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1.
Anal Chim Acta ; 1207: 339774, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35491036

RESUMO

Coordination polymers (CPs) with tunable structures and properties have been extensively explored in a variety of fields. In this work, we demonstrated the potential of stimuli-responsive CPs as a host of integrating enzymes to construct a portable immunoassay. By employing terbium ion (Tb3+) as a metal node and guanine monophosphate (GMP) as a bridge ligand, an alkaline phosphatase (ALP)-responsive Tb/GMP CPs was fabricated, which allows amyloglucosidase (GA) to be integrated to form GA@Tb/GMP composite. Owing to the size-selectivity of Tb/GMP CPs as a host, the loaded GA was physically isolated from its substrate starch. However, Tb/GMP CPs is highly sensitive to ALP, which can hydrolyze the phosphate group of GMP to destroy the structure of Tb/GMP CPs, leading to the release of GA from GA@Tb/GMP composite. The released GA can digest starch to produce glucoses and give a measured signal by personal glucose meter (PGM). This finding leads to a PGM-based portable immunoassay for the quantitative analysis of carcinoembryonic antigen (CEA), and satisfactory results with a detection limit of 0.28 ng/mL have been achieved. The successful determination of CEA in serum samples demonstrates its potential in practical application. We believe that this work can provide a remarkable insight for the rational design of stimuli-responsive CPs for a wide of applications.


Assuntos
Antígeno Carcinoembrionário , Polímeros Responsivos a Estímulos , Fosfatase Alcalina/análise , Glucose , Imunoensaio , Polímeros/química , Amido
3.
Front Neurol ; 13: 869230, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547367

RESUMO

Background: Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by pathogenic variation of the survival motor neuron (SMN) 1 gene. Symptoms of SMA include progressive limb muscle weakness, atrophy, and severe scoliosis. Nusinersen is an antisense oligonucleotide that can enhance the production of the SMN protein. Here, we report a case with scoliosis who received orthopedic surgery combined with Nusinersen intrathecal injections. Case Presentation: Scoliosis orthopedic surgery followed by Nusinersen intrathecal injections was given to a 16-year-old girl who had thoracic and lumbar scoliosis and type 3 SMA. Surgery was performed for T3-S2 posterolateral fusion (PLF), with a channel left on the vertebral laminae of L3-L4. The balance of the spine and pelvis was significantly improved and the height increased by 9 cm. Lumbar puncture was conducted with local anesthesia under ultrasound and CT guidance through the laminae channel and Nusinersen was successfully injected. Comparing the two approaches, real-time ultrasound guidance for intrathecal Nusinersen injections after spinal surgery is preferred, however, CT guidance is an alternative if the initial puncture procedure is difficult. After the aforementioned multidisciplinary treatment, a good outcome was achieved, as demonstrated by a 2-point increase in RULM and MFM32 scores 2 months later. Conclusion: Scoliosis orthopedic surgery combined with Nusinersen intrathecal injection is an effective treatment for SMA patients with scoliosis.

4.
Ann Transl Med ; 10(8): 452, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35571451

RESUMO

Background: Neoadjuvant radiotherapy (RT) for soft tissue sarcoma (STS) is widely used abroad, but rarely reported in China. We assessed the preliminary clinical outcomes of preoperative RT followed by surgery in patients with STS. Methods: A total of 19 patients (14 male, 5 female) with intermediate- or high-grade primary STS were treated with neoadjuvant RT in 2-Gy fractions over 25 sessions for a total dose of 50 Gy. Surgical resection was then performed. The pathologic specimens were reviewed for percentage of residual tumor cells. And the skin complications, wound complications and local recurrence and distant metastasis were also evaluated. Results: After neoadjuvant RT, 2 patients had progressive disease (PD), 6 showed a partial remission (PR), and 11 demonstrated stable disease (SD). The objective response rate (ORR) was 31.6%, and the disease control rate (DCR) was 89.5%. The median follow-up was 14.3 months (11.9-24.7 months). Six patients (31.6%) had wound complications: 3 cases of epidermal complications and 3 of severe complications (15.8%) comprising 2 cases of skin flap necrosis, and 1 case of local hematoma. The European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) histopathological response score was used to evaluate the post-RT response. A total of 9 patients (47.4%) achieved pathological complete remission (pCR). No recurrence was found, but metastasis occurred in 2 patients (10.5%) in the preliminary follow-up. Conclusions: Neoadjuvant RT for STS has a quietly high DCR and pathological remission rate. Surgical wound complications can be controlled after neoadjuvant RT.

