Bipolar Textile Composite Electrodes Enabling Flexible Tandem Solid-State Lithium Metal Batteries.

A majority of flexible and wearable electronics require high operational voltage that is conventionally achieved by serial connection of battery unit cells using external wires. However, this inevitably decreases the energy density of the battery module and may cause additional safety hazards. Herein, a bipolar textile composite electrode (BTCE) that enables internal tandem-stacking configuration to yield high-voltage (6 to 12 V class) solid-state lithium metal batteries (SSLMBs) is reported. BTCE is comprised of a nickel-coated poly(ethylene terephthalate) fabric (NiPET) core layer, a cathode coated on one side of the NiPET, and a Li metal anode coated on the other side of the NiPET. Stacking BTCEs with solid-state electrolytes alternatively leads to the extension of output voltage and decreased usage of inert package materials, which in turn significantly boosts the energy density of the battery. More importantly, the BTCE-based SSLMB possesses remarkable capacity retention per cycle of over 99.98% over cycling. The composite structure of BTCE also enables outstanding flexibility; the battery keeps stable charge/discharge characteristics over thousands of bending and folding. BTCE shows great promise for future safe, high-energy-density, and flexible SSLMBs for a wide range of flexible and wearable electronics.

Construction of a Pickering interfacial biocatalysis system in skim milk and enzymatic transesterification for enhancement of flavor and quality.

Despite considerable research efforts, lipase catalysis in a fluid milk system with aqueous multi-component mixtures containing multiple microphases, remains challenging. Pickering interfacial biocatalysis (PIB) platforms are typically fabricated with organic solvents/lipids and water. Whether a PIB with excellent catalytic performance can be constructed in complex milk mixtures remains unknown. Here, we challenged PIB with skim milk, and a small amount of flaxseed oil, and phytosterols as a model system for transesterification and lipolysis to enhance quality and flavor. The amino-modified mesoporous silica spheres (MSS-N) were employed as an emulsifier and carrier of lipase AYS (AYS@MSS-N). The conversion of phytosterol esters reached 75.5% at 1.5 h and prepared phytosterol ester-fortified milk with a content of 1.0 g/100 mL. The relative conversion rate remained above 70% after 6 cycles. In addition, the fortified milk showed an intensified and favorable effect on sensory traits through volatile flavor composition analysis. The findings provide a versatile alternative for PIB applications in complex environments, i.e., milk, which might inspire a new bioprocess strategy for dairy products.

Breathable Dual-Mode Leather-Like Nanotextile for Efficient Daytime Radiative Cooling and Heating.

Incorporating passive radiative cooling and heating into personal thermal management has attracted tremendous attention. However, most current thermal management materials are usually monofunctional with a narrow temperature regulation range, and lack breathability, softness, and stretchability, resulting in a poor wearer experience and limited application scenarios. Herein, a breathable dual-mode leather-like nanotextile (LNT) with asymmetrical wrinkle photonic microstructures and Janus wettability for highly efficient personal thermal management is developed via a one-step electrospinning technique. The LNT is synthesized by self-bonding a hydrophilic cooling layer with welding fiber networks onto a hydrophobic photothermal layer, constructing bilayer wrinkle structures that offer remarkable optical properties, a wetting gradient, and unique textures. The resultant LNT exhibits efficient cooling capacity (22.0 °C) and heating capacity (22.1 °C) under sunlight, expanding the thermal management zone (28.3 °C wider than typical textiles). Additionally, it possesses favorable breathability, softness, stretchability, and sweat-wicking capability. Actual wearing tests demonstrate that the LNT can provide a comfortable microenvironment for the human body (1.6-8.0 °C cooler and 1.0-7.1 °C warmer than typical textiles) in changing weather conditions. Such a wearable dual-mode LNT presents great potential for personal thermal comfort and opens up new possibilities for all-weather smart clothing.

Fermentative Production of Ergothioneine by Exploring Novel Biosynthetic Pathway and Remodulating Precursor Synthesis Pathways.

