RESUMO

Agrocybe chaxingu is a widely cultivated edible fungus in China, which is rich in nutrients and medicinal compounds. However, the lack of a high-quality genome hinders further research. In this study, we assembled the telomere-to-telomere genomes of two sexually compatible monokaryons (CchA and CchB) derived from a primarily cultivated strain AS-5. The genomes of CchA and CchB were 50.60 Mb and 51.66 Mb with contig N50 values of 3.95 Mb and 3.97 Mb, respectively. Each contained 13 complete chromosomes with telomeres at both ends. The high mapping rate, uniform genome coverage, high LAI score, all BUSCOs with 98.5%, and all base accuracy exceeding 99.999% indicated the high level of integrity and quality of these two assembled genomes. Comparison of the two genomes revealed that approximately 30% of the nucleotide sequences between homologous chromosomes were non-syntenic, including 19 translocations, 36 inversions, and 15 duplications. An additional gene CchA_000467 was identified at the Mat A locus of CchA, which was observed exclusively in the Cyclocybe cylindracea species complex. A total of 613 (4.26%) and 483 (3.4%) unique genes were identified in CchA and CchB, respectively, with over 80% of these being hypothetical proteins. Transcriptomic analysis revealed that the expression levels of unique genes in CchB were significantly higher than those in CchA, and both CchA and CchB had unique genes specifically expressed at stages of mycelium and fruiting body. It was indicated that the growth and development of the A. chaxingu strain AS-5 required the coordinated action of two different nuclei, with CchB potentially playing a more significant role. These findings contributed to a more profound comprehension of the growth and developmental processes of basidiomycetes.

RESUMO

Benzonitrile (BN, C6H5CN) has been detected in the cold molecular cloud Taurus molecular cloud-1 (TMC-1) in 2018, which is suggested to be a precursor in the formation of more complex nitrogen-containing aromatic interstellar compounds. In this study, we utilized mass-selected infrared (IR) photodissociation spectroscopy and quantum chemical calculations to investigate the structures and gaseous ion-molecule reactions of benzonitrile-ammonia (BN-NH3) and benzonitrile-methylamine (BN-MA) clusters. The spectral observations indicate that the cyclic hydrogen bonding structure predominates in both neutral clusters. After VUV (118 nm) single-photon ionization, a new C-N covalent bond formed between BN and NH3 in the (BN-NH3)+ cluster. However, proton sharing constitutes the primary structure of the (BN-MA)+ cluster. The two nitrogen-containing interstellar molecules react with BN to yield distinct products due to difference in charge distribution and molecular polarity in the ionized clusters. The reactions of BN with other molecules contribute to our understanding of the growth mechanisms of complex interstellar molecules.

RESUMO

Intrauterine adhesion (IUA) is characterized by the formation of fibrous scar tissue within the uterine cavity, which significantly impacts female reproductive health and even leads to infertility. Unfortunately, severe cases of IUA currently lack effective treatments. This study presents a novel approach that utilizes tumor necrosis factor-(TNF) stimulated gene 6 (TSG6)-modified exosomes (Exos) in conjunction with an injectable thermosensitive hydrogel (CS/GP) to mitigate the occurrence of IUA by reducing endometrium fibrosis in a mouse IUA model. This study demonstrate that TSG6-modified Exos effectively inhibits the activation of inflammatory M1-like macrophages during the initial stages of inflammation and maintains the balance of macrophage phenotypes (M1/M2) during the repair phase. Moreover, TSG6 inhibits the interaction between macrophages and endometrial stromal fibroblasts, thereby preventing the activation of stromal fibroblasts into myofibroblasts. Furthermore, this research indicates that CS/GP facilitates the sustained release of TSG6-modified Exos, leading to a significant reduction in both the manifestations of IUA and the extent of endometrium fibrosis. Collectively, through the successful construction of CS/GP loaded with TSG6-modified Exos, a reduction in the occurrence and progression of IUA is achieved by mitigating endometrium fibrosis. Consequently, this approach holds promise for the treatment of IUA.

