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1.
Nat Commun ; 12(1): 5976, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645826

RESUMO

In plants, cytosine DNA methylations (5mCs) can happen in three sequence contexts as CpG, CHG, and CHH (where H = A, C, or T), which play different roles in the regulation of biological processes. Although long Nanopore reads are advantageous in the detection of 5mCs comparing to short-read bisulfite sequencing, existing methods can only detect 5mCs in the CpG context, which limits their application in plants. Here, we develop DeepSignal-plant, a deep learning tool to detect genome-wide 5mCs of all three contexts in plants from Nanopore reads. We sequence Arabidopsis thaliana and Oryza sativa using both Nanopore and bisulfite sequencing. We develop a denoising process for training models, which enables DeepSignal-plant to achieve high correlations with bisulfite sequencing for 5mC detection in all three contexts. Furthermore, DeepSignal-plant can profile more 5mC sites, which will help to provide a more complete understanding of epigenetic mechanisms of different biological processes.

2.
Bioengineered ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34637688

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that poses great threat to women health. MiR-1224-5p is downregulated in the follicular fluid of patients with PCOS, but its role remains largely unknown. In this study, mice were treated with dehydroepiandrosterone (DHEA) to establish an in vivo model of PCOS. We found enhanced activation of NLRP3 inflammasome was accompanied with downregulation of miR-1224-5p in ovarian tissue of PCOS mice. The effect of miR-1224-5p was further explored in TNF-α-treated human granulosa-like tumor (KGN) cells. Upregulation of miR-1224-5p suppressed TNF-α-induced secretion of DHEA and testosterone. MiR-1224-5p attenuated TNF-α-induced inflammation by inhibiting NLRP3 inflammasome activation, IL-1ß synthesis and nuclear factor kappa B (NF-κB) p65 nuclear translocation. Notably, miR-1224-5p decreased the expression of Forkhead box O 1 (FOXO1) and its downstream gene thioredoxin interaction protein (TXNIP). Luciferase reporter assay confirmed FOXO1 as a target of miR-1224-5p. Upregulation of FOXO1 abolished miR-1224-5p-induced activation of NLRP3 inflammasome, demonstrating that miR-1224-5p might inhibit NLRP3 inflammasome activation through regulating FOXO1. This study provided novel insights into the pathogenesis of PCOS and suggested that miR-1224-5p might be a promising target for treating PCOS.

3.
Sci Total Environ ; 806(Pt 3): 150691, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34600995

RESUMO

Thousands of organic pollutants are intentionally and unintentionally discharged into water bodies, adversely affecting the ecological environment and human health. Screening for organic pollutants that pose a potential risk in aquatic environments is essential for risk management. This review evaluates the processes, methods, and technologies used to screen such pollutants in the aquatic environment and discuss their advantages and disadvantages, in addition to the challenges and knowledge gaps in this field. Combining non-target screening, target screening, and suspect screening is often effective for compiling a list of potential risk compounds and enables the quantitative analysis of these compounds. Sample preparation technologies and pollutant detection technologies considerably affect the results of pollutant screening. The limited amount of chemical and toxicological information contained in databases hinders the screening of organic pollutants with potential risk. Machine learning, high-throughput methods, and other technologies will increase the accuracy and convenience of screening for high-risk pollutants. This review provides an important reference for screening these compounds in aquatic environments and can be used in future pollutant screening and risk management.

4.
J Clin Invest ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34609966

RESUMO

Ferroptosis, an iron-dependent non-apoptotic cell death, is a highly regulated tumor suppressing process. However, functions and mechanisms of RNA binding proteins in regulation of evasion of ferroptosis during lung cancer progression are still largely unknown. Here we reported that the RNA binding protein RBMS1 participated in lung cancer development through mediating ferroptosis evasion. Through an shRNA-mediated systematic screen, we discovered that RBMS1 was a key ferroptosis regulator. Clinically, RBMS1 was elevated in lung cancer and its high expression was associated with reduced patient survival. Conversely, depletion of RBMS1 inhibited lung cancer progression both in vivo and in vitro. Mechanistically, RBMS1 interacted with the translation initiation factor eIF3d directly to bridge the 3'- and 5'-UTRs of SLC7A11. RBMS1 ablation inhibited the translation of SLC7A11, reduced SLC7A11-mediated cystine uptake and promotes ferroptosis. In a drug screen that targeted RBMS1, we further uncovered that nortriptyline hydrochloride decreased the level of RBMS1, thereby promoting ferroptosis. Importantly, RBMS1 depletion or inhibition by nortriptyline hydrochloride sensitized radioresistant lung cancer cells to radiotherapy. Our findings established RBMS1 as a translational regulator of ferroptosis and a prognostic factor with therapeutic potentials and clinical values.

