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1.
Bioact Mater ; 19: 198-216, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35510171

RESUMO

Hydrogen sulfide (H2S) plays an important role in regulating various pathological processes such as protecting mammalian cell from harmful injuries, promoting tissue regeneration, and regulating the process of various diseases caused by physiological disorders. Studies have revealed that the physiological effects of H2S are highly associated with its concentrations. At relatively low concentration, H2S shows beneficial functions. However, long-time and high-dose donation of H2S would inhibit regular biological process, resulting in cell dysfunction and apoptosis. To regulate the dosage of H2S delivery for precision medicine, H2S delivery systems with intelligent characteristics were developed and a variety of biocompatibility polymers have been utilized to establish intelligent polymeric H2S delivery systems, with the abilities to specifically target the lesions, smartly respond to pathological microenvironments, as well as real-timely monitor H2S delivery and lesion conditions by incorporating imaging-capable moieties. In this review, we focus on the design, preparation, and therapeutic applications of intelligent polymeric H2S delivery systems in cardiovascular therapy, inflammatory therapy, tissue regenerative therapy, cancer therapy and bacteria-associated therapy. Strategies for precise H2S therapies especially imaging-guided H2S theranostics are highlighted. Since H2S donors with stimuli-responsive characters are vital components for establishing intelligent H2S delivery systems, the development of H2S donors is also briefly introduced.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35932694

RESUMO

A protocol was developed, via a data-dependent high-resolution tandem mass spectrometry (ddHRMS/MS), to detect six biomarkers of dichlorvos in its metabolites and blood adducts of butyrylcholinesterase and albumin without using standard synthetic peptides. Firstly, the adducts of dimethoxy phosphonate (DMP-BChE) and the aged adducts of methoxy phosphonate (MxP-BChE) were isoloated by immunomagnetic separation (IMS), and then digested to DMP-nonapeptide and MxP-nonapeptide by pepsin. The dichlorvos and its metabolites (Trimethyl phosphate, Dimethyl phosphate) were analyzed in the supernatant of IMS treatment after protein precipitation. The precipitate was digested by pronase to phosphorylated tyrosine (DMP-Tyr), which were quantified by ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry (UPLC-MS). The linearity of detector response of all biomarkers was studied in their respective ranges, and the correlation coefficients (R2) were all greater than 0.9981. The limits of detection (LOD) and limits of quantification (LOQ) were 0.2-10 ng/mL and 0.5-20 ng/mL, respectively. The recoveries of the six biomarkers were 78.6-110.0 %, matrix effect were 64.1-106.8 %. Inter- and intra-assay precision had coefficients of variation of ≤13.2 % and ≤9.7 %, respectively. In addition, MxP- BChE, DMP-Tyr, TMP, DMP and DDVP were detected in the blood of three cases who died from DDVP poisoning, but DMP- BChE was not detected in all of them, which may be caused by the instability of DMP- BChE and its easy aging to form MxP-BCHE.

4.
Magn Reson Imaging ; 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35940378

RESUMO

Four-dimensional magnetic resonance imaging (4D-MRI) is becoming increasingly important in radiotherapy treatment planning for its ability to simultaneously provide 3D structural information and temporal profiles of the examined tissues in a non-ionizing manner. However, the relatively long acquisition time and the resulting motion artifacts severely limit the further application of 4D-MRI. In this paper, we propose a novel motion-aligned reconstruction method based on higher degree total variation and locally low-rank regularization (maHDTV-LLR) to recover 4D MR images from the highly undersampled Fourier coefficients. Specifically, we propose a two-stage reconstruction framework alternating between a motion alignment step and a regularized optimization reconstruction step. Moreover, we incorporate the 3D-HDTV and the locally low-rank penalties into a unified framework to simultaneously exploit the spatial and temporal correlation of the 4D-MRI data. A fast alternating minimization algorithm based on variable splitting is utilized to solve the optimization problem efficiently. The performance of the proposed method is demonstrated in the context of 4D cardiac and abdominal MR images reconstruction with high undersampling factors. Numerical results show that the proposed method enables accelerated 4D-MRI with improved image quality and reduced artifacts.

