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1.
Immunity ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38889716

RESUMO

Expression of the transcriptional regulator ZFP318 is induced in germinal center (GC)-exiting memory B cell precursors and memory B cells (MBCs). Using a conditional ZFP318 fluorescence reporter that also enables ablation of ZFP318-expressing cells, we found that ZFP318-expressing MBCs were highly enriched with GC-derived cells. Although ZFP318-expressing MBCs constituted only a minority of the antigen-specific MBC compartment, their ablation severely impaired recall responses. Deletion of Zfp318 did not alter the magnitude of primary responses but markedly reduced MBC participation in recall. CD40 ligation promoted Zfp318 expression, whereas B cell receptor (BCR) signaling was inhibitory. Enforced ZFP318 expression enhanced recall performance of MBCs that otherwise responded poorly. ZFP318-deficient MBCs expressed less mitochondrial genes, had structurally compromised mitochondria, and were susceptible to reactivation-induced cell death. The abundance of ZFP318-expressing MBCs, instead of the number of antigen-specific MBCs, correlated with the potency of prime-boost vaccination. Therefore, ZFP318 controls the MBC recallability and represents a quality checkpoint of humoral immune memory.

2.
J Am Chem Soc ; 146(17): 11679-11693, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38482849

RESUMO

Lipid nanoparticles (LNPs)-based messenger RNA (mRNA) therapeutics have emerged with promising potentials in the fields of infectious diseases, cancer vaccines, and protein replacement therapies; however, their therapeutic efficacy and safety can still be promoted by the optimization of LNPs formulations. Unfortunately, current LNPs suffer from increased production of reactive oxygen species during translation, which leads to a decreased translation efficiency and the onset of inflammation and other side effects. Herein, we synthesize a lipid-modified poly(guanidine thioctic acid) polymer to fabricate novel LNPs for mRNA vaccines. The acquired G-LNPs significantly promote the translation efficiency of loaded mRNA and attenuate inflammation after vaccination through the elimination of reactive oxygen species that are responsible for translational inhibition and inflammatory responses. In vivo studies demonstrate the excellent antitumor efficacy of the G-LNPs@mRNA vaccine, and two-dose vaccination dramatically increases the population and infiltration of cytotoxic T cells due to the intense antitumor immune responses, thus generating superior antitumor outcomes compared with the mRNA vaccine prepared from traditional LNPs. By synergy with immune checkpoint blockade, the tumor inhibition of G-LNPs@mRNA is further boosted, indicating that G-LNPs-based mRNA vaccines will be powerful and versatile platforms to combat cancer.


Assuntos
Vacinas Anticâncer , Lipídeos , Lipossomos , Nanopartículas , RNA Mensageiro , Vacinas Anticâncer/química , Vacinas Anticâncer/imunologia , Nanopartículas/química , Animais , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Lipídeos/química , Humanos , Ácido Tióctico/química , Ácido Tióctico/farmacologia , Polímeros/química , Guanidinas/química , Guanidinas/farmacologia , Linhagem Celular Tumoral
3.
Chem Soc Rev ; 52(9): 2911-2945, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-36987988

RESUMO

Vital biomacromolecules, such as RNA, DNA, polysaccharides and proteins, are synthesized inside cells via the polymerization of small biomolecules to support and multiply life. The study of polymerization reactions in living organisms is an emerging field in which the high diversity and efficiency of chemistry as well as the flexibility and ingeniousness of physiological environment are incisively and vividly embodied. Efforts have been made to design and develop in situ intra/extracellular polymerization reactions. Many important research areas, including cell surface engineering, biocompatible polymerization, cell behavior regulation, living cell imaging, targeted bacteriostasis and precise tumor therapy, have witnessed the elegant demeanour of polymerization reactions in living organisms. In this review, recent advances in polymerization in living organisms are summarized and presented according to different polymerization methods. The inspiration from biomacromolecule synthesis in nature highlights the feasibility and uniqueness of triggering living polymerization for cell-based biological applications. A series of examples of polymerization reactions in living organisms are discussed, along with their designs, mechanisms of action, and corresponding applications. The current challenges and prospects in this lifeful field are also proposed.


