MCPIP1 restrains mucosal inflammation by orchestrating the intestinal monocyte to macrophage maturation via an ATF3-AP1S2 axis.

OBJECTIVE: Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) is highly expressed in inflamed mucosa of inflammatory bowel disease (IBD) and negatively regulates immune response, while the underlying mechanisms regulating mucosal macrophage functions remain unknown. Here, we investigated the roles of MCPIP1 in modulating the differentiation and functions of intestinal macrophages in the pathogenesis of IBD. DESIGN: ScRNA-seq was used to cluster the monocyte/macrophage lineage from macrophage-specific Mcpip1-deficient (Mcpip1 ∆Mye) mice and Mcpip1 fl/fl littermates. The differentially expressed genes were confirmed by RNA-seq, luciferase assay, CUT&Tag assay and Western blotting. Effects of MCPIP1 and the activating transcription factor 3 (ATF3)-AP1S2 axis were assessed in patients with IBD. RESULTS: Mcpip1 ∆Mye mice developed more severe dextran sulfate sodium (DSS)-induced colitis characterised by an increase in macrophage migratory capacity and M1 macrophage polarisation but a decrease in the monocyte-to-macrophage maturation in gut mucosa compared with their littermates. ScRNA-seq unravelled a proinflammatory population (Ccr2+Il-1ß+Tlr2+Cx3cr1-Cd163-Mrc1-Ly6c+) of the monocyte/macrophage lineage from lamina propria CD11b+ cells and an arrest of Mcpip1 ∆Mye monocyte-to-macrophage maturation in an Atf3-Ap1s2 axis-dependent manner. Silencing of Ap1s2 or Atf3 markedly suppressed Mcpip1 ∆Mye macrophage migration, M1-like polarisation, and production of proinflammatory cytokines and chemokines. Notably, in vivo blockage of Ap1s2 ameliorated DSS-induced colitis in Mcpip1 ΔMye mice through enhancing intestinal macrophage maturation. Furthermore, MCPIP1, ATF3 and AP1S2 were highly expressed in inflamed mucosa of active patients with IBD and blockage of ATF3 or AP1S2 significantly suppressed IBD CD14+-derived M1-like macrophage polarisation and proinflammatory cytokine production. CONCLUSIONS: Macrophage-specific Mcpip1 deficiency polarises macrophages towards M1-like phenotype, arrests macrophage maturation and exacerbates intestinal inflammation in an Atf3-Ap1s2-dependent manner, thus providing novel mechanistic insight into intestinal macrophage functions during IBD.

ETS-1 facilitates Th1 cell-mediated mucosal inflammation in inflammatory bowel diseases through upregulating CIRBP.

BACKGROUND & AIMS: As a susceptibility gene for human inflammatory bowel diseases (IBD), how avian erythroblastosis virus E26 oncogene homolog-1 (ETS-1) modulates intestinal mucosal immune response remains unclear. Here we studied the potential roles of ETS-1 in the pathogenesis of IBD. METHODS: ETS-1 expression was examined in IBD patients. CD45RBhighCD4+ T cell-transfer colitis, dextran sulfate sodium (DSS)-induced colitis, and azomethane (AOM)/DSS-induced colitis-associated cancer (CAC) models were constructed to probe the function of ETS-1 in vivo. RNA-sequencing of CD4+ T cells from Ets-1 transgenic (Tg) mice was performed to decipher the key differentially expressed genes. Adenovirus transduction was conducted to verify the therapeutic potentials of ETS-1 in vivo. RESULTS: ETS-1 expression was significantly increased in CD4+ T cells from active IBD patients compared with healthy controls, which was upregulated by TNF-α but markedly suppressed by anti-TNF-α mAb therapy. More severe colitis was observed in Rag1-/- mice reconstituted with Ets-1TgCD45RBhighCD4+ T cells or in Ets-1 Tg mice after DSS exposure compared with controls, characterized by higher TNF-α and IFN-γ expression in inflamed colon. Ets-1 Tg mice were more prone to develop AOM/DSS-induced CAC, and bone marrow chimeras further proved that lamina propria immune cells but not intestinal epithelial cells contributed to the development of colitis. RNA-sequencing and luciferase analysis revealed cold-inducible RNA-binding protein (CIRBP) as a functional target of ETS-1 to promote Th1 cell-driven immune response. Consistently, intraperitoneal administration of adenovirus-m-cirbp-shRNA ameliorated trinitrobenzene sulfonic acid (TNBS)-induced colitis of Ets-1 Tg mice. CONCLUSIONS: Our data identify that ETS-1 is highly expressed in IBD patients and promotes Th1-driven mucosal inflammation through CIRBP. CIRBP may serve as a novel therapeutic target for treatment of human IBD.