5.
Ecotoxicol Environ Saf ; 239: 113642, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35588617

RESUMO

BACKGROUND: Serum vitamin D levels are associated with exposure to air pollution, however, the lagged effect of exposure to air pollution remains unknown in pregnant women. METHODS: Pregnant women who delivered at a maternity center in Shanghai, China, from 2015 to 2019 were included in the present study. The concentration of particulate matter 2.5 (PM2.5) before 25-Hydroxyvitamin D [25(OH)D] detection was estimated using the satellite-based grid models. The distributed lag non-linear models were performed to examine the lagged association between weekly-specific PM2.5 exposure and vitamin D deficiency (VDD) or serum 25(OH)D levels. RESULTS: Among the 58,025 pregnant women included in the study (mean age at conception, 30.77 ± 3.75 years; mean prepregnancy BMI, 21.09 ± 2.55 kg/m2), 61.32% were diagnosed with VDD. Weekly-specific PM2.5 exposure at weeks 1-10 before the detection of 25(OH)D was significantly associated with an increased incidence of VDD (p < 0.05). For every 10 µg/m3 increase in PM2.5 exposure, the serum 25(OH)D level decreased by 1.346 nmol/L (95%CI: 1.183-1.508 nmol/L). The association between average PM2.5 exposure and VDD at 1-10 weeks was more significant in weather conditions with low mean sunshine hours (OR: 1.246, 95%CI: 1.221-1.271). CONCLUSION: Our study provided suggestive evidence that PM2.5 exposure at 1-10 weeks before the 25(OH)D detection may decrease the circulating 25(OH)D levels in pregnant women and increase VDD risk in pregnant women. More attention should be paid to the long-term impact of PM2.5, in particular, during weather conditions with a relatively short duration of sunshine.

6.
Cancer Med ; 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35608250

RESUMO

BACKGROUND: Evidence on simultaneous resection for elderly patients (age ≥ 70 years) with colorectal liver metastasis (CRLM) is lacking. METHODS: Four hundred and eighty-two CRLM patients treated by simultaneous resection were categorised into young group (age < 70 years) and elderly group (age ≥ 70 years). Propensity score matching (PSM1) was performed to adjust for differences in baseline characteristics and compare short-term outcomes. An additional propensity score matching (PSM2) including short-term outcomes was performed to analyse survival. Subgroup analysis was performed in patients stratified by the Clinical Risk Score (CRS). RESULTS: After PSM1, 87 young group patients were matched to 50 elderly group patients. Patients in the elderly group had a significantly higher rate of overall post-operative complications (68.0% vs. 46.0%, p = 0.013). After PSM2, 89 young group patients were matched to 47 elderly group patients. Progression-free survival (PFS) was comparable between the two groups (median 11.0 months vs. 9.8 months, p = 0.346). Age ≥ 70 independently predicted worse overall survival (OS) (Hazard ratio, HR = 2.57, 95% confidence interval, CI 1.37-4.82) in multivariate analysis. In the subgroup multivariate analysis of patients with CRS score 3-5, age ≥ 70 was independently associated with worse PFS (HR = 1.62, 95% CI 1.01-2.62) and OS (HR = 2.34, 95% CI 1.26-4.35). CONCLUSIONS: Simultaneous resection for elderly CRLM patients is acceptable. Further studies are required to determine the optimal treatment for elderly CRLM patients with high CRS scores.

7.
Opt Lett ; 47(10): 2514-2517, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35561389

RESUMO

Multi-color fluorescence microscopy presents highly detailed biological samples interactively. However, current multi-color methods suffer from an intricate optical setup, complicated image analysis, or a long acquisition time. To address these issues, here we develop a simple multi-color method based on a customized colorimetry camera to enable the detection of multiple structures from single-shot acquisition. The unfiltered channel (W pixels) and color channels (R, G, B, and NIR pixels) in this customized camera simultaneously provide a broad detection wavelength range and high detection sensitivity. We built a simple optical setup by replacing the monochrome camera in a basic fluorescence microscopy system with a colorimetry camera, and developed effective image analysis procedures to reconstruct a multi-color image from a single frame of a raw image. We demonstrated single-shot four-color wide-field fluorescence imaging on fixed cos-7 cells with < 5% cross talk, which is comparable to the best reported values. Our method greatly simplifies both the optical system and image analysis in the widely used method of multi-color fluorescence microscopy, thus offering an effective and easy way to study multiple objects at the same time.

