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1.
Adv Healthc Mater ; : e2400930, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847291

ABSTRACT

Electrohydrodynamic (EHD) direct-writing has recently gained attention as a highly promising additive manufacturing strategy for fabricating intricate micro/nanoscale architectures. This technique is particularly well-suited for mimicking the extracellular matrix (ECM) present in biological tissue, which serves a vital function in facilitating cell colonization, migration, and growth. The integration of EHD direct-writing with other techniques has been employed to enhance the biological performance of scaffolds, and significant advancements have been made in the development of tailored scaffold architectures and constituents to meet the specific requirements of various biomedical applications. Here, a comprehensive overview of EHD direct-writing is provided, including its underlying principles, demonstrated materials systems, and biomedical applications. A brief chronology of EHD direct-writing is provided, along with an examination of the observed phenomena that occur during the printing process. The impact of biomaterial selection and architectural topographic cues on biological performance is also highlighted. Finally, the major limitations associated with EHD direct-writing are discussed.

2.
Heliyon ; 10(7): e29111, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38601604

ABSTRACT

Excessive smartphone use has become a growing issue among adolescents as they develop mentally and socially. While researchers have examined individual and technological predictors of smartphone addiction, few studies consider broader societal influences. This study explored how social pressures such as mimicry, coercion, and norms impact persistent conscious smartphone use (use stickiness) and unconscious smartphone use (use habit). A survey was administered in two phases to 309 college students at a university in Southern China to gather data on perceptions of social influences and their degree of smartphone overuse. The relationships were analysed using a structural equation model. The study confirms the impact of three social pressures - mimetic, coercive and normative - on adolescents' degree of smartphone overuse (use stickiness and use habit). The mimetic pressure positively impacted use stickiness but not use habit. The coercive pressure positively impacted both the use stickiness and the use habit. The normative pressure positively impacted use habit but not use stickiness. This study provides a novel perspective on overlooked social drivers of problematic smartphone tendencies among youth. Our study also provides insights for educators, parents, and policymakers to more effectively intervene in adolescent smartphone overuse.

3.
Nat Nanotechnol ; 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38491184

ABSTRACT

Multivalent presentation of ligands often enhances receptor activation and downstream signalling. DNA origami offers a precise nanoscale spacing of ligands, a potentially useful feature for therapeutic nanoparticles. Here we use a square-block DNA origami platform to explore the importance of the spacing of CpG oligonucleotides. CpG engages Toll-like receptors and therefore acts to activate dendritic cells. Through in vitro cell culture studies and in vivo tumour treatment models, we demonstrate that square blocks induce Th1 immune polarization when CpG is spaced at 3.5 nm. We observe that this DNA origami vaccine enhances DC activation, antigen cross-presentation, CD8 T-cell activation, Th1-polarized CD4 activation and natural-killer-cell activation. The vaccine also effectively synergizes with anti-PD-L1 for improved cancer immunotherapy in melanoma and lymphoma models and induces long-term T-cell memory. Our results suggest that DNA origami may serve as a platform for controlling adjuvant spacing and co-delivering antigens in vaccines.

4.
PLoS One ; 19(2): e0296849, 2024.
Article in English | MEDLINE | ID: mdl-38306318

ABSTRACT

This meta-analysis aims to systematically compare the efficacy between phacoemulsification (PE) combined with goniosynechialysis (GSL) and PE alone for primary angle-closure disease (PACD) patients. All the data were searched from the PubMed, EMBASE and the Cochrane Library. The Cochrane Handbook was used to evaluate the quality of the included studies. Additionally, this meta-analysis was performed by using the Revman 5.4 software. Nine randomized controlled trials (RCTs) were included in this study. Compared with PE alone group, PE+GSL could result significant reduction in the IOP (MD, 1.81; p = 0.002). In the instrumental subgroup, also more reduction of IOP was shown in the PE+GSL group (MD, 2.11; p = 0.02). In the viscogonioplasty (VGP) subgroup, there was not no statistical difference between PE alone group and PE+GSL group (MD, 1.53; p = 0.11). Also, more reduction of peripheral anterior synechiae (PAS) was shown in the PE+GSL group (MD,59.15; p<0.00001). For the change in angle open distance (AOD)500, AOD 750, trabecular-iris space (TISA)500, number of glaucoma medications and best corrected visual acuity (BCVA), there was no difference between two groups (p = 0.25, 0.35, 0.17, 0.56, 0.08). For TISA 750, more improvement was shown in the PE+GSL group (p<0.00001). Instrumental separation had better effect on lowering IOP when it combined with PE. Both instrumental separation and VGP could reduce postoperative PAS. The operation of GSL has no obvious effect on postoperative vision.


