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Paul Celan’s speech the “Meridian” addresses the fundamental question of how poetry can be possible in a world “after Auschwitz.” In contrast to the Platonic aesthetic system and classical art traditions, Celan draws upon Büchner’s concept of “Hostility to Art.” Amid the paradox of “the impossibility of writing” and “the loneliest loneliness,” Celan embraces the mission of “struggling with the German language,” speaking through a wounded mouth to reclaim a lost home for art. He employs a “grayer language” that distrusts beauty and turns toward truth, approaching a “meridian” of language in a way both “art-less” and “art-free.” On this “meridian,” Celan engages in a secret dialogue of poetry and thought with Others such as Mallarmé, Adorno, Nietzsche, and Heidegger, seeking to return to a realm that is at once uncanny and oriented toward the human.

Periodontal disease is a chronic infectious disease associated with a variety of bacteria, which can cause damage to the periodontal support structure and affect a variety of systemic system diseases such as cancer, cardiovascular disease, diabetes, rheumatoid arthritis, non-alcoholic fatty liver, and Alzheimer’s disease. Porphyromonas gingivalis ( P. gingivalis ) is the most important pathogenic bacteria for periodontal disease. It can produce outer membrane vesicles (OMVs) and release them into the environment, playing an important role in its pathogenesis. This article focuses on P. gingivalis OMVs, reviews its production and regulation, virulence components, mode of action and related diseases, with a view to providing new ideas for the prevention and treatment of diseases related to P. gingivalis infections.

Test anxiety is a common issue among college students, which can affect their physical and psychological health. However, effective interventions or therapeutic strategies are still lacking. This study aims to evaluate the potential effects of JYLP-326 on test anxious college students. Sixty anxious students were enrolled and randomly allocated to the placebo group and the probiotic group. Both groups were instructed to take placebo and JYLP-326 products twice per day for three weeks, respectively. Thirty unanxious students with no treatments were assigned to a regular control group. The anxiety, depression, and insomnia questionnaires were used to measure students' mental states at the baseline and the end of this study. 16S rRNA sequencing and untargeted metabolomics were performed to analyze the changes in the gut microbiota and fecal metabolism. The questionnaire results suggested that JYLP-326 administration could relieve the symptoms of anxiety, depression, and insomnia in test anxious students. The gut microbiomes of the placebo group showed a significantly greater diversity index than the control group (p < 0.05). An increased abundance of and at the genus level was observed in the placebo group, and the relative abundance of and decreased. Whereas, JYLP-326 administration could partly restore the disturbed gut microbiota. Additionally, test anxiety was correlated with disordered fecal metabolomics such as a higher Ethyl sulfate and a lower Cyclohexylamine, which could be reversed after taking JYLP-326. Furthermore, the changed microbiota and fecal metabolites were significantly associated with anxiety-related symptoms. The results indicate that the intervention of JYLP-326 could be an effective strategy to alleviate anxiety, depression, and insomnia in test anxious college students. The potential mechanism underlying this effect could be related to the regulation of gut microbiota and fecal metabolites.

Nonribosomal peptide synthetases (NRPSs) assemble a large group of structurally and functionally diverse natural products. While the iterative catalytic mechanism of bacterial NRPSs is known, it remains unclear how fungal NRPSs create products of desired length. Here we show that fungal iterative NRPSs adopt an alternate incorporation strategy. Beauvericin and bassianolide synthetases have the same C 1 -A 1 -T 1 -C 2 -A 2 -MT-T 2a -T 2b -C 3 domain organization. During catalysis, C 3 and C 2 take turns to incorporate the two biosynthetic precursors into the growing depsipeptide chain that swings between T 1 and T 2a /T 2b with C 3 cyclizing the chain when it reaches the full length. We reconstruct the total biosynthesis of beauvericin in vitro by reacting C 2 and C 3 with two SNAC-linked precursors and present a domain swapping approach to reprogramming these enzymes for peptides with altered lengths. These findings highlight the difference between bacterial and fungal NRPS mechanisms and provide a framework for the enzymatic synthesis of non-natural nonribosomal peptides. Nonribosomal peptides are important bioactive molecules that are synthetized by enzymes containing several catalytic domains. Here the authors describe the catalytic mechanism of fungal nonribosomal peptide synthetases and present an approach to modify these enzymes to produce specific nonribosomal peptides.