A Rebuilding-Free Nucleic Acid Detection Strategy Enables Ultrasensitive Genotyping, N-in-1 Logic Screening and Accurate Multiplex Assay of Dangerous Pathogens.

Sensitive, rapid and low-cost nucleic acid detection is critical for controlling infectious pathogens. Here, we develop a ready-to-use and multimodal detection based on a rebuilding-free, ultrasensitive and selective strategy named dual hairpin ligation-induced isothermal amplification pro (DHLApro). Taking influenza A, influenza B, MERS-CoV, SARS-CoV-2 as model targets, we demonstrate DHLApro provides ≈zM level ultra-sensitivity, being equaling to 0.45 copy/µL in original sample. By simply changing the recognition module, a set of DHLApro components can be applied to a new target without performance loss. Moreover, DHLApro innovatively allows flexible logic/multiplex assay using one set of primer, for example, the "N pathogens-in-1" OR gate screening and accurate multi-channel multiplex assay. Compared with traditional methods, the cost of this logic/multiplex assay has been largely reduced and the cross-interference between the multiple primer sets is also avoided.

Genome-wide DNA methylation analysis and biochemical responses provide insights into the initial domestication of halophyte Puccinellia tenuiflora.

KEY MESSAGE: Puccinellia tenuiflora was domesticated for two years by growing it under non-saline conditions, providing epigenetic and biochemical insights into the initial domestication of extreme halophytes. Some halophytes have economic value as crop species. The domestication of halophytes may offer hope in solving the problem of soil salinization. We domesticated a wild halophyte, Puccinellia tenuiflora, for two years by growing it under non-saline conditions in a greenhouse and used re-sequencing, genome-wide DNA methylation, biochemical, and transcriptome analyses to uncover the mechanisms underlying alterations in the halophyte's tolerance to saline following domestication. Our results showed that non-saline domestication altered the methylation status for a number of genes and transposable elements, resulting in a much higher frequency of hypomethylation than hypermethylation. These modifications to DNA methylation were observed in many critical salinity-tolerance genes, particularly their promoter regions or transcriptional start sites. Twenty-nine potassium channel genes were hypomethylated and three were hypermethylated, suggesting that the DNA methylation status of potassium channel genes was influenced by domestication. The accelerated uptake of potassium is a major salinity tolerance characteristic of P. tenuiflora. We propose that modifications to the DNA methylation of potassium channel genes may be associated with the development of salinity tolerance in this species. By assessing whether non-saline domestication could change the salinity tolerance of P. tenuiflora, we demonstrated that non-saline domesticated plants are less tolerant to saline, which may be attributable to altered sucrose metabolism. DNA methylation and transposable elements may, therefore, be integrated into an environment-sensitive molecular engine that promotes the rapid domestication of P. tenuiflora to enable its use as a crop plant.

Adaptive strategy of allohexaploid wheat to long-term salinity stress.