5.
Chin J Acad Radiol ; : 1-5, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34642650

RESUMO

Purpose: The Corona Virus Disease 2019 (COVID-19) was first reported in December 2019 from an outbreak of unexplained pneumonia in Wuhan (Hubei, China) that subsequently spread rapidly around the world. Because of the public health emergency, chest CT has been widely used for sensitive detection and diagnosis, monitoring the changes of lesions and also for treatment evaluation. The purpose of this study was to investigate radiation dose and image quality of chest CT scans received by COVID-19 patients and to evaluate the oncogenic risk of multiple chest CT examinations. Methods: A retrospective review of 33 patients with RT-PCR confirmed COVID-19 infection was performed from January 31, 2020 to February 19, 2020. The date of each CT exam and respective radiation dose for each exam was recorded for all patients. Multiple pulmonary CT scans were obtained during diagnosis and treatment procedure. Scan frequency, total scan times, radiation dose, and image quality were determined. Results: Thirty-three patients (15 males and 18 females, age 21-82 years) with confirmed COVID-19 pneumonia underwent a total of 143 chest CT scans. The number of CT scans per patient was 4 ± 1, with a range of 2-6. The time interval between two consecutive chest CT scans was 3 ± 1 days. The average effective dose from a single chest CT scan was 1.21 ± 0.10 mSv, with a range of 1.02-1.44 mSv. The average cumulative effective dose per patient was 5.25 ± 1.52 mSv, with a range of 2.24-7.48 mSv. The maximum cumulative effective dose was 7.48 mSv for six CT examinations during COVID-19 treatment. Based on subjective image quality analysis, the visual scoring of CT findings was 11.23 ± 1.35 points out of 15 points. Conclusions: The frequency, total number and image quality of chest CT scans should be reviewed carefully to guarantee minimally required CT scans during the COVID-19 management.

6.
Sci Total Environ ; : 151025, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34662606

RESUMO

Dewatering treatment is an essential step to diminish sludge volume, cut down transportation costs, and improve subsequent disposal efficiency. In this study, ozone-peroxymonosulfate (O3/PMS) oxidation process was employed to ameliorate sludge dewaterability. Sludge capillary suction time (CST) and water content (Wc) of dewatered sludge cake could reduce from 70.5 s and 81.93% to 26.7 s and 65.65%, respectively, under the optimal dosage of 30 mg/g TS O3 and 0.4 mmol/g TS PMS. The increased sludge zeta potential, particle size, and fluidity promoted sludge dewatering performance apparently. The decreased hydrophilic, fluorescent EPS components and proteins/peptides-like + Lipids percentage in EPS as well as the ratio of α-helix/(ß-sheet + random coil) of treated EPS protein secondary structure was greatly responsible for the enhanced sludge dewaterability. SO4- and OH were detected in ozone-peroxymonosulfate process to crack sludge flocs, eliminate hydrophilic substances and liberate bound water. Moreover, the concentrations of both heavy metals and polycyclic aromatic hydrocarbons (PAHs) of sludge after O3/PMS conditioning were decreased, and the stability and toxicity of heavy metals were also reduced, except Zn. In conclusion, this work offered a comprehensive insight based on ozone-peroxymonosulfate (O3/PMS) advanced oxidation for improving the sludge dewaterability and environmental implication.