Subject(s)
Glaucoma, Angle-Closure , Iris Diseases , Phacoemulsification , Humans , Trabecular Meshwork/pathology , Intraocular Pressure , Glaucoma, Angle-Closure/complications , Glaucoma, Angle-Closure/surgery , Glaucoma, Angle-Closure/pathology , Gonioscopy , Tissue Adhesions/pathology , Randomized Controlled Trials as Topic
5.
Semin Ophthalmol ; 39(1): 60-65, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37400160

ABSTRACT

PURPOSES: The purpose of this meta-analysis is to systematically compare the alignment accuracy and post uncorrected distance visual acuity (UDVA) between image-guided marking and manual marking for toric intraocular lens (IOL) in cataract surgery. METHODS: This work was done through the data searched from the PubMed, EMBASE and the Cochrane Library. The Cochrane Handbook was also used to evaluate the quality of the included studies. In addition, this meta-analysis was performed using Revman 5.4 software. RESULTS: A total of 6 randomized controlled trials (RCTs) were included. Compared with manual marking group, image-guided marking group had less toric IOL axis misalignment (MD, -1.98; 95%CI, -3.27 to -0.68; p = .003), less postoperative astigmatism (MD, -0.13; 95%CI, -0.21 to -0.05; p = .001), better postoperative UDVA (MD, -0.02; 95%CI, -0.04 to -0.01; p = .0003) and smaller difference vector (MD, -0.10; 95%CI, -0.14 to -0.06; p(0.00001). For the proportion of patients with residual refractive cylinder within 0.5 D, there was no difference between two groups (p = .07). CONCLUSION: Image-guided marking is prior to manual marking. As it can bring less toric IOL axis misalignment, less postoperative astigmatism, better postoperative UDVA and smaller difference vector for the patients with toric IOL implantation.


Subject(s)
Astigmatism , Cataract , Lenses, Intraocular , Phacoemulsification , Humans , Lens Implantation, Intraocular , Astigmatism/surgery , Randomized Controlled Trials as Topic , Refraction, Ocular , Cataract/complications
6.
Adv Sci (Weinh) ; 11(7): e2304332, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38032118

ABSTRACT

Microfluidic 3D cell culture devices that enable the recapitulation of key aspects of organ structures and functions in vivo represent a promising preclinical platform to improve translational success during drug discovery. Essential to these engineered devices is the spatial patterning of cells from different tissue types within a confined microenvironment. Traditional fabrication strategies lack the scalability, cost-effectiveness, and rapid prototyping capabilities required for industrial applications, especially for processes involving thermoplastic materials. Here, an approach to pattern fluid guides inside microchannels is introduced by establishing differential hydrophilicity using pressure-sensitive adhesives as masks and a subsequent selective coating with a biocompatible polymer. Optimal coating conditions are identified using polyvinylpyrrolidone, which resulted in rapid and consistent hydrogel flow in both the open-chip prototype and the fully bonded device containing additional features for medium perfusion. The suitability of the device for dynamic 3D cell culture is tested by growing human hepatocytes in the device under controlled fluid flow for a 14-day period. Additionally, the study demonstrated the potential of using the device for pharmaceutical high-throughput screening applications, such as predicting drug-induced liver injury. The approach offers a facile strategy of rapid prototyping thermoplastic microfluidic organ chips with varying geometries, microstructures, and substrate materials.


Subject(s)
Hepatocytes , Microfluidics , Humans , Microfluidics/methods , Cell Culture Techniques, Three Dimensional , Hydrogels
7.
Polymers (Basel) ; 15(24)2023 Dec 05.
Article in English | MEDLINE | ID: mdl-38139871

ABSTRACT

This article introduces a one-step extrusion-based fused deposition modeling (FDM) approach for the challenging separation of polypropylene (PP) and polyethylene terephthalate (PET) during recycling. A shear screw printer (SSP) with shear elements was designed, and it was compared to a conventional single-screw printer (CSP) to investigate the differences in print stability, degradation levels, tensile performance, molecular orientation, and crystallization when preparing recycled PP and recycled PET blends. Although the retention effect of the SSP screw slightly increases the degradation of the blended rPP/rPET, the strong shear (2.6 × 104 s-1) applied near the extrusion exit improves the blending efficiency. The SSP also enhances molecular orientation, modulus of the parts, and reduces performance fluctuations. Additionally, the SSP has the potential to simplify the recycling process, enabling the transformation of blended recycled materials into products with just one melt process.