Assuntos

Moléculas de Adesão Celular , Modelos Animais de Doenças , Endométrio , Exossomos , Fibrose , Hidrogéis , Ativação de Macrófagos , Animais , Feminino , Endométrio/patologia , Endométrio/metabolismo , Camundongos , Moléculas de Adesão Celular/metabolismo , Hidrogéis/química , Exossomos/metabolismo , Exossomos/química , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Aderências Teciduais/prevenção & controle , Células RAW 264.7

RESUMO

BACKGROUND: Co-infection of JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) is uncommon in kidney transplant recipients, and the prognosis is unclear. This study aimed to investigate the effect of concurrent JCPyV-DNAemia on graft outcomes in BKPyV-infected kidney transplant recipients with polyomavirus-associated nephropathy (PyVAN). METHODS: A total of 140 kidney transplant recipients with BKPyV replication and PyVAN, 122 without concurrent JCPyV-DNAemia and 18 with JCPyV-DNAemia were included in the analysis. Least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to identify prognostic factors for graft survival. A nomogram for predicting graft survival was created and evaluated. RESULTS: The median tubulitis score in the JCPyV-DNAemia-positive group was higher than in JCPyV-DNAemia-negative group ( P  = 0.048). At last follow-up, the graft loss rate in the JCPyV-DNAemia-positive group was higher than in the JCPyV-DNAemia-negative group (50% versus 25.4%; P  = 0.031). Kaplan-Meier analysis showed that the graft survival rate in the JCPyV-DNAemia-positive group was lower than in the JCPyV-DNAemia-negative group ( P  = 0.003). Least absolute shrinkage and selection operator regression and multivariate Cox regression analysis demonstrated that concurrent JCPyV-DNAemia was an independent risk factor for graft survival (hazard ratio = 4.808; 95% confidence interval: 2.096-11.03; P  < 0.001). The nomogram displayed favorable discrimination (C-index = 0.839), concordance, and clinical applicability in predicting graft survival. CONCLUSIONS: Concurrent JCPyV-DNAemia is associated with a worse graft outcome in BKPyV-infected kidney transplant recipients with PyVAN.

Assuntos

DNA Viral , Sobrevivência de Enxerto , Transplante de Rim , Infecções por Polyomavirus , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Feminino , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/virologia , Infecções por Polyomavirus/diagnóstico , Adulto , DNA Viral/sangue , Estudos Retrospectivos , Vírus BK/patogenicidade , Fatores de Risco , Nefropatias/cirurgia , Nefropatias/virologia , Nefropatias/mortalidade , Nefropatias/diagnóstico , Infecções Tumorais por Vírus/virologia , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/mortalidade , Resultado do Tratamento , Coinfecção , Nomogramas , Rejeição de Enxerto/virologia , Idoso

RESUMO

Background: The low osteogenic differentiation potential and attenuated anti-inflammatory effect of adipose-derived stem cells (ADSCs) from animals with type 2 diabetes mellitus (T2DM) limits osseointegration of the implant. However, the underlying mechanisms are not fully understood. Methods: Western blotting and qRT-PCR analyses were performed to investigate the effects of PTEN on the osteogenic capacity of ADSCs of T2DM rats (TADSCs). We conducted animal experiments in T2DM-Sprague Dawley (SD) rats to evaluate the osteogenic capacity of modified TADSC sheets in vivo. New bone formation was assessed by micro-CT and histological analyses. Results: In this study, adipose-derived stem cells of T2DM rats exhibited an impaired osteogenic capacity. RNA-seq analysis showed that PTEN mRNA expression was upregulated in TADSCs, which attenuated the osteogenic capacity of TADSCs by inhibiting the AKT/mTOR/HIF-1α signaling pathway. miR-140-3p, which inhibits PTEN, was suppressed in TADSCs. Overexpression or inhibition of PTEN could correspondingly reduce or enhance the osteogenic ability of TADSCs by regulating the AKT/mTOR/HIF-1α signaling pathway. TADSCs transfected with PTEN siRNA resulted in higher and lower expressions of genes encoded in M2 macrophages (Arg1) and M1 macrophages (iNOS), respectively. In the T2DM rat model, PTEN inhibition in TADSC sheets promoted macrophage polarization toward the M2 phenotype, attenuated inflammation, and enhanced osseointegration around implants. Conclusion: Upregulation of PTEN, which was partially due to the inhibition of miR-140-3p, is important for the attenuated osteogenesis by TADSCs owing to the inhibition of the AKT/mTOR/HIF-1α signaling pathway. Inhibition of PTEN significantly improves the anti-inflammatory effect and osteogenic capacity of TADSCs, thus promoting peri-implant bone formation in T2DM rats. Our findings offer a potential therapeutic approach for modifying stem cells derived from patients with T2DM to enhance osseointegration.

