attenuated the inhibitory effects of self S-RNase on pollen tube growth by stabilizing the actin cytoskeleton and enhancing cell wall integrity. These results indicate that abnormal expression of PbLRXA2.1 and PbLRXA2.2 is involved in the loss of self-incompatibility in 'Jinzhui'. The PbLRXA2.1 and PbLRXA2.2 promoters were directly bound by the ABRE-binding factor PbABF.D.2. Knockdown of PbABF.D.2 decreased PbLRXA2.1 and PbLRXA2.2 expression and inhibited pollen tube growth. Notably, the expression of PbLRXA2.1, PbLRXA2.2, and PbABF.D.2 was repressed by self S-RNase, suggesting that self S-RNase can arrest pollen tube growth by restricting the PbABF.D.2-PbLRXA2.1/PbLRXA2.2 signal cascade. These results provide novel insight into pollen tube growth arrest by self S-RNase.

Searching Reproducible Brain Features using NeuroMark: Templates for Different Age Populations and Imaging Modalities.

A primary challenge to the data-driven analysis is the balance between poor generalizability of population-based research and characterizing more subject-, study- and population-specific variability. We previously introduced a fully automated spatially constrained independent component analysis (ICA) framework called NeuroMark and its functional MRI (fMRI) template. NeuroMark has been successfully applied in numerous studies, identifying brain markers reproducible across datasets and disorders. The first NeuroMark template was constructed based on young adult cohorts. We recently expanded on this initiative by creating a standardized normative multi-spatial-scale functional template using over 100,000 subjects, aiming to improve generalizability and comparability across studies involving diverse cohorts. While a unified template across the lifespan is desirable, a comprehensive investigation of the similarities and differences between components from different age populations might help systematically transform our understanding of the human brain by revealing the most well-replicated and variable network features throughout the lifespan. In this work, we introduced two significant expansions of NeuroMark templates first by generating replicable fMRI templates for infants, adolescents, and aging cohorts, and second by incorporating structural MRI (sMRI) and diffusion MRI (dMRI) modalities. Specifically, we built spatiotemporal fMRI templates based on 6,000 resting-state scans from four datasets. This is the first attempt to create robust ICA templates covering dynamic brain development across the lifespan. For the sMRI and dMRI data, we used two large publicly available datasets including more than 30,000 scans to build reliable templates. We employed a spatial similarity analysis to identify replicable templates and investigate the degree to which unique and similar patterns are reflective in different age populations. Our results suggest remarkably high similarity of the resulting adapted components, even across extreme age differences. With the new templates, the NeuroMark framework allows us to perform age-specific adaptations and to capture features adaptable to each modality, therefore facilitating biomarker identification across brain disorders. In sum, the present work demonstrates the generalizability of NeuroMark templates and suggests the potential of new templates to boost accuracy in mental health research and advance our understanding of lifespan and cross-modal alterations.

Self-supervised multimodal learning for group inferences from MRI data: Discovering disorder-relevant brain regions and multimodal links.

In recent years, deep learning approaches have gained significant attention in predicting brain disorders using neuroimaging data. However, conventional methods often rely on single-modality data and supervised models, which provide only a limited perspective of the intricacies of the highly complex brain. Moreover, the scarcity of accurate diagnostic labels in clinical settings hinders the applicability of the supervised models. To address these limitations, we propose a novel self-supervised framework for extracting multiple representations from multimodal neuroimaging data to enhance group inferences and enable analysis without resorting to labeled data during pre-training. Our approach leverages Deep InfoMax (DIM), a self-supervised methodology renowned for its efficacy in learning representations by estimating mutual information without the need for explicit labels. While DIM has shown promise in predicting brain disorders from single-modality MRI data, its potential for multimodal data remains untapped. This work extends DIM to multimodal neuroimaging data, allowing us to identify disorder-relevant brain regions and explore multimodal links. We present compelling evidence of the efficacy of our multimodal DIM analysis in uncovering disorder-relevant brain regions, including the hippocampus, caudate, insula, - and multimodal links with the thalamus, precuneus, and subthalamus hypothalamus. Our self-supervised representations demonstrate promising capabilities in predicting the presence of brain disorders across a spectrum of Alzheimer's phenotypes. Comparative evaluations against state-of-the-art unsupervised methods based on autoencoders, canonical correlation analysis, and supervised models highlight the superiority of our proposed method in achieving improved classification performance, capturing joint information, and interpretability capabilities. The computational efficiency of the decoder-free strategy enhances its practical utility, as it saves compute resources without compromising performance. This work offers a significant step forward in addressing the challenge of understanding multimodal links in complex brain disorders, with potential applications in neuroimaging research and clinical diagnosis.