5.
Front Pharmacol ; 13: 932807, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910373

RESUMO

Recently, there has been a rapidly expanding interest in a new nanomaterial, graphene quantum dots (GQDs), owing to its profound potential in various advanced applications. At present, the study of GQDs mainly focuses on the new synthesis methods and surface modification. However, revealing the intracellular distribution of GQDs is currently not available, limiting in-depth understanding of its biological regulatory mechanism. To fill up this gap, the visualization study of red fluorescent graphene quantum dots (Red-GQDs) is helpful to clarify their subcellular distribution and metabolism in living cells system. Here, in this study, two-photon laser confocal microscopy was used to deeply analyze the uptake and subcellular distribution of Red-GQDs by HeLa cells at different concentrations and times through visual observation and discussed the effect of Red-GQDs on the metabolic of HeLa cells. The results indicated that Red-GQDs could be well-absorbed by HeLa cells and further revealed the differential distribution of Red-GQDs in different organelles (lysosomes and mitochondria) in a time-dependent manner. In addition, we confirmed that Red-GQDs significantly affect cell biological functions. Low concentrations of Red-GQDs are related to the autophagy pathway of cells, and high concentrations of Red-GQDs can induce ferroptosis in cells and promote the secretion of cellular exosomes. In the present study, the distribution and metabolic pathways of Red-GQDs in the subcellular structure of cells were characterized in detail through visual analysis, which can bring positive reference for the application of Red-GQDs in the future.

6.
Oxid Med Cell Longev ; 2022: 7411824, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910849

RESUMO

Salvianolic acid A (SAA) is one of bioactive polyphenol extracted from a Salvia miltiorrhiza (Danshen), which was widely used to treat cardiovascular disease in traditional Chinese medicine. SAA has been reported to be protective in cardiovascular disease and ischemia injury, with anti-inflammatory and antioxidative effect, but its role in acute lung injury (ALI) is still unknown. In this study, we sought to investigate the therapeutic effects of SAA in a murine model of lipopolysaccharide- (LPS-) induced ALI. The optimal dose of SAA was determined by comparing the attenuation of lung injury score after administration of SAA at three different doses (low, 5 mg/kg; medium, 10 mg/kg; and, high 15 mg/kg). Dexamethasone (DEX) was used as a positive control for SAA. Here, we showed that the therapeutic effect of SAA (10 mg/kg) against LPS-induced pathologic injury in the lungs was comparable to DEX. SAA and DEX attenuated the increased W/D ratio and the protein level, counts of total cells and neutrophils, and cytokine levels in the BALF of ALI mice similarly. The oxidative stress was also relieved by SAA and DEX according to the superoxide dismutase and malondialdehyde. NET level in the lungs was elevated in the injured lung while SAA and DEX reduced it significantly. LPS induced phosphorylation of Src, Raf, MEK, and ERK in the lungs, which was inhibited by SAA and DEX. NET level and phosphorylation level of Src/Raf/MEK/ERK pathway in the neutrophils from acute respiratory distress syndrome (ARDS) patients were also inhibited by SAA and DEX in vitro, but the YEEI peptide reversed the protective effect of SAA completely. The inhibition of NET release by SAA was also reversed by YEEI peptide in LPS-challenged neutrophils from healthy volunteers. Our data demonstrated that SAA ameliorated ALI via attenuating inflammation, oxidative stress, and neutrophil NETosis. The mechanism of such protective effect might involve the inhibition of Src activation.


