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2.
Light Sci Appl ; 11(1): 7, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34974532

RESUMO

Chaos in nonlinear dynamical systems is featured with irregular appearance and with high sensitivity to initial conditions. Near-infrared light chaos based on semiconductor lasers has been extensively studied and has enabled various applications. Here, we report a fully-developed hyperchaos in the mid-infrared regime, which is produced from interband cascade lasers subject to the external optical feedback. Lyapunov spectrum analysis demonstrates that the chaos exhibits three positive Lyapunov exponents. Particularly, the chaotic signal covers a broad frequency range up to the GHz level, which is two to three orders of magnitude broader than existed mid-infrared chaos solutions. The interband cascade lasers produce either periodic oscillations or low-frequency fluctuations before bifurcating to hyperchaos. This hyperchaos source is valuable for developing long-reach secure optical communication links and remote chaotic Lidar systems, taking advantage of the high-transmission windows of the atmosphere in the mid-infrared regime.

3.
Bioengineered ; 13(1): 1702-1716, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35012442

RESUMO

Long non-coding RNA zinc finger antisense 1 (ZFAS1) has been probed in cerebral ischemia, while the regulatory mechanism of ZFAS1 in focal cerebral ischemia (FCI) via binding to microRNA (miR)-144-5p remains rarely explored. This study aims to decipher the function of ZFAS1 on FCI via sponging miR-144-5p to modulate fibroblast growth factor 7 (FGF7). The focal cerebral ischemia rat model was established by occlusion of the middle cerebral artery (MCAO) Lentivirus vectors altering ZFAS1, miR-144-5p or FGF7 expression were injected into rats before MCAO. Then, ZFAS1, miR-144-5p, and FGF7 levels were detected, the inflammatory factor level, oxidative stress level, angiogenesis, neurological function injury and neuronal apoptosis were assessed. The binding relations among ZFAS1, miR-144-5p and FGF7 were validated. ZFAS1 and FGF7 expression was elevated, while miR-144-5p expression was reduced in FCI rats. Decreased ZFAS1 or FGF7 or enriched miR-144-5p repressed the inflammatory response, oxidative stress, neuronal apoptosis, while it improved angiogenesis, and neurological function recovery; while up-regulated ZFAS1 exerted opposite effects. The augmented miR-144-5p or silenced FGF7 reversed the effects of enriched ZFAS1. ZFAS1 sponged miR-144-5p that targeted FGF7. Inhibition of lncRNA ZFAS1 improves functional recovery and angiogenesis after FCI via miR-144-5p/FGF7 axis. This study provides novel therapeutic targets for FCI treatment.

4.
J Digit Imaging ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35018538

RESUMO

Advanced bronchoscopic lung volume reduction treatment (BLVR) is now a routine care option for treating patients with severe emphysema. Patterns of low attenuation clusters indicating emphysema and functional small airway disease (fSAD) on paired CT, which may provide additional insights to the target selection of the segmental or subsegmental lobe of the treatments, require further investigation. The low attenuation clusters (LACS) were segmented to identify the scalar and spatial distribution of the lung destructions, in terms of 10 fractions scales of low attenuation density (LAD) located in upper lobes and lower lobes. The LACs of functional small airway disease (fSAD) were delineated by applying the technique of parametric response map (PRM) on the co-registered CT image data. Both emphysematous LACs of inspiratory CT and fSAD LACs on expiratory CT were used to derive the coefficients of the predictive model for estimating the airflow limitation. The voxel-wise severity is then predicted using the regional LACs on the co-registered CT to indicate the functional localization, namely, the bullous parametric response map (BPRM). A total of 100 subjects, 88 patients with mild to very severe COPD and 12 control participants with normal lung functions (FEV1/FVC % > 70%), were evaluated. Pearson's correlations between FEV1/FVC% and LAV%HU-950 of severe emphysema are - 0.55 comparing to - 0.67 and - 0.62 of LAV%HU-856 of air-trapping and LAV%fSAD respectively. Pearson's correlation between FEV1/FVC% and FEV1/FVC% predicted by the proposed model using LAD% of HU-950 and fSAD on BPRM is 0.82 (p < 0.01). The result of the Bullous Parametric Response Map (BPRM) is capable of identifying the less functional area of the lung, where the BLVR treatment is aimed at removing from a hyperinflated area of emphysematous regions.