7.
Pak J Pharm Sci ; 34(3(Special)): 1203-1209, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34602390

RESUMO

This work aims to analyze the effect of the ethanol extract from Polygonatum odoratum on high glucose-induced tubular epithelial cell apoptosis and oxidative stress. HK-2 injury of tubular epithelial cells was induced by high glucose, and the ethanol extract from Polygonatum odoratum was given. HK-2 cell activity and apoptosis were detected by MTT method and flow cytometry, respectively. Western blot was performed to analyze Cleaved-caspase3, Pro-caspase3, Nrf2, HO-1 protein expression. The levels of MDA, GSH, SOD were evaluated using commercial Kit. si-Nrf2 was transfected into HK-2 cells and high-glucose induction and ethanol extract from Polygonatum odoratum were given to observe the changes of cell apoptosis and oxidative stress. Ethanol extract from Polygonatum odoratum increased the high glucose-induced HK-2 cell activity, Pro-caspase3, Nrf2, HO-1 protein, GSH, SOD levels and decreased its apoptosis rate, Cleaved-caspase3 protein and MDA levels, showing statistically significant difference (p<0.05). After Nrf2 interference, high glucose-induced HK-2 cell activity, Pro-caspase3 protein, GSH, and SOD levels were decreased under the action of ethanol extract from Polygonatum odoratum, while the apoptosis rate, Cleaved-caspase3 protein, and MDA levels were increased significantly (p<0.05). The ethanol extract from Polygonatum odoratum can inhibit high glucose-induced tubular epithelial cell apoptosis and reduce oxidative stress by activating the Nrf2-ARE signaling pathway.

8.
Opt Express ; 29(18): 29275-29291, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34615040

RESUMO

For performance enhancement of functional diffuse optical tomography (fDOT), we propose a tandem method that takes advantage of the inversion filtering and the long short term memory (LSTM) classification to simultaneously suppress the physiological interferences and physical noises in fDOT. In the former phase, the absorption perturbation maps over the scalp-skull (SS) and cerebral-cortex (CC) layers are firstly pre-reconstructed using a two-layer topography scheme. Then, the recovered SS-map is inversed into measurement space by the forward calculation to estimate the intensity changes associated with the physiological interferences. Finally, the raw measurements are adaptively filtered with reference to the estimated intensity changes for accomplishing the model-based full three-dimension (3D) reconstruction. In the later phase, for further removing the randomly distributed physical noises, mainly instrumental noise, a LSTM network based fusion strategy is applied, where a pixel-wise binary mask of "activated" or "inactive" state is generated by performing LSTM classification and then fused with the 3D reconstruction. The results of the simulative investigation and in-vivo experiment show the proposed tandem scheme achieves improved performance in fDOT using a cost-effective and physically explicable way. Thus, the proposed method can be promisingly applied in real-time neuroimaging to acquire cortical neural activation information with improved reliability, quantification and resolution.

9.
ACS Appl Mater Interfaces ; 13(37): 44844-44859, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34505760

RESUMO

New solid polymer electrolytes are of particular interest for next-generation high-energy batteries since they can overcome the limited voltage window of conventional polyether-based electrolytes. Herein, a flame-retardant phosphorus-containing polymer, poly(dimethyl(methacryloyloxy)methyl phosphonate) (PMAPC1) is introduced as a promising polymer matrix. Free-standing membranes are easily obtained by mixing PMAPC1 with lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) and a small amount of acetonitrile (AN). LiTFSI/AN mixed aggregates are formed that act as plasticizers and enable ionic conductivities up to 1.6 × 10-3 S cm-1 at 100 °C. The high content of LiTFSI used in our electrolytes leads to the formation of a stable LiF solid-electrolyte interphase, which can effectively suppress Li dendrites and the chemical degradation of AN in contact with Li. Accordingly the electrolyte membranes exhibit a wide electrochemical stability window above 4.7 V versus Li+/Li and fire-retardant properties due to the presence of the phosphorus-containing polymer. Atomistic molecular modeling simulations have been performed to determine the structure of the electrolytes on the microscopic scale and to rationalize the trends in ionic conductivity and the transport regime as a function of the electrolyte composition. Finally, our electrolyte membranes enable stable cycling performance for LiFePO4|PMAPC1 + LiTFSI + AN|Li batteries.

