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1.
Insect Sci ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34231971

RESUMO

U1 small nuclear ribonucleoproteins (U1 snRNP) associates with 5' splice sites in the form of ribonucleoprotein particles, is highly conserved among species. The physiological functions of U1 snRNP in a lepidopteran model insect Bombyx mori is mostly unknown. Here we showed that U1 snRNP plays an important role in the development of silkworm. Knockout of U1 snRNP in silkworm showed either delayed or stationary 1st-instar larva development compared with the wild type group. U1 snRNP deletion mutants exhibited abnormal cellular phenotypes with enlarged cell nucleus, scanty cytoplasm, and enlarged nuclei. RNA-seq analysis revealed that genes involved in metabolic pathway, biosynthesis of secondary metabolites and steroid hormone biosynthesis were significantly affected by U1 snRNP depletion. Taken together, our study suggests that U1 snRNP homeostasis plays an important role in silkworm development. This article is protected by copyright. All rights reserved.

2.
Mater Sci Eng C Mater Biol Appl ; 127: 112225, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225870

RESUMO

Many medical and chemical applications require the precise supply of antimicrobial components in a controlled manner at the location of mature biofilm deposits. This work reports a facile strategy to fabricate nanoscale metal-organic frameworks (NMOFs) coencapsulating the antibacterial ligand (lysine carbon dots, Lys-CDs) and targeted drug (folic acid, FA) in one pot to improve antibiofilm efficiency against established biofilms. The resulting products are characterized by transmission electron microscopy, field-emission scanning electron microscopy, powder x-ray diffraction, and ultraviolet-visible spectroscopy. The results show that Lys-CDs could coordinate with Zn2+ and the adding of FA inhibits the coordination of Lys-CDs with central ions of Zn. The Lys-CDs and FA are successfully exposed with the NMOFs disintegrating in the acid environment of bacterial metabolites. We are surprised to find a sharp increase of reactive oxygen species (ROS) inside the bacterial cells by FA functionalizing NMOFs, which undoubtedly enhance the antibacterial and antibiofilm activity. The as-synthesized ZIF-8-based nanocomposites also show the peroxidase-like activity in an acid environment, and produce extremely active hydroxyl radicals resulting in the improved antibacterial and antibiofilm activity. The possible mechanisms of antibacterial activities indicate that the presence of FA is significant in the sense of targeting bacteria. This study shows a novel approach to construct acid stimulation supply system which may be helpful for the research of antibiofilms.


Assuntos
Ácido Fólico , Estruturas Metalorgânicas , Antibacterianos/farmacologia , Bactérias , Biofilmes , Espécies Reativas de Oxigênio
3.
Bone Joint J ; 103-B(7 Supple B): 135-144, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34192911

RESUMO

AIMS: Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system's response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue. METHODS: Patient peri-implant fibrotic tissue was analyzed for NETs biomarkers. To enhance osseointegration in loose implant conditions, an innate immune system pathway (NETs) was either inhibited (Pad4-/- mice) or resolved with a pharmacological agent (DNase 1) in a murine model of osseointegration failure. RESULTS: NETs biomarkers were identified in peri-implant fibrotic tissue collected from aseptic loosening patients and at the bone-implant interface in a murine model of osseointegration failure. Inhibition (Pad4-/- ) or resolution (DNase 1) of NETs improved osseointegration and reduced fibrotic tissue despite loose implant conditions in mice. CONCLUSION: This study identifies a biological target (NETs) for potential noninvasive treatments of aseptic loosening by discovering a novel connection between the innate immune system and post-injury bone remodelling caused by implant loosening. By inhibiting or resolving NETs in an osseointegration failure murine model, fibrotic tissue encapsulation around an implant is reduced and osseointegration is enhanced, despite loose implant conditions. Cite this article: Bone Joint J 2021;103-B(7 Supple B):135-144.