8.
Redox Biol ; 53: 102326, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35525025

RESUMO

The nonunion following a fracture is associated with severe patient morbidity and economic consequences. Currently, accumulating studies are focusing on the importance of macrophages during fracture repair. However, details regarding the process by which macrophages facilitate endochondral ossification (EO) are largely unknown. In this study, we present evidence that apoptotic chondrocytes (ACs) are not inert corpses awaiting removal, but positively modulate the osteoinductive ability of macrophages. In vivo experiments revealed that fatty acid (FA) metabolic processes up-regulated following EO. In vitro studies further uncovered that FAs derived from ACs are taken up by macrophages mainly through macrophage scavenger receptor 1 (MSR1). Then, our functional experiments confirmed that these exogenous FAs subsequently activate peroxisome proliferator-activated receptor α (PPARα), which further facilitates lipid droplets generation and fatty acid oxidation (FAO). Mechanistically, elevated FAO is involved in up-regulating the osteoinductive effect by generating BMP7 and NAD+/SIRT1/EZH2 axis epigenetically controls BMP7 expression in macrophages cultured with ACs culture medium. Our findings advanced the concept that ACs could promote bone regeneration by regulating metabolic and function reprogram in macrophages and identified macrophage MSR1 represents a valuable target for fracture treatments.

9.
Int J Biol Macromol ; 209(Pt A): 1516-1525, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35452701

RESUMO

Elevated expressions of transforming growth factor ß1 (TGF-ß1) have been implicated in the pathogenesis of liver fibrosis, thus attenuating the excessive TGF-ß1's activity by TGF-ß1-binding peptide is an ideal strategy for the treatment of liver fibrosis. However, the application of small peptide as a pharmaceutical agent is obstacle due to difficult preparation and non-selective delivery. The I-plus sequences of circumsporozoite protein (CSP-I) possesses high affinity for heparan sulfate proteoglycans, which are primarily located on liver tissues. TGF-ß1-binding peptide P15 holds specific ability of binding to TGF-ß1. In this study, we describe an approach to efficiently preparing liver-targeting peptide P15-CSP-I, which is conjugation of the sequences of P15 to the N-terminus of CSP-I, from the cleavage of biological macromolecule SUMO-tagged P15-CSP-I. In vitro and ex vivo binding assay showed that P15-CSP-I specifically targeted to the hepatocytes and liver tissues. Moreover, P15-CSP-I inhibited cell proliferation, migration and invasion, and decreased fibrosis-related proteins expression in TGF-ß1-activated HSCs in vitro. Furthermore, P15-CSP-I ameliorated liver morphology and decreased the fibrosis responses in vivo. Taken together, P15-CSP-I may be a potential candidate for targeting therapy on liver fibrosis due to its high efficient preparation, specific liver-targeting potential and improved anti-liver fibrotic activity.