8.
Heliyon ; 9(10): e20855, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37867850

ABSTRACT

Background: This retrospective study investigated the safety and efficiency of lens cortex removal assisted by a fluid-based capsular polishing technique called a fluid jet. Methods: This was a retrospective case study. A total of 300 patients were included in this study. All patients underwent phacoemulsification using two different surgical sequences: a fluid jet before irrigation/aspiration (I/A) and an I/A before the fluid jet. They were divided into two groups: the fluid jet before I/A group (group 1, 150 eyes) and the I/A before the fluid jet group (group 2, 150 eyes). The frequencies of posterior capsule rupture (PCR) and posterior capsule being sucked into the I/A tip were recorded. The times of the fluid jet, I/A cortex, and entire procedure were noted. Results: PCR occurred only in group 2. Compared with group 1, the posterior capsule being sucked into the I/A tip was more frequent in group 2 (P = 0.003). The fluid jet time was longer in group 1 than that in group 2 (P < 0.001). The I/A cortex time was shorter in group 1, and total time for fluid jet and I/A cortex together was shorter in group 2 (P = 0.014 and P = 0.007, respectively). However, the time of the entire procedure was shorter in group 1 (P < 0.001). Conclusions: Fluid jet-assisted lens cortex removal is safe, time-saving, and simple to perform.

9.
Materials (Basel) ; 16(11)2023 May 27.
Article in English | MEDLINE | ID: mdl-37297146

ABSTRACT

Shear and thermal processing can greatly influence nanoparticles' orientation and dispersion, affecting the nanocomposites' conductivity and mechanical properties. The synergistic effects of shear flow and Carbon nanotubes (CNTs) nucleating ability on the crystallization mechanisms have been proven. In this study, Polylactic acid/Carbon nanotubes (PLA/CNTs) nanocomposites were produced by three different molding methods: compression molding (CM), conventional injection molding (IM), and interval injection molding (IntM). Solid annealing at 80 °C for 4 h and pre-melt annealing at 120 °C for 3 h was applied to research the CNTs' nucleation effect and the crystallized volume exclusion effect on the electrical conductivity and mechanical properties. The volume exclusion effect only significantly impacts the oriented CNTs, causing the conductivity along the transverse direction to rise by about seven orders of magnitude. In addition, the tensile modulus of the nanocomposites decreases with the increased crystallinity, while the tensile strength and modulus decrease.

10.
Polymers (Basel) ; 15(10)2023 May 19.
Article in English | MEDLINE | ID: mdl-37242948

ABSTRACT

The orientation and dispersion of nanoparticles can greatly influence the conductivity and mechanical properties of nanocomposites. In this study, the Polypropylene/ Carbon Nanotubes (PP/CNTs) nanocomposites were produced using three different molding methods, i.e., compression molding (CM), conventional injection molding (IM), and interval injection molding (IntM). Various CNTs content and shear conditions give CNTs different dispersion and orientation states. Then, three electrical percolation thresholds (4 wt.% CM, 6 wt.% IM, and 9 wt.% IntM) were obtained by various CNTs dispersion and orientations. Agglomerate dispersion (Adis), agglomerate orientation (Aori), and molecular orientation (Mori) are used to quantify the CNTs dispersion and orientation degree. IntM uses high shear to break the agglomerates and promote the Aori, Mori, and Adis. Large Aori and Mori can create a path along the flow direction, which lead to an electrical anisotropy of nearly six orders of magnitude in the flow and transverse direction. On the other hand, when CM and IM samples already build the conductive network, IntM can triple the Adis and destroy the network. Moreover, mechanical properties are also been discussed, such as the increase in tensile strength with Aori and Mori but showing independence with Adis. This paper proves that the high dispersion of CNTs agglomerate goes against forming a conductivity network. At the same time, the increased orientation of CNTs causes the electric current to flow only in the orientation direction. It helps to prepare PP/CNTs nanocomposites on demand by understanding the influence of CNTs dispersion and orientation on mechanical and electrical properties.