Limited Song Mixing Without Genomic Gene Flow in a Contact Zone Between Two Songbird Species.

Song is considered to play an important role in the maintenance of prezygotic reproductive isolation between closely related songbird species. Therefore, song mixing in a contact zone between closely related species is often considered as evidence of hybridization. The Sichuan Leaf Warbler Phylloscopus forresti and the Gansu Leaf Warbler Phylloscopus kansuensis, which diverged 2 million years ago, have formed a contact zone in the south of the Gansu Province of China, where mixed songs have been observed. In this study, we investigated the potential causes and consequences of song mixing by integrating bioacoustic, morphological, mitochondrial, and genomic data with field ecological observations. We found that the two species display no apparent morphological differences, whereas their songs differ dramatically. We demonstrated that ∼11% of the males in the contact zone sang mixed songs. Two males singing mixed song were genotyped, and both were found to be P. kansuensis. Despite the presence of mixed singers, population genomic analyses detected no signs of recent gene flow between the two species, although two possible cases of mitochondrial introgression were identified. We conclude that the rather limited song mixing does not lead to, or result from, hybridization, and hence does not result in the breakdown of reproductive barriers between these cryptic species.

The associations of post-stroke delirium with outcomes: a systematic review and meta-analysis.

BACKGROUND: Published data on whether post-stroke delirium (PSD) is an independent predictor of outcomes in patients with acute stroke are inconsistent and have not yet been synthesized and quantified via meta-analyses. METHODS: This systematic review and meta-analysis followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The study protocol involved a search of the PubMed, Embase, PsycINFO, and Medline databases from 1946 to November 1, 2023, of which prospective observational and case-control studies were included. The quality of the included studies was rated using the Newcastle Ottawa Scale. Pooled effect estimates calculated using a random-effects model were expressed as the odds ratios (ORs), hazard ratios (HRs), and standardized mean differences (SMDs) with 95% confidence intervals (CIs). The protocol was registered in PROSPERO (CRD42023472551). RESULTS: The search yielded 39 eligible articles comprising 3295 and 9643 patients with and without PSD, respectively. Thirty studies were high quality, while 9 had moderate quality. The primary analyses, adequately adjusting for predefined confounders, showed that PSD was significantly associated with mortality risk (average follow-up of 19.50 months; OR, 3.47; 95% CI, 2.35-5.12; I2, 26.0%) and poor neurological function (average follow-up of 21.75 months; OR, 3.62; 95% CI, 2.15-6.09; I2, 0). Secondary analyses, with or without inadequate adjustment, showed that PSD was significantly associated with prolonged hospital length of stay, increased risk of institutionalization, poor cognitive outcomes, and quality of life after discharge. CONCLUSIONS: This systematic review and meta-analysis provides evidence that PSD was independently associated with mortality and poor neurological function after controlling for pre-specified confounders. The prevention of PSD remains a high clinical and research priority.

PEDF-34 attenuates neurological deficit and suppresses astrocyte-dependent neuroinflammation by modulating astrocyte polarization via 67LR/JNK/STAT1 signaling pathway after subarachnoid hemorrhage in rats.