10.
J Virol ; : e0190521, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35481780

RESUMO

Removal of 5' cap on cellular mRNAs by the African swine fever virus (ASFV) decapping enzyme g5R protein (g5Rp) is beneficial to viral gene expression during the early stages of infection. As the only nucleoside diphosphate-linked moiety X (Nudix) decapping enzyme encoded in the ASFV genome, g5Rp works in both the degradation of cellular mRNA and the hydrolyzation of the diphosphoinositol polyphosphates. Here, we report the structures of dimeric g5Rp and its complex with inositol hexakisphosphate (InsP6). The two g5Rp protomers interact head to head to form a dimer, and the dimeric interface is formed by extensive polar and nonpolar interactions. Each protomer is composed of a unique N-terminal helical domain and a C-terminal classic Nudix domain. As g5Rp is an mRNA-decapping enzyme, we identified key residues, including K8, K94, K95, K98, K175, R221, and K243 located on the substrate RNA binding interfaces of g5Rp which are important to RNA binding and decapping enzyme activity. Furthermore, the g5Rp-mediated mRNA decapping was inhibited by InsP6. The g5Rp-InsP6 complex structure showed that the InsP6 molecules occupy the same regions that primarily mediate g5Rp-RNA interaction, elucidating the roles of InsP6 in the regulation of the viral decapping activity of g5Rp in mRNA degradation. Collectively, these results provide the structural basis of interaction between RNA and g5Rp and highlight the inhibitory mechanism of InsP6 on mRNA decapping by g5Rp. IMPORTANCE ASF is a highly contagious hemorrhagic viral disease in domestic pigs which causes high mortality. Currently, there are still no effective vaccines or specific drugs available against this particular virus. The protein g5Rp is the only viral mRNA-decapping enzyme, playing an essential role in the machinery assembly of mRNA regulation and translation initiation. In this study, we solved the crystal structures of g5Rp dimer and complex with InsP6. Structure-based mutagenesis studies revealed critical residues involved in a candidate RNA binding region, which also play pivotal roles in complex with InsP6. Notably, InsP6 can inhibit g5Rp activity by competitively blocking the binding of substrate mRNA to the enzyme. Our structure-function studies provide the basis for potential anti-ASFV inhibitor designs targeting the critical enzyme.

11.
Adv Sci (Weinh) ; : e2200307, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35435329

RESUMO

The excessive dependence on fossil fuels contributes to the majority of CO2 emissions, influencing on the climate change. One promising alternative to fossil fuels is green hydrogen, which can be produced through water electrolysis from renewable electricity. However, the variety and complexity of hydrogen evolution electrocatalysts currently studied increases the difficulty in the integration of catalytic theory, catalyst design and preparation, and characterization methods. Herein, this review first highlights design principles for hydrogen evolution reaction (HER) electrocatalysts, presenting the thermodynamics, kinetics, and related electronic and structural descriptors for HER. Second, the reasonable design, preparation, mechanistic understanding, and performance enhancement of electrocatalysts are deeply discussed based on intrinsic and extrinsic effects. Third, recent advancements in the electrocatalytic water splitting technology are further discussed briefly. Finally, the challenges and perspectives of the development of highly efficient hydrogen evolution electrocatalysts for water splitting are proposed.

12.
Cell Death Discov ; 8(1): 178, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35396503

RESUMO

Myocardial infarction (MI) is a fatal heart disease that affects millions of lives worldwide each year. This study investigated the roles of HIF-1α/lncRNA-TUG1 in mitochondrial dysfunction and pyroptosis in MI. CCK-8, DHE, lactate dehydrogenase (LDH) assays, and JC-1 staining were performed to measure proliferation, reactive oxygen species (ROS), LDH leakage, and mitochondrial damage in hypoxia/reoxygenation (H/R)-treated cardiomyocytes. Enzyme-linked immunoassay (ELISA) and flow cytometry were used to detect LDH, creatine kinase (CK), and its isoenzyme (CK-MB) levels and caspase-1 activity. Chromatin immunoprecipitation (ChIP), luciferase assay, and RNA-immunoprecipitation (RIP) were used to assess the interaction between HIF-1α, TUG1, and FUS. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry were used to measure HIF-1α, TUG1 and pyroptosis-related molecules. Hematoxylin and eosin (HE), 2,3,5-triphenyltetrazolium chloride (TTC), and terminal deoxynucleotidyl transferase dUTP risk end labelling (TUNEL) staining were employed to examine the morphology, infarction area, and myocardial injury in the MI mouse model. Mitochondrial dysfunction and pyroptosis were induced in H/R-treated cardiomyocytes, accompanied by an increase in the expression of HIF-α and TUG1. HIF-1α promoted TUG1 expression by directly binding to the TUG1 promoter. TUG1 silencing inhibited H/R-induced ROS production, mitochondrial injury and the expression of the pyroptosis-related proteins NLRP3, caspase-1 and GSDMD. Additionally, H/R elevated FUS levels in cardiomyocytes, which were directly inhibited by TUG1 silencing. Fused in sarcoma (FUS) overexpression reversed the effect of TUG1 silencing on mitochondrial damage and caspase-1 activation. However, the ROS inhibitor N-acetylcysteine (NAC) promoted the protective effect of TUG1 knockdown on H/R-induced cardiomyocyte damage. The in vivo MI model showed increased infarction, myocardial injury, ROS levels and pyroptosis, which were inhibited by TUG1 silencing. HIF-1α targeting upregulated TUG1 promotes mitochondrial damage and cardiomyocyte pyroptosis by combining with FUS, thereby promoting the occurrence of MI. HIF-1α/TUG1/FUS may serve as a potential treatment target for MI.