BACKGROUND: Most studies of crop salinity tolerance are conducted under short-term stress condition within one growth stage. Understanding of the mechanisms of crop response to long-term salinity stress (LSS) is valuable for achieving the improvement of crop salinity tolerance. In the current study, we exposed allohexaploid wheat seeds to LSS conditions from germination stage to young seedling stage for 30 days. To elucidate the adaptive strategy of allohexaploid wheat to LSS, we analyzed chloroplast ultrastructure, leaf anatomy, transcriptomic profiling and concentrations of plant hormones and organic compatible solutes, comparing stressed and control plants. RESULTS: Transcriptomic profiling and biochemical analysis showed that energy partitioning between general metabolism maintenance and stress response may be crucial for survival of allohexaploid wheat under LSS. Under LSS, wheat appeared to shift energy from general maintenance to stress response through stimulating the abscisic acid (ABA) pathway and suppressing gibberellin and jasmonic acid pathways in the leaf. We further distinguished the expression status of the A, B, and D homeologs of any gene triad, and also surveyed the effects of LSS on homeolog expression bias for salinity-tolerant triads. We found that LSS had similar effects on expression of the three homeologs for most salinity-tolerant triads. However, in some of these triads, LSS induced different effects on the expression of the three homeologs. CONCLUSIONS: The shift of the energy from general maintenance to stress response may be important for wheat LSS tolerance. LSS influences homeolog expression bias of salinity-tolerant triads.

Monocyte Chemotactic Protein 1-Induced Protein 1 Is Highly Expressed in Inflammatory Bowel Disease and Negatively Regulates Neutrophil Activities.

Monocyte chemotactic protein 1-induced protein 1 (MCPIP-1) is highly expressed in activated immune cells and plays an important role in negatively regulating immune responses. However, its role in regulating neutrophil functions in the pathogenesis of inflammatory bowel disease (IBD) is still unclear. Here, we found that MCPIP-1 was markedly increased at both the transcriptional and translational levels in inflamed mucosa of IBD patients compared with healthy controls, which was mainly expressed in neutrophils. Interestingly, MG-132, a proteasome inhibitor reducing the degradation of MCPIP-1, further facilitated neutrophils to express MCPIP-1 in vitro. Importantly, MCPIP-1 markedly downregulated the production of ROS, MPO, and proinflammatory cytokines (e.g., interleukin-1ß, interleukin-6, tumor necrosis factor-α, interleukin-8, and interferon-γ) and suppressed the migration of IBD neutrophils. Consistently, the same functional changes were observed in neutrophils from mice with myeloid-targeted overexpression of MCPIP-1 as MG-132 did. Altogether, these findings suggest that MCPIP-1 plays a negative role in regulating neutrophil activities through suppressing the production of ROS, MPO, and proinflammatory cytokines and inhibiting the migration. MG-132 may partially modulate the function of neutrophils via the induction of MCPIP-1. Therefore, targeting MCPIP-1 or exogenous supplementation of MG-132 may provide a therapeutic approach in the treatment of IBD.

Vitamin D-deficiency induces eosinophil spontaneous activation.

Eosinophils (Eo) play a critical role in immunity and immune inflammation. The maintenance of Eo homeostasis is not fully understood yet. Vitamin D (VitD) is involved in the regulation of a large number of biochemical reactions. This study tests a hypothesis that VitD receptor (VDR) contributes to the homeostasis of Eos. In this study, EoL-1 cells (an Eo cell line) were cultured in the presence or absence of calcitriol. The Eo-mediators, including major basic protein (MBP), Eo peroxidase (EPX), Eo cationic protein (ECP) and Eo-derived neurotoxin (EDN), were assessed in the culture supernatant and in EoL-1 cells. We observed that, in a VitD deficient environment, EoL-1 cells produced high levels of the Eo-mediators, including MBP, EPX, ECP and EDN, which could be suppressed by the addition of calcitriol to the culture. EoL-1 cells expressed VitD receptor (VDR), which was up regulated by exposure to calcitriol. VDR formed complexes with the transcription factors of the Eo-mediators, which prevented the transcription factors to bind to the promoters of the Eo-mediators, and therefore prevented the Eo-mediated gene transcription. The Eo spontaneous activation was also found in the intestinal mucosa of VDR-deficient mice, in which the intestinal epithelial barrier dysfunction was observed. In conclusion, VDR contributes to the maintenance of the homeostasis of Eos by regulating the gene transcription of the Eo mediators. The VDR-deficiency is one of the causative factors inducing Eo spontaneous activation. This phenomenon may be taken into account in the management of the Eo-related diseases.

Clinicopathological and Ileocolonoscopic Characteristics in Patients with Nodular Lymphoid Hyperplasia in the Terminal Ileum.