BACKGROUND: Reactive astrocytes participate in various pathophysiology after subarachnoid hemorrhage (SAH), including neuroinflammation, glymphatic-lymphatic system dysfunction, brain edema, BBB disruption, and cell death. Astrocytes transform into two new reactive phenotypes with changed morphology, altered gene expression, and secretion profiles, termed detrimental A1 and beneficial A2. This study investigates the effect of 67LR activation by PEDF-34, a PEDF peptide, on neuroinflammation and astrocyte polarization after the experimental SAH. METHODS: A total of 318 male adult Sprague-Dawley rats were used in experiments in vivo, of which 272 rats were subjected to the endovascular perforation model of SAH and 46 rats underwent sham surgery. 67LR agonist (PEDF-34) was administrated intranasally 1 h after SAH. 67LR-specific inhibitor (NSC-47924) and STAT1 transcriptional activator (2-NP) were injected intracerebroventricularly 48 h before SAH. Short- and long-term neurological tests, brain water content, immunostaining, Nissl staining, western blot, and ELISA assay were performed. In experiments in vitro, primary astrocyte culture with hemoglobin (Hb) stimulation was used to mimic SAH. The expression of the PEDF-34/67LR signaling pathway and neuro-inflammatory cytokines were assessed using Western blot, ELISA, and immunohistochemistry assays both in vivo and in vitro. RESULTS: Endogenous PEDF and 67LR expressions were significantly reduced at 6 h after SAH. 67LR was expressed in astrocytes and neurons. Intranasal administration of PEDF-34 significantly reduced brain water content, pro-inflammatory cytokines, and short-term and long-term neurological deficits after SAH. The ratio of p-JNK/JNK and p-STAT1/STAT1 and the expression of CFB and C3 (A1 astrocytes marker), significantly decreased after PEDF-34 treatment, along with fewer expression of TNF-α and IL-1ß at 24 h after SAH. However, 2-NP (STAT1 transcriptional activator) and NSC-47924 (67LR inhibitor) reversed the protective effects of PEDF-34 in vivo and in vitro by promoting A1 astrocyte polarization with increased inflammatory cytokines. CONCLUSION: PEDF-34 activated 67LR, attenuating neuroinflammation and inhibiting astrocyte A1 polarization partly via the JNK/STAT1 pathway, suggesting that PEDF-34 might be a potential treatment for SAH patients.

Nitrogen-Doped Carbon Dots Modified Fe-Co Sulfide Nanosheets as High-Efficiency Electrocatalysts toward Oxygen Evolution Reaction.

Developing high-efficiency and stable oxygen evolution reaction (OER) electrocatalysts is an imperative requirement to produce green and clean hydrogen energy. In this work, the FeCoSy /NCDs composite with nitrogen-doped carbon dots (NCDs) modified Fe-Co sulfide (FeCoSy ) nanosheets is prepared by using a facile and mild one-pot solvothermal method. Benefiting from the low crystallinity and the synergistic effect between FeCoSy and NCDs, the optimal FeCoSy /NCDs-3 composite exhibits an overpotential of only 284 mV at 10 mA cm-2 , a small Tafel value of 52.1 mV dec-1 , and excellent electrochemical durability in alkaline solution. Remarkably, unlike ordinary metal sulfide electrocatalysts, the morphology, components, and structure of the FeCoSy /NCDs composite can be well retained after OER test. The NCDs modified FeCoSy composite with excellent electrocatalytic performance provides an effective approach to boost metal sulfide electrocatalysts for practical application.

Modulating Surface Architecture and Electronic Conductivity of Li-rich Manganese-Based Cathode.

Li-rich manganese-based cathode (LRMC) has attracted intense attention to developing advanced lithium-ion batteries with high energy density. However, LRMC is still plagued by poor cyclic stability, undesired rate capacity, and irreversible oxygen release. To address these issues, herein, a feasible polyvinylidene fluoride (PVDF)-assisted interface modification strategy is proposed for modulating the surface architecture and electronic conductivity of LRMC by intruding the F-doped carbon coating, spinel structure, and oxygen vacancy on the LRMC, which can greatly enhance the cyclic stability and rate capacity, and restrain the oxygen release for LRMC. As a result, the modified material delivers satisfactory cyclic performance with a capacity retention of 90.22% after 200 cycles at 1 C, an enhanced rate capacity of 153.58 mAh g-1 at 5 C and 126.32 mAh g-1 at 10 C, and an elevated initial Coulombic efficiency of 85.63%. Moreover, the thermal stability, electronic conductivity, and structure stability of LRMC are also significantly improved by the PVDF-assisted interface modification strategy. Therefore, the strategy of simultaneously modulating the surface architecture and the electronic conductivity of LRMC provides a valuable idea to improve the comprehensive electrochemical performance of LRMC, which offers a promising reference for designing LRMC with high electrochemical performance.

In Situ Implanting ZrW2O7(OH)2(H2O)2 Nanorods into Hierarchical Functionalized Metal-Organic Framework via Solvent-Free Approach for Upgrading Catalytic Performance.