11.
FASEB J ; 37(4): e22873, 2023 04.
Article in English | MEDLINE | ID: mdl-36929360

ABSTRACT

Trabecular meshwork (TM) cell dysfunction is the leading cause of elevated intraocular pressure (IOP) and glaucoma. The long non-coding RNA (lncRNA) small nucleolar RNA host gene 11 (SNHG11) is associated with cell proliferation and apoptosis, but its biological functions and role in glaucoma pathogenesis remain unclear. In the present study, we investigated the role of SNHG11 in TM cells using immortalized human TM and glaucomatous human TM (GTM3 ) cells and an acute ocular hypertension mouse model. SNHG11 expression was depleted using siRNA targeting SNHG11. Transwell assays, quantitative real-time PCR analysis (qRT-PCR), western blotting, and CCK-8 assay were used to evaluate cell migration, apoptosis, autophagy, and proliferation. Wnt/ß-catenin pathway activity was inferred from qRT-PCR, western blotting, immunofluorescence, and luciferase reporter and TOPFlash reporter assays. The expression of Rho kinases (ROCKs) was detected using qRT-PCR and western blotting. SNHG11 was downregulated in GTM3 cells and mice with acute ocular hypertension. In TM cells, SNHG11 knockdown inhibited cell proliferation and migration, activated autophagy, and apoptosis, repressing the Wnt/ß-catenin signaling pathway, and activated Rho/ROCK. Wnt/ß-catenin signaling pathway activity increased in TM cells treated with ROCK inhibitor. SNHG11 regulated Wnt/ß-catenin signaling through Rho/ROCK by increasing GSK-3ß expression and ß-catenin phosphorylation at Ser33/37/Thr41 while decreasing ß-catenin phosphorylation at Ser675. We demonstrate that the lncRNA SNHG11 regulates Wnt/ß-catenin signaling through Rho/ROCK via ß-catenin phosphorylation at Ser675 or GSK-3ß-mediated phosphorylation at Ser33/37/Thr41, affecting cell proliferation, migration, apoptosis, and autophagy. Through its effects on Wnt/ß-catenin signaling, SNHG11 is implicated in glaucoma pathogenesis and is a potential therapeutic target.


Subject(s)
Glaucoma , Ocular Hypertension , RNA, Long Noncoding , Humans , Animals , Mice , Wnt Signaling Pathway/physiology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , beta Catenin/genetics , beta Catenin/metabolism , Trabecular Meshwork/metabolism , Glycogen Synthase Kinase 3 beta/genetics , Glycogen Synthase Kinase 3 beta/metabolism , Cell Proliferation/genetics , Glaucoma/genetics , Glaucoma/metabolism , Ocular Hypertension/metabolism , Cell Line, Tumor
12.
Heliyon ; 9(1): e12959, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36820174

ABSTRACT

People's dependence on technology in the digital environment has increasingly become the focus of academic and social attention. Social media, in particular, with the functions of connecting with others and maintaining interactions, has become an inseparable part of people's lives. Although the formation of problematic use of social media has been extensively discussed by scholars, it is mainly confined to the individual level and lacks a macro perspective from the external environment. This study draws on the perspective of institutional theory and introduces copresence as a mediating role, aiming to investigate the influence mechanism of social environmental forces on individuals' problematic use of social media. An online survey (N = 462) was conducted to collect data and test the research model. Our data were analyzed using the structural equation modeling (SEM) approach. Results show that social environmental forces exert an impact on problematic use of social media through the sense of copresence, and only mimetic force can directly affect behavior outcomes while the other two forces can not. Besides, social environmental forces have a relationship with people's sense of copresence while using social media. Among them, mimetic force and normative force positively correlate with copresence while coercive force is negatively related to copresence. Furthermore, copresence is found to influence problematic use of social media positively. Practical and theoretical implications are discussed.