10.
Free Radic Biol Med ; 175: 216-225, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34474106

RESUMO

Nitric oxide (NO) plays an important role in cardiovascular and immune systems. Quantification of blood nitrite and nitrate, two relatively stable metabolites of NO (generally as NOx), has been acknowledged, in part, representing NO bioactivity. Dysregulation of NOx had been reported in SARS-CoV-2 infected populations, but whether patients recovered from COVID-19 disease present with restored NOx is unknown. In this study, serum NO2- and NO3- were quantified and analyzed among 109 recovered adults in comparison to a control group of 166 uninfected adults. Nitrite or nitrate levels were not significantly different among mild-, common-, severe- and critical-type patients. However, these recovered patients had dramatically lower NO2- and NO2-/NO3- than the uninfected group (p < 0.0001), with significantly higher NO3- levels (p = 0.0023) than the uninfected group. Nitrate and nitrite/nitrate were positively and negatively correlated with patient age, respectively, with age 65 being a turning point among recovered patients. These results indicate that low NO2-, low NO2-/NO3- and high NO3- may be potential biomarkers of long-term poor or irreversible outcomes after SARS-CoV-2 infection. It suggests that NO metabolites might serve as a predictor to track the health status of recovered COVID-19 patients, highlighting the need to elucidate the role of NO after SARS-CoV-2 infection.


Assuntos
COVID-19 , Nitritos , Adulto , Idoso , Biomarcadores , Humanos , Nitratos , Óxido Nítrico , SARS-CoV-2
11.
J Healthc Eng ; 2021: 2254594, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567478

RESUMO

The aim of this study is to explore the clinical effect of deep learning-based MRI-assisted arthroscopy in the early treatment of knee meniscus sports injury. Based on convolutional neural network algorithm, Adam algorithm was introduced to optimize it, and the magnetic resonance imaging (MRI) image super-resolution reconstruction model (SRCNN) was established. Peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) were compared between SRCNN and other algorithms. Sixty patients with meniscus injury of knee joint were studied. Arthroscopic surgery was performed according to the patients' actual type of injury, and knee scores were evaluated for all patients. Then, postoperative scores and MRI results were analyzed. The results showed that the PSNR and SSIM values of the SRCNN algorithm were (42.19 ± 4.37) dB and 0.9951, respectively, which were significantly higher than those of other algorithms (P < 0.05). Among patients with meniscus injury, 17 cases (28.33%) were treated with meniscus suture, 39 cases (65.00%) underwent secondary resection, 3 cases (5.00%) underwent partial resection, and 1 case (1.67%) underwent full resection. After meniscus suture, secondary resection, partial resection, and total resection, the knee function scores of patients after treatment were (83.17 ± 8.63), (80.06 ± 7.96), (84.34 ± 7.74), and (85.52 ± 5.97), respectively. There was no great difference in knee function scores after different methods of treatment (P > 0.05), and there were considerable differences compared with those before treatment (P < 0.01). Compared with the results of arthroscopy, there was no significant difference in the grading of meniscus injury by MRI (P > 0.05). To sum up, the SRCNN algorithm based on the deep convolutional network algorithm improved the MRI image quality and the diagnosis of knee meniscus injuries. Arthroscopic knee surgery had good results and had great clinical application and promotion value.

12.
Biomolecules ; 11(8)2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34439747

RESUMO

Endo-ß-1,3-glucanase plays an essential role in the deconstruction of ß-1,3-d-glucan polysaccharides through hydrolysis. The gene (1650-bp) encoding a novel, bi-modular glycoside hydrolase family 64 (GH64) endo-ß-1,3-glucanase (GluY) with a ricin-type ß-trefoil lectin domain (RICIN)-like domain from Cellulosimicrobium funkei HY-13 was identified and biocatalytically characterized. The recombinant enzyme (rGluY: 57.5 kDa) displayed the highest degradation activity for laminarin at pH 4.5 and 40 °C, while the polysaccharide was maximally decomposed by its C-terminal truncated mutant enzyme (rGluYΔRICIN: 42.0 kDa) at pH 5.5 and 45 °C. The specific activity (26.0 U/mg) of rGluY for laminarin was 2.6-fold higher than that (9.8 U/mg) of rGluYΔRICIN for the same polysaccharide. Moreover, deleting the C-terminal RICIN domain in the intact enzyme caused a significant decrease (>60%) of its ability to degrade ß-1,3-d-glucans such as pachyman and curdlan. Biocatalytic degradation of ß-1,3-d-glucans by inverting rGluY yielded predominantly d-laminaripentaose. rGluY exhibited stronger growth inhibition against Candida albicans in a dose-dependent manner than rGluYΔRICIN. The degree of growth inhibition of C. albicans by rGluY (approximately 1.8 µM) was approximately 80% of the fungal growth. The superior anti-fungal activity of rGluY suggests that it can potentially be exploited as a supplementary agent in the food and pharmaceutical industries.