13.
Polymers (Basel) ; 14(8)2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35458253

RESUMO

A detailed kinetic analysis of pyrolysis processes of Tennis string polyurethane (TSPU) waste and waterborne polyurethane (WPU) waste was carried out in the present paper. Non-isothermal pyrolysis characterizations of two wastes were acquired through thermogravimetric determinations under the constant heating rates of 5, 10, 15 and 20 K/min. Experimental results showed that the pyrolysis processes of TSPU and WPU were mainly characteristic of three stages and two stages, respectively. Two pyrolysis performance indices, the devolatilization index (DI) and heat-resistance index (HRI), were used to interpret the heating rate effect on the pyrolysis features and different thermal dependences of TSPU and WPU. Isoconversional kinetic analysis was thoroughly performed with model-free and model-fitting methods. By using Starink, Vyazovkin-Dollimore and Coats-Redfern methods, the activation energies thus obtained were in the range of 103.3~148.3 kJ/mol and 92.5~204.3 kJ/mol, respectively, for TSPU and WPU, over the entire pyrolysis process. Their respective pre-exponential factor lnA values were determined to be within 17.94~33.42 min-1 and 16.56~20.82 min-1. Thermodynamic parameters in terms of ΔG#, ΔH# and ΔS# throughout the entire pyrolysis process were also calculated. Finally, by means of the model-fitting Coats-Redfern method, the most appropriate mechanism functions were ascertained for, respectively, describing multi-stage pyrolysis degradations of TSPU and WPU waste. These results may offer meaningful support for designing any industrial pyrolysis reactor to dispose of polyurethane wastes.

14.
J Cancer ; 13(6): 1758-1767, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399716

RESUMO

Background: This study aims to develop a nomogram to predict early recurrence in colorectal liver metastases (CRLM) patients who received neoadjuvant chemotherapy (NAC) followed by hepatectomy. Methods: The primary cohort included 144 CRLM patients treated in the same ward, and 40 CRLM patients from another ward were allocated to the validation cohort. The minimum p value method was used to find the optimal cut-off point for early recurrence. Predictors of early recurrence were determined by univariate analysis and multivariate logistic regression. Nomogram for early recurrence was constructed and area under the receiver operating characteristic curve (AUROC), calibration curves, and decision curve analysis (DCA) were used to evaluate its performance. Results: The optimal cut-off point for the definition of early recurrence was 11 months. Patients with early recurrence have significantly worse post-recurrence survival (median 23.5 months vs. 35.7 months, P=0.012) and overall survival (median 31.8 months vs. 59.0 months, P<0.001). Preoperative creatinine ≥ 63.5 µmol/L (P=0.035), synchronous liver metastasis (P=0.030), non-R0 resection (P=0.044), postoperative complications (P=0.009) and NAC Cycles ≥ 4 (P=0.003) were independent predictors of early recurrence. A nomogram with favorable discrimination (AUROC of 0.754 in the primary cohort and 0.882 in the validation cohort) and calibration was constructed to predict early recurrence. The DCA results also indicated good clinical applicability. Conclusions: This is the first study to identify elevated preoperative creatinine as an independent predictor of early recurrence of CRLM treated with hepatectomy after NAC. This study developed a nomogram that particularly incorporated preoperative creatinine to predict early recurrence in CRLM patients receiving NAC to aid clinical decision-making.