Assuntos
DNA , Proteínas , Polimerização , DNA/química , Tiram
4.
Int J Mol Sci ; 25(2)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38256123

RESUMO

Ca2+ plays a crucial role as a secondary messenger in plant development and response to abiotic/biotic stressors. Calcium-dependent protein kinases (CDPKs/CPKs) are essential Ca2+ sensors that can convert Ca2+ signals into downstream phosphorylation signals. However, there is limited research on the function of CDPKs in the context of wheat-Puccinia striiformis f. sp. tritici (Pst) interaction. In this study, we aimed to address this gap by identifying putative CDPK genes from the wheat reference genome and organizing them into four phylogenetic clusters (I-IV). To investigate the expression patterns of the TaCDPK family during the wheat-Pst interaction, we analyzed time series RNA-seq data and further validated the results through qRT-PCR assays. Among the TaCDPK genes, TaCDPK7 exhibited a significant induction during the wheat-Pst interaction, suggesting that it has a potential role in wheat resistance to Pst. To gain further insights into the function of TaCDPK7, we employed virus-induced gene silencing (VIGS) to knock down its expression which resulted in impaired wheat resistance to Pst, accompanied by decreased accumulation of hydrogen peroxide (H2O2), increased fungal biomass ratio, reduced expression of defense-related genes, and enhanced pathogen hyphal growth. These findings collectively suggest that TaCDPK7 plays an important role in wheat resistance to Pst. In summary, this study expands our understanding of wheat CDPKs and provides novel insights into their involvement in the wheat-Pst interaction.


Assuntos
Peróxido de Hidrogênio , Puccinia , Triticum , Triticum/genética , Peróxido de Hidrogênio/farmacologia , Filogenia , Proteínas Quinases/genética
5.
Angew Chem Int Ed Engl ; 63(13): e202318515, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38320193

RESUMO

Insufficient accumulation of lipid nanoparticles (LNPs)-based mRNA vaccines in antigen presenting cells remains a key barrier to eliciting potent antitumor immune responses. Herein, we develop dendritic cells (DCs) targeting LNPs by taking advantage of mannose receptor-mediated endocytosis. Efficient delivery of mRNA to DCs is achieved in vitro and in vivo utilizing the sweet LNPs (STLNPs-Man). Intramuscular injection of mRNA vaccine (STLNPs-Man@mRNAOVA ) results in a four-fold higher uptake by DCs in comparison with commercially used LNPs. Benefiting from its DCs targeting ability, STLNPs-Man@mRNAOVA significantly promotes the antitumor performances, showing a comparable therapeutic efficacy by using one-fifth of the injection dosage as the vaccine prepared from normal LNPs, thus remarkably avoiding the side effects brought by conventional mRNA vaccines. More intriguingly, STLNPs-Man@mRNAOVA exhibits the ability to downregulate the expression of cytotoxic T-lymphocyte-associated protein 4 on T cells due to the blockade of CD206/CD45 axis, showing brilliant potentials in promoting antitumor efficacy combined with immune checkpoint blockade therapy.


Assuntos
Vacinas Anticâncer , Lipossomos , Nanopartículas , Neoplasias , Humanos , Apresentação de Antígeno , Vacinas de mRNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Dendríticas/metabolismo , Neoplasias/terapia , Neoplasias/metabolismo
6.
Pharmacol Res ; 188: 106676, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36693599

RESUMO

Age-related gastrointestinal decline contributes to whole-organism frailty and mortality. Genistein is known to have beneficial effects on age-related diseases, but its precise role in homeostasis of the aging gut remains to be elucidated. Here, wild-type aging mice and Zmpste24-/- progeroid mice were used to investigate the role of genistein in lifespan and homeostasis of the aging gut in mammals. A series of longitudinal, clinically relevant measurements were performed to evaluate the effect of genistein on healthspan. It was found that dietary genistein promoted a healthier and longer life and was associated with a decrease in the levels of systemic inflammatory cytokines in aging mice. Furthermore, dietary genistein ameliorated gut dysfunctions, such as intestinal inflammation, leaky gut, and impaired epithelial regeneration. A distinct genistein-mediated alteration in gut microbiota was observed by increasing Lachnospira abundance and short-chain fatty acid (SCFA) production. Further fecal microbiota transplantation and dirty cage sharing experiments indicated that the gut microbiota from genistein-fed mice rejuvenated the aging gut and extended the lifespan of progeroid mice. It was demonstrated that genistein-associated SCFAs alleviated tumor necrosis factor alpha-induced intestinal organoid damage. Moreover, genistein-associated propionate promoted regulatory T cell-derived interleukin 10 production, which alleviated macrophage-derived inflammation. This study provided the first data, to the authors' knowledge, indicating that dietary genistein modulates homeostasis in the aging gut and extends the healthspan and lifespan of aging mammals. Moreover, the existence of a link between genistein and the gut microbiota provides a rationale for dietary interventions against age-associated frailty.