Bone tissue engineering is becoming an ideal strategy to replace autologous bone grafts for surgical bone repair, but the multihierarchical complexity of natural bone is still difficult to emulate due to the lack of suitable biomaterials. Supramolecular peptide nanofiber hydrogels (SPNHs) are emerging biomaterials because of their inherent biocompatibility, satisfied biodegradability, high purity, facile functionalization, and tunable mechanical properties. This review initially focuses on the multihierarchical fabrications by SPNHs to emulate natural bony extracellular matrix. Structurally, supramolecular peptides based on distinctive building blocks can assemble into nanofiber hydrogels, which can be used as nanomorphology‐mimetic scaffolds for tissue engineering. Biochemically, bioactive motifs and bioactive factors can be covalently tethered or physically absorbed to SPNHs to endow various functions depending on physiological and pharmacological requirements. Mechanically, four strategies are summarized to optimize the biophysical microenvironment of SPNHs for bone regeneration. Furthermore, comprehensive applications about SPNHs for bone tissue engineering are reviewed. The biomaterials can be directly used in the form of injectable hydrogels or composite nanoscaffolds, or they can be used to construct engineered bone grafts by bioprinting or bioreactors. Finally, continuing challenges and outlook are discussed. This review proposes a novel concept to construct bone repair biomaterials based on supramolecular peptide nanofiber hydrogels, namely multihierarchical fabrications by structural design, biochemical functionalization, and mechanical optimization. Then, it discusses the comprehensive applications of supramolecular peptide nanofiber hydrogels for bone tissue engineering, i.e., from injectable hydrogels or composite nanoscaffolds to bioprinting or bioreactors to construct engineered bone grafts.

Cellular diversification is critical for specialized functions of the brain including learning and memory 1 . Single-cell RNA sequencing facilitates transcriptomic profiling of distinct major types of neuron 2 – 4 , but the divergence of transcriptomic profiles within a neuronal population and their link to function remain poorly understood. Here we isolate nuclei tagged 5 in specific cell types followed by single-nucleus RNA sequencing to profile Purkinje neurons and map their responses to motor activity and learning. We find that two major subpopulations of Purkinje neurons, identified by expression of the genes Aldoc and Plcb4 , bear distinct transcriptomic features. Plcb4 + , but not Aldoc + , Purkinje neurons exhibit robust plasticity of gene expression in mice subjected to sensorimotor and learning experience. In vivo calcium imaging and optogenetic perturbation reveal that Plcb4 + Purkinje neurons have a crucial role in associative learning. Integrating single-nucleus RNA sequencing datasets with weighted gene co-expression network analysis uncovers a learning gene module that includes components of FGFR2 signalling in Plcb4 + Purkinje neurons. Knockout of Fgfr2 in Plcb4 + Purkinje neurons in mice using CRISPR disrupts motor learning. Our findings define how diversification of Purkinje neurons is linked to their responses in motor learning and provide a foundation for understanding their differential vulnerability to neurological disorders. Subpopulations of Purkinje neurons display distinct transcriptomic responses and functions in associative learning.

This review summarizes recent progress in the development of cobalt-based catalytic centers as the most potentially useful alternatives to noble metal-based electrocatalysts (Pt-, Ir-, and Ru-based) towards the oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and hydrogen evolution reaction (HER) in acid and alkaline media. A series of cobalt-based high-performance electrocatalysts have been designed and synthesized including cobalt oxides/chalcogenides, Co–Nx/C, Co-layered double hydroxides (LDH), and Co–metal-organic frameworks (MOFs). The strategies of controllable synthesis, the structural properties, ligand effect, defects, oxygen vacancies, and support materials are thoroughly discussed as a function of the electrocatalytic performance of cobalt-based electrocatalysts. Finally, prospects for the design of novel, efficient cobalt-based materials, for large-scale application and opportunities, are encouraged.