Ergothioneine (EGT) is a naturally occurring derivative of histidine with diverse applications in the medicine, cosmetic, and food industries. Nevertheless, its sustainable biosynthesis faces hurdles due to the limited biosynthetic pathways, complex metabolic network of precursors, and high cost associated with fermentation. Herein, efforts were made to address these limitations first by reconstructing a novel EGT biosynthetic pathway from Methylobacterium aquaticum in Escherichia coli and optimizing it through plasmid copy number. Subsequently, the supply of precursor amino acids was promoted by engineering the global regulator, recruiting mutant resistant to feedback inhibition, and blocking competitive pathways. These metabolic modifications resulted in a significant improvement in EGT production, increasing from 35 to 130 mg/L, representing a remarkable increase of 271.4%. Furthermore, an economical medium was developed by replacing yeast extract with corn steep liquor, a byproduct of wet milling of corn. Finally, the production of EGT reached 595 mg/L with a productivity of 8.2 mg/L/h by exploiting fed-batch fermentation in a 10 L bioreactor. This study paves the way for exploring and modulating a de novo biosynthetic pathway for efficient and low-cost fermentative production of EGT.

Efficient Fermentative Production of ß-Alanine from Glucose through Multidimensional Engineering of Escherichia coli.

ß-Alanine, a valuable ß-type amino acid, is experiencing increased demand due to its multifaceted applications in food flavoring, nutritional supplements, pharmaceuticals, and the chemical industry. Nevertheless, the sustainable biosynthesis of ß-alanine currently faces challenges due to the scarcity of robust strains, attributed to the complexities of modulating multiple genes and the inherent physiological constraints. Here, systems metabolic engineering was implemented in Escherichia coli to overcome these limitations. First, an efficient l-aspartate-α-decarboxylase (ADC) was recruited for ß-alanine biosynthesis. To conserve phosphoenolpyruvate flux, we subsequently modified the endogenous glucose assimilation system by inactivating the phosphotransferase system (PTS) and introducing an alternative non-PTS system, which increased ß-alanine production to 1.70 g/L. The supply of key precursors, oxaloacetate and l-aspartate, was synergistically improved through comprehensive modulation, including strengthening main flux and blocking bypass metabolism, which significantly increased the ß-alanine titer to 3.43 g/L. Next, the expression of ADC was optimized by promoter and untranslated region (UTR) engineering. Further transport engineering, which involved disrupting ß-alanine importer CycA and heterologously expressing ß-alanine exporter NCgI0580, improved ß-alanine production to 8.48 g/L. Additionally, corn steep liquor was used to develop a cost-effective medium. The final strain produced 74.03 g/L ß-alanine with a yield of 0.57 mol/mol glucose during fed-batch fermentation.

Unveiling the Regulatory Role of SIRT1 in Oxidative Stress Response of bovine mammary cells.

High-yield dairy cows typically undergo intense cellular metabolism, leading to oxidative stress in their mammary tissues. Our study found that these high-yield cows had significantly elevated levels of hydrogen peroxide (H2O2), lipoperoxidase, and total antioxidant capacity in their blood, compared with ordinary cows. This increased oxidative stress is associated with heightened expression of genes such as GCLC, GCLM and SIRT1 and proteins such as SIRT1 in the mammary tissue of high-yield cows. MAC-T cells were stimulated with H2O2 at a concentration equal to the average H2O2 level in the serum of ethically high-yielding cows, as detected by an assay kit. Our observations revealed that short-term exposure (12 h) to H2O2 upregulated the expression of SIRT1 gene and protein. It also increased gene expression for SOD2, CAT, GCLC, GCLM, PGC-1α, and NQO1, elevated the phosphorylation of AMPK, and enhanced protein expression of PGC-1α, NQO1, Nrf2, and HO-1, while reducing the phosphorylation of NF-κB. Additionally, short-term H2O2 stimulation resulted in increased total antioxidant capacity, SOD, GSH, and CAT levels in the mammary epithelial cells of dairy cows. In contrast, prolonged exposure to H2O2 (24 h) yielded opposite results, indicating reduced antioxidant capacity. Further investigation showed that SIRT1 inhibitor (EX 527) could reverse the enhanced cellular antioxidant capacity triggered by short-term oxidative stress. However, it is crucial to note that while 12 h H2O2 stimulation improved antioxidant capacity, reactive oxygen species (ROS) and malondialdehyde (MDA) levels inside the cell gradually increased over time, suggesting greater damage under long-term stimulation. Conversely, the SIRT1 activator (SRT 2104) could reverse the reduced cellular antioxidant capacity caused by long-term oxidative stress and significantly inhibit the accumulation of ROS and MDA. Notably, SRT 2104 demonstrated similar effects in MAC-T cells during lactation. In summary, SIRT1 plays a crucial role in regulating the antioxidant capacity of mammary epithelial cells in dairy cows. This discovery provides valuable insights into the antioxidant mechanisms of mammary cells, which can serve as a theoretical foundation for future mammary health strategies.