Assuntos
Lesão Pulmonar Aguda , Doenças Cardiovasculares , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Animais , Ácidos Cafeicos , Doenças Cardiovasculares/patologia , Humanos , Lactatos , Lipopolissacarídeos/farmacologia , Pulmão/patologia , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno , Neutrófilos/metabolismo
7.
RSC Adv ; 12(30): 19686-19694, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35919374

RESUMO

In this research, a nitrogen- (N) and sulfur- (S) codoped carbon dot (CDs-IPM)-based sensor was synthesized using a single-step hydrothermal method. Specifically, microcrystalline cellulose (MCC) was the main raw material, which was extracted from banana pseudo-stem-based waste, while autonomous sulfonic acid-functionalized ionic liquid (SO3H-IL) and polyethylene glycol 400 (PEG 400) acted as the N, S dopant, and surface modifier, respectively. Comprehensive spectroscopic characterization of the synthesized CDs-IPM revealed the introduction of S, N atoms in the matrix with existence of surface oxygenic functional groups. The CDs-IPM possessed enhanced photoluminescence (PL) intensity, synthetic yield, and PL quantum yield (PLQY). Additionally, electron transfer between the CDs-IPM, hexavalent chromium (Cr(vi)), and subsequent ascorbic acid (AA) succeeded in turning the fluorescence on and off. The detection limit was 17 nM for Cr(vi), while it was 103 nM for AA. Our study data can simplify the process of synthesis of CDs utilizing biodegradable starting materials. The probe reported in this study may serve as a valuable addition to the field of environment monitoring by virtue of its enhanced detection sensitivity, high selectivity, and stability.

8.
Orphanet J Rare Dis ; 17(1): 307, 2022 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927746

RESUMO

BACKGROUND AND AIMS: Immunoglobulin G4-related disease (IgG4-RD) is a multisystem fibroinflammatory condition. The aim of the present study was to characterize the clinical features and therapeutic response of patients with IgG4-RD and identify risk factors for disease relapse. METHODS: We collected baseline data of eligible patients with IgG4-RD and analyzed clinical features by interview and review of medical records. The patients who received glucocorticoids (GC) therapy with at least 3 months follow-up were used to characterize the therapeutic response and identify risk factors for relapse. RESULT: Totally 127 IgG4-RD patients, including 92 males and 35 females, were enrolled in the present study. The median age of onset was 63.0 years, ranging from 23 to 86. The pancreas, bile duct and lymph nodes were the most frequently involved organs. The serum IgG4 level was elevated in 94.5% of the patients and was correlated with the number of organs involved. Patients classified as head and neck limited group were more likely to be female. Compared to Mikulicz syndrome and systemic involvement group, pancreato-hepatobiliary group had higher aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, bilirubin and lower IgG4 level. Mikulicz syndrome and systemic involvement group had the highest IgG4-RD RI score, IgG level. Among 92 patients who received medical therapy with at least 3 months follow-up, 76 received GC alone or in combination with immunomodulator (IM) and 16 patients did not take GC. 74 out of the 76 patients (97.3%) achieved remission, with 59 of them remained in remission and 15 of them relapsed. Whereas 16 patients did not take GC, among them, 6 patients achieved remission with one relapsed. On multivariate analysis, higher initial score of ACR/EULAR IgG4-RD Classification Criteria and GC withdrawal were independent predictors for relapse. CONCLUSION: Four phenotypes of IgG4-RD showed different demographic and serological features. GC + IM therapy was safe and effective and might protect patients from relapse. The independent risk factors of relapse were GC withdrawal and higher score of ACR/EULAR IgG4-RD Classification Criteria.


Assuntos
Doença Relacionada a Imunoglobulina G4 , China , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulina G/uso terapêutico , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/patologia , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Masculino , Recidiva , Estudos Retrospectivos
9.
Anal Chim Acta ; 1221: 340099, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35934345

RESUMO

Monitoring the glycolysis pathway remains an analytical challenge as most metabolites involved are sugar phosphates. Structural similarity, instability, high polarity, and rich negative charges of sugar phosphates make LC-MS based analysis challenging. Here, we developed an improved workflow integrating uniformly 13C-labeled yeast metabolite extract, TiO2-based enrichment, differential stable isotope labeling phosphate methylation, porous graphic carbon column, and selected reaction monitoring acquisition. Uniformly 13C labeled yeast metabolite extract was used as internal standards while differential stable isotope labeled sugar phosphates worked as calibrants. The established method was validated in human plasma, platelet and cultured HeLa cells. The limits of quantification ranged between 0.25 and 0.54 pmol on column. The method was adapted and its applicability tested for human platelets in which activation with collagen-related peptide (CRP) clearly showed the upregulation of some SPx metabolites. The results document that this newly established method can be successfully used to monitor glycolysis in different biological samples. As an extension, more phosphorylated and carboxylated metabolites from the central carbon metabolism (pentose phosphate cycle, TCA cycle) were tested as well. This method showed superior performance, especially for multiple phosphorylated and carboxylated metabolites. For quantitative purpose, the concept of SPx in three sets (12C-analytes, U-13C-IS, deuterated calibrants) has the potential to be adapted for more anionic metabolites.


