Silicon nanoparticles (SiNPs) have attractive potential applications in biological and medical fields, and yet their impact on animals is still controversial, and there have been no reports of their ...effects on hematopoiesis. In this study, the effects of SiNPs on hemocytes and hematopoiesis were investigated by administering SiNPs via a vascular injection into an invertebrate model, the silkworm. Our results show that the ability of SiNPs to enter different types of circulating hemocytes and their impact on those hemocytes differed significantly. Rapid accumulation of SiNPs was observed in granulocytes, oenocytoids, and spherulocytes, which have immune functions in the circulating hemolymph, whereas SiNPs did not easily enter prohemocytes, which can differentiate into granulocytes, oenocytoids, and spherulocytes and replenish them. The SiNPs that entered the hemocytes initiated autophagy and apoptosis via the lysosomal/mitochondrial pathway. High-dose SiNPs weakly stimulated lysosomal activity in hematopoietic organs, but did not lead to a significant increase in reactive oxygen species or severe autophagy or apoptosis in the organ tissues. We suggest that the damage caused by high-dose SiNPs to hematopoiesis is self-healing, because few SiNPs entered the hematopoietic stem cells in the circulating hemolymph, so the damage to the hematopoietic tissues was limited.
•SiNPs selectively entered circulating hemocytes and induced apoptosis.•The hematopoiesis of hematopoietic organs reduced by SiNPs.•Hematopoietic organs secreted hemocytes return to normal after Self-healing.
Tirofiban is a highly selective nonpeptide antagonist of glycoprotein IIb/IIIa receptor, which reversibly inhibits platelet aggregation. It remains uncertain whether intravenous tirofiban is ...effective to improve functional outcomes for patients with large vessel occlusion ischemic stroke undergoing endovascular thrombectomy.
To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion.
This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 55 hospitals in China, enrolling 948 patients with stroke and proximal intracranial large vessel occlusion presenting within 24 hours of time last known well. Recruitment took place between October 10, 2018, and October 31, 2021, with final follow-up on January 15, 2022.
Participants received intravenous tirofiban (n = 463) or placebo (n = 485) prior to endovascular thrombectomy.
The primary outcome was disability level at 90 days as measured by overall distribution of the modified Rankin Scale scores from 0 (no symptoms) to 6 (death). The primary safety outcome was the incidence of symptomatic intracranial hemorrhage within 48 hours.
Among 948 patients randomized (mean age, 67 years; 391 41.2% women), 948 (100%) completed the trial. The median (IQR) 90-day modified Rankin Scale score in the tirofiban group vs placebo group was 3 (1-4) vs 3 (1-4). The adjusted common odds ratio for a lower level of disability with tirofiban vs placebo was 1.08 (95% CI, 0.86-1.36). Incidence of symptomatic intracranial hemorrhage was 9.7% in the tirofiban group vs 6.4% in the placebo group (difference, 3.3% 95% CI, -0.2% to 6.8%).
Among patients with large vessel occlusion acute ischemic stroke undergoing endovascular thrombectomy, treatment with intravenous tirofiban, compared with placebo, before endovascular therapy resulted in no significant difference in disability severity at 90 days. The findings do not support use of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke.
Chinese Clinical Trial Registry Identifier: ChiCTR-IOR-17014167.
Hirschsprung disease (HSCR) is a heterogeneous group of neurocristopathy characterized by the absence of the enteric ganglia along a variable length of the intestine. Genetic defects play a major ...role in the pathogenesis of HSCR, whereas family studies of pathogenic variants in all the known genes (loci) only demonstrate incomplete penetrance and variable expressivity for unknown reasons. Here, we applied large-scale, quantitative proteomics of human colon tissues from 21 patients using isobaric tags for relative and absolute quantification. method followed by bioinformatics analysis. Selected findings were confirmed by parallel reaction monitoring verification. At last, the interesting differentially expressed proteins were confirmed by Western blot. A total of 5341 proteins in human colon tissues were identified. Among them, 664 proteins with >1.2-fold difference were identified in six groups: groups A1 and A2 pooled protein from the ganglionic and aganglionic colon of male, long-segment HSCR patients (n = 7); groups B1 and B2 pooled protein from the ganglionic and aganglionic colon of male, short-segment HSCR patients (n = 7); and groups C1 and C2 pooled protein from the ganglionic and aganglionic colon of female, short-segment HSCR patients (n = 7). Based on these analyses, 49 proteins from five pathways were selected for parallel reaction monitoring verification, including ribosome, endocytosis, spliceosome, oxidative phosphorylation, and cell adhesion. The downregulation of three neuron projection development genes ARF4, KIF5B, and RAB8A in the aganglionic part of the colon was verified in 15 paired colon samples using Western blot. The findings of this study will shed new light on the pathogenesis of HSCR and facilitate the development of therapeutic targets.