Improving Catalytic Efficiency of L-Arabinose Isomerase from Lactobacillus plantarum CY6 towards D-Galactose by Molecular Modification.

L-Arabinose isomerase (L-AI) has been commonly used as an efficient biocatalyst to produce D-tagatose via the isomerization of D-galactose. However, it remains a significant challenge to efficiently synthesize D-tagatose using the native (wild type) L-AI at an industrial scale. Hence, it is extremely urgent to redesign L-AI to improve its catalytic efficiency towards D-galactose, and herein a structure-based molecular modification of Lactobacillus plantarum CY6 L-AI (LpAI) was performed. Among the engineered LpAI, both F118M and F279I mutants showed an increased D-galactose isomerization activity. Particularly, the specific activity of double mutant F118M/F279I towards D-galactose was increased by 210.1% compared to that of the wild type LpAI (WT). Besides the catalytic activity, the substrate preference of F118M/F279I was also largely changed from L-arabinose to D-galactose. In the enzymatic production of D-tagatose, the yield and conversion ratio of F118M/F279I were increased by 81.2% and 79.6%, respectively, compared to that of WT. Furthermore, the D-tagatose production of whole cells expressing F118M/F279I displayed about 2-fold higher than that of WT cell. These results revealed that the designed site-directed mutagenesis is useful for improving the catalytic efficiency of LpAI towards D-galactose.

Discovery of novel CDK9 inhibitor with tridentate ligand: Design, synthesis and biological evaluation.

Cyclin-dependent kinase 9 (CDK9) plays a role in transcriptional regulation, which had become an attractive target for discovery of antitumor agent. In this work, beyond traditional CDK9 inhibitor with bidentate ligands in ATP binding domain, a series of novel CDK9 inhibitor with tridentate ligand were designed and synthesized. Surprisingly, this unique tridentate ligand structure endows better CDK9 inhibition selectivity compared to other CDK subtypes, and the lead candidate compound Z4-7a showed effective proliferation inhibition in HCT116 cells with acceptable pharmacokinetic properties. Research on the mechanism indicated that Z4-7a could induce apoptosis in the HCT116 cell line by inhibiting phosphorylation of RNA polymerase II at Ser2, which resulted in the inhibition of apoptosis-related genes and proteins expression. In brief, introduction of tridentate ligand might work as a promising strategy for the development of novel selective CDK9 inhibitor.

The role and mechanism of cinnamaldehyde in cancer.

As cancer continues to rise globally, there is growing interest in discovering novel methods for prevention and treatment. Due to the limitations of traditional cancer therapies, there has been a growing emphasis on investigating herbal remedies and exploring their potential synergistic effects when combined with chemotherapy drugs. Cinnamaldehyde, derived from cinnamon, has gained significant attention for its potential role in cancer prevention and treatment. Extensive research has demonstrated that cinnamaldehyde exhibits promising anticancer properties by modulating various cellular processes involved in tumor growth and progression. However, challenges and unanswered questions remain regarding the precise mechanisms for its effective use as an anticancer agent. This article aims to explore the multifaceted effects of cinnamaldehyde on cancer cells and shed light on these existing issues. Cinnamaldehyde has diverse anti-cancer mechanisms, including inducing apoptosis by activating caspases and damaging mitochondrial function, inhibiting tumor angiogenesis, anti-proliferation, anti-inflammatory and antioxidant. In addition, cinnamaldehyde also acts as a reactive oxygen species scavenger, reducing oxidative stress and preventing DNA damage and genomic instability. This article emphasizes the promising therapeutic potential of cinnamaldehyde in cancer treatment and underscores the need for future research to unlock novel mechanisms and strategies for combating cancer. By providing valuable insights into the role and mechanism of cinnamaldehyde in cancer, this comprehensive understanding paves the way for its potential as a novel therapeutic agent. Overall, cinnamaldehyde holds great promise as an anticancer agent, and its comprehensive exploration in this article highlights its potential as a valuable addition to cancer treatment options.