Assuntos
Fosfatos Açúcares , Espectrometria de Massas em Tandem , Carbono , Cromatografia Líquida/métodos , Glicólise , Células HeLa , Humanos , Metilação , Fosfatos , Saccharomyces cerevisiae , Fosfatos Açúcares/análise , Espectrometria de Massas em Tandem/métodos
10.
Ultrason Sonochem ; 88: 106105, 2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35921713

RESUMO

The effects of air thawing (AT), water thawing (WT), slightly acidic electrolyzed water (ET), ultrasound-assisted water thawing (WUT) and ultrasound-assisted slightly acidic electrolyzed water (EUT) on the quality and myofibrillar protein (MP) structure of chicken breasts were investigated. The results showed that WUT and EUT could significantly improve the thawing rate compared with AT, WT, and ET groups. The EUT group not only had lower thawing loss, but also their immobilized and free water contents were similar to fresh sample according to the low-field nuclear magnetic resonance (LF NMR) results. The EUT treatment had no adverse effect on the primary structure of the protein. The secondary and tertiary structures of MP were more stable in the EUT group according to Raman and fluorescence spectra. The muscle fibers microstructure from EUT group was neater and more compact compared with other thawing methods. Therefore, EUT treatment could be considered as a novel potential thawing method in the food industry.

11.
J Biochem Mol Toxicol ; : e23182, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35938691

RESUMO

Aberrant expression of microRNA-497 (miR-497) is associated with tumor progression, but the molecular mechanisms in tumorigenesis remain largely unknown. Here, we report that miR-497 expression is downregulated in esophageal squamous cell carcinoma (ESCC) clinical samples. Consistently, upregulation of miR-497 inhibits ESCC cell malignant properties and tumor growth in vivo. Importantly, we uncovered that miR-497 upregulation suppressed ESCC cell growth and tumor growth by inhibiting Smurf2. Mechanistically, we showed that Smurf2 was a target of miR-497, and mediated YY1 expression to elevate HIF2α expression, thereby enhancing the malignancy of ESCC cells. Together, our study uncovered the role of the miR-497-mediated Smurf2/YY1/HIF2α axis in tumor growth and metastasis, which might provide potential therapeutic targets for human ESCC.

12.
Anal Chem ; 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913997

RESUMO

Coupling capillary electrophoresis (CE) to mass spectrometry (MS) is a powerful strategy to leverage a high separation efficiency with structural identification. Traditional CE-MS interfacing relies upon voltage to drive this process. Additionally, sheathless interfacing requires that the electrophoresis generates a sufficient volumetric flow to sustain the ionization process. Vibrating sharp-edge spray ionization (VSSI) is a new method to interface capillary electrophoresis to mass analyzers. In contrast to traditional interfacing, VSSI is voltage-free, making it straightforward for CE and MS. New nanoflow sheath CE-VSSI-MS is introduced in this work to reduce the reliance on the separation flow rate to facilitate the transfer of analyte to the MS. The nanoflow sheath VSSI spray ionization functions from 400 to 900 nL/min. Using the new nanoflow sheath reported here, volumetric flow rate through the separation capillary is less critical, allowing the use of a small (i.e., 20 to 25 µm) inner diameter separation capillary and enabling the use of higher separation voltages and faster analysis. Moreover, the use of a nanoflow sheath enables greater flexibility in the separation conditions. The nanoflow sheath is operated using aqueous solutions in the background electrolyte and in the sheath, demonstrating the separation can be performed under normal and reversed polarity in the presence or absence of electroosmotic flow. This includes the use of a wider pH range as well. The versatility of nanoflow sheath CE-VSSI-MS is demonstrated by separating cationic, anionic, and zwitterionic molecules under a variety of separation conditions. The detection sensitivity observed with nanoflow sheath CE-VSSI-MS is comparable to that obtained with sheathless CE-VSSI-MS as well as CE-MS separations with electrospray ionization interfacing. A bare fused silica capillary is used to separate cationic ß-blockers with a near-neutral background electrolyte at concentrations ranging from 1.0 nM to 1.0 µM. Under acidic conditions, 13 amino acids are separated with normal polarity at a concentration ranging from 0.25 to 5 µM. Finally, separations of anionic compounds are demonstrated using reversed polarity under conditions of suppressed electroosmotic flow through the use of a semipermanent surface coating. With a near-neutral separation electrolyte, anionic nonsteroidal anti-inflammatory drugs are detected over a concentration range of 0.1 to 5.0 µM.