Nodular lymphoid hyperplasia (NLH) in the small intestine is a rare benign lesion, characterized by the presence of multiple small nodules on the surface of the intestine. To define the clinicopathological and colonoscopic characteristics in Chinese patients with ileal NLH, we collected 65 patients with NLH in the terminal ileum from the endoscopic database in our hospital and clinical data from medical records. Histology and immunohistochemical staining were performed in the biopsies. The results demonstrated that the main symptoms included diarrhea (70.8%), abdominal pain (60.0%), hematochezia (46.2%), anemia (40.0%), and hypoproteinemia (21.5%). Enteroscopy revealed multiple, sporadic, granular or round-shaped nodules with diameters between 2 and 5 mm in the terminal ileum. The histology revealed the nodules consisted of mass lymphoid follicles in the lamina propria and submucosa of the terminal ileum. The follicles contained mitotically active germinal centers surrounded by well-defined lymphocyte mantles and composed predominantly of CD20+ B cells. The diseases found in patients with NLH included chronic diarrhea, Crohn's disease, ischemic enterocolitis and allergic purpura. The level of hemoglobin in NLH patients who had diarrhea and hematochezia remarkably decreased as compared with those in patients with chronic diarrhea. In conclusion, ileocolonoscopic screening is an important step to find the NLH in terminal ileum patients with diarrhea, abdominal pain, hematochezia, and hypoproteinemia. Histological examination is necessary for the exclusion of malignancy and chronic inflammation.

Critical Role of p53 and K-ras in the Diagnosis of Early Colorectal Cancer: a One-year, Single-center Analysis.

Background: Colorectal cancer (CRC) is strongly associated with colorectal polyps, which has become the third most common cancer in China. In the present study, we revealed the susceptible population and risk factors of colorectal polyps, and analyzed the expression of Ki-67, p53 and K-ras in the intestinal mucosa of patients with colorectal polyps in order to explore their significance in the detection and prognosis of CRC at an early stage. Materials and Methods: Total 801 cases of colorectal polyps were collected during endoscopic resection including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Expression of Ki-67, p53 and K-ras in the intestinal mucosa was detected by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Histological analysis was performed by Hematoxylin and eosin (HE) staining. Categorical variables were compared by one-way ANOVA, Pearson test, Spearman test, Kruskal-Wallis test and analysis of regression. Results: Of all patients with colorectal polyps, 90.76% of patients (n = 727) were ≥ 50 years old. 530 cases (66.17%) were males compared with 271 females (33.83%) in all 801 cases. More importantly, 1.03% patients (n = 7) underwent polypectomy and histological examination was confirmed to be the early stage of CRC. The expression of p53 was found to be significantly decreased, while K-ras was increased in tumor tissues of CRC compared with that in hyperplastic polyps and healthy controls. Conclusions: 1.03% patients (n = 7) underwent polypectomy was confirmed to be the early stage of CRC. Histological analysis for expression of p53 and K-ras can guarantee to screen the early stage of CRC.

Increased Community-Associated Infections Caused by Panton-Valentine Leukocidin-Negative MRSA, Shanghai, 2005-2014.

During 2005-2014, community-associated methicillin-resistant Staphylococcus aureus infections increased in Shanghai, China. Most infections were caused by sequence type 59 S. aureus that lacked Panton-Valentine leukocidin. This finding challenges the notion that Panton-Valentine leukocidin is necessary for epidemiologic success of community-associated methicillin-resistant S. aureus.

Novel bispecific nanobody mitigates experimental intestinal inflammation in mice by targeting TNF-α and IL-23p19 bioactivities.