Assuntos
Fragilidade , Microbioma Gastrointestinal , Camundongos , Animais , Longevidade , Genisteína/farmacologia , Ácidos Graxos Voláteis/farmacologia , Envelhecimento , Inflamação , Homeostase , Camundongos Endogâmicos C57BL , Mamíferos
7.
Small ; 18(32): e2203307, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35843875

RESUMO

Metal-organic frameworks (MOFs), known as porous coordination polymers, have attracted intense interest as electrode materials for supercapacitors (SCs) owing to their advantageous features including high surface area, tunable porous structure, structural diversity, etc. However, the insulating nature of most MOFs has impeded their further electrochemical applications. A common solution for this issue is to transform pristine MOFs into more stable and conductive metal compounds/porous carbon materials through pyrolysis, which however losses the inherent merits of MOFs. To find a consummate solution, recently a surge of research devoted to improving the electrical conductivity of pristine MOFs for SCs has been carried out. In this review, the most related research work on pristine MOF-based materials is reviewed and three effective strategies (chemical structure design of conductive MOFs (c-MOFs), composite design, and binder-free structure design) which can significantly increase their conductivity and consequently the electrochemical performance in SCs are proposed. The conductivity enhancement mechanism in each approach is well analyzed. The representative research works on using pristine MOFs for SCs are also critically discussed. It is hoped that the new insights can provide guidance for developing high-performance electrode materials based on pristine MOFs with high conductivity for SCs in the future.

8.
Microb Cell Fact ; 20(1): 122, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34182992

RESUMO

BACKGROUND: The development and utilization of probiotics had many environmental benefits for replacing antibiotics in animal production. Bacteria in the intestinal mucosa have better adhesion to the host intestinal epithelial cells compared to bacteria in the intestinal contents. In this study, lactic acid bacteria were isolated from the intestinal mucosa of broiler chickens and investigated as the substitution to antibiotic in broiler production. RESULTS: In addition to acid resistance, high temperature resistance, antimicrobial sensitivity tests, and intestinal epithelial cell adhesion, Enterococcus faecium PNC01 (E. faecium PNC01) was showed to be non-cytotoxic to epithelial cells. Draft genome sequence of E. faecium PNC01 predicted that it synthesized bacteriocin to perform probiotic functions and bacteriocin activity assay showed it inhibited Salmonella typhimurium from invading intestinal epithelial cells. Diet supplemented with E. faecium PNC01 increased the ileal villus height and crypt depth in broiler chickens, reduced the relative length of the cecum at day 21, and reduced the relative length of jejunum and ileum at day 42. Diet supplemented with E. faecium PNC01 increased the relative abundance of Firmicutes and Lactobacillus, decreased the relative abundance of Bacteroides in the cecal microbiota. CONCLUSION: E. faecium PNC01 replaced antibiotics to reduce the feed conversion rate. Furthermore, E. faecium PNC01 improved intestinal morphology and altered the composition of microbiota in the cecum to reduce feed conversion rate. Thus, it can be used as an alternative for antibiotics in broiler production to avoid the adverse impact of antibiotics by altering the gut microbiota.


Assuntos
Antibacterianos/farmacologia , Galinhas/crescimento & desenvolvimento , Galinhas/microbiologia , Enterococcus faecium/fisiologia , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Probióticos , Ração Animal/análise , Ração Animal/microbiologia , Animais , Bacteriocinas/farmacologia , Ceco/anatomia & histologia , Ceco/efeitos dos fármacos , Suplementos Nutricionais/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Íleo/anatomia & histologia , Íleo/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Jejuno/anatomia & histologia , Jejuno/efeitos dos fármacos , Masculino , RNA Ribossômico 16S
9.
Org Biomol Chem ; 17(27): 6574-6579, 2019 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-31237308

RESUMO

Fluorene-based 3D-grid-FTPA was synthesised with a total yield of 55% via the one-pot formation of six C(sp2)-C(sp3) bonds through a BF3·Et2O-mediated Friedel-Crafts reaction of A2-type bifluorene tertiary alcohol (BIOH) and two B3-type triphenylamines. At the same time, Un-grid-FTPA (2.7%) and 2D-grid-FTPA (5.6%) were obtained as by-products from this synthesis method. In addition, the effect of stereoisomers of BIOH was evaluated to demonstrate that Rac-BIOH is a better A2-type building block to prepare 3D-grid-FTPA in a relatively high yield. Furthermore, 3D-grid-FTPA showed excellent chemical, thermal, and photo-stabilities.