13.
Semin Ophthalmol ; 38(5): 457-464, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36384397

ABSTRACT

PURPOSES: The purpose of this meta-analysis is to systematically compare the efficacy and safety between combined surgery (phacoemulsification combined with trabeculectomy) and phacoemulsification for primary angle­closure glaucoma (PACG) patients. METHODS: This work was done through the data searched from the PubMed, EMBASE and the Cochrane Library. The Cochrane Handbook was also used to evaluate the quality of the included studies. In addition, this meta-analysis was performed using Revman 5.4 software. RESULTS: A total of seven randomized controlled trials (RCTs) were included. Compared with phacoemulsification alone, combined surgery resulted in significant reduction in the IOP (MD = -1.45, 95%CI, -2.38 to -0.51, p = .002). And more reduction in number of glaucoma medications was shown in the combined surgery group (MD, -0.59; 95%CI, -1.01 to -0.17; p = .006). For the improvement of the best corrected visual acuity (BCVA), there was no statistical differences between two groups (MD, 0.05; 95%CI, -0.01 to 0.11; p = .08). In subgroup analysis, the BCVA improved more significantly for medically controlled PACG patients in the phacoemulsification alone group (MD, 0.09; 95%CI, 0.01 to 0.07; p = .02). Compared with the phacoemulsification alone group, more complications were shown in the combined surgery group (RR, 0.22; 95%CI, 0.09 to 0.56; p = .001). CONCLUSION: For lowering IOP, combined surgery was superior to phacoemulsification alone for PACG patients. Meanwhile, combined surgery generated more complications. For medically controlled PACG patients, phacoemulsification alone is more conducive to the improvement of BCVA.


Subject(s)
Cataract Extraction , Cataract , Glaucoma, Angle-Closure , Glaucoma , Phacoemulsification , Trabeculectomy , Humans , Phacoemulsification/methods , Glaucoma, Angle-Closure/surgery , Intraocular Pressure , Glaucoma/surgery , Trabeculectomy/methods , Cataract/complications , Treatment Outcome
14.
Semin Ophthalmol ; 38(3): 283-293, 2023 Apr.
Article in English | MEDLINE | ID: mdl-35912896

ABSTRACT

PURPOSES: The purpose of this meta-analysis is to systematically compare the safety, efficacy, and predictability of small incision lenticule extraction (SMILE) and laser in situ keratomileusis (LASIK). METHODS: This study covered the data searched from the PubMed, the EMBASE and the Cochrane Library. The Cochrane Handbook was also referred to as evaluating the quality of the included studies. In addition, this meta-analysis was performed using Revman 5.4 software. RESULTS: A total of 11 randomized controlled trails (RCTs) were included. The proportion of eyes with refraction within ±0.5D was higher in LASIK group compared with SMILE group (RR, 0.91; 95% CI, 0.83 to 0.99; p = .04). The spherical aberration (SA) was smaller in SMILE group compared with LASIK group (RR, -0.12; 95% CI, -0.23 to -0.01; p = .04). There were no significant differences between two groups with regard to final mean refractive spherical equivalent (SE) (MD, -0.04; 95% CI, -0.12 to 0.03; p = .22), proportion of eyes losing one or more lines of corrected distance visual acuity (CDVA) (RR, 1.14; 95% CI, 0.58 to 2.27; p = .70), proportion of eyes with uncorrected distance visual acuity (UCVA) of 20/20 or better (RR, 0.99; 95% CI, 0.94 to 1.05; p = .71), postoperative mean logMAR UCVA (MD, 0.01; 95% CI, -0.00 to 0.03; p = .13), postoperative refraction within ±1.0D (RR, 1.00; 95% CI, 0.98 to 1.02; p = .60), postoperative astigmatism within ±0.25, 0.5 and 1.0D (RR, 0.80, 0.99, 1.00; 95% CI, 0.35 to 1.83, 0.94 to 1.05, 0.98 to 1.02; p = .60, 0.86, 0.87), postoperative higher order aberrations (HOAs) (RR, 0.00; 95% CI, -0.16 to 0.16; p = .99). CONCLUSION: For predictability, LASIK was superior to SMILE. There were comparably safety and efficacy for the correction of myopia and myopic astigmatism in SMILE and LASIK. SA was smaller after SMILE than after LASIK.