5.
Drug Deliv ; 29(1): 214-228, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34985397

RESUMO

The refractory diabetic wound has remained a worldwide challenge as one of the major health problems. The impaired angiogenesis phase during diabetic wound healing partly contributes to the pathological process. MicroRNA (miRNA) is an essential regulator of gene expression in crucial biological processes and is a promising nucleic acid drug in therapeutic fields of the diabetic wound. However, miRNA therapies have limitations due to lacking an effective delivery system. In the present study, we found a significant reduction of miR-31-5p expression in the full-thickness wounds of diabetic mice compared to normal mice. Further, miR-31-5p has been proven to promote the proliferation, migration, and angiogenesis of endothelial cells. Thus, we conceived the idea of exogenously supplementing miR-31-5p mimics to treat the diabetic wound. We used milk-derived exosomes as a novel system for miR-31-5p delivery and successfully encapsulated miR-31-5p mimics into milk exosomes through electroporation. Then, we proved that the miR-31-5p loaded in exosomes achieved higher cell uptake and was able to resist degradation. Moreover, our miRNA-exosomal formulation demonstrated dramatically improved endothelial cell functions in vitro, together with the promotion of angiogenesis and enhanced diabetic wound healing in vivo. Collectively, our data showed the feasibility of milk exosomes as a scalable, biocompatible, and cost-effective delivery system to enhance the bioavailability and efficacy of miRNAs.

6.
Mater Today Bio ; 13: 100189, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34977528

RESUMO

Immunotherapy has led to an expansion of the treatment of malignancies, but its effect in prostate cancer (PCa) patients is modest. Chemoimmunotherapy is a promising approach that has attracted substantial attention. Although the widely used clinical chemotherapeutic drug doxorubicin (DOX) elicits immunogenic cell death (ICD), its weak ICD effect and the abnormal vasculature of tumors severely limit its efficacy in chemoimmunotherapy. Ingenol-3-angelate (I3A), an emerging antitumor drug with dual chemotherapeutic and immune response-eliciting effects, is expected to exert synergistic effects when administered in combination with DOX. I3A induces the ICD of PCa cells by triggering mitophagy and apoptosis and promotes the normalization of tumor vessels, resulting in sufficient infiltration of immune cells into tumors. A synergistic effect of I3A and DOX was observed in vitro at a molar ratio of 1:4. To codeliver this ratio of I3A and DOX to tumor and ensure their uptake, we designed a dual-targeting delivery system, polylactide-poly(ethylene) glycol-2-(3-((S)-5-amino-1-carboxypentyl)-ureido) pentanedioate/triphenylphosphonium (PLA-PEG-ACUPA/TPP), which targets prostate-specific membrane antigen (PSMA) and mitochondria. Delivery of these nanomedicines led to inhibited tumor growth and a strong antitumor immune response. This study sheds light on the mitophagic and antiangiogenic mechanisms underlying I3A treatment of PCa and provides a strategy for combining vascular normalization and chemoimmunotherapy for PCa treatment.

7.
iScience ; 25(1): 103684, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-34977495

RESUMO

The COVID-19 outbreak poses a serious threat to global public health. Effective countermeasures and approved therapeutics are desperately needed. In this study, we screened a small molecule library containing the NCI-DTP compounds to identify molecules that can prevent SARS-CoV-2 cellular entry. By applying a luciferase assay-based screening using a pseudotyped SARS-CoV-2-mediated cell entry assay, we identified a small molecule compound Q34 that can efficiently block cellular entry of the pseudotyped SARS-CoV-2 into human ACE2-expressing HEK293T cells, and inhibit the infection of the authentic SARS-CoV-2 in human ACE2-expressing HEK293T cells, human iPSC-derived neurons and astrocytes, and human lung Calu-3 cells. Importantly, the safety profile of the compound is favorable. There is no obvious toxicity observed in uninfected cells treated with the compound. Thus, this compound holds great potential as both prophylactics and therapeutics for COVID-19 and future pandemics by blocking the entry of SARS-CoV-2 and related viruses into human cells.

8.
Methods Mol Biol ; 2378: 205-219, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34985702

RESUMO

Evidence from genetic studies in human and mice indicates that defective skeletal development is one of the major phenotypic outcomes for aberrant UPR signaling. Visualization of morphological alterations in whole-mount skeleton and protein secretion and UPR activation on tissue sections is the very first step to investigate skeletal phenotypes of UPR-related mouse models. In this chapter, we introduce the major techniques that have been frequently used in our laboratory to study UPR-induced skeletal disorders with genetically modified mice and provide descriptive directions of mouse genotyping, bone tissue grossing, whole-mount skeletal staining, immunostaining assays of matrix secretion, and UPR activation.