RESUMO

Agrocybe chaxingu is an edible and medicinal mushroom widely cultivated in China (Liu et al. 2021). Agrocybe chaxingu is extremely well-liked for the unique flavor and nutritional value. In May 2021, a serious white mucus disease was observed in the farms of A. chaxingu in the Ganxian district of Ganzhou City, Jiangxi Province, China, with an approximate disease incidence of 20%. In the years of 2022 and 2023, the same white mucus disease on A. chaxingu was observed in the farms in Nanchang City, Jiujiang City and Guangchang County, Jiangxi Province, China. The disease generally occurs on the media, stipe or pileus of A. chaxingu under condition of high humidity. The plasmodial slime molds migrated from the surface of culture media (78% hardwood sawdust, 15% wheat bran, 5% tea seed shell, 1% lime, and 1% gypsum) to the base of fruiting bodies, stipes and finally to pilei, showing as moist, sticky, and white reticulated structures. The infected fruiting bodies of A. chaxingu were completely covered by reticulated plasmodia, displaying a white or pale-yellow color. This resulted in the growth cessation, wilting and eventual death of fruiting body. Microscopic observation found that the plasmodia of slime mold enveloped the hyphae of A. chaxingu, resulting in the fragmentation of the hyphae. The disease can spread quickly, resulting in a 30% reduction in production. Slime mold cultures were isolated by transferring diseased fruiting bodies of A. chaxingu onto oat-agar medium (2% agar and 1% oatmeal) at 25 ℃. The isolates can be obtained after being subcultured for two to three generations. Purified plasmodia were placed on the semi-defined medium (1% tryptone, 1% glucose, 0.15% yeast extract, chick embryo extract and a balanced salt solution) to confirm the absence of bacteria (Daniel et al. 1964) and thus obtained the pure culture. Specimen of the voucher has been deposited in the Institute of Agricultural Applied Microbiology, Jiangxi Academy of Agricultural Sciences as number IAAM-W0002. The vegetative plasmodia have a large and well-developed scalloped structure that were white or milky white in colour. The white plasmodium became opaque pale yellow when exposed to light before fruiting. The veins merged and thickened. Fruiting bodies can be formed on the lid or side of the Petri dish under light condition. The fruiting bodies formed papillae with irregular shape, and then the color changed from translucent yellow to greyish black. Spores were usually spherical or subglobose, free, greyish brown in mass, purplish brown, 7-12 µm in diameter under light microscopy. These morphological characteristics were found to be consistent with those of Fuligo gyrosa (Synonym: Physarum gyrosum) (Kim et al. 2009; Shi et al. 2005; Jahn 1902). The identity of the isolates was further confirmed by sequence analysis of the 18S ribosomal RNA gene with primer SMNUR101/NS4 (Rusk et al. 1995; White et al. 1990). Using BLASTn searches, the sequence of 18S rRNA gene (GenBank accession number OR186216) matched the sequence of F. gyrosa (GenBank accession number LC744593) with the identity of 99.91% and coverage of 97%. A phylogenetic tree based on the 18S rRNA gene also demonstrated that the slime mold clustered with F. gyrosa. Over ten isolates have been obtained from the diseased A. chaxingu samples in different factories and identified as F. gyrosa. To test the pathogenicity of F. gyrosa, five healthy young fruiting bodies (three to five days of primordium) of A. chaxingu cultivated in mushroom-growing room were gently inoculated by a 12 mm diameter oat-agar medium with plasmodia at 24 ± 2 ℃ and then were kept with relative humidity of 90%-95%. Five fruiting bodies inoculated with a 12 mm oat-agar medium served as controls. After 5 days, white mucus characteristics and three fifths of death symptoms were observed on the fruiting bodies inoculated with the plasmodia, while the controls remained asymptomatic. The slime mold on the inoculated fruiting bodies was morphologically identical to F. gyrosa that was observed on the initial diseased fruiting bodies. It was also observed the envelopment A. chaxingu hyphae by the plasmodia of slime mold and fragmentation of the hyphae, and the fragmentation was not observed in the controls. Reisolations were prepared from the inoculated fruiting bodies and confirmed to be F. gyrosa based on morphological characteristics and 18S rRNA sequence, thus fulfilling Koch's postulates. Fuligo gyrosa has been reported to cause severe disease in oriental melon in Korea (Kim et al. 2009). This is the first report of F. gyrosa causing white mucus disease in cultivated A. chaxingu. The findings will provide important information on prevention and control of the disease, and be helpful for the development of A. chaxingu industry.