13.
Cell Death Dis ; 13(8): 671, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918330

RESUMO

Sustained expression of programmed cell death receptor-1 (PD-1) is correlated with the exhaustion of T cells, and blockade of the PD-1 pathway is an effective immunotherapeutic strategy for treating various cancers. However, response rates are limited, and many patients do not achieve durable responses. Thus, it is important to seek additional strategies that can improve anticancer immunity. Here, we report that the bromodomain and extraterminal domain (BET) inhibitor JQ1 inhibits PD-1 expression in Jurkat T cells, primary T cells, and T-cell exhaustion models. Furthermore, JQ1 dramatically impaired the expression of PD-1 and T-cell immunoglobulin mucin-domain-containing-3 (Tim-3) and promoted the secretion of cytokines in T cells from patients with acute myeloid leukemia (AML). In line with that, BET inhibitor-treated CD19-CAR T and CD123-CAR T cells have enhanced anti-leukemia potency and resistant to exhaustion. Mechanistically, BRD4 binds to the NFAT2 and PDCD1 (encoding PD-1) promoters, and NFAT2 binds to the PDCD1 and HAVCR2 (encoding Tim-3) promoters. JQ1-treated T cells showed downregulated NFAT2, PD-1, and Tim-3 expression. In addition, BET inhibitor suppressed programmed death-ligand 1 (PD-L1) expression and cell growth in AML cell lines and in primary AML cells. We also demonstrated that JQ1 treatment led to inhibition of leukemia progression, reduced T-cell PD-1/Tim-3 expression, and prolonged survival in MLL-AF9 AML mouse model and Nalm6 (B-cell acute lymphoblastic leukemia cell)-bearing mouse leukemia model. Taken together, BET inhibition improved anti-leukemia immunity by regulating PD-1/PD-L1 expression, and also directly suppressed AML cells, which provides novel insights on the multiple effects of BET inhibition for cancer therapy.


Assuntos
Antígeno B7-H1 , Leucemia Mieloide Aguda , Proteínas do Tecido Nervoso/metabolismo , Receptores de Superfície Celular/metabolismo , Animais , Linhagem Celular Tumoral , Receptor Celular 2 do Vírus da Hepatite A , Leucemia Mieloide Aguda/tratamento farmacológico , Camundongos , Proteínas Nucleares/uso terapêutico , Receptor de Morte Celular Programada 1 , Linfócitos T , Fatores de Transcrição/uso terapêutico
14.
Cell Mol Life Sci ; 79(8): 407, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35804197

RESUMO

Brown and beige adipose tissues dissipate chemical energy in the form of heat to maintain your body temperature in cold conditions. The impaired function of these tissues results in various metabolic diseases in humans and mice. By bioinformatical analyses, we identified a functional thermogenic regulator of adipose tissue, Androgen-dependent tissue factor pathway inhibitor [TFPI]-regulating protein (Adtrp), which was significantly overexpressed in and functionally activated the mature brown/beige adipocytes. Hereby, we knocked out Adtrp in mice which led to multiple abnormalities in thermogenesis, metabolism, and maturation of brown/beige adipocytes causing excess lipid accumulation in brown adipose tissue (BAT) and cold intolerance. The capability of thermogenesis in brown/beige adipose tissues could be recovered in Adtrp KO mice upon direct ß3-adrenergic receptor (ß3-AR) stimulation by CL316,243 treatment. Our mechanistic studies revealed that Adtrp by binding to S100 calcium-binding protein b (S100b) indirectly mediated the secretion of S100b, which in turn promoted the ß3-AR mediated thermogenesis via sympathetic innervation. These results may provide a novel insight into Adtrp in metabolism via regulating the differentiation and thermogenesis of adipose tissues in mice.