13.
Neurogastroenterol Motil ; : e14196, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34337833

RESUMO

BACKGROUND: Constipation is a gastrointestinal symptom with high incidence rate and large number of patients. It is becoming one of the urgent medical problems. Poor intestinal motility is one of the important causes of constipation. Current drug treatments for constipation are associated with many side effects; thus, it is necessary to study more effective treatment methods and potential mechanism. METHODS: A zebrafish model of intestinal motility obstruction was established by loperamide hydrochloride to evaluate the effect of probiotic, food ingredients, and combination on intestinal peristalsis according to intestinal peristalsis frequency counts. The gastrointestinal survival ability of the best probiotics was evaluated by surface hydrophobicity, self-aggregation, acid and bile salt tolerance, and gastrointestinal transit tolerance. Interactions between probiotics and food ingredients were studied in vivo and in vitro. The expression of 5-HT was detected by ELISA and fluorescence immunoassay, and 5-HT related genes were detected by RT-PCR. KEY RESULTS: We obtained the probiotics, food ingredients, and combination that effectively promoted intestinal peristalsis, X11 and YRL577, P. persica and KGM, KGM + X11, respectively. Both KGM and P. persica promoted colonization of probiotics in vivo. KGM + X11 could effectively promote the increase in 5-HT synthesis in zebrafish via up-regulating gene expression of TPH-1, TPH-2, and 5-HTR and down-regulating gene expression of SERT. The specific in-depth mechanism needs further study. CONCLUSIONS AND INFERENCES: The combinations of KGM with X11 effectively promoted intestinal peristalsis. We provide a theoretical basis for new modalities that can promote intestinal peristalsis and alleviate constipation.

14.
Cell Biochem Funct ; 39(7): 854-859, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34250629

RESUMO

Carcinogenesis is characterized by abnormal regulation of cell growth and cell death. IK is a novel cell mitosis regulator that may contribute to carcinogenesis. Previous studies showed that the loss of IK expression resulted in cell mitotic arrest and even cell death. Besides, IK can also inhibit the interferon gamma (IFN-γ)-induced expression of human leukocyte antigen (HLA) class II antigen, which is associated with tumour immune microenvironment. To gain insight into the current research progress regarding IK, we conducted a review and searched the limited literature on IK using PubMed or Web of Science. In this review, we discussed the possible biological functions and mechanisms of IK in cancer and its immune microenvironment. Future perspectives of IK were also mentioned to explore its clinical significance.

15.
Curr Top Med Chem ; 21(14): 1251-1267, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34238160

RESUMO

BACKGROUND AND OBJECTIVE: Mesenchymal stem cells (MSCs), particularly bone MSCs (BMSCs) offer great potentials for targeted therapeutic applications owing to their migratory and differentiation capacities. Significant advances have been achieved in the differentiation of hepatocyte or hepatocyte-like cells both in vitro and in vivo. However, there is limited knowledge on the differentiation of BMSCs into bipotential hepatic progenitor cells or cholangiocyte. This study reviews the potentials and advances in using MSCs as vehicles for targeted drug delivery and proposes a new method for the induction of differentiation in rat BMSCs into hepatic progenitor cells in vitro and assesses the differential and migratory capacities. METHODS: The BMSCs of Sprague Dawley (SD) rats were harvested from the femur and the tibiae of the rats. After isolation and culturing, BMSCs from Passage 1 were used for the study. The in vitro differentiation of the hepatic progenitor cells was performed using a 2-step induction approach after 5-day serum deprivation from the BMSCs and culturing in Dulbecco's modified eagle medium. Spontaneous in vitro differentiation of BMSCs was examined in the absence of growth factors for 15 days as control treatment. Hepatocytes differentiation was achieved by exposing the culture to collagen type I-coated plates. Cholangiocytes differentiation was achieved with replating the BMC-HepPCs on a layer of Matrigel. Immunofluorescence was conducted on twelve-well plates to determine cell differentiations. Real-Time Quantitative Reverse Transcription PCR (qRTPCR) was used to determine the total RNA extracted using the Trizol LS reagent. In the hepatocyte differentiation group, after periodic acid-schiff (PAS) staining for glycogen, inverted microscope was used to determine differentiations and undifferentiated BMC-HepPCs served as controls. The amount of low-density lipoprotein (LDL) uptake by the BMSCs-derived hepatocytes was assessed using fluorescence microscopy. The secretion of rat albumin was quantified using a quantitative ELISA kit. RESULTS: Differentiation induction is indicative of the sequential supplementation of sodium butyrate and cytokines, which are involved in the embryonic development of the mammalian liver. Hepatic progenitor cells, derived from bone marrow, can be differentiated bidirectionally in vitro into both hepatocyte and cholangiocyte cell-lines. The differentiated cells, including hepatic progenitor cells, hepatocytes, and bile duct-like cells, were identified and analyzed at mRNA and protein levels. CONCLUSION: Our findings show that BMSCs can be utilized as novel bipotential hepatic progenitor cells and thereby for hepatobiliary disease treatment or hepatobiliary tissue-engineering.