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•Large-scale, quantitative proteomics of human colon tissues from Hirschsprung disease patients.•Parallel reaction monitoring, Western blotting, and immunohistochemical staining for validation.•Four pathways related to differentially expressed proteins: ribosome, endocytosis, spliceosome, and axon guidance.•Downregulation of ARF4, KIF5B, and RAB8A in the aganglionic (stenotic) colon segment.
Quantitative proteomics revealed differentially expressed proteins in paired colon tissues from 21 patients diagnosed with Hirschsprung disease (HSCR). Hierarchical clustering suggests that the protein abundancy and expression pattern in normal intestinal tissues are closely related to gender. Gene ontology enrichment analysis revealed spliceosome, axon guidance, and extracellular exosome as the most related biological processes/molecular functions. Three neuron projection development molecules, ARF4, KIF5B, and RAB8A, were downregulated in the aganglionic segment which may be involved in the pathogenesis of HSCR.
This prospective study explored the value of synchronous tele-ultrasound (US) to aid doctors inexperienced in US with breast US examinations.
In total, 99 patients were enrolled. Two trainee doctors ...who were inexperienced in US (trainee A TA and trainee B TB) and one doctor who was an expert in US completed the US examinations sequentially. TA completed the US examinations independently, while TB was instructed by the expert using synchronous tele-US. Subsequently, the expert performed on-site US examinations in person. Separately, they selected the most clinically significant nodule as the target nodule. Consistency with the expert and image quality were compared between TA and TB to evaluate tele-US. Furthermore, TB and the patients evaluated tele-US through questionnaires.
TB demonstrated higher consistency with the expert in terms of target nodule selection than TA (93.3% vs. 63.3%, P<0.001). TB achieved good inter-observer agreement (ICC, >0.75) with the expert on five US features (5/9, 55.6%), while TA only did so for one (1/9, 11.1%) (P=0.046). TB's image quality was higher than TA's in gray value, time gain compensation, depth, color Doppler adjustment, and the visibility of key information (P=0.018, P<0.001, P<0.001, P=0.033, and P=0.006, respectively). The comprehensive assessment score was higher for TB than for TA (3.96±0.82 vs. 3.09±0.87, P<0.001). Tele-US was helpful in 69.7% of US examinations and had a training effect in 68.0%. Furthermore, 63.6% of patients accepted tele-US and 60.6% were willing to pay.
Tele-US can help doctors inexperienced in US to perform breast US examinations.
Several natural anaerobic fungus-methanogen co-cultures have been isolated from rumen and feces source of herbivores with strong fiber degrading ability. In this study, we isolated 7 Neocallimastix ...with methanogen co-cultures from the rumen of yaks grazing on the Qinghai Tibetan Plateau. Based on morphological characteristics and internal transcribed spacer 1 sequences (ITS1), all the fungi were identified as Neocallimastix frontalis. The co-cultures were confirmed as the one fungus – one methanogen pattern by the PCR-denatured gradient gel electrophoresis (DGGE) assay. All the methanogens were identified as Methanobrevibacter ruminantium by 16s rRNA gene sequencing. We investigated the biodegrading capacity of the co-culture (N. frontalis + M. ruminantium) Yaktz1 on wheat straw, corn stalk and rice straw in a 7 days-incubation. The in vitro dry matter digestibility (IVDMD), acid detergent fiber digestibility (ADFD) and neural detergent fiber digestibility (NDFD) values of the substrates in the co-culture were significantly higher than those in the mono-culture N. frontalis Yaktz1. The co-culture exhibited high polysaccharide hydrolase (xylanase and FPase) and esterase activities. The xylanase in the co-culture reached the highest activity of 12500 mU/ml on wheat straw at the day 3 of the incubation. At the end of the incubation, 3.00 mmol–3.29 mmol/g dry matter of methane were produced by the co-culture. The co-culture also produced high level of acetate (40.00 mM–45.98 mM) as the end-product during the biodegradation. Interestingly, the N. frontalis Yaktz1 mono-culture produced large amount of lactate (8.27 mM–11.60 mM) and ethanol (163.11 mM–242.14 mM), many times more than those recorded in the previously reported anaerobic fungi. Our data suggests that the (N. frontalis + M. ruminantium) Yaktz1 co-culture and the N. frontalis Yaktz1 mono-culture both have great potentials for different industrial use.
•Yaktz 1-7 natural co-cultures of fungus Neocallimastix frontalis and methanogen Methanobrevibacter ruminantium were isolated from rumen fluids of yaks grazing on Qinghai Tibetan Plateau.•Co-culture (N. frontalis + M. ruminantium) Yaktz1 had strong lignocelluloses degrading capacity by exhibiting higher xylanase activity.•Co-culture (N. frontalis + M. ruminantium) Yaktz1 produces larger amount of methane than previously reported natural fungus-methanogen co-cultures•The mono-culture N. frontalis Yaktz1 was efficient in converting the lignocelluosic materials into high yield of ethanol and lactate.