Assuntos
Tecido Adiposo Branco , Proteínas de Membrana/metabolismo , Termogênese , Adipócitos Marrons/metabolismo , Tecido Adiposo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Temperatura Baixa , Lipoproteínas , Camundongos , Subunidade beta da Proteína Ligante de Cálcio S100/genética
16.
Biomed Opt Express ; 13(6): 3615-3628, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35781971

RESUMO

Dynamic OCT angiography (OCTA) is an attractive approach for monitoring stimulus-evoked hemodynamics; however, a 4D (3D space and time) dataset requires a long acquisition time and has a large data size, thereby posing a great challenge to data processing. This study proposed a GPU-based real-time data processing pipeline for dynamic inverse SNR-decorrelation OCTA (ID-OCTA), offering a measured line-process rate of 133 kHz for displaying OCT and OCTA cross-sections in real time. Real-time processing enabled automatic optimization of angiogram quality, which improved the vessel SNR, contrast-to-noise ratio, and connectivity by 14.37, 14.08, and 9.76%, respectively. Furthermore, motion-contrast 4D angiographic imaging of stimulus-evoked hemodynamics was achieved within a single trail in the mouse retina. Consequently, a flicker light stimulus evoked an apparent dilation of the retinal arterioles and venules and an elevation of the decorrelation value in the retinal plexuses. Therefore, GPU ID-OCTA enables real-time and high-quality angiographic imaging and is particularly suitable for hemodynamic studies.

17.
Front Microbiol ; 13: 929241, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35783376

RESUMO

Nanopore sequencing has been widely used for the real-time detection and surveillance of pathogens with portable MinION. Nanopore adaptive sequencing can enrich on-target sequences without additional pretreatment. In this study, the performance of adaptive sequencing was evaluated for viral genome enrichment of clinical respiratory samples. Ligation-based nanopore adaptive sequencing (LNAS) and rapid PCR-based nanopore adaptive sequencing (RPNAS) workflows were performed to assess the effects of enrichment on nasopharyngeal swab samples from human adenovirus (HAdV) outbreaks. RPNAS was further applied for the enrichment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from nasopharyngeal swab samples to evaluate sensitivity and timeliness. The RPNAS increased both the relative abundance (7.87-12.86-fold) and data yield (1.27-2.15-fold) of HAdV samples, whereas the LNAS increased only the relative abundance but had no obvious enrichment on the data yield. Compared with standard nanopore sequencing, RPNAS detected the SARS-CoV-2 reads from two low-abundance samples, increased the coverage of SARS-CoV-2 by 36.68-98.92%, and reduced the time to achieve the same coverage. Our study highlights the utility of RPNAS for virus enrichment directly from clinical samples, with more on-target data and a shorter sequencing time to recover viral genomes. These findings promise to improve the sensitivity and timeliness of rapid identification and genomic surveillance of infectious diseases.