Subject(s)
Astigmatism , Keratomileusis, Laser In Situ , Myopia , Humans , Astigmatism/surgery , Randomized Controlled Trials as Topic , Refraction, Ocular , Corneal Stroma/surgery , Myopia/surgery , Lasers, Excimer/therapeutic use , Treatment Outcome
16.
Adv Drug Deliv Rev ; 191: 114542, 2022 12.
Article in English | MEDLINE | ID: mdl-36179916

ABSTRACT

The surfaces of human internal organs are lined by a mucus layer that ensures symbiotic relationships with commensal microbiome while protecting against potentially injurious environmental chemicals, toxins, and pathogens, and disruption of this layer can contribute to disease development. Studying mucus biology has been challenging due to the lack of physiologically relevant human in vitro models. Here we review recent progress that has been made in the development of human organ-on-a-chip microfluidic culture models that reconstitute epithelial tissue barriers and physiologically relevant mucus layers with a focus on lung, colon, small intestine, cervix and vagina. These organ-on-a-chip models that incorporate dynamic fluid flow, air-liquid interfaces, and physiologically relevant mechanical cues can be used to study mucus composition, mechanics, and structure, as well as investigate its contributions to human health and disease with a level of biomimicry not possible in the past.


Subject(s)
Models, Biological , Mucus , Humans , Colon , Lab-On-A-Chip Devices , Microbiota , Microfluidics , Mucus/physiology
17.
Int J Mol Sci ; 23(17)2022 Sep 03.
Article in English | MEDLINE | ID: mdl-36077471

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), has provoked more than six million deaths worldwide and continues to pose a major threat to global health. Enormous efforts have been made by researchers around the world to elucidate COVID-19 pathophysiology, design efficacious therapy and develop new vaccines to control the pandemic. To this end, experimental models are essential. While animal models and conventional cell cultures have been widely utilized during these research endeavors, they often do not adequately reflect the human responses to SARS-CoV-2 infection. Therefore, models that emulate with high fidelity the SARS-CoV-2 infection in human organs are needed for discovering new antiviral drugs and vaccines against COVID-19. Three-dimensional (3D) cell cultures, such as lung organoids and bioengineered organs-on-chips, are emerging as crucial tools for research on respiratory diseases. The lung airway, small airway and alveolus organ chips have been successfully used for studies on lung response to infection by various pathogens, including corona and influenza A viruses. In this review, we provide an overview of these new tools and their use in studies on COVID-19 pathogenesis and drug testing. We also discuss the limitations of the existing models and indicate some improvements for their use in research against COVID-19 as well as future emerging epidemics.


Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Animals , COVID-19 Vaccines , Humans , Lung , Pandemics/prevention & control
18.
Mol Ther Nucleic Acids ; 29: 923-940, 2022 Sep 13.
Article in English | MEDLINE | ID: mdl-36032397

ABSTRACT

The current coronavirus disease 2019 (COVID-19) pandemic highlights the need for broad-spectrum antiviral therapeutics. Here we describe a new class of self-assembling immunostimulatory short duplex RNAs that potently induce production of type I and type III interferon (IFN-I and IFN-III). These RNAs require a minimum of 20 base pairs, lack any sequence or structural characteristics of known immunostimulatory RNAs, and instead require a unique sequence motif (sense strand, 5'-C; antisense strand, 3'-GGG) that mediates end-to-end dimer self-assembly. The presence of terminal hydroxyl or monophosphate groups, blunt or overhanging ends, or terminal RNA or DNA bases did not affect their ability to induce IFN. Unlike previously described immunostimulatory small interfering RNAs (siRNAs), their activity is independent of Toll-like receptor (TLR) 7/8, but requires the RIG-I/IRF3 pathway that induces a more restricted antiviral response with a lower proinflammatory signature compared with immunostimulant poly(I:C). Immune stimulation mediated by these duplex RNAs results in broad-spectrum inhibition of infections by many respiratory viruses with pandemic potential, including severe acute respiratory syndrome coronavirus (SARS-CoV)-2, SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus (HCoV)-NL63, and influenza A virus in cell lines, human lung chips that mimic organ-level lung pathophysiology, and a mouse SARS-CoV-2 infection model. These short double-stranded RNAs (dsRNAs) can be manufactured easily, and thus potentially could be harnessed to produce broad-spectrum antiviral therapeutics.