Assuntos
Desoxirribonuclease I/imunologia , Armadilhas Extracelulares/imunologia , Osseointegração/fisiologia , Proteína-Arginina Desiminase do Tipo 4/imunologia , Tíbia/cirurgia , Animais , Interface Osso-Implante , Modelos Animais de Doenças , Fibrose/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Falha de Prótese
4.
J Clin Neurosci ; 90: 94-98, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34275588

RESUMO

OBJECTIVE: This study aimed to investigate the value of Barthel, PLAN, and NIHSS scores for predicting death in the 5-year follow-up after patients with AIS are discharged and find a simple and convenient predictive scale. METHODS: Data were prospectively collected from 678 patients with AIS. Patients' death after 5 years of follow-up was considered the final event. The predictors of death were examined through single-factor and multivariate analysis. The receiver operating characteristic curve (ROC) of the patients' Barthel, PLAN, and NIHSS scores was drawn, and the area under the curve (AUC) was calculated. Differences in the predictive power of the three scales were compared using MedCalc. The goodness of fit between predictive and actual models was evaluated with the Hosmer-Lemeshow method. RESULTS: Multivariate analysis suggested that the BI score was an independent predictor of death from AIS in the 5-year follow-up. The Barthel, PLAN, and NIHSS scale scores predicted the 5-year mortality AUC values of AIS were 0.687 [95% CI, (0.649-0.722)], 0.621 [95% CI, (0.583-0.659)], 0.637 [95% CI, (0.599-0.674)], the Hosmer-Lemeshow test revealed P > 0.05, indicating that the three models had a good fit. In pairwise comparison, the AUC value of the BI score was significantly greater than that of the NIHSS scores (Pc = 0.0189). BI and PLAN scores were very close to statistical significance (Pc = 0.0513). However, PLAN and NIHSS scores had no significant differences (Pc = 1.7493). CONCLUSION: Simple BI scores had a high predictive value for the death of Chinese patients with AIS within 5 years.

5.
Nano Lett ; 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34279108

RESUMO

The disease caused by SARS-CoV-2 infection threatens human health. In this study, we used high-pressure homogenization technology not only to efficiently drive the bacterial membrane to produce artificial vesicles but also to force the fusion protein ClyA-receptor binding domain (RBD) to pass through gaps in the bacterial membrane to increase the contact between ClyA-RBD and the membrane. Therefore, the load of ClyA-RBD on the membrane is substantially increased. Using this technology, we constructed a "ring-like" bacterial biomimetic vesicle (BBV) loaded with polymerized RBD (RBD-BBV). RBD-BBVs injected subcutaneously can accumulate in lymph nodes, promote antigen uptake and processing, and elicit SARS-CoV-2-specific humoral and cellular immune responses in mice. In conclusion, we evaluated the potential of this novel bacterial vesicle as a vaccine delivery system and provided a new idea for the development of SARS-CoV-2 vaccines.

6.
Ecotoxicol Environ Saf ; 221: 112463, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34198188

RESUMO

BACKGROUND: Cooking oil fumes (COF) is one of the primary sources of indoor air pollution in China, which is associated with respiratory diseases such as acute lung injury and lung cancer. However, evidence of COF toxic effect was few. OBJECTIVES: The research was aimed to investigate the toxic effect and the underlying mechanisms induced by COF. METHODS: The female Wistar rats were randomly divided into several groups, including control group, COF exposure group and VE protection group, and instilled intratracheally with different COF suspensions (0.2, 2, 20 mg/kg) or saline once every 3 days for 30 days. After 24 h of final exposure, all rat were anesthetic euthanasia to draw materials. The alveolar lavage fluid (BALF) was for inflammatory cell count. The lung homogenate was to determine the biochemical indexes such as oxidative stress, apoptosis factors, carcinogenic toxicity and endoplasmic reticulum (ER) stress. The left lung was made for immunohistochemical and histopathological analysis. RESULTS: The results showed that the levels of oxidative stress (ROS), apoptosis factors (NF-κB), carcinogenic toxicity (P53 and 8-OhdG), ER stress (IRE-1α and Caspase-12) in 2 mg/kg and 20 mg/kg COF exposure groups were significantly increased compared with the saline groups. The above pathological changes were improved after vitamin E (VE) supplementation. In addition, the immunohistochemical and histopathological analysis found the same trend. CONCLUSION: The COF had health risk of heredity and potential carcinogenicity. Besides, COFs can not only induce oxidative stress, but also induce ER stress in lung and airway epithelial cells of female rats through the unfolded protein reaction (UPR) pathway. It revealed that the oxidative stress and ER stress interacted in aggravating lung injury. VE could effectively alleviate the lung injury causing by COF exposure.