BACKGROUND: Inflammatory bowel diseases (IBDs) pose significant challenges in terms of treatment non-response, necessitating the development of novel therapeutic approaches. Although biological medicines that target TNF-α (tumour necrosis factor-α) have shown clinical success in some IBD patients, a substantial proportion still fails to respond. METHODS: We designed bispecific nanobodies (BsNbs) with the ability to simultaneously target human macrophage-expressed membrane TNF-α (hmTNF-α) and IL-23. Additionally, we fused the constant region of human IgG1 Fc (hIgG1 Fc) to BsNb to create BsNb-Fc.  Our study encompassed in vitro and in vivo characterization of BsNb and BsNb-Fc. RESULTS: BsNb-Fc exhibited an improved serum half-life, targeting capability and effector function than BsNb. It's demonstrated that BsNb-Fc exhibited superior anti-inflammatory effects compared to the anti-TNF-α mAb (infliximab, IFX) combined with anti-IL-12/IL-23p40 mAb (ustekinumab, UST) by Transwell co-culture assays. Notably, in murine models of acute colitis brought on by 2,4,6-trinitrobenzene sulfonic acid（TNBS) and dextran sulphate sodium (DSS), BsNb-Fc effectively alleviated colitis severity. Additionally, BsNb-Fc outperformed the IFX&UST combination in TNBS-induced colitis, significantly reducing colon inflammation in mice with colitis produced by TNBS and DSS. CONCLUSION: These findings highlight an enhanced efficacy and improved biostability of BsNb-Fc, suggesting its potential as a promising therapeutic option for IBD patients with insufficient response to TNF-α inhibition. KEY POINTS: A bispecific nanobody (BsNb) was created to target TNF-α and IL-23p19, exhibiting high affinity and remarkable stability. BsNb-Fc inhibited the release of cytokines in CD4+T cells during co-culture experiments. BsNb-Fc effectively alleviated colitis severity in mouse model with acute colitis induced by DSS or TNBS, outperforming the IFX&UST combination.

Dysregulation of CD177+ neutrophils on intraepithelial lymphocytes exacerbates gut inflammation via decreasing microbiota-derived DMF.

Neutrophils synergize with intestinal resident intraepithelial lymphocytes (IELs) to serve as the first-line defense and maintain intestinal homeostasis. However, the underlying mechanisms whereby neutrophils regulate IELs to inhibit intestinal inflammation are still not completely understood. Here, we found that depletion of neutrophils (especially CD177+ subset) caused expansion of colitogenic TCRγδ+CD8αα+ IELs, increased intestinal inflammation, and dysbiosis after dextran sulfate sodium exposure or Citrobacter rodentium infection in mice. scRNA-seq analysis revealed a pyroptosis-related gene signature and hyperresponsiveness to microbiota in TCRγδ+CD8αα+ IELs from colitic Cd177-/- mice. Microbiota-derived fumarate and its derivative dimethyl fumarate (DMF), as well as fumarate-producing microbiotas, decreased in the feces of colitic Cd177-/- mice. Elimination of dysbiosis by antibiotics treatment or co-housing procedure and DMF supplementation restrained TCRγδ+CD8αα+ IEL activation. Consistently, DMF significantly alleviated intestinal mucosal inflammation in mice through restricting gasdermin D (GSDMD)-induced pyroptosis of TCRγδ+CD8αα+ IELs. Therefore, our data reveal that neutrophils inhibit intestinal inflammation by promoting microbiota-derived DMF to regulate TCRγδ+CD8αα+ IEL activation in a GSDMD-mediated pyroptosis-dependent manner, and that DMF may serve as a therapeutic target for the management of intestinal inflammation.

Effects of Super-Activated Platelet Lysate on Early Healing of Tooth Extraction Sockets in Rats.

Purpose: To evaluate the effect of super-activated platelet lysate (sPL) on wound healing of tooth extraction sockets in rats. Methods: Rat models of the tooth extraction socket were established. Thirty-six rats were divided into control and sPL groups and sacrificed on days 7, 14, and 28 after tooth extraction. Bone formation in tooth extraction sockets were observed by microscopic computed tomography (micro-CT) and hematoxylin and eosin (HE) staining; osteoprotegerin (OPG), receptor activator of nuclear factor kappa-Β ligand (RANKL), interleukin 6(IL-6), and tumor necrosis factor-alpha (TNF-α) proteins were detected by immunohistochemistry; and chemokine and osteogenic gene expressions were detected by polymerase chain reaction (PCR). Results: sPL accelerated soft tissue wound healing in the extraction socket of rats. Micro-CT showed that the amount of bone formation and bone volume fraction were higher in the sPL group than the control 14 days after extraction. HE staining showed promotion of the formation of bony trabeculae by sPL in the apical third of the extraction socket 7 days after extraction and more mature and organized bony trabeculae in the sPL group than the control 14 days after extraction; mature bony trabeculae filling most of the fossa with lesser bone porosity in the socket in the sPL group than the control 28 days after extraction. Immunohistochemistry showed that sPL induced OPG expressions 7 and 14 days after tooth extraction but did not affect the RANKL expression while transiently promoting the IL-6 expression 7 days after extraction. PCR showed that sPL promoted chemokine expressions 7 and 14 days after extraction. The expressions of osteogenesis-related factors were higher in the sPL group than the control 7 and 28 days after extraction, while the opposite trend was observed 14 days after extraction. Conclusion: sPL has a transient pro-inflammatory effect and promotes soft tissue healing and bone formation during early wound healing of extraction sockets in rats.