10.
J Craniofac Surg ; 26(2): 584-6, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25759925

RESUMO

Crouzon syndrome is an autosomal dominant craniosynostosis syndrome caused by mutation in the fibroblast growth factor receptor 2 (FGFR-2). Numerous findings from animal studies imply a critical role for FGFRs in the regulation of skeletal development. Here, we report 2 unrelated patients with Crouzon syndrome accompanied by elbow deformity. Subsequently, we analyzed the sequence of the FGFR2 gene and found that both of the patients carried the Cys342Arg mutation. The findings suggest that the C342R mutation in FGFR2 may cause Crouzon syndrome and elbow deformity in Chinese patients.


Assuntos
Povo Asiático/genética , Disostose Craniofacial/genética , Articulação do Cotovelo/anormalidades , Mutação/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Substituição de Aminoácidos/genética , Arginina/genética , Criança , Pré-Escolar , China , Cisteína/genética , Feminino , Triagem de Portadores Genéticos , Humanos , Luxações Articulares/genética , Masculino , Olécrano/anormalidades , Fenótipo
11.
J Craniofac Surg ; 26(2): 592-4, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25759927

RESUMO

It has been known for several years that mutations in the fibroblast growth factor receptor (FGFR2) result in syndromic craniosynostosis including Apert, Crouzon, or Pfeiffer syndromes. Here, we report on a child with a clinically diagnosed Crouzon syndrome that shows the missense point mutation S267P in FGFR2 gene. The mutation is firstly identified in Crouzon syndrome. Our observations expand the molecular spectrum of FGFR2 mutations in the syndrome.


Assuntos
Disostose Craniofacial/genética , Mutação de Sentido Incorreto/genética , Mutação Puntual/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Criança , China , Disostose Craniofacial/diagnóstico , Análise Mutacional de DNA , Humanos , Masculino , Análise de Sequência de DNA , Tomografia Computadorizada por Raios X
12.
J Craniofac Surg ; 26(2): 557-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25692891

RESUMO

Crouzon is an autosomal dominant craniosynostosis syndrome caused by mutation in the fibroblast growth factor receptor (FGFR)-2 gene. Recent findings from animal studies imply a critical role for FGFs in the regulation of mineralization. Here, we presented a 5-year-old girl with severe meningeal calcification. Subsequently, we analyzed FGFR2 mutation and identified a mutation of Cys342Tyr. The findings suggest that abnormal calcification was atypical phenotype of Crouzon patients with Cys342Tyr mutation in FGFR2.


Assuntos
Calcinose/genética , Disostose Craniofacial/genética , Triagem de Portadores Genéticos , Meninges/fisiopatologia , Mutação/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Substituição de Aminoácidos/genética , Animais , Criança , Cistina/genética , Análise Mutacional de DNA , Feminino , Humanos , Fenótipo , Tirosina/genética
13.
J Craniofac Surg ; 26(2): 336-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25759915

RESUMO

PURPOSE: The aim of this study was to correct facial disharmony with or without occlusal dysfunction. METHODS: Based on computed tomography and presurgical design, restoration of normal skeleton relationship is a priority for selected facial deformities. Combination of different osteotomies for facial skeleton was chosen in 1-stage operation such as orthognathic surgery, zygomatic reduction, and mandibular angle reduction. Supplementary surgeries was considered in some cases as substitute implantation or autologous fat graft. RESULTS: All the 50 patients (hemifacial microsomia, Romberg syndrome, mandibular condyle hyperplasia, secondary cleft palate, and Crouzon syndrome) received surgeries, and their facial appearance improved significantly. Yearly follow-up shows that the symmetry and balance of the facial proportion approach normal, whereas most of their occlusal relationship has been significantly improved after the first stage of surgery. CONCLUSIONS: For most facial disharmony with or without occlusal dysfunction, skeleton-first surgery is a feasible strategy.