Assuntos
Poluentes Atmosféricos/toxicidade , Culinária , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Óleos/toxicidade , Animais , Apoptose/efeitos dos fármacos , Feminino , Pulmão/efeitos dos fármacos , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Vitamina E/uso terapêutico
7.
BMC Public Health ; 21(1): 1327, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229637

RESUMO

BACKGROUND: Musculoskeletal disorders (MSDs), a common type of occupational diseases, have become the main cause of absenteeism and early retirement in the occupational population, as well as a major risk factor for occupational disability. The purpose of this study was to investigate the effects of occupational stress and mental health on MSDs in coal miners in Xinjiang, China, to provide a theoretical basis for reducing the incidence of MSDs in coal miners and improving their physical and mental health. METHODS: In this study, stratified cluster random sampling was used to randomly select six coal mining companies in Xinjiang, and 1675 coal miners were surveyed by questionnaire. The status of occupational stress, mental health and MSDs among coal miners was investigated by means of the Effort-Reward Imbalance questionnaire (ERI), Symptom Checklist-90(SCL-90), and Musculoskeletal disorders scale (MSDs) questionnaire. RESULTS: The prevalence of MSDs among coal miners was higher, and there were statistical differences among different sexes, ages, working years, shifts, types of work, educational level and monthly income (P < 0.001). The prevalence of MSDs in different body parts in the occupational stress group and mental disorder group was higher than that in the normal group. The results of multivariate logistic regression analysis showed that females had an increased risk of developing MSDs (OR = 2.23, 95% CI.:1.50,3.33). The risk of MSDs was higher with age < 30 years (30-39 years,OR = 2.39, 95% CI.,1.68,3.40; 40-49 years,OR = 2.15, 95% CI.:1.52,3.04; 50-60 years:OR = 3.25, 95% CI.:2.09,5.07), and the longer the working years, the higher the risk of MSDs (OR = 1.90, 95% CI.:1.38,2.62). The two shifts group (OR = 2.18, 95% CI.:1.59,2.98) had an increased risk of developing MSDs compared with the fixed day shift group. The risk of MSDs was lower in heading drivers (OR = 0.41, 95% CI.:0.29,0.60,) and transport workers (OR = 0.30, 95% CI.:0.20,0.43). The higher the education level, the lower the risk of MSDs (high school: OR = 0.46, 95% CI.:0.34,0.62, junior college and above: OR = 0.12, 95% CI.:0.08,0.17), and the higher the monthly income, the lower the risk of MSDs (OR = 0.50, 95% CI.:0.34,0.74). Occupational stress (OR = 1.32, 95% CI.:1.05,1.67) and mental disorder(OR = 2.94, 95% CI.:2.25,3.84) increased the risk of MSDs. A Bayesian network diagram showed that occupational stress and MSDs have direct effects on mental disorders, and occupational stress can have indirect effects on mental disorders through MSDs. CONCLUSION: Our research shows that MSDs are common among coal miners. Occupational stress and psychological disorders can increase the incidence of MSDs.

8.
Hepatology ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34242426

RESUMO

The research by Liao et al.(1) showed that postdiagnosis aspirin use improved the mortality of various subtypes of biliary tract cancer (BTC). The results were impressive, with the adjusted hazard ratios of mortality ranging from 0.51 to 0.58, and all subgroup analyses were statistically significant. However, we think that some other aspects should be discussed.

9.
J Biomol Struct Dyn ; : 1-10, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34243690

RESUMO

Our previous studies found that the C-X-C motif chemokine receptor 5 (CXCR5) loss leads to retinal pigment epithelium (RPE) dysfunction and AMD pathogenesis. The current study aimed to characterize the G protein-coupled receptor (GPCR) structure of CXCR5 and analyze its interactions with AMD-related risk genes. The sequence alignments, homology model of CXCR5 and structural assessment analysis were performed. Data and text mining were then performed to identify AMD-related risk genes and their interaction with CXCR5 using statistical and mathematical algorithms. Sequence alignment and phylogenetic tree analysis revealed that human CXCR5 was highly similar (85.4839%) to the rabbit. The least similarity (33.871%) was found to be in zebrafish compared to the other species. The CXCR5 model structural assessment and secondary structure analysis exhibited an excellent model. Network analysis revealed that IL10, TNF, ICAM1, CXCL1, CXCL8, APP, TLR4, SELL, C3, IL17A and CCR2 were the most connected genes CXCR5. These findings suggest that CXCR5 signaling may regulate the biological function of RPE and modulate AMD pathophysiology via GPCR signaling and interacting with identified AMD risk genes. In summary, the data presented here provide novel and crucial insights into the molecular mechanisms of CXCR5 involvement in AMD.Communicated by Ramaswamy H. Sarma.