RESUMO

Polymer-lined autoclaves are commonly believed to be highly durable and inert in hydrothermal reactions. Herein, we use the hydrothermal synthesis of AlPO-18 zeolite as a case study to demonstrate that the choice of autoclave materials (polytetrafluoroethylene or para-polyphenylene) does significantly affect the product of zeolite synthesis. A small amount of glass fiber in the PPL-lined autoclave unexpectedly functions as a source of silicon and yields SAPO-34 instead of AlPO-18 as the product. The outcomes of 19 successive experiments conducted with a single PPL-lined autoclave exhibit significant variations, further highlighting that the impurities arising from the autoclaves should be considered during the hydrothermal synthesis procedure. In contrast to SAPO-34 synthesized by the conventional method, which displays only Si(4Al) at a low Si/Al ratio, SAPO-34 synthesized in the PPL-lined autoclave exhibits multiple silicon coordination environments. This outcome provides new physical insights into the silicon incorporation mechanism and proposes a viable strategy for regulating the silicon coordination environment at low Si/Al ratios.

RESUMO

Gestational diabetes mellitus (GDM) is a gestational disorder characterized by hyperglycemia, that can lead to dysfunction of diverse cells in the body, especially the immune cells. It has been reported that immune cells, specifically natural killer (NK) cells, play a crucial role in normal pregnancy. However, it remains unknown how hyperglycemia affects NK cell dysfunction thus participates in the development of GDM. In this experiment, GDM mice were induced by an intraperitoneal injection of streptozotocin (STZ) after pregnancy and it has been found that the intrauterine growth restriction occurred in mice with STZ-induced GDM, accompanied by the changed proportion and function of NK cells. The percentage of cytotoxic CD27-CD11b+ NK cells was significantly increased, while the proportion of nourished CD27-CD11b- NK cells was significantly reduced in the decidua of GDM mice. Likewise, the same trend appeared in the peripheral blood NK cell subsets of GDM patients. What's more, after intrauterine reinfusion of NK cells to GDM mice, the fetal growth restriction was alleviated and the proportion of NK cells was restored. Our findings provide a theoretical and experimental basis for further exploring the pathogenesis of GDM.

Assuntos

Diabetes Mellitus Experimental , Diabetes Gestacional , Hiperglicemia , Humanos , Gravidez , Feminino , Camundongos , Animais , Retardo do Crescimento Fetal/etiologia , Células Matadoras Naturais