Assuntos
Hemiatrofia Facial/cirurgia , Imageamento Tridimensional/métodos , Ritidoplastia/métodos , Adolescente , Adulto , Hemiatrofia Facial/diagnóstico , Feminino , Humanos , Masculino , Adulto Jovem
14.
J Periodontol ; 95(3): 233-243, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37515595

RESUMO

BACKGROUND: Clinical probing is commonly recommended to evaluate peri-implant conditions. In a situation of peri-implant mucositis or peri-implantitis, the peri-implant seal healing from the disruption of soft tissue caused by probing has not yet been studied. This study aimed to investigate soft tissue healing after standardized clinical probing around osseointegrated implants with peri-implant mucositis in a dog model. METHODS: Three transmucosal implants in each hemi-mandible of six dogs randomly assigned to the peri-implant healthy group or peri-implant mucositis group were probed randomly in the mesial or distal site as probing groups (PH or PM), the cross-sectional opposite sites as unprobed control groups. Histomorphometric measurements of implant shoulder (IS)-most coronal level of alveolar bone contact to the implant surface (BCI), apical termination of the junctional epithelium (aJE)-BCI, mucosal margin (MM)-BCI, and MM-aJE were performed at 1 day, 1 week, and 2 weeks after probing. Apoptosis, proliferation, proinflammatory cytokines, and matrix metalloproteinases (MMPs) of peri-implant soft tissue were estimated by immunofluorescent analysis. RESULTS: In the PM group, apical migration of junctional epithelium was revealed by significantly decreased aJE-BCI from 1 day to 2 weeks in comparison to unprobed sites (p < 0.05), while no significant differences were found in the PH group. Immunofluorescent analysis showed higher levels of interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), MMP-1, and MMP-8, together with exaggerated apoptosis and proliferation of peri-implant soft tissue in the PM group. CONCLUSION: Within the limitations, standardized clinical probing might lead to apical migration of the junctional epithelium in a situation of peri-implant mucositis.


Assuntos
Implantes Dentários , Mucosite , Peri-Implantite , Animais , Cães , Implantes Dentários/efeitos adversos , Estudos Transversais , Cicatrização
15.
Adv Mater ; 36(23): e2311574, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38433564

RESUMO

Dendritic cell (DC) maturation is a crucial process for antigen presentation and the initiation of T cell-mediated immune responses. Toll-like receptors play pivotal roles in stimulating DC maturation and promoting antigen presentation. Here, a novel message RNA (mRNA) cancer vaccine is reported that boosts antitumor efficacy by codelivering an mRNA encoding tumor antigen and a TLR7/8 agonist (R848) to DC using supramolecular lipid nanoparticles (SMLNP) as a delivery platform, in which a new ionizable lipid (N2-3L) remarkably enhances the translation efficiency of mRNA and a ß-cyclodextrin (ß-CD)-modified ionizable lipid (Lip-CD) encapsulates R848. The incorporation of R848 adjuvant into the mRNA vaccine through noncovalent host-guest complexation significantly promotes DC maturation and antigen presentation after vaccination, thus resulting in superior antitumor efficacy in vivo. Moreover, the antitumor efficacy is further boosted synergized with immune checkpoint blockade by potentiating the anticancer capability of cytotoxic T lymphocytes infiltrated in tumor sites. This work indicates that SMLNP shows brilliant potential as next-generation delivery system in the development of mRNA vaccines with high efficacy.


Assuntos
Vacinas Anticâncer , Células Dendríticas , Imidazóis , Imunoterapia , Lipídeos , Nanopartículas , Receptor 7 Toll-Like , Receptor 8 Toll-Like , Animais , Nanopartículas/química , Vacinas Anticâncer/química , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Camundongos , Lipídeos/química , Imidazóis/química , Vacinas de mRNA/química , beta-Ciclodextrinas/química , RNA Mensageiro/genética , RNA Mensageiro/química , Neoplasias/terapia , Linhagem Celular Tumoral , Antígenos de Neoplasias/imunologia , Humanos , Camundongos Endogâmicos C57BL , Lipossomos
16.
Life (Basel) ; 13(5)2023 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-37240754