Two nanoscale polytantalotungstates (POTTs), Cs5K4{Cr3Ta3P2W15O622(H2O)12}·15H2O (1) and Cs8.5K8Na2H5.5{Cr4Ta3P2W15O624(H2O)12}·53H2O (2), based on unprecedented {Cr3Ta6} and {Cr4Ta12} clusters, ...respectively, were hydrothermally synthesized. A photocatalytic study revealed that 1 and 2 exhibit significant photocatalytic water splitting activities.
Fungal endophytic communities and metabolite profiles in the aerial and underground parts of plants differ exerting complex influences on each other through mechanisms that largely remain unknown.
...Ephedra sinica
is a model for studying the interactions between endophytic fungi in different plant tissues that exhibit contrasting pharmacological activities. In this study, the endophytic fungal community and metabolites in the stems (Ea) and roots (Eb) of
E. sinica
were systematically investigated using metagenomic and metabolomic approaches, and their relationships were further analyzed. Results showed that OTU48 and OTU30589 were endophytic fungi shared by Ea and Eb, respectively. The genera of
Phyllosticta
fungi were specifically and abundantly present in Ea, whereas
Talaromyces
,
Aporospora
, and
Aspergillus
fungi were specific and abundant in Eb. A total of 17 significant differential metabolites were observed between Ea and Eb. Ephedrine and methylephedrine were mainly present in Ea, whereas ephedrannin A and mahuannin A were present in Eb. Nine endophytic fungi significantly (
P
< 0.05 or 0.01) correlated with several differential metabolites. The results of this study further substantiate the differential formation of secondary metabolites in specific plant tissues.
Avian reovirus (ARV) causes arthritis, tenosynovitis, runting-stunting syndrome (RSS), malabsorption syndrome (MAS) and immunosuppression in chickens. σB is one of the major structural proteins of ...ARV, which is able to induce group-specific antibodies against the virus.
The present study described the identification of two linear B-cell epitopes in ARV σB through expressing a set of partially overlapping and consecutive truncated peptides spanning σB screened with two monoclonal antibodies (mAbs) 1F4 and 1H3-1.The data indicated that (21)KTPACW(26) (epitope A) and (32)WDTVTFH(38) (epitope B) were minimal determinants of the linear B cell epitopes. Antibodies present in the serum of ARV-positive chickens recognized the minimal linear epitopes in Western blot analyses. By sequence alignment analysis, we determined that the epitopes A and B were not conserved among ARV, duck reovirus (DRV) and turkey reovirus (TRV) strains. Western blot assays, confirmed that epitopes A and B were ARV-specific epitopes, and they could not react with the corresponding peptides of DRV and TRV.
We identified (21)KTPACW(26) and (32)WDTVTFH(38) as σB -specific epitopes recognized by mAbs 1F4 and 1H3-1, respectively. The results in this study may have potential applications in development of diagnostic techniques and epitope-based marker vaccines against ARV groups.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Energy metabolism is important for the proliferation of microsporidia in infected host cells, but there is limited information on the host response. The energy metabolism response of silkworm (Bombyx ...mori) to microsporidia may help manage Nosema bombycis infections. We analyzed differentially expressed genes in the B.mori midgut transcriptome at two significant time points of microsporidia infection. A total of 1448 genes were up-regulated, while 315 genes were down-regulated. A high proportion of genes were involved in the phosphatidylinositol signaling system, protein processing in the endoplasmic reticulum, and glycerolipid metabolism at 48 h post infection (h p.i.), and a large number of genes were involved in the TCA cycle and protein processing at 120 h p.i. These results showed that the early stages of microsporidia infection affected the basic metabolism and biosynthesis processes of the silkworm. Knockout of Bm_nscaf2860_46 (Bombyx mori isocitrate dehydrogenase, BmIDH) and Bm_nscaf3027_062 (Bombyx mori hexokinase, BmHXK) reduced the production of ATP and inhibited microsporidia proliferation. Host fatty acid degradation, glycerol metabolism, glycolysis pathway, and TCA cycle response to microsporidia infection were also analyzed, and their importance to microsporidia proliferation was verified. These results increase our understanding of the molecular mechanisms involved in N. bombycis infection and provide new insights for research on microsporidia control.
Nosema bombycis can be vertically transmitted in silkworm eggs. The traditional prevention and control strategies for microsporidia are difficult and time-consuming, and this is a problem in silkworm culture. Research has mainly focused on host gene functions related to microsporidia infection and host immune responses after microsporidia infection. Little is known about the metabolic changes occurring in the host after infection. Understanding the metabolic changes in the silkworm host could aid in the recognition of host genes important for microsporidia infection and growth. We analyzed host metabolic changes and the main participating pathways at two time points after microsporidia infection and screened the microsporidia-dependent host energy metabolism genes BmIDH and BmHXK. The results revealed genes that are important for the proliferation of Nosema bombycis. These results illustrate how microsporidia hijack the host genome for their growth and reproduction.
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•Microsporidia promotes host metabolic pathways of glucose and lipid metabolism.•BmIDH and BmHXK are important for cellular ATP production after parasite infection.•Microsporidia proliferation is dependent on BmIDH and BmHXK.•Reliance on metabolic pathways could be a potential anti-microsporidia strategy.
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