RESUMO

PURPOSE: The extensive use of vancomycin has led to the development of Staphylococcus aureus strains with varying degrees of resistance to vancomycin. The present study aimed to explore the molecular causes of vancomycin resistance by conducting a proteomics analysis of subcellular fractions isolated from vancomycin-intermediate resistant S. aureus (VISA) and vancomycin-sensitive S. aureus (VSSA) strains. METHODS: We conducted proteomics analysis of subcellular fractions isolated from 2 isogenic S. aureus strains: strain 11 (VSSA) and strain 11Y (VISA). We used an integrated quantitative proteomics approach assisted by bioinformatics analysis, and comprehensively investigated the proteome profile. Intensive bioinformatics analysis, including protein annotation, functional classification, functional enrichment, and functional enrichment-based cluster analysis, was used to annotate quantifiable targets. RESULTS: We identified 128 upregulated proteins and 21 downregulated proteins in strain 11Y as compared to strain 11. The largest group of differentially expressed proteins was composed of enzymatic proteins associated with metabolic and catalytic activity, which accounted for 32.1% and 50% of the total proteins, respectively. Some proteins were indispensable parts of the regulatory networks of S. aureus that were altered with vancomycin treatment, and these proteins were related to cell wall metabolism, cell adhesion, proteolysis, and pressure response. CONCLUSION: Our proteomics study revealed regulatory proteins associated with vancomycin resistance in S. aureus. Some of these proteins were involved in the regulation of cell metabolism and function, which provides potential targets for the development of strategies to manage vancomycin resistance in S. aureus.

Assuntos

Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Staphylococcus aureus/genética , Vancomicina/farmacologia , Vancomicina/uso terapêutico , Proteômica , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana

RESUMO

BACKGROUND: Stabilization and increased activity of hypoxia-inducible factor 1-α (HIF-1α) can directly increase cancellous bone formation and play an essential role in bone modeling and remodeling. However, whether an increased HIF-1α expression in adipose-derived stem cells (ADSCs) increases osteogenic capacity and promotes bone regeneration is not known. RESULTS: In this study, ADSCs transfected with small interfering RNA and HIF-1α overexpression plasmid were established to investigate the proliferation, migration, adhesion, and osteogenic capacity of ADSCs and the angiogenic ability of human umbilical vein endothelial cells (HUVECs). Overexpression of HIF-1α could promote the biological functions of ADSCs, and the angiogenic ability of HUVECs. Western blotting showed that the protein levels of osteogenesis-related factors were increased when HIF-1α was overexpressed. Furthermore, the influence of upregulation of HIF-1α in ADSC sheets on osseointegration was evaluated using a Sprague-Dawley (SD) rats implant model, in which the bone mass and osteoid mineralization speed were evaluated by radiological and histological analysis. The overexpression of HIF-1α in ADSCs enhanced bone remodeling and osseointegration around titanium implants. However, transfecting the small interfering RNA (siRNA) of HIF-1α in ADSCs attenuated their osteogenic and angiogenic capacity. Finally, it was confirmed in vitro that HIF-1α promotes osteogenic differentiation and the biological functions in ADSCs via the VEGF/AKT/mTOR pathway. CONCLUSIONS: This study demonstrates that HIF-1α has a critical ability to promote osteogenic differentiation in ADSCs by coupling osteogenesis and angiogenesis via the VEGF/AKT/mTOR signaling pathway, which in turn increases osteointegration and bone formation around titanium implants.

Assuntos

Subunidade alfa do Fator 1 Induzível por Hipóxia , Osteogênese , Proteínas Proto-Oncogênicas c-akt , Animais , Humanos , Ratos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Neovascularização Fisiológica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , RNA Interferente Pequeno , Transdução de Sinais , Titânio , Serina-Treonina Quinases TOR/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo

RESUMO

Diabetic cardiomyopathy (DCM) is one of the main complications in type I diabetic patients. Activated macrophage is critical for directing the process of inflammation during the development of DCM. The present study focused on the roles of CD226 on macrophage function during the DCM progression. It has been found that the number of cardiac macrophages in the hearts of streptozocin (STZ)-induced diabetes mice was significantly increased compared with that in non-diabetes mice, and the expression level of CD226 on cardiac macrophages in STZ-induced diabetes mice was higher than that in non-diabetes mice. CD226 deficiency attenuated the diabetes-induced cardiac dysfunction and decreased the proportion of CD86+ F4/80+ macrophages in the diabetic hearts. Notably, adoptive transfer of Cd226-/- - bone marrow derived macrophages (BMDMs) alleviated diabetes-induced cardiac dysfunction, which may be due to the attenuated migration capacity of Cd226-/- -BMDM under high glucose stimulation. Furthermore, CD226 deficiency decreased the macrophage glycolysis accompanying by the downregulated hexokinase 2 (HK2) and lactate dehydrogenase A (LDH-A) expression. Taken together, these findings revealed the pathogenic roles of CD226 played in the process of DCM and provided a basis for the treatment of DCM.