Enhancement of nitrogen on core taxa recruitment by Penicillium oxalicum stimulated microbially-driven soil formation in bauxite residue.

Microbially-driven soil formation process is an emerging technology for the ecological rehabilitation of alkaline tailings. However, the dominant microorganisms and their specific roles in soil formation processes remain unknown. Herein, a 1-year field-scale experiment was applied to demonstrate the effect of nitrogen input on the structure and function of the microbiome in alkaline bauxite residue. Results showed that the contents of nutrient components were increased with Penicillium oxalicum (P. oxalicum) incorporation, as indicated by the increasing of carbon and nitrogen mineralization and enzyme metabolic efficiency. Specifically, the increasing enzyme metabolic efficiency was associated with nitrogen input, which shaped the microbial nutrient acquisition strategy. Subsequently, we evidenced that P. oxalicum played a significant role in shaping the assemblages of core bacterial taxa and influencing ecological functioning through intra- and cross-kingdom network analysis. Furthermore, a recruitment experiment indicated that nitrogen enhanced the enrichment of core microbiota (Nitrosomonas, Bacillus, Pseudomonas, and Saccharomyces) and may provide benefits to fungal community bio-diversity and microbial network stability. Collectively, these results demonstrated nitrogen-based coexistence patterns among P. oxalicum and microbiome and revealed P. oxalicum-mediated nutrient dynamics and ecophysiological adaptations in alkaline microhabitats. It will aid in promoting soil formation and ecological rehabilitation of bauxite residue. ENVIRONMENT IMPLICATION: Bauxite residue is a highly alkaline solid waste generated during the Bayer process for producing alumina. Attempting to transform bauxite residue into a stable soil-like substrate using low-cost microbial resources is a highly promising engineering. However, the dominant microorganisms and their specific roles in soil formation processes remain unknown. In this study, we evidenced the nitrogen-based coexistence patterns among Penicillium oxalicum and microbiome and revealed Penicillium oxalicum-mediated nutrient dynamics and ecophysiological adaptations in alkaline microhabitats. This study can improve the understanding of core microbes' assemblies that affect the microbiome physiological traits in soil formation processes.

Ultrasound-assisted intensification of Pickering interfacial biocatalysis preparation of vitamin A aliphatic esters.

A novel approach to ultrasound-assisted Pickering interfacial biocatalysis (PIB) has been proposed and implemented for the efficient enzymatic transesterification production of vitamin A fatty acid esters. This is the first instance of exploiting the synergistic effect of ultrasound and the bifunctional modification of enzyme supports to accelerate biocatalytic performance in PIB systems. The optimal conditions were determined to be ultrasound power of 70 W, on/off time of 5 s/5 s, substrate molar ratio of 1:1, enzyme addition of 2 %, and a volume ratio of n-hexane to PBS of 3:1, a temperature of 40 °C, and a time of 30 min. The application of ultrasound technology not only improved lipase activity but also allowed for a reduction in emulsion droplet size to enhance interfacial mass transfer.Bifunctional modification of silica-based supports enhanced stability of immobilized enzymes by increasing hydrogen bonding while maintaining the active interface microenvironment. Compared with a non-ultrasound-assisted PIB system stabilized by mono-modified immobilized enzyme particles, the catalytic efficacy (CE) of the novel system reached 8.18 mmol g-1 min-1, which was enhanced by 3.33-fold, while the interfacial area was found to have increased by 17.5-fold. The results facilitated the conversion of vitamin A palmitate (VAP), vitamin A oleate (VAO), vitamin A linoleate (VAL), and vitamin A linolenate (VALn), with conversion rates of approximately 98.2 %, 97.4 %, 96.1 %, and 94.7 %, respectively. This represents the most efficient example that has been reported to our knowledge. Furthermore, the system demonstrated improved reusability, with a conversion rate of 62.1 % maintained even after 10 cycles. The findings presented in this paper provide valuable insights into an efficient and conveniently promising protocol for the development of PIB systems.