10.
Environ Sci Technol ; 55(14): 10164-10174, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34213316

RESUMO

Mass-independent fractionation (MIF) of stable even mass number mercury (Hg) isotopes is observed in rainfall and gaseous elemental Hg0 globally and is used to quantify atmospheric Hg deposition pathways. The chemical reaction and underlying even-Hg MIF mechanism are unknown however and speculated to be caused by Hg photo-oxidation on aerosols at the tropopause. Here, we investigate the Hg isotope composition of free tropospheric Hg0 and oxidized HgII forms at the high-altitude Pic du Midi Observatory. We find that gaseous oxidized Hg has positive Δ199Hg, Δ201Hg, and Δ200Hg and negative Δ204Hg signatures, similar to rainfall Hg, and we document rainfall Hg Δ196Hg to be near zero. Cloud water and rainfall Hg show an enhanced odd-Hg MIF of 0.3‰ compared to gaseous oxidized HgII, potentially indicating the occurrence of in-cloud aqueous HgII photoreduction. Diurnal MIF observations of free tropospheric Hg0 show how net Hg0 oxidation in high-altitude air masses leads to opposite even- and odd-MIF in Hg0 and oxidized HgII. We speculate that even-Hg MIF takes place by a molecular magnetic isotope effect during HgII photoreduction on aerosols that involves magnetic halogen nuclei. A Δ200Hg mass balance suggests that global Hg deposition pathways in models are likely biased toward HgII deposition. We propose that Hg cycling models could accommodate the Hg-isotope constraints on emission and deposition fluxes.

11.
Genomics ; 113(5): 3058-3071, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34242709

RESUMO

BACKGROUND: Retinal microglial cells (RMCs) play crucial roles in maintaining normal visual functions in a healthy eye. However, the underlying mechanisms of RMCs over-activation manifesting the alterations of sensome profile and inflammation state, which contribute to various retinal neurodegenerative diseases, remain elusive. Here, we aimed to identify the core set of sensome and pro-inflammatory genes and their regulators using transcriptome and data mining approaches. METHODS: We performed paired-end RNA-sequencing in primary microglial cell cultures treated with TNFα/IFNϒ (10 ng/ml for 12 h) and PBS as a control. Gene enrichment analysis and hierarchical clustering for the differentially expressed transcripts highlight functional pathways and network perturbations. We examined overlaps of the mouse microglial gene expression profiles with the data-mined human sensome and pro-inflammatory marker genes. The core sets of sensome and pro-inflammatory genes were selected and predicted for transcription factors (TFs). The identified TFs in RNA-Seq are validated by the quantitative PCR method. RESULTS: TNFα/IFNϒ induced 668 differentially expressed transcripts in retinal microglial cells relative to the control. Furthermore, gene enrichment analysis and the gene expression network revealed activated microglial genes, biological, molecular and inflammatory pathways. The overlapping analysis of the TNFα/IFNϒ-activated microglia genes and the data-mined human gene sets revealed 22 sensome and 61 pro-inflammatory genes. Based on network analysis, we determined 10 genes as the core sets of sensome and pro-inflammatory genes and predicted the top ten TFs that regulate them. The SP110, IRF1, FLI1, SP140 (sensome) and RELB, BATF2, NFKB2, TRAFD1, SP100, NFKB1 (inflammation) are differentially expressed between the TNFα/IFNϒ activated and the non-activated microglia which were validated by quantitative PCR. The outcomes indicate that these transcriptional regulators are highly expressed and may regulate the sensome and inflammatory genes of RMCs and switch them to over-activation. CONCLUSION: Our results comprise a powerful, cross-species functional genomics resource for sensome and inflammation of RMCs, which may provide novel therapeutic approaches to prevent retinal neurodegenerative diseases.