15.
Orthop Surg ; 14(5): 868-875, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35434964

RESUMO

OBJECTIVES: To analyze the causes of misdiagnosis and missed diagnosis in spinal osteoid osteoma, and to put forward solutions to improve diagnosis accuracy and treatment efficacy in patients. METHODS: We performed a retrospective cohort study on patients with spinal osteoid osteoma in Beijing Jishuitan Hospital from January 1983 to September 2019. All patients underwent surgery. The outcome measures were the extent of local pain, nocturnal pain, radicular symptoms of extremities after surgery, and reduction or disappearance of lesions on CT after surgery. RESULTS: Thirty-seven patients with spinal osteoid osteoma were recruited in the study. A total of 27% were female, and the mean (SD) age at diagnosis was 21.3 (8.7) years. A total of 87.0% of patients presented with nocturnal pain, and 94.7% of patients were responsive to NSAIDS treatment. The mean (SD) time from the initial onset of symptoms to the final diagnosis was 14.7 (12.5) months. Only four of 37 (10.8%) patients were correctly diagnosed with spinal osteoid osteoma on the first visit to the local hospital. CT is associated with a higher diagnosis rate than X-ray or MRI on the first visit. Surgical navigation was used in 88.9% of patients who underwent curettage resection, and in 10% of patients who underwent en bloc resection. A total of 37 of 37 patients (100%) reported relief of local pain and radicular symptoms of extremities after surgery, and no recurrence of tumors was found during follow-ups. CONCLUSIONS: Spinal CTs are recommended to be performed if osteoid osteoma is suspected based on clinical manifestation, including nocturnal pain and responsiveness to NSAIDS treatment, to avoid misdiagnosis and missed diagnosis of spinal osteoid osteoma.


Assuntos
Neoplasias Ósseas , Osteoma Osteoide , Neoplasias da Coluna Vertebral , Anti-Inflamatórios não Esteroides/uso terapêutico , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/cirurgia , Erros de Diagnóstico , Feminino , Humanos , Masculino , Diagnóstico Ausente , Osteoma Osteoide/diagnóstico , Osteoma Osteoide/cirurgia , Dor , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/cirurgia
16.
Analyst ; 147(10): 2164-2169, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35441615

RESUMO

Although accurate base-pairing ensures specificity of molecular recognition, DNA polymerization and DNA amplification, there are many non-specific pairings that arise from mismatched pairs, such as the T/G wobble pair. We have found that by using 2-S-TTP (STTP), we can minimize T/G mismatch, improve the DNA polymerization specificity and enhance the detection sensitivity (up to 20 fold), without significantly compromising the polymerization efficiency (the extension rate ratio of TTP vs.STTP is 1.08). With the STTP strategy, DNA polymerization is more specific and allows the detection of pathogens (such as COVID-19) in single digits (up to 5 copies), which is not possible with conventional RT-PCR. We have discovered that STTP can generally promote much higher specificity and sensitivity in DNA polymerization and nucleic acid detection than canonical TTP.

17.
Nat Commun ; 13(1): 1745, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365631

RESUMO

Neurological manifestations are a significant complication of coronavirus disease (COVID-19), but underlying mechanisms aren't well understood. The development of animal models that recapitulate the neuropathological findings of autopsied brain tissue from patients who died from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are critical for elucidating the neuropathogenesis of infection and disease. Here, we show neuroinflammation, microhemorrhages, brain hypoxia, and neuropathology that is consistent with hypoxic-ischemic injury in SARS-CoV-2 infected non-human primates (NHPs), including evidence of neuron degeneration and apoptosis. Importantly, this is seen among infected animals that do not develop severe respiratory disease, which may provide insight into neurological symptoms associated with "long COVID". Sparse virus is detected in brain endothelial cells but does not associate with the severity of central nervous system (CNS) injury. We anticipate our findings will advance our current understanding of the neuropathogenesis of SARS-CoV-2 infection and demonstrate SARS-CoV-2 infected NHPs are a highly relevant animal model for investigating COVID-19 neuropathogenesis among human subjects.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Encéfalo , Células Endoteliais , Humanos , Primatas
18.
BMC Genom Data ; 23(1): 26, 2022 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-35395709

RESUMO

BACKGROUND: Amphioxus is a model organism for vertebrate evolutionary research. The significant contrast between morphological phenotypic similarity and high-level genetic polymorphism among amphioxus populations has aroused scientists' attention. Here we resequenced 21 amphioxus genomes to over 100X depth and mapped them to a haploid reference. RESULTS: More than 11.5 million common SNPs were detected in the amphioxus population, which mainly affect genes enriched in ion transport, signal transduction and cell adhesion, while protein structure analysis via AlphaFold2 revealed that these SNPs fail to bring effective structural variants. CONCLUSIONS: Our work provides explanation for "amphioxus polymorphism paradox" in a micro view, and generates an enhanced genomic dataset for amphioxus research.