Assuntos

Antígenos de Diferenciação de Linfócitos T , Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Animais , Camundongos , Diabetes Mellitus Experimental/complicações , Glicólise , Coração , Macrófagos , Antígenos de Diferenciação de Linfócitos T/genética

RESUMO

Nitrogen-doped graphene (NG) was synthesized via direct thermal annealing treatment. The obtained NG showed outstanding removal ability for tetracycline (TC) ascribed to enhanced adsorption and persulfate activation. The maximum TC adsorption capacity calculated from the Langmuir model of NG was 227.3 mg/g, which was 1.66 times larger than nitrogen-free graphene. The coexistence of NG and persulfate (PS) exhibited complete degradation of TC within 120 min attributed to the successful modification of nitrogen. Further analysis demonstrated that non-radical electron transfer was the dominant degradation pathway, which was different from the widely acknowledgeable radical mechanism. An electron donor-mediator-acceptor system was introduced, in which TC, NG, and PS performed as electron donor, mediator, and acceptor, respectively. The potential intermediates in the TC degradation process were detected and toxicity assessment was also performed. In addition, more than 75.8% of total organic carbon was removed, and excellent reusability was manifested in multiple adsorption and degradation experiments.

Assuntos

Grafite , Poluentes Químicos da Água , Adsorção , Nitrogênio , Antibacterianos , Tetraciclina/análise , Oxidantes , Poluentes Químicos da Água/análise

RESUMO

In this study, zein-soy isoflavone complex (ZSI) emulsifiers were fabricated using ultrasound-assisted dynamic high-pressure micro fluidization to stabilise highinternal phase pickering emulsions. Ultrasound-assisted dynamic high-pressure micro-fluidization enhanced surface hydrophobicity, zeta potential, and soy isoflavone binding capacity, while it decreased particle size, especially during ultrasound and subsequent microfluidization. The treated ZSI could produce small droplet clusters and gel-like structures, with excellent viscoelasticity, thixotropy and creaming stability owing to their neutral contact angles. Ultrasound and subsequent micro fluidization treatment of the ZSI complexes were highly effective in preventing droplet flocculation and coalescence after long-term storage or centrifugation due to their higher surface load, thicker multi-layer interfacial structure, and stronger electronic repulsion between the oil droplets. This study provides insights and extends our current knowledge of how non-thermal technology affects the interfacial distribution of plant based particles and the physical stability of emulsions.

Assuntos

Isoflavonas , Zeína , Emulsões , Ultrassonografia , Emulsificantes , Cetonas

RESUMO

AIMS: To evaluate the potential applications of soy protein-glucan-catechin (SGC) complexes prepared with different ultrasound times in stabilising high internal phase Pickering emulsion (HIPPE) and delivering curcumin. METHODS: The SGC complexes were characterised by particle size, morphology, zeta potential, Fourier transform infra-red, and fluorescence spectroscopy. Formation and stability of curcumin emulsions were monitored by droplet size, microstructure, rheological property, lipid oxidation, and in vitro digestion. RESULTS: Short-time ultrasound-induced complexes (SGC-U15) exhibited a small size and wettability of ∼82.5°. The chemical stability and bioaccessibility of curcumin was greatly improved by SGC-U15-stabilised HIPPEs, even after 70 days of storage, heating at 100 °C for 30 min, ultraviolet irradiation for 120 min, and in vitro digestion, owing to the formation of elastic gel-like structure at the oil/water interfaces. CONCLUSION: Our findings may contribute to the design of emulsion-based delivery systems using ultrasound-induced protein-polysaccharide-polyphenol complexes.

Assuntos

Catequina , Curcumina , Nanopartículas , beta-Glucanas , Emulsões , Proteínas de Soja

RESUMO

Ink jet printing is for the first time introduced into the synthesis of aluminophosphate (AlPO) and silicoaluminophosphate (SAPO) zeolite. As a high-throughput technique, 256 zeolite precursors with multiple formulations could be obtained within 2 h, while the product phase was regulated relative to the variant compositions.