Phase structure engineering of MnCo2Ox within electrospun carbon nanofibers towards high-performance lithium-ion batteries.

Metal oxides are prospective alternative anode materials to the commercial graphite for lithium ion batteries (LIBs), while their practical application is seriously hampered by their poor conductivities and large volume changes. Herein, we report the controllable synthesis of amorphous/crystalline MnCo2Ox nanoparticles within porous carbon nanofibers (marked as MCO@CNFs) through a facile electrospinning strategy and subsequent annealing reactions. The phase structures from Co/MnOX to amorphous MnCo2Ox and crystalline MnCo2O4.5 can be readily tuned by thermal reduction/oxidation under controlled atmosphere and temperature. When examined as anode for LIBs, the optimized MCO@CNFs delivers a high stable capacity of 780.3 mA h g-1 at 200 mA g-1 after 250 cycles, which is attributed to the synergistic effect of the distinctive amorphous structure and defective carbon nanofiber matrices. Specifically, the amorphous structure with rich defects offers more reactive sites and multiple pathways for the Li+ diffusion, while carbon hybridization sufficiently improves the electrode conductivities as well as buffers the volume changes. More importantly, we demonstrate a convenient synthesis strategy to control the metal-to-oxide structure evolution within carbon matrices, which is of great importance in exploring high-performance electrodes for next generation LIBs.

GPR65 promotes intestinal mucosal Th1 and Th17 cell differentiation and gut inflammation through downregulating NUAK2.

G protein-coupled receptor 65 (GPR65), a susceptibility gene for inflammatory bowel diseases (IBD), has been identified to promote Th17 cell pathogenicity and induce T cell apoptosis. However, the potential role of GPR65 in modulating CD4+ T cell immune responses in the pathogenesis of IBD stills not entirely understood. Here, we displayed that GPR65 expression was increased in inflamed intestinal mucosa of IBD patients and positively associated with disease activity. It was expressed in CD4+ T cells and robustly upregulated through the TNF-α-caspase 3/8 signalling pathway. Ectopic expression of GPR65 significantly promoted the differentiation of peripheral blood (PB) CD4+ T cells from IBD patients and HC to Th1 and Th17 cells in vitro. Importantly, conditional knockout of Gpr65 in CD4+ T cells ameliorated trinitrobenzene sulfonic acid (TNBS)-induced acute murine colitis and a chronic colitis in Rag1-/- mice reconstituted with CD45RBhigh CD4+ T cells in vivo, characterised by attenuated Th1 and Th17 cell immune response in colon mucosa and decreased infiltration of CD4+ T cells, neutrophils and macrophages. RNA-seq analysis of Gpr65ΔCD4 and Gpr65flx/flx CD4+ T cells revealed that NUAK family kinase 2 (Nuak2) acts as a functional target of Gpr65 to restrict Th1 and Th17 cell immune response. Mechanistically, GPR65 deficiency promoted NUAK2 expression via the cAMP-PKA-C-Raf-ERK1/2-LKB1-mediated signalling pathway. Consistently, silencing of Nuak2 facilitated the differentiation of Gpr65ΔCD4 and Gpr65flx/flx CD4+ T cells into Th1 and Th17 cells. Therefore, our data point out that GPR65 promotes Th1 and Th17 cell immune response and intestinal mucosal inflammation by suppressing NUAK2 expression, and that targeting GPR65 and NUAK2 in CD4+ T cells may represent a novel therapeutic approach for IBD.