Assuntos
Anfioxos , Animais , Genoma/genética , Genômica , Anfioxos/genética , Polimorfismo de Nucleotídeo Único/genética , Análise de Sequência de DNA
19.
J Oncol ; 2022: 8656865, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432534

RESUMO

The goal of this study was to investigate the homeobox (HOX) gene expression status and its prognostic value in glioblastoma multiforme (GBM) and to uncover the biological processes related to its expression. The prognostic value of HOX genes in GBM was systematically investigated by a genome-wide analysis of HOX gene expression profiles in GBM patient samples in The Cancer Genome Atlas (TCGA) project (microarray dataset) and validation datasets. Using the differentially expressed gene (DEG) analysis and a Cox regression model, we discovered that the HOXC6 could stratify patients into significantly different survival (p = 0.0012, log-rank test) groups in the training cohort. TCGA RNA-seq and GSE16011 datasets were used for validation. Multivariate Cox and stratification analysis indicated that HOXC6 was an independent prognostic factor after adjusting for other clinical covariates. Bioinformatic analysis suggested that the HOXC6 might be involved in the cell cycle-related biological processes and pathways that are well established in the context of glioblastoma tumorigenesis. We further explored the bioinformatic implications by gene set enrichment analysis (GSEA). Tumor cell biology experiments verified the role of HOXC6 in proliferation and cell cycle progression. In conclusion, HOXC6 might be a candidate biomarker gene for individual treatment optimization of glioblastoma. HOXC6 expression has a significant prognostic value and is related to the cell cycle process in glioblastoma.

20.
J Am Heart Assoc ; 11(6): e022003, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35261290

RESUMO

Background In participants with concomitant chronic coronary disease and advanced chronic kidney disease (CKD), the effect of treatment strategies on the timing of dialysis initiation is not well characterized. Methods and Results In ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease), 777 participants with advanced CKD and moderate or severe ischemia were randomized to either an initial invasive or conservative management strategy. Herein, we compare the proportion of randomized participants with non-dialysis-requiring CKD at baseline (n=362) who initiated dialysis and compare the time to dialysis initiation between invasive versus conservative management arms. Using multivariable Cox regression analysis, we also sought to identify the effect of invasive versus conservative chronic coronary disease management strategies on dialysis initiation. At a median follow-up of 23 months (25th-75th interquartile range, 14-32 months), dialysis was initiated in 18.9% of participants (36/190) in the invasive strategy and 16.9% of participants (29/172) in the conservative strategy (P=0.22). The median time to dialysis initiation was 6.0 months (interquartile range, 3.0-16.0 months) in the invasive group and 18.2 months (interquartile range, 12.2-25.0 months) in the conservative group (P=0.004), with no difference in procedural acute kidney injury rates between the groups (7.8% versus 5.4%; P=0.26). Baseline clinical factors associated with earlier dialysis initiation were lower baseline estimated glomerular filtration rate (hazard ratio [HR] associated with 5-unit decrease, 2.08 [95% CI, 1.72-2.56]; P<0.001), diabetes (HR, 2.30 [95% CI, 1.28-4.13]; P=0.005), hypertension (HR, 7.97 [95% CI, 1.09-58.21]; P=0.041), and Hispanic ethnicity (HR, 2.34 [95% CI, 1.22-4.47]; P=0.010). Conclusions In participants with non-dialysis-requiring CKD in ISCHEMIA-CKD, randomization to an invasive chronic coronary disease management strategy (relative to a conservative chronic coronary disease management strategy) is associated with an accelerated time to initiation of maintenance dialysis for kidney failure. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01985360.


Assuntos
Doença das Coronárias , Cardiopatias , Insuficiência Renal Crônica , Doença das Coronárias/complicações , Taxa de Filtração Glomerular , Cardiopatias/complicações , Humanos , Isquemia/complicações , Diálise Renal/métodos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia
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