RESUMO

In aging laying hens, reproductive changes reduce egg quality. Bacillus subtilis natto (B. subtilis) is a versatile bacterium with high vitamin K2 content, providing health benefits for animals and humans. This study investigated the effect of B. subtilis natto NB205 and its mutant NBMK308 on egg quality in aging laying hens. Results showed that NB205 and NBMK308 supplementation significantly improved albumen height (p < 0.001), Haugh units (p < 0.05), and eggshell thickness (p < 0.001) compared to the control group. Supplementation also increased ovalbumin expression, regulated tight junction (TJ) proteins, reduced pro-inflammatory cytokine levels, and improved the health and productivity of aging laying hens by regulating key apoptosis-related genes in the magnum part of the oviduct. There were differences in the expression of vitamin K-dependent proteins (VKDPs) in the magnum between NB205 and NBMK308, but no significant differences in the improvement of egg quality. Supplementation with NB205 and NBMK308 can improve egg quality in aging laying hens.

17.
Environ Sci Pollut Res Int ; 30(10): 26687-26702, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36369447

RESUMO

Mining causes extreme heavy metal (HM) contamination to surrounding environments and poses threats to soil microbial community. The effects of HMs on soil microbial communities are not only related to their total amounts but also associated with the distribution of chemical fractions. However, the effects of chemical fractions on soil microbes and their interactions remain largely unclear. Here we investigated soil physicochemical properties and bacterial and fungal communities of soil samples from the control area and lightly (L), moderately (M), and heavily (H) contaminated areas, respectively, which were collected from long-term Pb-Zn slag contamination area in the southern China. The results showed that bacterial and fungal community composition and structure were significantly affected by HMs, while community diversity was not significantly affected by HMs. The critical environmental factor affecting bacterial and fungal communities was pH, and the impacts of chemical fractions on their changes were more significant than the total amounts of HMs. Variance partitioning analysis (VPA) revealed fungal community changes were mostly driven by HM total amounts, but bacterial community changes were mostly driven by soil chemical properties. Co-occurrence network indicated that interactions among species of fungal network were sparser than that of bacterial network, but fungal network was more stable, due to a more significant number of keystone taxa and a lower percentage of positive associations. These illustrated that the fungal community might serve as indicator taxa for HM-contaminated status, and specific HM-responsive fungal species such as Triangularia mangenotii, Saitozyma podzolica, and Cladosporium endophytica, and genus Rhizophagus can be considered relevant bioindicators due to their less relative abundance in contaminated areas. Additionally, HM-responsive bacterial OTUs representing five genera within Sulfurifustis, Thiobacillus, Sphingomonas, Qipengyuania, and Sulfurirhabdus were found to be tolerant to HM stress due to their high relative abundance in contaminated levels.


Assuntos
Metais Pesados , Microbiota , Poluentes do Solo , Solo/química , Chumbo/análise , Microbiologia do Solo , Metais Pesados/análise , Bactérias , Zinco/análise , China , Poluentes do Solo/análise
18.
Anim Nutr ; 12: 128-137, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36683879

RESUMO

The current study investigated the effects of intermittent feeding (IF) and fasting strategies at different times post-hatch on muscle growth and white striping (WS) breast development. In the first trial, 32 one-day-old Abor Acre broilers were fed ad libitum (AL) for 3 d post-hatch and then randomly allotted into 4 feeding strategies including AL, 1h-IF group (1 h IF, 4 times feeding/d, 1 h each time), 1.5h-IF (1.5 h IF, 4 times feeding/d, 1.5 h each time), and fasting (1d acute fasting, 6 d free access to feed) groups and fed for 7 d. Although angiogenic genes including VEGFA, VEGFR1, and VEGFR2, and myogenic genes including MYOG and MYOD were upregulated (P < 0.05), the breast muscle satellite cell (SC) number and PAX7, MYF5 expression were decreased by the IF strategies (P < 0.05). One-day fasting at 6 d of age also upregulated angiogenic genes and MYOD expression (P < 0.05), downregulated MYF5 expression (P < 0.05), but did not change SC number (P > 0.05). In the second trial, 384 one-day-old birds were fed AL for 1 wk and then randomly allotted to the above 4 feeding strategies starting at 8 d of age until 42 d of age. Similarly, IF and fasting strategies upregulated the expression of angiogenic and myogenic genes (P < 0.05). Both 1h-IF and 1.5h-IF increased breast muscle SC number (P < 0.05). At slaughter, breast muscle fiber diameter of 1.5h-IF was smaller but the SC number was larger than that of the birds fed AL (P < 0.05). The IF and fasting strategies prevented WS development, and reduced breast WS scores and triglyceride content (P < 0.05) without changing the body weight (P > 0.05). Fasting and 1h-IF reduced the expression of adipogenic genes ZNF423 and PDGFRα (P < 0.05). Moreover, IF and fasting strategies reduced fibrosis in breast muscle and reduced skeletal muscle-specific E3 ubiquitin ligases (TRIM63 and MAFBX) (P < 0.05). Fasting significantly reduced CASPASE-3 in breast muscle (P < 0.05). In conclusion, IF starting in the first week decreases SC number. Compared to AL, IF or fasting promotes muscular angiogenesis, increases SC number, prevents muscle degeneration, and prevents the development of WS without impairing the growth performance of broiler chickens.