16.
Surg Radiol Anat ; 43(10): 1703-1709, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34232369

RESUMO

PURPOSE: Vascularized pedicled bone-grafting from the cuboid to the talus provides low donor site morbidity and satisfactory outcomes in patients with early-stage talar avascular necrosis. We investigated the anatomy of the rotational vascularized pedicled bone graft from the cuboid. METHODS: 15 embalmed cadaver specimens were perfused with red latex via the popliteal artery. The lateral malleolus was dissected. The course of the lateral tarsal artery and the vascular territory in the cuboid supplied by the lateral tarsal artery were observed. Vessel diameters were measured. RESULTS: The course of the lateral tarsal artery to the cuboid was consistent, and a vascularized pedicle of the lateral tarsal artery was present in all specimens. Mean diameter of the lateral tarsal artery was 1.40 ± 0.12 mm (range 1.67-1.25). Mean length of the vascularized pedicle was 67.15 ± 3.18 mm (range 62.43-74.36). The pedicle bone graft was long enough to reach the bony border of both the lateral and medial malleolus. CONCLUSION: A vascularized pedicled cuboid bone graft based on the lateral tarsal artery has clinical utility for early-stage talar avascular necrosis.

17.
Gastrointest Endosc ; 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34197834

RESUMO

BACKGROUND AND AIMS: Gene therapy could provide curative therapies to many inherited monogenic liver diseases. Clinical trials have largely focused on adeno-associated viruses (AAVs) for liver gene delivery. These vectors, however, are limited by small packaging size, capsid immune responses, and inability to redose. As an alternative, nonviral, hydrodynamic injection through vascular routes can successfully deliver plasmid DNA (pDNA) into mouse liver but has achieved limited success in large animal models. METHODS: We explored hydrodynamic delivery of pDNA through the biliary system into the liver of pigs using ERCP and a power injector to supply hydrodynamic force. Human factor IX (hFIX), deficient in hemophilia B, was used as a model gene therapy. RESULTS: Biliary hydrodynamic injection was well tolerated without significant changes in vital signs, liver enzymes, hematology, or histology. No off-target pDNA delivery to other organs was detected by polymerase chain reaction. Immunohistochemistry revealed that 50.19% of the liver stained positive for hFIX after hydrodynamic injection at 5.5 mg pDNA, with every hepatic lobule in all liver lobes demonstrating hFIX expression. hFIX-positive hepatocytes were concentrated around the central vein, radiating outward across all 3 metabolic zones. Biliary hydrodynamic injection in pigs resulted in significantly higher transfection efficiency than mouse vascular hydrodynamic injection at matched pDNA per liver weight dose (32.7%-51.9% vs 18.9%, P < .0001). CONCLUSIONS: Biliary hydrodynamic injection using ERCP can achieve higher transfection efficiency into hepatocytes compared with AAVs at magnitudes of less cost in a clinically relevant human-sized large animal. This technology may serve as a platform for gene therapy of human liver diseases.