Superhalide-Anion-Motivator Reforming-Enabled Bipolar Manipulation toward Longevous Energy-Type Zn||Chalcogen Batteries.

Neutrophilic superhalide-anion-triggered chalcogen conversion-based Zn batteries, despite latent high-energy merit, usually suffer from a short lifespan caused by dendrite growth and shuttle effect. Here, a superhalide-anion-motivator reforming strategy is initiated to simultaneously manipulate the anode interface and Se conversion intermediates, realizing a bipolar regulation toward longevous energy-type Zn batteries. With ZnF2 chaotropic additives, the original large-radii superhalide zincate anion species in ionic liquid (IL) electrolytes are split into small F-containing species, boosting the formation of robust solid electrolyte interphases (SEI) for Zn dendrite inhibition. Simultaneously, ion radius reduced multiple F-containing Se conversion intermediates form, enhancing the interion interaction of charged products to suppress the shuttle effect. Consequently, Zn||Se batteries deliver a ca. 20-fold prolonged lifespan (2000 cycles) at 1 A g-1 and high energy/power density of 416.7 Wh kgSe-1/1.89 kW kgSe-1, outperforming those in F-free counterparts. Pouch cells with distinct plateaus and durable cyclability further substantiate the practicality of this design.

Mitochondria-Regulated Information Processing Nanosystem Promoting Immune Cell Communication for Liver Fibrosis Regression.

Liver fibrosis is a coordinated response to tissue injury that is mediated by immune cell interactions. A mitochondria-regulated information-processing (MIP) nanosystem that promotes immune cell communication and interactions to inhibit liver fibrosis is designed. The MIP nanosystem mimics the alkaline amino acid domain of mitochondrial precursor proteins, providing precise targeting of the mitochondria. The MIP nanosystem is driven by light to modulate the mitochondria of hepatic stellate cells, resulting in the release of mitochondrial DNA into the fibrotic microenvironment, as detected by macrophages. By activating the STING signaling pathway, the developed nanosystem-induced macrophage phenotype switches to a reparative subtype (Ly6Clow) and downstream immunostimulatory transcriptional activity, fully restoring the fibrotic liver to its normal tissue state. The MIP nanosystem serves as an advanced information transfer system, allowing precise regulation of trained immunity, and offers a promising approach for effective liver fibrosis immunotherapy with the potential for clinical translation.

The impact of antibiotic exposure on antibiotic resistance gene dynamics in the gut microbiota of inflammatory bowel disease patients.

Background: While antibiotics are commonly used to treat inflammatory bowel disease (IBD), their widespread application can disturb the gut microbiota and foster the emergence and spread of antibiotic resistance. However, the dynamic changes to the human gut microbiota and direction of resistance gene transmission under antibiotic effects have not been clearly elucidated. Methods: Based on the Human Microbiome Project, a total of 90 fecal samples were collected from 30 IBD patients before, during and after antibiotic treatment. Through the analysis workflow of metagenomics, we described the dynamic process of changes in bacterial communities and resistance genes pre-treatment, during and post-treatment. We explored potential consistent relationships between gut microbiota and resistance genes, and established gene transmission networks among species before and after antibiotic use. Results: Exposure to antibiotics can induce alterations in the composition of the gut microbiota in IBD patients, particularly a reduction in probiotics, which gradually recovers to a new steady state after cessation of antibiotics. Network analyses revealed intra-phylum transfers of resistance genes, predominantly between taxonomically close organisms. Specific resistance genes showed increased prevalence and inter-species mobility after antibiotic cessation. Conclusion: This study demonstrates that antibiotics shape the gut resistome through selective enrichment and promotion of horizontal gene transfer. The findings provide insights into ecological processes governing resistance gene dynamics and dissemination upon antibiotic perturbation of the microbiota. Optimizing antibiotic usage may help limit unintended consequences like increased resistance in gut bacteria during IBD management.