9.
J Hazard Mater ; 425: 128007, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-34986569

RESUMO

Removal of radioactive 133Ba, 60Co and 63Ni and their nonradioactive isotopes through ion exchange method would be highly beneficial for the safe disposal of liquid industrial waste, and it also bears importance for the emergency response to nuclear accident. Herein, we report the employment of an indium sulfide [CH3CH2NH3]6In8S15 (InS-2) with exchangeable ethylammonium cations for efficient and selective uptake of Ba2+, Co2+ and Ni2+. The corner-sharing linkage of P1-{In8S17} clusters in InS-2 endow the layered structure with nanoscale windows, which facilitates both transfer and accommodation of the large hydrated divalent metal ions. This results in ultrafast exchange kinetics (10-20 min) and top-level exchange capacities of 211.73 mg g-1 for Ba2+, 103.57 mg g-1 for Co2+, and 111.78 mg g-1 for Ni2+. Particularly, InS-2 achieves ultrahigh Kd values of 2.3 × 105 mL g-1 for Ba2+, 2.0 × 105 mL g-1 for Co2+ and 1.6 × 105 mL g-1 for Ni2+, corresponding to remarkable removal efficiencies larger than 99.4% (C0 ~ 6 ppm). InS-2 shows high ß and γ irradiation resistance, wide pH durability (pH 3-13 for Ba2+, pH 3-11 for Co2+ and Ni2+), and outstanding selectivity against competitor ions (e.g. Na+, K+, Mg2+, Ca2+). The InS-2-filled ion exchange column exhibits a fantastic removal effect (R > 99%) for mixed Ba2+, Co2+, Ni2+, as well as Sr2+. The ultralong column-treatment on 20000 BVs of flow reveals an affinity order of Co2+ > Ni2+ > Ba2+ > Sr2+ for InS-2, which gives deep insights into the adsorption process and interaction between competitor ions. This excellent uptake of Ba2+ (Ra by analogy), Co2+ and Ni2+ ions by InS-2 highlights the great potential of metal chalcogenides as a type of promising materials for minimizing contamination in complex wastewater.

10.
Small ; : e2105890, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35072345

RESUMO

This work reports a molecular-scale capacitance effect of the double helical nucleic acid duplex structure for the first time. By quantitatively conducting large sample measurements of the electrostatic field effect using a type of high-accuracy graphene transistor biosensor, an unusual charge-transport behavior is observed in which the end-immobilized nucleic acid duplexes can store a part of ionization electrons like molecular capacitors, other than electric conductors. To elucidate this discovery, a cascaded capacitive network model is proposed as a novel equivalent circuit of nucleic acid duplexes, expanding the point-charge approximation model, by which the partial charge-transport observation is reasonably attributed to an electron-redistribution behavior within the capacitive network. Furthermore, it is experimentally confirmed that base-pair mismatches hinder the charge transport in double helical duplexes, and lead to directly identifiable alterations in electrostatic field effects. The bioelectronic principle of mismatch impact is also self-consistently explained by the newly proposed capacitive network model. The mesoscopic nucleic acid capacitance effect may enable a new kind of label-free nucleic acid analysis tool based on electronic transistor devices. The in situ and real-time nucleic acid detections for virus biomarkers, somatic mutations, and genome editing off-target may thus be predictable.

11.
Photodiagnosis Photodyn Ther ; 37: 102711, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34986426

RESUMO

PURPOSE: Dental caries detection, especially the accurate detection of early caries, facilitates prompt interventions. It is reasonably common to use fluorescence imaging for classification and evaluation of caries, but lacks a quantitative, precise and easy-to-use characterization for practical applications. In this study a quantitative approach for caries stage detection by correlating caries spectral and chromatic features was examined. METHODS: A 405 nm LED light source was used as the excitation source. A hyperspectral imaging camera is employed to collect 336 spectral data of different caries stages. Four critical intervals for different stages of caries were extracted by fluorescence spectral features. The mapping relationship between caries spectral and chromatic features was established by Fast Formula Fitting (FFF) and Neural Network Fitting (NNF) methods. RESULTS: The 470-780 nm spectral power distribution was proved to be the best matching color waveband guiding the selection of filters in future instrument development. The correlation coefficients for the two fitting methods were 0.990 and 0.999, respectively. Both methods achieved caries stage prediction at the pixel level with high accuracy using color information. The visualization region in the chromaticity diagram was created. CONCLUSIONS: This quantitative method enables accurate prediction of caries on the entire tooth surface and facilitates the development of portable and low-cost caries detection instruments.