12.
Cell Transplant ; 30: 9636897211027819, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34238029

RESUMO

BACKGROUND: Ovarian cancer is the most lethal gynecological malignancy, and chemotherapy remains the cornerstone for ovarian cancer management. Due to the unsatisfactory prognosis, a better understanding of the underlying molecular carcinogenesis is urgently required. METHODS: Assays for determining cell growth, cell motility, and apoptosis were employed to evaluate the potential antitumor effects of metformin against ovarian cancer cells. Molecular biological methods were employed to explore the underlying mechanism. Human ovarian cancer samples and Gene Expression Profiling Interactive Analysis (GEPIA) dataset were used for uncovering the clinical significances of mesothelin (MSLN) on ovarian cancer. RESULTS: In the present work, we found that metformin treatment led to cell growth and cell migration inhibition, and induced cell apoptosis. Metformin administration also impaired cancer cell stemness and the capillary-like structure formation capacity of SKOV3 cells. On mechanism, metformin treatment remarkably reduced mesothelin (MSLN) expression, downregulated IL-6/STAT3 signaling activity, subsequently resulted in VEGF and TGFß1 expression. We also observed an oncogenic function of MSLN on ovarian cancer. CONCLUSIONS: Collectively, our findings suggested that metformin exerts anticancer effects by suppressing ovarian cancer cell malignancy, which attributed to MSLN inhibition mediated IL6/STAT3 signaling and VEGF and TGFß1 downregulation.

13.
BMC Med ; 19(1): 154, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34284787

RESUMO

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy elicits durable antitumor responses in patients with many types of cancer. Genomic mutations may be used to predict the clinical benefits of ICI therapy. NOTCH homolog-4 (NOTCH4) is frequently mutated in several cancer types, but its role in immunotherapy is still unclear. Our study is the first to study the association between NOTCH4 mutation and the response to ICI therapy. METHODS: We tested the predictive value of NOTCH4 mutation in the discovery cohort, which included non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, esophagogastric cancer, and bladder cancer patients, and validated it in the validation cohort, which included non-small cell lung cancer, melanoma, renal cell carcinoma, colorectal cancer, esophagogastric cancer, glioma, bladder cancer, head and neck cancer, cancer of unknown primary, and breast cancer patients. Then, the relationships between NOTCH4 mutation and intrinsic and extrinsic immune response mechanisms were studied with multiomics data. RESULTS: We collected an ICI-treated cohort (n = 662) and found that patients with NOTCH4 mutation had better clinical benefits in terms of objective response rate (ORR: 42.9% vs 25.9%, P = 0.007), durable clinical benefit (DCB: 54.0% vs 38.1%, P = 0.021), progression-free survival (PFS, hazard ratio [HR] = 0.558, P < 0.001), and overall survival (OS, HR = 0.568, P = 0.006). In addition, we validated the prognostic value of NOTCH4 mutation in an independent ICI-treated cohort (n = 1423). Based on multiomics data, we found that NOTCH4 mutation is significantly associated with enhanced immunogenicity, including a high tumor mutational burden, the expression of costimulatory molecules, and activation of the antigen-processing machinery, and NOTCH4 mutation positively correlates activated antitumor immunity, including infiltration of diverse immune cells and various immune marker sets. CONCLUSIONS: Our findings indicated that NOTCH4 mutation serves as a novel biomarker correlated with a better response to ICI therapy.

14.
Neuroimmunomodulation ; : 1-11, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34218221

RESUMO

BACKGROUND: Despite the vitamin D treatment in patients with multiple sclerosis (MS), there continues to be controversial discrepancy in outcomes according to the current research. Many systematic reviews have evaluated the effect of vitamin D as an adjuvant treatment in patients with MS; however, there is no consensus on the optimum administration time and dosage of vitamin D intake. A meta-analysis for exploring the different administration time and dosage of vitamin D is warranted. METHODS: Randomized controlled trials (RCTs) on the effect of different administration time and dosage of vitamin D in patients with MS were recorded within 7 databases. This meta-analysis was performed with 2 clinical outcomes: EDSS (Expanded Disability Status Scale) and relapses during research. RESULTS: The pooled results indicated that receiving different administration time and dosage of vitamin D as an adjuvant treatment had no significant therapeutic effect on MS according to the EDSS scores and relapses during research. CONCLUSION: According to our meta-analysis, the administration of vitamin D in different dosages (ranging from 2,857 to 14,007 IU/day) and treatment period (ranging from 6 to 24 months) did not affect the clinical outcomes (EDSS and relapses during research) in patients with MS. Additional RCTs should be conducted to explore whether a longer duration and a larger dosage of vitamin D without serious adverse effects might produce therapeutic effects in patients with MS.