Neoseiulus mites as biological control agents against Megalurothrips usitatus (Thysanoptera: Thripidae) and Frankliniella intonsa (Thysanoptera: Thripidae) on cowpea crop: laboratory to field.

Megalurothrips usitatus (Bagnall) (Thysanoptera: Thripidae) and Frankliniella intonsa (Trybom) (Thysanoptera: Thripidae) have been detrimental to cowpea production in many countries. Laboratory experiments were conducted to determine the prey stage preference and functional response of 2 predatory mites species, Neoseiulus barkeri (Hughes) (Acari: Phytoseiidae), and Neoseiulus californicus (McGregor) (Acari: Phytoseiidae), towards 2 thrips species (TS), M. usitatus, and F. intonsa, at varying densities and life stages on cowpea. Results shown that Neoseiulus species had a preference for different life stages of prey. Neoseiulus barkeri consumed more M. usitatus nymphs, while N. californicus consumed more F. intonsa (second-instar nymphs). The functional response of the 2 Neoseiulus spp. to nymphs of 2 TS was Type II on cowpea. The higher attack rate coefficient (a') and shorter handling time (Th) values were found on N. barkeri against M. usitatus, and a similar trend was found for those in N. californicus against F. intonsa. Field-caged trials were conducted to evaluate the effectiveness of Neoseiulus spp. in controlling 2 TS. The results have shown that Neoseiulus spp. was effective in controlling the 2 TS, with varying control efficacies at high or low release rates. The study provided valuable information on using Neoseiulus spp. as biological control agents against M. usitatus and F. intonsa in cowpea crops.

A Living Microecological Hydrogel with Microbiota Remodeling and Immune Reinstatement for Diabetic Wound Healing.

Dysregulated skin microbiota and compromised immune responses are the major etiological factors for non-healing diabetic wounds. Current antibacterial strategies fail to orchestrate immune responses and indiscriminately eradicate bacteria at the wound site, exacerbating the imbalance of microbiota. Drawing inspiration from the beneficial impacts that probiotics possess on microbiota, a living microecological hydrogel containing Lactobacillus plantarum and fructooligosaccharide (LP/FOS@Gel) is formulated to remodel dysregulated skin microbiota and reinstate compromised immune responses, cultivating a conducive environment for optimal wound healing. LP/FOS@Gel acts as an "evocator," skillfully integrating the skin microecology, promoting the proliferation of Lactobacillus, Ralstonia, Muribaculum, Bacillus, and Allobaculum, while eradicating colonized pathogenic bacteria. Concurrently, LP/FOS@Gel continuously generates lactic acid to elicit a reparative macrophage response and impede the activation of the nuclear factor kappa-B pathway, effectively alleviating inflammation. As an intelligent microecological system, LP/FOS@Gel reinstates the skin's sovereignty during the healing process and effectively orchestrates the harmonious dialogue between the host immune system and microorganisms, thereby fostering the healing of diabetic infectious wounds. These remarkable attributes render LP/FOS@Gel highly advantageous for pragmatic clinical applications.

TET activity safeguards pluripotency throughout embryonic dormancy.

Dormancy is an essential biological process for the propagation of many life forms through generations and stressful conditions. Early embryos of many mammals are preservable for weeks to months within the uterus in a dormant state called diapause, which can be induced in vitro through mTOR inhibition. Cellular strategies that safeguard original cell identity within the silent genomic landscape of dormancy are not known. Here we show that the protection of cis-regulatory elements from silencing is key to maintaining pluripotency in the dormant state. We reveal a TET-transcription factor axis, in which TET-mediated DNA demethylation and recruitment of methylation-sensitive transcription factor TFE3 drive transcriptionally inert chromatin adaptations during dormancy transition. Perturbation of TET activity compromises pluripotency and survival of mouse embryos under dormancy, whereas its enhancement improves survival rates. Our results reveal an essential mechanism for propagating the cellular identity of dormant cells, with implications for regeneration and disease.