Host-guest catalyst provides new opportunities for targeted applications and the development of new strategies for preparing host-guest catalysts is highly desired. Herein, an in situ solvent-free approach is developed for implanting ZrW2O7(OH)2(H2O)2 nanorods (ZrW-NR) in nitro-functionalized UiO-66(Zr) (UiO-66(Zr)-NO2) with hierarchical porosity, and the encapsulation of ZrW-NR enables the as-prepared host-guest catalyst remarkably enhanced catalytic performance for both for oxidative desulfurization (ODS) and acetalization reactions. ZrW-NR@UiO-66(Zr)-NO2 can eliminate 500 ppm sulfur within 9 min at 40 °C in ODS, and can transform 5.6 mmol benzaldehyde after 3 min at room temperature in acetalization reaction. Its turnover frequencies reach 72.3 h-1 at 40 °C for ODS which is 33.4 times higher than UiO-66(Zr)-NO2, and 28140 h-1 for acetalization which is the highest among previous reports. Density functional theory calculation result indicates that the W sites in ZrW-NR can decompose H2O2 to WVI-peroxo intermediates that contribute to catalytic activity for the ODS reaction. This work opens a new solvent-free approach for preparing MOFs-based host-guest catalysts to upgrade their redox and acid performance.

Multifunctional DNA-Based Hydrogel Promotes Diabetic Alveolar Bone Defect Reconstruction.

Diabetic alveolar bone defect (DABD) causes persistent bacterial infection, prolonged inflammation, and delayed bone healing, making it a considerable clinical challenge. In this study, by integrating silver nanoclusters (AgNCs) and M2 macrophage-derived extracellular vesicles (M2EVs), a multifunctional DNA-based hydrogel, called Agevgel, is developed with antibacterial, anti-inflammatory, immunomodulatory, and osteogenic properties to promote DABD rebuilding. AgNCs are tightly embedded into the DNA scaffolds and exhibit effective anti-bacterial activity, while immunomodulatory M2EVs are encapsulated within the shape-variable DNA scaffolds and exhibit potent anti-inflammatory and osteogenic properties. The results reveal that Agevgel effectively prolongs the local retention time and bioactivity of M2EVs in vivo. In particular, the sustained release of M2EVs can last for at least 7 days when applying Agevgel to DABD. Compared to free M2EVs or Aggel (AgNCs encapsulated within the DNA hydrogel) treatments, the Agevgel treatment accelerates the defect healing rate of alveolar bone and dramatically improves the trabecular architecture. Mechanistically, Agevgel plays a key role in regulating macrophage polarization and promoting the expression of proliferative and osteogenic factors. In summary, Agevgel provides a comprehensive treatment strategy for DABD with a great clinical translational value, highlighting the application of DNA hydrogels as an ideal bioscaffolds for periodontal diseases.

Pseudomonas ZY-1 and Bacillus FY-1 protecting the rice seedlings from the harm of Pseudomonas aeruginosa via indirect seawead lysis.

The local ecosystems, fishery and human health are all threatened by water blooms, so effectively controlling water blooms has become an urgent and challenging issue. Biological control of water blooms is given priority due to its low cost, high efficiency and environmental friendliness. In this study, Pseudomonas ZY-1 and Bacillus FY-1, two highly-effective algicidal bacteria strains which are able to indirectly lyse algae by separating and screening from the vigorous water body in the paddy alga of Northeast China were obtained. The two bacterial strains have stronger ability to lyse alga in the bacterial liquid concentration of 106 CFU/ml, and the alga-lysing rate on 7 d reached 84.03% and 83.11% respectively. The active substance secreted by ZY-1 is not sensitive to the changes of temperature and pH value, while as FY-1 cell-free filtrate is not stable in high temperature above 50 ℃ and pH of 5, it requires the sun light to have the algaecidal effect. The cell-free filtrates of strains ZY-1 and FY-1 had the best lysis effect on Microcystis aeruginosa cells, and the chlorophyll a content of algae decreased to 0.13 ± 0.02 mg/L and 0.14 ± 0.03 mg/L respectively and the Fv/Fm of Microcystis aeruginosa decreased by 97.22% after 7 days. The algaecidal process of ZY-1 and FY-1 may be that the cell-free filtrate inhibits the photosynthesis of Microcystis aeruginosa, and meanwhile it avoids the regeneration and repair of photosynthesis of algal cells by affecting the gene expression and damaging the repair system of algal cells, so the membrane lipid peroxidation is exacerbated and then the membrane of algal cells is broken, the algal cells can't do normal life activities, and finally the algal cell would be killed. The rice seedlings in the algal liquid treatment group are short and show root dysplasia, few roots and brown roots. After treated with cell-free filtrate of ZY-1 and FY-1, the oxidative damage of the rice is obviously reduced, and the harm from Microcystis aeruginosa is reduced, which has the repair effect to the roots of rice seedlings and its aboveground growth. The cell-free filtrate of FY-1 works better than ZY-1. The bacteria strains of ZY-1 and FY-1 have the indirect algaecide trait, which makes them the potential environmentally-friendly algaecidal bacteria and they show broad application in the agricultural production and the control of water blooms.