15.
Front Immunol ; 12: 673248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211467

RESUMO

Background: Hepatocellular carcinoma (HCC) has a high risk of recurrence after surgical resection, particularly among patients with multifocal HCC. Genomic heterogeneity contributes to the early recurrence. Few studies focus on targeted next-generation sequencing (tNGS) to depict mutational footprints of heterogeneous multifocal HCC. Methods: We conducted tNGS with an ultra-deep depth on 31 spatially distinct regions from 11 resected multifocal HCC samples. Matched preoperative peripheral circulating-free DNA (cfDNA) were simultaneously collected. Genomic alterations were identified and compared to depict the heterogeneity of multifocal HCC. Results: Widespread intertumoral heterogeneity of driver mutations was observed in different subfoci of multifocal HCC. The identified somatic mutations were defined as truncal drivers or branchy drivers according to the phylogenetic reconstruction. TP53 and TERT were the most commonly altered truncal drivers in multifocal HCC, while the most frequently mutated branchy driver was TSC2. HCC patients with a higher level of intertumoral heterogeneity, defined by the ratio of truncal drivers less than 50%, had a shorter RFS after surgical resection (HR=0.17, p=0.028). Genome profiling of cfDNA could effectively capture tumor-derived driver mutations, suggesting cfDNA was a non-invasive strategy to gain insights of genomic alterations in patients with resected multifocal HCC. Conclusions: Truncal mutations and the level of genomic heterogeneity could be identified by tNGS panel in patients with resected multifocal HCC. cfDNA could serve as a non-invasive and real-time auxiliary method to decipher the intertumoral heterogeneity and identify oncodrivers of multifocal HCC.

16.
J Bone Miner Res ; 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34076292

RESUMO

The importance of a local tissue immune response in healing injured tissues such as skin and lung is well established. Little is known about whether sterile wounds elicit lymph node (LN) responses and inflammatory responses after injury of musculoskeletal tissues that are mechanically loaded during the repair response. We investigated LN and tissue immune responses in a tibial implant model of joint replacement surgery where wounded tissue is subjected to movement and mechanical loading postoperatively. Draining inguinal and iliac LNs expanded postoperatively, including increases in regulatory T cells and activation of a subset of T cells. Thus, tissue injury was actively sensed in secondary lymphoid organs, with the potential to activate adaptive immunity. Joint tissues exhibited three temporally distinct immune response components, including a novel interferon (IFN) response with activation of signal transducer and activator of transcription (STAT) and interferon regulatory factor (IRF) pathways. Fibrovascular tissue formation was not associated with a macrophage type 2 (M2) reparative immune response, but instead with delayed induction of interleukin-1 family (IL-1ß, IL-33, IL-36), IL-17, and prostaglandin pathway genes concomitant with transforming growth factor (TGF)-ß and growth factor signaling, fibroblast activation, and tissue formation. Tissue remodeling was associated with activity of the HOX antisense intergenic RNA (HOTAIR) pathway. These results provide insights into immune responses and regulation of tissue healing after knee arthroplasty that potentially can be used to develop therapeutic strategies to improve healing, prevent arthrofibrosis, and improve surgical outcomes. © 2021 American Society for Bone and Mineral Research (ASBMR).

17.
BMC Genomics ; 22(1): 439, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118883

RESUMO

BACKGROUND: B-BOX (BBX) proteins are zinc-finger transcription factors with one or two BBX domains and sometimes a CCT domain. These proteins play an essential role in regulating plant growth and development, as well as in resisting abiotic stress. So far, the BBX gene family has been widely studied in other crops. However, no one has systematically studied the BBX gene in cotton. RESULTS: In the present study, 17, 18, 37 and 33 BBX genes were detected in Gossypium arboreum, G. raimondii, G. hirsutum and G. barbadense, respectively, via genome-wide identification. Phylogenetic analysis showed that all BBX genes were divided into 5 main categories. The protein motifs and exon/intron structures showed that each group of BBX genes was highly conserved. Collinearity analysis revealed that the amplification of BBX gene family in Gossypium spp. was mainly through segmental replication. Nonsynonymous (Ka)/ synonymous (Ks) substitution ratios indicated that the BBX gene family had undergone purification selection throughout the long-term natural selection process. Moreover, transcriptomic data showed that some GhBBX genes were highly expressed in floral organs. The qRT-PCR results showed that there were significant differences in GhBBX genes in leaves and shoot apexes between early-maturing materials and late-maturing materials at most periods. Yeast two-hybrid results showed that GhBBX5/GhBBX23 and GhBBX8/GhBBX26 might interact with GhFT. Transcriptome data analysis and qRT-PCR verification showed that different GhBBX genes had different biological functions in abiotic stress and phytohormone response. CONCLUSIONS: Our comprehensive analysis of BBX in G. hirsutum provided a basis for further study on the molecular role of GhBBXs in regulating flowering and cotton resistance to abiotic stress.