Cell-free biosynthesis and engineering of ribosomally synthesized lanthipeptides.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a major class of natural products with diverse chemical structures and potent biological activities. A vast majority of RiPP gene clusters remain unexplored in microbial genomes, which is partially due to the lack of rapid and efficient heterologous expression systems for RiPP characterization and biosynthesis. Here, we report a unified biocatalysis (UniBioCat) system based on cell-free gene expression for rapid biosynthesis and engineering of RiPPs. We demonstrate UniBioCat by reconstituting a full biosynthetic pathway for de novo biosynthesis of salivaricin B, a lanthipeptide RiPP. Next, we delete several protease/peptidase genes from the source strain to enhance the performance of UniBioCat, which then can synthesize and screen salivaricin B variants with enhanced antimicrobial activity. Finally, we show that UniBioCat is generalizable by synthesizing and evaluating the bioactivity of ten uncharacterized lanthipeptides. We expect UniBioCat to accelerate the discovery, characterization, and synthesis of RiPPs.

Differential gene expression and immune cell infiltration in maedi-visna virus-infected lung tissues.

BACKGROUND: Maedi-visna virus (MVV) is a lentivirus that infects monocyte/macrophage lineage cells in sheep, goats, and wild ruminants and causes pneumonia, mastitis, arthritis, and encephalitis. The immune response to MVV infection is complex, and a complete understanding of its infection and pathogenesis is lacking. This study investigated the in vivo transcriptomic patterns of lung tissues in sheep exposed to MVV using the RNA sequencing technology. RESULT: The results indicated that 2,739 genes were significantly differentially expressed, with 1,643 downregulated genes and 1,096 upregulated genes. Many variables that could be unique to MVV infections were discovered. Gene Ontology analysis revealed that a significant proportion of genes was enriched in terms directly related to the immune system and biological responses to viral infections. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the most enriched pathways were related to virus-host cell interactions and inflammatory responses. Numerous immune-related genes, including those encoding several cytokines and interferon regulatory factors, were identified in the protein-protein interaction network of differentially expressed genes (DEGs). The expression of DEGs was evaluated using real-time polymerase chain reaction and western blot analysis. CXCL13, CXCL6, CXCL11, CCR1, CXCL8, CXCL9, CXCL10, TNFSF8, TNFRSF8, IL7R, IFN-γ, CCL2, and MMP9 were upregulated. Immunohistochemical analysis was performed to identify the types of immune cells that infiltrated MVV-infected tissues. B cells, CD4+ and CD8+ T cells, and macrophages were the most prevalent immune cells correlated with MVV infection in the lungs. CONCLUSION: Overall, the findings of this study provide a comprehensive understanding of the in vivo host response to MVV infection and offer new perspectives on the gene regulatory networks that underlie pathogenesis in natural hosts.

KIF11 UFMylation Maintains Photoreceptor Cilium Integrity and Retinal Homeostasis.

The photoreceptor cilium is vital for maintaining the structure and function of the retina. However, the molecular mechanisms underlying the photoreceptor cilium integrity and retinal homeostasis are largely unknown. Herein, it is shown that kinesin family member 11 (KIF11) localizes at the transition zone (connecting cilium) of the photoreceptor and plays a crucial role in orchestrating the cilium integrity. KIF11 depletion causes malformations of both the photoreceptor ciliary axoneme and membranous discs, resulting in photoreceptor degeneration and the accumulation of drusen-like deposits throughout the retina. Mechanistic studies show that the stability of KIF11 is regulated by an interplay between its UFMylation and ubiquitination; UFMylation of KIF11 at lysine 953 inhibits its ubiquitination by synoviolin 1 and thereby prevents its proteasomal degradation. The lysine 953-to-arginine mutant of KIF11 is more stable than wild-type KIF11 and also more effective in reversing the ciliary and retinal defects induced by KIF11 depletion. These findings identify a critical role for KIF11 UFMylation in the maintenance of photoreceptor cilium integrity and retinal homeostasis.