Polyvinylpyrrolidone regulated synthesis of mesoporous titanium niobium oxide as high-performance anode for lithium-ion batteries.

TiNb2O7 (TNO) as a promising candidate anode for lithium-ion batteries (LIBs) shows obvious advantages in terms of specific capacity and safety, but which undergoes the intrinsic poor electrical and ionic conductivity. Herein, we propose a simple synthesis strategy of mesoporous TNO via a polymeric surfactant-mediated evaporation-induced sol-gel method, using polyvinylpyrrolidone (PVP) with different molecular weights (average Mw: 10000/58000/1300000) as the regulating agent, which greatly affects the lithium storage performance of the as-prepared TNO. The optimized TNO (i.e., PVP of 58000) delivers a high reversible capacity of 303.1 mAh/g at 1 C, with a retention rate of 73.4% (222.5 mAh/g) after 300 cycles. Even at 5 C, a high reversible capacity of 185.6 mAh/g can be achieved, with a retention rate of 72.3% after 1000 cycles. The superior lithium storage behavior is attributed to the fine mesoporous framework consisting of interconnected TNO nanocrystallites with high specific surface area and high mesoporosity, which greatly increases the active sites, improves the Li+ diffusion kinetics and alleviates volume fluctuation induced by the repetitive Li+ insertion-extraction processes.

MCPIP-1-Mediated Immunosuppression of Neutrophils Exacerbates Acute Bacterial Peritonitis and Liver Injury.

Monocyte chemotactic protein-1-induced protein-1 (MCPIP-1) is highly expressed in activated immune cells and negatively regulates immune responses, while the mechanisms underlying the immunoregulation of neutrophils in acute bacterial infection and liver injury remain elusive. Here, we examined the role of MCPIP-1 in regulating neutrophil functions during acute bacterial peritonitis and liver injury. Mice with myeloid cell-specific overexpression (McpipMye-tg) or knockout (McpipΔMye) of MCPIP-1 were generated. We found that reactive oxygen species and myeloperoxidase production, formation of neutrophil extracellular traps, and migratory capacity were deficient in McpipMye-tg neutrophils but enhanced in McpipΔMye neutrophils. The recruitment of neutrophils and pathogen clearance were markedly suppressed in McpipMye-tg mice following intraperitoneal infection with Salmonella typhimurium while intensified in McpipΔMye mice. Severe acute S. typhimurium-infected peritonitis and liver injury occurred in McpipMye-tg mice but were alleviated in McpipΔMye mice. RNA sequencing, RNA-binding protein immunoprecipitation and qPCR analysis revealed that MCPIP-1 downregulated the protective functions of neutrophils via degrading the mRNA of cold inducible RNA-binding protein. Consistently, MCPIP-1 was highly expressed in neutrophils of patients with acute infectious diseases, especially in those with liver injury. Collectively, we uncover that MCPIP-1 negatively regulates the antibacterial capacities of neutrophils, leading to exacerbating severe acute bacterial peritonitis and liver injury. It may serve as a candidate target for maintaining neutrophil homeostasis to control acute infectious diseases.

Multiomics analysis provides insights into alkali stress tolerance of sunflower (Helianthus annuus L.).