12.
J Agric Food Chem ; 70(2): 634-645, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-34985260

RESUMO

A high glucosinolate (GSL) concentration, an undesirable substance, has severely restricted rapeseed (Brassica species) development. We performed widely targeted metabolomics analysis based on the ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) technology to analyze the metabolic profiles and identify the differential metabolites and GSL components in response to different nitrogen (N) levels in two rapeseed varieties. A total of 341 metabolites and 38 GSL components were detected in the seeds. A total of 188 differential metabolites, including 34 GSL components, were identified in response to different treatments, which were mapped into 2-oxocarboxylic acid metabolism, tryptophan metabolism, and GSL biosynthesis. Key indicators of GSL components highly responsible for different N levels under two contrasting varieties were recognized, i.e., 1-methylpropyl GSL and 4-methylthiobutyl GSL. This study suggests that the efficient N management and variety selection are important strategies for developing rapeseed with low GSLs.


Assuntos
Brassica napus , Brassica rapa , Glucosinolatos , Nitrogênio , Espectrometria de Massas em Tandem
13.
EMBO Mol Med ; : e15227, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34994081

RESUMO

The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor-binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1ß and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.

14.
Am J Hum Genet ; 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35065708

RESUMO

Mucus obstruction is a central feature in the cystic fibrosis (CF) airways. A genome-wide association study (GWAS) of lung disease by the CF Gene Modifier Consortium (CFGMC) identified a significant locus containing two mucin genes, MUC20 and MUC4. Expression quantitative trait locus (eQTL) analysis using human nasal epithelia (HNE) from 94 CF-affected Canadians in the CFGMC demonstrated MUC4 eQTLs that mirrored the lung association pattern in the region, suggesting that MUC4 expression may mediate CF lung disease. Complications arose, however, with colocalization testing using existing methods: the locus is complex and the associated SNPs span a 0.2 Mb region with high linkage disequilibrium (LD) and evidence of allelic heterogeneity. We previously developed the Simple Sum (SS), a powerful colocalization test in regions with allelic heterogeneity, but SS assumed eQTLs to be present to achieve type I error control. Here we propose a two-stage SS (SS2) colocalization test that avoids a priori eQTL assumptions, accounts for multiple hypothesis testing and the composite null hypothesis, and enables meta-analysis. We compare SS2 to published approaches through simulation and demonstrate type I error control for all settings with the greatest power in the presence of high LD and allelic heterogeneity. Applying SS2 to the MUC20/MUC4 CF lung disease locus with eQTLs from CF HNE revealed significant colocalization with MUC4 (p = 1.31 × 10-5) rather than with MUC20. The SS2 is a powerful method to inform the responsible gene(s) at a locus and guide future functional studies. SS2 has been implemented in the application LocusFocus.

15.
Cell Cycle ; : 1-17, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34974804

RESUMO

Intervertebral disc degeneration (IDD) constitutes the pathological foundation of most musculoskeletal disorders of the spine. Previous studies have noted that cell proliferation is a common feature of IDD. Bioinformatics indicated that aberrantly expressed long non-coding RNAs (lncRNAs) were involved in the development of IDD. In this study, we aimed to investigate the function of lncRNA HOTAIR in the proliferation of human nucleus pulposus (NP) cells of IDD in vitro and further clarified its mechanism. The expression of HOTAIR and miR-130b was quantified by qRT-PCR in nucleus pulposus (NP) tissues. Furthermore, NP cells proliferation were assayed by CCK8 and Immunostaining. Dual-luciferase reporter and RIP assay were used to examine the expression of HOTAIR, PTEN, and their co-target gene miR-130b. Western blotting was used to test AKT expression. Our in vitro experiments on human normal NP cells observed that HOTAIR was significantly dysregulated in IDD. Further, HOTAIR can suppress proliferation by directly targeting miR-130b. In addition, Both HOTAIR and PTEN were confirmed to target miR-130b, and miR-130b upregulation reversed the phenomenon of ectopic expression of HOTAIR. More importantly, HOTAIR upregulation significantly reduced CyclinD1 protein expression by PTEN/AKT signaling pathway. Our findings suggest that HOTAIR may bind to miR-130b and subsequently increased CyclinD1 expression via PTEN/Akt pathway. Thereby, HOTAIR could become a potential target for the treatment of IDD.