Assuntos
Regulação da Expressão Gênica de Plantas , Gossypium , Perfilação da Expressão Gênica , Genoma de Planta , Gossypium/genética , Gossypium/metabolismo , Família Multigênica , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
18.
Forensic Sci Int ; 325: 110869, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34147939

RESUMO

Morphology-based classification of inkjet documents has the characteristics of low cost and high efficiency, but this method usually requires measurement and analysis of a large number of printed characters. This paper proposes a novel method for detecting the source of printed documents using a few printed letters. A dataset containing data pertaining to various inkjet printers, including 27 models of inkjets from HP, Canon, and Epson, and their printed documents were gathered. The specifications of the various brands and models of inkjets are summarised, and the characteristics of the microscopic appearance of the printheads are presented. Principal component analysis (PCA) of the variables was applied to describe the proximity between the specimens, and a two-dimensional kernel density estimation was used to describe the variation between and within printer brands and models. Then, specific cases were simulated by random sampling based on the collected inkjet dataset. Multivariate kernel density estimation was used to estimate the numerator and denominator probability distribution for computing the likelihood ratio (LR). The result of K-nearest neighbour analysis showed classification accuracy as high as 98%. The evaluation of the LR presented a significant result (EER=0, RMEP=0, RMED=0.07). This method helps to find a specific inkjet from even a few letters in the printed document for tactical purposes.

19.
Clin Chim Acta ; 520: 95-100, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34107314

RESUMO

BACKGROUND: Breast malignancy is the most frequently diagnosed malignancy in women worldwide, and the diagnosis relies on invasive examinations. However, most clinical breast changes in women are benign, and invasive diagnostic approaches cause unnecessary suffering for the patients. Thus, a novel noninvasive approach for discriminating malignant breast lesions from benign lesions is needed. METHODS: We performed cell-free DNA (cfDNA) sequencing on plasma samples from 173 malignant breast lesion patients, 158 benign breast lesion patients, and 102 healthy women. We then analyzed the cfDNA-based nucleosome profiles, which reflect the various tissues of origin and transcription factor activities. Moreover, by using machine learning classifiers along with the cfDNA sequencing data, we built classifiers for discriminating benign from malignant breast lesions. Receiver operating characteristic curve analyses were used to evaluate the performance of the classifiers. RESULTS: cfDNA-based nucleosome profiles reflected the various tissues of origin and transcription factor activities in benign and malignant breast lesions. The cfDNA-based transcription factor activities and breast malignancy-specific transcription factor-binding site accessibility profiles could accurately distinguish benign and malignant breast lesions, with area under the curve values of 0.777 and 0.824, respectively. CONCLUSIONS: Our proof-of-principle study established a methodology for noninvasively discriminating benign from malignant breast lesions.


Assuntos
Neoplasias da Mama , Ácidos Nucleicos Livres , Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Ácidos Nucleicos Livres/genética , Diagnóstico Diferencial , Feminino , Humanos , Nucleossomos/genética , Curva ROC
20.
J Orthop Res ; 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34191350

RESUMO

There has been increasing interest in the use of a synthetic absorbable calcium sulfate (CaSO4 ) for local antibiotic delivery in orthopaedic infections. The purpose of this study was to quantify elution kinetics of six antibiotics (amikacin, meropenem, fosfomycin, minocycline, cefazolin, and dalbavancin) from a clinically relevant CaSO4 bead model and compare elution and antimicrobial activity to the current clinical gold standards: vancomycin and tobramycin. Antibiotic-loaded synthetic CaSO4 beads were immersed in phosphate buffered saline and incubated at 37°C. Eluent was harvested at eight time points over 28 days. Antibiotic concentrations were measured by high performance liquid chromatography to quantify elution rates. CaSO4 beads demonstrated burst release kinetics. Dalbavancin, cefazolin, and minocycline all demonstrated similar elution profiles to vancomycin. Amikacin and meropenem demonstrated favorable elution profiles and durations of above-minimum inhibitory concentration when compared to tobramycin. Clinical Significance: This study provides important novel data regarding the utility of amikacin, meropenem and dalbavancin as alternative choices to place in CaSO4 carriers when treating orthopaedic infections.

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