19.
Nat Biotechnol ; 40(9): 1370-1377, 2022 09.
Article in English | MEDLINE | ID: mdl-35788567

ABSTRACT

The usefulness of live attenuated virus vaccines has been limited by suboptimal immunogenicity, safety concerns or cumbersome manufacturing processes and techniques. Here we describe the generation of a live attenuated influenza A virus vaccine using proteolysis-targeting chimeric (PROTAC) technology to degrade viral proteins via the endogenous ubiquitin-proteasome system of host cells. We engineered the genome of influenza A viruses in stable cell lines engineered for virus production to introduce a conditionally removable proteasome-targeting domain, generating fully infective PROTAC viruses that were live attenuated by the host protein degradation machinery upon infection. In mouse and ferret models, PROTAC viruses were highly attenuated and able to elicit robust and broad humoral, mucosal and cellular immunity against homologous and heterologous virus challenges. PROTAC-mediated attenuation of viruses may be broadly applicable for generating live attenuated vaccines.


Subject(s)
Influenza Vaccines , Influenza, Human , Orthomyxoviridae Infections , Animals , Ferrets , Humans , Influenza Vaccines/genetics , Influenza, Human/prevention & control , Mice , Orthomyxoviridae Infections/prevention & control , Proteasome Endopeptidase Complex , Proteolysis , Vaccines, Attenuated/genetics
20.
J Ophthalmol ; 2022: 5231545, 2022.
Article in English | MEDLINE | ID: mdl-35859780

ABSTRACT

Purpose: To determine the structure-function relationship between cluster mean defect (MD) offered by standard automated perimetry and corresponding sector peripapillary retinal nerve fiber layer thickness (pRNFLT) measured with optical coherence tomography (OCT) in primary open angle glaucoma (POAG). Method: 39 healthy eyes (control group), 43 early POAG eyes (global MD ≤ 6 dB, early group), 30 moderate POAG eyes (global MD between 6 and 12 dB, moderate group), and 53 advanced POAG eyes (global MD > 12 dB, advanced group) underwent visual field (VF) examination with Octopus perimeter (dynamic strategy/G2 pattern) and peripapillary retinal nerve fiber layer thickness measurements with RTVue-100 FD-OCT. Spearman analysis was used to investigate the correlation between cluster MDs provided by Octopus perimeter and corresponding sector pRNFLT for the total sample and each subgroup, respectively. Then, linear (y = a+ bx) and curvilinear (quadratic, y = a+bx + cx 2) regression analyses were employed to investigate the model for the cluster MD-sector pRNFLT pair with significant correlation. The strength of the relationship was characterized with correlation coefficient (ρ) and coefficient of determination (R 2). For the cluster-sector pair that could be fitted by both models, Wilcoxon signed rank test of absolute residuals was used to compare the goodness of fit. Results: Correlation between cluster MDs and corresponding sector pRNFLT was significant for all clusters in the total sample (ρ values: -0.572 to 0.832, P < 0.001) and in the POAG group (ρ values: -0.551 to -0.777, P < 0.001). The highest ρ values were found for cluster-sector pair 9 and pair 3, respectively. The curvilinear (quadratic) model provided better fit for all 10 cluster-sector pairs in the total sample (R 2 values: 0.431-0.687, P < 0.001) and in the POAG group (R 2 values: 0.364-0.594, P < 0.01). The highest R 2 values were found also for cluster-sector pair 9 and pair 3, respectively. In the control group, no significant correlation was found for any cluster-sector pair (P > 0.01). In the early group, correlation was significant for cluster-sector pairs 3, 8, and 9 (ρ values: -0.449, -0.627, and -0.815, resp., P < 0.01). In the moderate group, correlation was significant for pairs 2, 3, 8, and 9 (ρ values: -0.703, -0.556, -0.680, and -0.637, resp., P < 0.01). In the advanced group, correlation was significant (P < 0.01) for all 10 pairs (ρ values: -0.395 to -0.699, P < 0.001) except for pairs 2, 3, and 8, and the highest ρ value was found for pair 1. For all cluster-sector pairs with significant correlation in the early, moderate, and advanced groups, only linear model could be fitted (P < 0.01), except for pair 9 in the early group and pair 5 in the advanced group. Conclusions: Cluster MD of the Octopus visual field showed significant moderate-to-strong negative correlation and curvilinear (quadratic) relationship with the corresponding sector pRNFLT for POAG. This type of regional structure-function relationship varied according to the severity of POAG, and at each stage, the significantly correlated cluster-sector pairs mainly showed linear relationship. The results could provide guidance for better utilization of this regional structure-function method in the management of different stages of POAG.

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