16.
Mol Neurobiol ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34982407

RESUMO

piRNAs (PIWI-interacting RNAs) are a class of small non-coding RNAs (ncRNAs) abundantly expressed in germline cells and involved in suppressing the transposon activity. Interestingly, recent studies have found piRNA expression in the central nervous system (CNS), yet the underlying biological significance remains largely unknown. In this study, we investigated the expression and function of piRNAs during the retinoic acid (RA)-mediated neuronal differentiation in NT2 cells, a human embryonal carcinoma cell line. We identified a cohort of differentially expressed piRNAs by microarray. Two piRNAs, DQ582359 and DQ596268, were increasingly upregulated during the RA-induced differentiation and involved in regulating the expression of neuronal markers, MAP2 and TUBB3. Furthermore, these piRNAs were found to associate with cold-shock domain (CSD)-containing RNA binding proteins, DIS3, DIS3L2, and YB-1. Markedly, overexpression of these piRNAs further enhanced the protein levels of MAP2 and TUBB3, potentially by downregulating DIS3, DIS3L2, and YB-1. Hence, our study has identified a novel somatic function of piRNAs in regulating neuronal gene expression. The interaction of piRNA with some CSD-containing proteins can be further explored to enhance neuronal differentiation to treat neurodegenerative diseases.

17.
J Mol Med (Berl) ; 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34997250

RESUMO

Diabetes is primarily characterized by hyperglycemia, and its high incidence is often very costly to patients, their families, and national economies. Unsurprisingly, the number and function of endothelial progenitor cells (EPCs) decrease in patients resulting in diabetic wound non-healing. As precursors of endothelial cells (ECs), these cells were discovered in 1997 and found to play an essential role in wound healing. Their function, number, and role in wound healing has been widely investigated. Hitherto, a lot of complex molecular mechanisms have been discovered. In this review, we summarize the mechanisms of how hyperglycemia affects the function and number of EPCs and how the affected cells impact wound healing. We aim to provide a complete summary of the relationship between diabetic hyperglycosemia, EPCs, and wound healing, as well as a better comprehensive platform for subsequent related research.

18.
J Am Coll Cardiol ; 79(1): e9, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34991795
19.
Int J Biol Macromol ; 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35051504

RESUMO

Mas related G-protein-coupled receptor member X2 (MrgX2) has been identified as the crucial receptor in drug induced pseudo-allergic reactions and allergic diseases. In this research, the first type of fluorescent agonists (ZX1, ZX2 and ZX3) for MrgX2 were developed by conjugating environment-sensitive fluorophore coumarin to MrgX2 selective agonists (R)-ZINC-3573. Their environment-sensitive property was confirmed by the dramatically increase of fluorescent intensity after binding to the hydrophobic ligand binding domain MrgX2, which help to overcome the high background signal. Based on these characteristics, they can be used for selective visualization of MrgX2 in living cells even with their own background interference. Among these fluorescent agonists, compound ZX2 possessed splendid spectroscopic properties, outstanding pharmacological activities (EC50 = 0.93 µM, KD = 1.97 µM). And a competitive binding assay was established with ZX2 to analysis the binding affinity of MrgX2 agonists, which shown high coherence with the results of cell membrane chromatography. To our knowledge, these probes are the first fluorescent ligands of MrgX2 with agonistic activity and environment-sensitive property, which is expected to use for the development of MrgX2 molecular pharmacology and serve as a convenient high-throughput screening tool for the drug candidates targeting MrgX2.

20.
J Pers Med ; 12(1)2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-35055378

RESUMO

BACKGROUND: To evaluate the effectiveness and safety of radiofrequency ablation (RFA) treatment for benign thyroid nodules (BTNs) in five medical centers in Taiwan. METHODS: From April 2016 to July 2020, 762 patients underwent ultrasound guided RFA treatment of 826 benign thyroid nodules at five medical centers in Taiwan. The RFA procedure was performed by radiologists, otolaryngologists, or surgeons. Patients were grouped into three subgroups according to the initial volume of BTNs. The volume reduction ratio (VRR) of each nodule, and complications were analyzed at 1, 3, and 6 months after RFA treatment and the three groups compared. RESULTS: The large nodular group showed greater VRR compared to the other two groups at first 1-month follow-up. At 6-months follow-up, there was no significant difference of VRR among the three groups. Goiters with difference in size can attain a successful VRR (>50%) although different specialists demonstrated variable VRR after 6-months follow-up. A total of 40 (4.8%) complications were reported. All patients recovered spontaneously without surgery intervention. CONCLUSIONS: The reliability and safety of RFA for benign thyroid nodules had been established. RFA has gradually become an alternative to surgery in the treatment of benign thyroid nodules in Taiwan.

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