18.
Mol Ther Oncolytics ; 26: 15-26, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35784403

RESUMO

Although chimeric antigen receptor T (CAR-T) cells have achieved remarkable successes in hematological malignancies, the efficacies of CAR-T cells against solid tumors remains unsatisfactory. Heterogeneous antigen expression is one of the obstacles on its effective elimination of solid cancer cells. DNAX-activating protein 10 (DAP10) interacts with natural killer group 2D (NKG2D), acting as an adaptor that targets various malignant cells for surveillance. Here, we designed a DAP10 chimeric receptor that utilized native NKG2D on T cells to target NKG2D ligand-expressing cancer cells. We then tandemly incorporated it with anti-glypican 3 (GPC3) single-chain variable fragment (scFv) to construct a dual-antigen-targeting system. T cells expressing DAP10 chimeric receptor (DAP10-T cells) displayed with an enhancement on both cytotoxicity and cytokine secretion against solid cancer cell lines, and its tandem connection with anti-GPC3 scFv (CAR GPC3-DAP10-T cells) exhibited a dual-antigen-targeting capacity on eliminating heterogeneous cancer cells in vitro and suppressing the growth of heterogeneous cancer in vivo. Thus, this novel dual-targeting system enabled a high efficacy on killing cancer cells and extended the recognition profile of CAR-T cells toward tumors, which providing a potential strategy on treatment of solid cancer clinically.

19.
Forensic Sci Res ; 7(2): 228-237, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35784418

RESUMO

In this report, we applied the TissueFAXS 200 digital pathological analysis system to rapidly and accurately identify neutrophils during regeneration of contused skeletal muscle, and to provide information for follow-up studies on neutrophils to estimate wound age. Rat injury model was established, and skeletal muscle samples were obtained from the control group and contusion groups at 1, 1.5, 2, 3, 4, and 6 h, as well as at 1, 3, 5, and 15 d post-injury (n = 5 per group). The expression of nuclei and neutrophils was detected by hematoxylin and eosin (HE) staining and immunohistochemical (IHC) staining. A total of 20 injury site areas of 0.25 mm2 (0.5 mm × 0.5 mm) were then randomly selected at all time points. A TissueFAXS 200 digital pathological analysis system was used to identify the positive and negative numbers. Knowledge of five professional medical workers were considered the gold standard to measure the false positive rate (FPR), false negative rate (FNR), sensitivity, specificity, and area under the curve (AUC) of receiver operating characteristic (ROC) curves. As a result, with a staining area of neutrophils from 8 µm2 to 15 µm2, the FPR was 4.28%-12.14%, the FNR was 12.42%-64.08%, the sensitivity was 35.92%-87.58%, the specificity was 87.86%-95.72%, the Youden index was 0.316-0.754, the accuracy was 82.80%-88.30%, and the AUC was 0.771-0.826. The AUC was largest when the cut-off value of the staining area was 12 µm2. Our results show that this software-based method is more accurate than the human eye in evaluating neutrophil infiltration. Based on the sensitivity and specificity, neutrophils can be accurately identified during regeneration of contused skeletal muscle. The TissueFAXS 200 digital pathological analysis system can also be used to optimize conditions for different cell types under various injury conditions to determine the optimal cut-off value of the staining area and provide optimal conditions for further study. Furthermore, it will provide evidence for forensic pathology cases.

20.
Neuropsychiatr Dis Treat ; 18: 1363-1374, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35818374

RESUMO

Purpose: This study used the graph-theory approach, degree centrality (DC) to analyze whole-brain functional networks at the voxel level in children with ASD, and investigated whether DC changes were correlated with any clinical variables in ASD children. Methods: The current study included 86 children with ASD and 54 matched healthy subjects Aged 2-5.5 years. Next, chloral hydrate induced sleeping-state functional magnetic resonance imaging (ss-fMRI) datasets were acquired from these ASD and healthy subjects. For a given voxel, the DC was calculated by calculating the number of functional connections with significantly positive correlations at the individual level. Group differences were tested using two-sample t-tests (p < 0.01, AlphaSim corrected). Finally, relationships between abnormal DCs and clinical variables were investigated via Pearson's correlation analysis. Results: Children with ASD exhibited low DC values in the right middle frontal gyrus (MFG) (p < 0.01, AlphaSim corrected). Furthermore, significantly negative correlations were established between the decreased average DC values within the right MFG in ASD children and the total ABC scores, as well as with two ABC subscales measuring highly relevant impairments in ASD (ie, stereotypes and object-use behaviors and difficulties in language). Conclusion: Taken together, the results of our ss-fMRI study suggest that abnormal DC may represent an important contribution to elucidation of the neuropathophysiological mechanisms of preschoolers with ASD.

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