RESUMO

BK polyomavirus (BKPyV) infection is the main factor affecting the prognosis of kidney transplant recipients, as no antiviral agent is yet available. A better understanding of the renal-cell-type tropism of BKPyV can serve to develop new treatment strategies. In this study, the single-cell transcriptomic analysis demonstrated that the ranking of BKPyV tropism for the kidney was proximal tubule cells (PT), collecting duct cells (CD), and glomerular endothelial cells (GEC) according to the signature of renal cell type and immune microenvironment. In normal kidneys, we found that BKPyV infection-related transcription factors P65 and CEBPB were PT-specific transcription factors, and PT showed higher glycolysis/gluconeogenesis activities than CD and GEC. Furthermore, in the BKPyV-infected kidneys, the percentage of late viral transcripts in PT was significantly higher than in CD and GEC. In addition, PT had the smallest cell-cell interactions with immune cells compared to CD and GEC in both normal and BKPyV-infected kidneys. Subsequently, we indirectly demonstrated the ranking of BKPyV tropism via the clinical observation of sequential biopsies. Together, our results provided in-depth insights into the renal cell-type tropism of BKPyV in vivo at single-cell resolution and proposed a novel antiviral target.

Assuntos

Vírus BK , Transplante de Rim , Infecções por Polyomavirus , Humanos , Vírus BK/genética , Transcriptoma , Células Endoteliais , Rim , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/genética , Antivirais

RESUMO

BACKGROUND: Microgravity directly disturbs the reorganization of the cytoskeleton, exerting profound effects on the physiological process of macrophages. Although it has been established that macrophage M1/M2 polarization could be manipulated by the surface nanostructure of biomaterial in our previous study under normal gravity, how will inflammatory monocytes (iMos)-derived macrophages respond to diverse nanostructured Ti surfaces under normal gravity or microgravity remains unrevealed. RESULTS: In this study, Cytochalasin D, a cytoskeleton relaxant, was employed to establish the simulated microgravity (SMG) environment. Our results showed that human iMos polarized into M2c macrophages on NT5 surface but M1 type on NT20 surface with divergent inflammatory phenotypes according to the profile of macrophage polarization featured molecules under normal gravity. However, such manipulative effects of NTs surfaces on iMos-derived macrophages were strikingly weakened by SMG, characterized by the altered macrophage morphology, changed cytokine secretion profile, and decreased cell polarization capacity. CONCLUSIONS: To our knowledge, this is the first metallic implantable material study focusing on the functions of specific monocyte subsets and its crucial role of the cytoskeleton in materials-mediated host immune response, which enriches our mechanism knowledge about the crosstalk between immunocytes and biomaterials. The results obtained in the present study may also provide potential targets and strategies for biomaterial development and clinical treatment via precise immune-regulation under normal gravity and microgravity.

Assuntos

Monócitos , Nanoestruturas , Humanos , Nanoestruturas/química , Materiais Biocompatíveis , Citoesqueleto

RESUMO

A functional vasculature for survival remains a challenge for tissue regeneration, which is indispensable for oxygen and nutrient supply. Utilizing mesenchymal stromal cells (MSCs) to alleviate tissue ischemia and repair dysfunctional or damaged endothelium is a promising strategy. Compared to other populations of MSCs, adipose-derived stromal cells (ASCs) possess a more significant proangiogenic potential and are abundantly available. Cell sheet technology has recently been widely utilized in bone engineering. Compared to conventional methods of seeding seed cell suspension onto biological scaffolds, cell sheet technology prevents cell loss and preserves the extracellular matrix (ECM). Nevertheless, the proangiogenic potential of ASC sheets remains unknown. In this study, rat ASC sheets were constructed, and their macro- and microstructures were examined. In addition, we investigated the effects of ASCs and ASC sheets on the biological properties and angiogenic capacity of endothelial cells (ECs). The results demonstrated that the ASC sheets gradually thickened as the number of cells and ECM increased over time and that the cells were in an active state of secretion. Similar to ASC-CM, the conditioned medium (CM) of ASC sheets could significantly enhance the proliferative capacity of ECs. ASC sheet-CM has significant advantages over ASC-CM in promoting the migration and angiogenesis of ECs, where the exosomes secreted by ASC sheets play an essential role. Therefore, using ASC sheets for therapeutic tissue and organ regeneration angiogenesis may be a valuable strategy.