19.
Nat Commun ; 14(1): 8042, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38052844

RESUMO

The respiratory system, especially the lung, is the key site of pathological injury induced by SARS-CoV-2 infection. Given the low feasibility of targeted delivery of antibodies into the lungs by intravenous administration and the short half-life period of antibodies in the lungs by intranasal or aerosolized immunization, mRNA encoding broadly neutralizing antibodies with lung-targeting capability can perfectly provide high-titer antibodies in lungs to prevent the SARS-CoV-2 infection. Here, we firstly identify a human monoclonal antibody, 8-9D, with broad neutralizing potency against SARS-CoV-2 variants. The neutralization mechanism of this antibody is explained by the structural characteristics of 8-9D Fabs in complex with the Omicron BA.5 spike. In addition, we evaluate the efficacy of 8-9D using a safe and robust mRNA delivery platform and compare the performance of 8-9D when its mRNA is and is not selectively delivered to the lungs. The lung-selective delivery of the 8-9D mRNA enables the expression of neutralizing antibodies in the lungs which blocks the invasion of the virus, thus effectively protecting female K18-hACE2 transgenic mice from challenge with the Beta or Omicron BA.1 variant. Our work underscores the potential application of lung-selective mRNA antibodies in the prevention and treatment of infections caused by circulating SARS-CoV-2 variants.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Animais , Camundongos , Feminino , Anticorpos Amplamente Neutralizantes , SARS-CoV-2/genética , COVID-19/prevenção & controle , Anticorpos Neutralizantes , Camundongos Transgênicos , RNA Mensageiro/genética , Pulmão , Anticorpos Antivirais , Glicoproteína da Espícula de Coronavírus/genética
20.
Front Nutr ; 9: 747705, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35548562

RESUMO

Growing evidence of intestinal microbiota-muscle axis provides a possibility to improve meat quality of broilers through regulating intestinal microbiota. Water-holding capacity is a crucial factor to evaluate the meat quality. High quality of water-holding capacity is usually described as a low drip-losing rate. This study aimed to explore the relationship between intestinal microbiota and water-holding capacity of muscle in broilers. According to our results, two native breeds of broilers (the Arbor Acres broilers and the Beijing-You broilers) exhibited remarkable differences in microbiota composition. However, the regular of gut bacteria compositions gradually became similar when the two breeds of broiler were raised in a same feeding environment. Therefore, this similar regular of intestinal microbiota induced similar water-holding capacity of the muscle from the two breeds. In subsequent fecal microbiota transplantation (FMT) experiments, the intestinal microbiota community of the Arbor Acres broilers was remodeling by oral gavage of bacterial suspension that was derived from the Beijing-You broilers. Then, not only body weight and abdominal fat rate were increased, but also drip loss of muscle was decreased in the Arbor Acres broilers. Additionally, muscle fiber diameter of biceps femoris muscle and expression of MyoD1 were notably enlarged. Muscle fiber diameter and related genes were deemed as important elements for water-holding capacity of muscle. Simultaneously, we screened typical intestinal bacteria in both the two native breeds of broilers by 16S rDNA sequencing. Lachnoclostridium was the only bacteria genus associated with drip-losing rate, meat fiber diameter, body weight, and abdominal fat rate. Importance: Higher body weight and superior meat quality in livestock imply an adequate source of protein and substantial commercial value. Regulating the intestinal microbiota of broilers is a promising approach to optimize commercial phenotypes. Our results indicate that the intestinal microbiota profile could be reconstructed by external factors, leading to advantageous changes in muscle characteristics. The cecum microbiota of native broilers have the ability to improve certain meat quality and production performance. The population of Lachnoclostridium spp. could be used to regulate body weight and drip-losing rate in broilers, but more study is needed.

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