18.
Infect Dis Ther ; 10(3): 1733-1745, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34244957

RESUMO

INTRODUCTION: This study aimed to evaluate the utility of metagenomic next-generation sequencing (mNGS) for the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus-infected patients. METHODS: We conducted a retrospective study. A total of 60 non-human immunodeficiency virus-infected PJP patients and 134 patients diagnosed with non-PJP pneumonia were included. P. jirovecii and other co-pathogens identified by mNGS in bronchoalveolar lavage fluid and/or blood samples were analyzed. Using clinical composite diagnosis as the reference standard, we compared the diagnostic performance of mNGS in PJP with conventional methods, including Gomori methenamine silver staining and serum (1,3)-ß-D-glucan. Modifications of antimicrobial treatment for PJP patients after the report of mNGS results were also reviewed. RESULTS: mNGS reached a sensitivity of 100% in diagnosing PJP, which was remarkably higher than Gomori methenamine silver staining (25.0%) and serum (1,3)-ß-D-glucan (67.4%). The specificity of mNGS (96.3%) significantly surpassed serum (1,3)-ß-D-glucan (81.4%). Simultaneous mNGS of bronchoalveolar lavage fluid and blood samples was performed in 21 out of 60 PJP patients, and it showed a concordance rate of 100% in detecting P. jirovecii. Besides, mNGS showed good performance in identifying co-pathogens of PJP patients, among which cytomegalovirus and Epstein-Barr virus were most commonly seen. Initial antimicrobial treatment was modified in 71.7% of PJP patients after the report of mNGS results. CONCLUSION: mNGS is a useful diagnostic tool with good performance for the diagnosis of PJP and the detection of co-pathogens. mNGS of bronchoalveolar lavage fluid and/or blood samples is suggested in patients with presumptive diagnosis of PJP. Blood samples may be a good alternative to bronchoalveolar lavage fluid for mNGS when bronchoscopic examination is not feasible.

19.
Redox Rep ; 26(1): 124-133, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34323675

RESUMO

OBJECTIVES: Nitric oxide (NO) plays a vital role in neurological development. As an easily accessible and non-invasive fluid, saliva hasn't been evaluated for nitrite among children with autism spectrum disorder (ASD). This study aims to quantify saliva nitrite and explore its relation with serum NO. METHODS: Saliva sampling and pretreatment methods were optimized, followed by NO measurement via chemiluminescence for 126 ASD children and 129 normally developing children (ND). RESULTS: In the ASD group, saliva nitrite was significantly higher than that in the ND, with concentrations of 4.97 ± 3.77 µM and 2.66 ± 2.07 µM (p < 0.0001), respectively. Positive correlation was observed between saliva NO2- and serum NO3- in ASD children, which didn't exist in the ND group. Male children in the ASD group had significantly higher NO than that in boys of the ND group, without significant difference between girls in both groups. Correlation was not found between saliva or serum NO and severity of these ASD children. DISCUSSION: It is reported for the first time that saliva nitrite was positively correlated with serum nitrate in ASD children, with significantly higher NO only in autistic boys. Non-invasive saliva might serve as a predictor of health status of ASD children.

20.
Crit Rev Anal Chem ; : 1-20, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284659

RESUMO

Surface-enhanced Raman spectroscopy (SERS) is an advanced and powerful analysis tool. Due to the advantages of high sensitivity, high resolution, and nondestructive testing, it has been widely used in physics, chemistry, material science and other fields. In recent years, substantial progress has been made in developing flexible platforms for the design and fabrication of SERS substrates. One important kind of the flexible platforms is based on electrospun nanofibers. Electrospun nanofibers not only have unique advantages such as easy preparation, high porosity and large specific surface area, but also can increase the number of hotspots when combined with precious metal nanomaterials, thereby enhancing the SERS signal and expanding the application scope. In this review, we firstly focus on two strategies for the fabrication of metal nanostructure decorated in/on the electrospun nanofibers, namely in-situ and ex-situ. Then the applications of these SERS substrates in the fields of quantitative analysis, monitoring chemical reactions and recyclable detection are introduced in detail. Finally, the challenges as well as perspectives are presented to offer a guideline for the future exploration of these SERS substrates. We expect that it will provide new inspiration for the development of electrospun nanofiber-based SERS substrates.

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