Alkali stress is an extreme complex stress type, which exerts negative effects on plants via chemical destruction, osmotic stress, ion injury, nutrient deficiency, and oxygen deficiency. Soil alkalization has produced severe problems in some area, while plant alkali tolerance is poorly understood. Sunflower (Helianthus annuus L.) is an important oilseed crop with strong alkali tolerance. Here we exposed sunflower plants to alkali stress (NaHCO3/Na2CO3 = 9:1; pH 8.7) for whole life cycle. We applied transcriptomics, metabolomics, lipidomics and phytohormone analysis to elucidate the alkali tolerance mechanism of sunflower plant. Lipidomic analysis showed that alkali stress enhanced accumulation of saccharolipids and glycerolipids and lowered the accumulation of glycerophospholipids in sunflower seeds, indicating that alkali stress can change the lipid components of sunflower seeds, and that cultivating sunflower plants on alkalized farmlands will change the quality of sunflower seed oils. In addition, alkali stress downregulated expression of two rate-controlling genes of glycolysis in the leaves of sunflower but upregulated their expression in the roots. Enhanced glycolysis process provided more carbon sources and energy for alkali stress response of sunflower roots. Under alkali stress, accumulation of many fatty acids, amino acids, carbohydrates, and organic acids was greatly stimulated in sunflower roots. Alkali stress enhanced ACC, GA1, and ABA concentrations in the leaves but not in the roots, however, alkali stress elevated accumulation of BR (typhasterol) and CTK (Isopentenyladenosine) in the roots. We propose that multiple phytohormones and bioactive molecules interact to mediate alkali tolerance of sunflower.

Comparative Genomics and Transcriptomics of the Extreme Halophyte Puccinellia tenuiflora Provides Insights Into Salinity Tolerance Differentiation Between Halophytes and Glycophytes.

Halophytes and glycophytes exhibit clear differences in their tolerance to high levels of salinity. The genetic mechanisms underlying this differentiation, however, remain unclear. To unveil these mechanisms, we surveyed the evolution of salinity-tolerant gene families through comparative genomic analyses between the model halophyte Puccinellia tenuiflora and glycophytic Gramineae plants, and compared their transcriptional and physiological responses to salinity stress. Under salinity stress, the K+ concentration in the root was slightly enhanced in P. tenuiflora, but it was greatly reduced in the glycophytic Gramineae plants, which provided a physiological explanation for differences in salinity tolerance between P. tenuiflora and these glycophytes. Interestingly, several K+ uptake gene families from P. tenuiflora experienced family expansion and positive selection during evolutionary history. This gene family expansion and the elevated expression of K+ uptake genes accelerated K+ accumulation and decreased Na+ toxicity in P. tenuiflora roots under salinity stress. Positively selected P. tenuiflora K+ uptake genes may have evolved new functions that contributed to development of P. tenuiflora salinity tolerance. In addition, the expansion of the gene families involved in pentose phosphate pathway, sucrose biosynthesis, and flavonoid biosynthesis assisted the adaptation of P. tenuiflora to survival under high salinity conditions.

The Surge of Hypervirulent ST398 MRSA Lineage With Higher Biofilm-Forming Ability Is a Critical Threat to Clinics.

The global increase of community-associated (CA) infections with methicillin-resistant Staphylococcus aureus (MRSA) is a major healthcare problem. Although sequence type (ST) 398 MRSA was first described as a livestock-associated (LA) lineage, human-adapted MRSA (HO-MRSA) ST398 without livestock contact has subsequently been reported from China in our previous study and other later research. The proportion of ST398 HO-MRSA has also remarkably increased in recent years in China. Based on 3878 S. aureus isolates that were collected in a general hospital between 2008 and 2018, we identified 56 ST398 HO-MRSA isolates. The four early appearing isolates of them have been sequenced by whole-genome sequencing (WGS) in our previous study. Here, by usage of WGS on the later-appearing 52 isolates and analyzing the phylogenetic dynamics of the linage, we found that 50 isolates clustered together with the former 4 isolates, making it a main clade out of MSSA clones and other MRSA clones, although ST398 HO-MRSA evolved with multiple origins. Drug resistance and virulence gene analysis based on the WGS data demonstrated that ST398 HO-MRSA main clade exhibited a similar pattern in both parts. Furthermore, they all carried a conserved variant of prophage 3 to guarantee virulence and a short SCCmec type V element of class D to maintain considerable lower methicillin resistance. Further phenotypical research verified that the epidemic HO-MRSA ST398 displayed enhanced biofilm formation ability when keeping high virulence. The dual advantages of virulence and biofilm formation in the HO-MRSA ST398 subtype promote their fitness in the community and even in the healthcare environment, which poses a serious threat in clinical S. aureus infections. Therefore, further surveillance is required to prevent and control the problematic public health impact of HO-MRSA ST398 in the future.