Cyclin-dependent kinase 2 (CDK2) is a crucial regulator of the eukaryotic cell cycle. However it is well established that monomeric CDK2 lacks regulatory activity, which needs to be aroused by its positive regulators, cyclins E and A, or be phosphorylated on the catalytic segment. Interestingly, these activation steps bring some dynamic changes on the 3D-structure of the kinase, especially the activation segment. Until now, in the monomeric CDK2 structure, three binding sites have been reported, including the adenosine triphosphate (ATP) binding site (Site I) and two non-competitive binding sites (Site II and III). In addition, when the kinase is subjected to the cyclin binding process, the resulting structural changes give rise to a variation of the ATP binding site, thus generating an allosteric binding site (Site IV). All the four sites are demonstrated as being targeted by corresponding inhibitors, as is illustrated by the allosteric binding one which is targeted by inhibitor ANS (fluorophore 8-anilino-1-naphthalene sulfonate). In the present work, the binding mechanisms and their fluctuations during the activation process attract our attention. Therefore, we carry out corresponding studies on the structural characterization of CDK2, which are expected to facilitate the understanding of the molecular mechanisms of kinase proteins. Besides, the binding mechanisms of CDK2 with its relevant inhibitors, as well as the changes of binding mechanisms following conformational variations of CDK2, are summarized and compared. The summary of the conformational characteristics and ligand binding mechanisms of CDK2 in the present work will improve our understanding of the molecular mechanisms regulating the bioactivities of CDK2.

Background Isolated microspore culture is a useful biotechnological technique applied in modern plant breeding programs as it can produce doubled haploid (DH) plants and accelerate the development of new varieties. Furthermore, as a single-cell culture technique, the isolated microspore culture provides an excellent platform for studying microspore embryogenesis. However, the reports on isolated microspore culture are rather limited in rice due to the low callus induction rate, poor regeneration capability, and high genotypic dependency. The present study developed an effective isolated microspore culture protocol for high-frequency androgenesis in four japonica rice genotypes. Several factors affecting the isolated microspore culture were studied to evaluate their effects on callus induction and plantlet regeneration. Results Low-temperature pre-treatment at 4 ℃ for 10–15 days could effectively promote microspore embryogenesis in japonica rice. A simple and efficient method was proposed for identifying the microspore developmental stage. The anthers in yellow-green florets located on the second type of primary branch on the rice panicle were found to be the optimal stage for isolated microspore culture. The most effective induction media for callus induction were IM2 and IM3, depending on the genotype. The optimal concentration of 2, 4-D in the medium for callus induction was 1 mg/L. Callus induction was negatively affected by a high concentration of KT over 1.5 mg/L. The differentiation medium suitable for japonica rice microspore callus comprised 1/2 MS, 2 mg/L 6-BA, 0.5 mg/L NAA, 30 g/L sucrose, and 6 g/L agar. The regeneration frequency of the four genotypes ranged from 61–211 green plantlets per 100 mg calli, with Chongxiangjing showing the highest regeneration frequency. Conclusions This study presented an efficient protocol for improved callus induction and green plantlet regeneration in japonica rice via isolated microspore culture, which could provide valuable support for rice breeding and genetic research.

Background Salt stress is a major abiotic stress that threatens crop production globally. Among various growth stages, seed germination, crucial for seedling establishment and crop population, is highly sensitive to salt stress. Therefore, it is essential to explore the molecular mechanisms at this stage for the breeding of salt-tolerant crops and global food security. Results In this study, two salt-tolerant (B080 and B084) and two salt-sensitive (B004 and B005) naked barley landraces were exposed to salt stress for 7 days during germination and their transcriptome were compared to identify differentially expressed genes (DEGs) related to salt stress. In totally, 2348, 1847, 2251, and 1251 DEGs were obtained in B080, B084, B004, and B005, respectively. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment of DEGs were analyzed. Eight DEGs were further validated by qPCR. Although there were only two genes significantly differential expressed, the upregulation and downregulation trends of all genes were consistent with mRNA-seq data. Conclusions The analysis of DEGs between salt-tolerant and salt-sensitive naked barley landraces under salt stress, as well as their GO and KEGG enrichment, could reveal and enrich the molecular mechanism of salt tolerance in naked barley.