Optimal Time-to-Surgery Recommendations Based on Primary Tumor Volume Regression for Patients with Resectable Esophageal Cancer after Neoadjuvant Chemoradiotherapy: A Retrospective Study.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) has shown promise in improving the prognosis of individuals with locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, the factors influencing tumor response and long-term survival in these patients remain unknown. The optimal timing for surgery after the completion of radiotherapy in LA-ESCC remains controversial. Therefore, this study was designed to identify biomarkers and to determine the optimal post-NCRT time-to-surgery (TTS) for patients with LA-ESCC. METHODS: This retrospective study included patients with resectable LA-ESCC who underwent NCRT between May 2017 and June 2021. The tumor shrinkage rate was calculated as the difference between the pre- and post-primary gross tumor volume (GTVp) divided by the pre-GTVp. Univariate and multivariate Cox regression analyses and Kaplan-Meier curves were used to calculate overall survival (OS) and progression-free survival (PFS). RESULTS: We collected data from 248 patients with resectable LA-ESCC who underwent computed tomography (CT) scans before the initiation of treatment. The median follow-up time was 37.7 months. The optimal cutoff of tumor shrinkage was 45%. In the univariate and multivariate analyses, we found a significant association between the tumor shrinkage rate and PFS (p = 0.001). Among the subgroup of patients who responded to treatment, extending the TTS was associated with improved OS (p = 0.037) and PFS (p = 0.028). CONCLUSIONS: For patients with resectable LA-ESCC, the tumor shrinkage rate is an independent prognostic factor for PFS. Thus, for responders, prolonging TTS is recommended to obtain a better OS.

The antimicrobial property of JY-1, a complex mixture of Traditional Chinese Medicine, is linked to it abilities to suppress biofilm formation and disrupt membrane permeability.

The substantial increase of infections, caused by novel, sudden, and drug-resistant pathogens, poses a significant threat to human health. While numerous studies have demonstrated the antibacterial and antiviral effects of Traditional Chinese Medicine, the potential of a complex mixture of traditional Chinese Medicine with a broad-spectrum antimicrobial property remains underexplored. This study aimed to develop a complex mixture of Traditional Chinese Medicine (TCM), JY-1, and investigate its antimicrobial properties, along with its potential mechanism of action against pathogenic microorganisms. Antimicrobial activity was assessed using a zone of inhibition assay and the drop plate method. Hyphal induction of Candida albicans was conducted using RPMI1640 medium containing 10% FBS, followed by microscopic visualization. Quantitative real-time PCR (RT-qPCR) was employed to quantify the transcript levels of hyphal-specific genes such as HWP1 and ALS3. The impact of JY-1 on biofilm formation was evaluated using both the XTT reduction assay and scanning electron microscopy (SEM). Furthermore, the cell membrane integrity was assessed by protein and nucleic acid leakage assays. Our results clearly showed that JY-1 significantly inhibits the vegetative growth of Candida spp. and Cryptococcus spp. In addition, this complex mixture is effectively against a wide range of pathogenic bacteria, including Staphylococcus aureus, Vancomycin-resistant enterococci, Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae. More interestingly, JY-1 plays a direct anti-viral role against the mammalian viral pathogen vesicular stomatitis virus (VSV). Further mechanistic studies indicate that JY-1 acts to reduce the expression of hyphal specific genes HWP1 and ALS3, resulting in the suppression of the hyphal formation of C. albicans. The antimicrobial property of JY-1 could be attributed to its ability to reduce biofilm formation and disrupt the cell membrane permeability, a process resulting in microbial cell death and the release of cellular contents. Taken together, our work identified a potent broad-spectrum antimicrobial agent, a complex mixture of TCM which might be developed as a potential antimicrobial drug.