RESUMO

Peri-implantitis is characterized by inflammatory cell infiltration and hyperactivation of the osteoclasts surrounding dental implants which can result in bone resorption and ultimately implant failure. Therefore, coordinating the activity of inflammatory response and bone-resorbing osteoclasts is crucial for the prevention of peri-implantitis. Asperuloside (ASP), an iridoid glycoside, has significant anti-inflammatory activities, suggesting the great potential in attenuating peri-implantitis bone resorption. A ligature-induced peri-implantitis model in the maxilla of rats was established, and the effects of ASP on preventing peri-implantitis were evaluated after four weeks of ligation using micro-CT and histological staining. RT-PCR, western blotting, tartrate-resistant acid phosphatase (TRAP), and immunofluorescent staining were conducted on osteoclasts to confirm the mechanisms of ASP on osteoclastogenesis. The results show that ASP could lead to attenuation of alveolar bone resorption in peri-implantitis by inhibiting osteoclast formation and decreasing pro-inflammatory cytokine levels in vivo. Furthermore, ASP could inhibit osteoclastogenesis by downregulating expression levels of transcription factors nuclear factor of activated T-cell (NFATc1) via restraining the activations of nuclear factor kappa beta (NF-κB) and the phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2). In conclusion, ASP could significantly attenuate bone resorption in peri-implantitis via inhibition of osteoclastogenesis by suppressing NF-κB and ERK1/2 signaling pathways activations.

RESUMO

Background: We developed a pragmatic dichotomous grading criterion to stratify the acute tubular injury (ATI) of deceased-donor kidneys. We intended to verify the predictive value of this criterion for the prognosis of deceased-donor kidney transplantation. Methods: The allografts with ATI were classified into severe and mild groups. Severe ATI was defined as the presence of extreme and diffuse flattening of the tubular epithelial cells, or denudement of the tubular basement membrane. The clinical delayed graft function (DGF) risk index was calculated based on a regression model for posttransplant DGF using 17 clinical parameters related to donor-recipient characteristics. Results: A total of 140 recipients were enrolled: 18 severe and 122 mild ATI. Compared with the mild ATI group, the severe ATI group had more donors after cardiac death, higher median donor terminal serum creatinine level (dScr), and longer median cold ischemia time. Severe ATI had a higher DGF rate (55.6% vs 14.6%, p < 0.001), longer DGF recovery time (49.6 vs 26.3 days, p < 0.001), and a lower estimated glomerular filtration rate (eGFR) at 1 month (23.5 vs 54.0 ml/min/1.73 m2, p < 0.001), 3 months (40.4 vs 59.0, p = 0.001), and 6 months after transplant (46.8 vs 60.3, p = 0.033). However, there was no significant difference in eGFR at 1 year or beyond, graft, and patient survival. The predictive value of combined dScr with ATI severity for DGF rate and DGF recovery time was superior to that of dScr alone. The predictive value of the combined DGF risk index with ATI severity for DGF was also better than that of the DGF risk index alone; however, the association of the DGF risk index with DGF recovery time was not identified. Chronic lesions including glomerulosclerosis, interstitial fibrosis, arterial intimal fibrosis, and arteriolar hyalinosis were associated with declined posttransplant 1-year eGFR. Conclusion: Based on our pragmatic dichotomous grading criterion for ATI in a preimplantation biopsy, donor kidneys with severe ATI increased DGF risk, prolonged DGF recovery, and decreased short-term graft function but demonstrated favorable long-term graft function. Our grading method can offer additive valuable information for assessing donor kidneys with acute kidney injury and may act as an effective supplementary index of the Banff criteria.

Assuntos

Função Retardada do Enxerto , Transplante de Rim , Função Retardada do Enxerto/patologia , Fibrose , Sobrevivência de Enxerto , Humanos , Rim/patologia , Transplante de Rim/métodos , Prognóstico