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1.
Polymers (Basel) ; 16(10)2024 May 11.
Article in English | MEDLINE | ID: mdl-38794563

ABSTRACT

In this study, electrospun scaffolds were fabricated using polycaprolactone (PCL) loaded with varying concentrations of ß-carotene (1.2%, 2.4%, and 3.6%) via the electrospinning technique. The electrospinning process involved the melting of PCL in acetic acid, followed by the incorporation of ß-carotene powder under constant stirring. Raman spectroscopy revealed a homogeneous distribution of ß-carotene within the PCL matrix. However, the ß-carotene appeared in particulate form, rather than being dissolved and blended with the PCL matrix, a result also confirmed by thermogravimetric analysis. Additionally, X-ray diffraction analysis indicated a decrease in crystallinity with increasing ß-carotene concentration. Mechanical testing of the scaffolds demonstrated an increase in ultimate strain, accompanied by a reduction in ultimate stress, indicating a potential plasticizing effect. Moreover, antimicrobial assays revealed a marginal antibacterial effect against Escherichia coli for scaffolds with higher ß-carotene concentrations. Conversely, preliminary biological assessment using KUSA-A1 mesenchymal cells indicated enhanced cellular proliferation in response to the scaffolds, suggesting the potential biocompatibility and cell-stimulating properties of ß-carotene-loaded PCL scaffolds. Overall, this study provides insights into the fabrication and characterization of electrospun PCL scaffolds containing ß-carotene, laying the groundwork for further exploration in tissue engineering and regenerative medicine applications.

2.
Nanoscale ; 16(20): 9985-9997, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38695726

ABSTRACT

Silver nanoparticles (AgNPs) hold great promise for several different applications, from colorimetric sensors to antimicrobial agents. Despite their widespread incorporation in consumer products, limited understanding of the detrimental effects and cellular antioxidant responses associated with AgNPs at sublethal concentrations persists, raising concerns for human and ecological well-being. To address this gap, we synthesized AgNPs of varying sizes and evaluated their cytotoxicity against human dermal fibroblasts (HDF). Our study revealed that toxicity of AgNPs is a time- and size-dependent process, even at low exposure levels. AgNPs exhibited low short-term cytotoxicity but high long-term impact, particularly for the smallest NPs tested. Raman microspectroscopy was employed for in-time investigations of intracellular molecular variations during the first 24 h of exposure to AgNPs of 35 nm. Subtle protein and lipid degradations were detected, but no discernible damage to the DNA was observed. Signals associated with antioxidant proteins, such as superoxide dismutase (SOD), catalase (CAT) and metallothioneins (MTs), increased over time, reflecting the heightened production of these defense agents. Fluorescence microscopy further confirmed the efficacy of overexpressed antioxidant proteins in mitigating ROS formation during short-term exposure to AgNPs. This work provides valuable insights into the molecular changes and remedial strategies within the cellular environment, utilizing Raman microspectroscopy as an advanced analytical technique. These findings offer a novel perspective on the cytotoxicity mechanism of AgNPs, contributing to the development of safer materials and advice on regulatory guidelines for their biomedical applications.


Subject(s)
Antioxidants , Fibroblasts , Metal Nanoparticles , Silver , Spectrum Analysis, Raman , Superoxide Dismutase , Silver/chemistry , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Humans , Antioxidants/pharmacology , Antioxidants/chemistry , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/cytology , Superoxide Dismutase/metabolism , Catalase/metabolism , Cell Survival/drug effects , Metallothionein/metabolism , Reactive Oxygen Species/metabolism
3.
Infection ; 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38652225

ABSTRACT

PURPOSE: Physicians may administer Nirmatrelvir-ritonavir to patients who have been symptomatic for more than 5 days. There is currently no clear evidence to support this approach. METHODS: A real-world study was conducted to investigate the potential relationship between the administration of Nirmatrelvir-ritonavir and the rates of intubation or in-hospital mortality among COVID-19 patients who experienced symptoms for more than 5 days. The end point was a composite event of intubation or in-hospital mortality. The outcomes between those patients who received Nirmatrelvir-ritonavir and those who did not were compared. RESULTS: A total of 847 patients were included in the analysis. Among them, 312 patients (36.84%) received Nirmatrelvir-ritonavir. Within the entire population, 86 patients (10.15%) experienced intubation or in-hospital mortality. The main analysis indicated that there was a significant association between the application of Nirmatrelvir-ritonavir and intubation or in-hospital mortality, with an odds ratio of 0.50 (95% confidence interval, 0.28 to 0.87; P = 0.0153) using inverse probability of treatment weighting. The finding was consistent with multiple sensitivity analyses. CONCLUSIONS: The application of Nirmatrelvir-ritonavir was associated with a significantly reduced risk of intubation or death in hospitalized COVID-19 patients who experienced symptoms for more than 5 days as compared to those who did not receive the treatment.

4.
Int J Biol Macromol ; 265(Pt 2): 131099, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38522706

ABSTRACT

Radical prostatectomy (RP) can cause neurogenic erectile dysfunction (ED), which negatively affects the quality of life of patients with prostate cancer. Currently, there is a dearth of effective therapeutic strategies. Although stem cell therapy is promising, direct cell transplantation to injured cavernous nerves is constrained by poor cell colonization. In this study, poly-L-lactic acid (PLLA)/gelatin electrospun membranes (PGEM) were fabricated to load bone marrow-derived mesenchymal stem cells (BM-MSCs) as a patch to be placed on injured nerves to alleviate ED. This study aimed to establish a promising and innovative approach to mitigate neurogenic ED post-RP and lay the foundation for modifying surgical procedures. Electrospinning and molecular biotechnology were performed in vitro and in vivo, respectively. It was observed that PGEM enhanced the performance of BM-MSCs and Schwann cells due to their excellent mechanical properties and biocompatibility. The transplanted PGEM and loaded BM-MSCs synergistically improved bilateral cavernous nerve injury-related ED and the corresponding histopathological changes. Nevertheless, transplantation of BM-MSCs alone has been verified to be ineffective. Overall, PGEM can serve as an ideal carrier to supply a more suitable survival environment for BM-MSCs and Schwann cells, thereby promoting the recovery of injured cavernous nerves and erectile function.


Subject(s)
Erectile Dysfunction , Mesenchymal Stem Cells , Polyesters , Male , Rats , Animals , Humans , Erectile Dysfunction/etiology , Erectile Dysfunction/therapy , Gelatin/metabolism , Penis/innervation , Penis/pathology , Bone Marrow/pathology , Quality of Life , Rats, Sprague-Dawley , Disease Models, Animal , Mesenchymal Stem Cells/metabolism
5.
J Am Chem Soc ; 146(9): 5908-5915, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38391353

ABSTRACT

Unconventional superconductivity in bulk materials under ambient pressure is extremely rare among the 3d transition metal compounds outside the layered cuprates and iron-based family. It is predominantly linked to highly anisotropic electronic properties and quasi-two-dimensional (2D) Fermi surfaces. To date, the only known example of a Co-based exotic superconductor is the hydrated layered cobaltate, NaxCoO2·yH2O, and its superconductivity is realized in the vicinity of a spin-1/2 Mott state. However, the nature of the superconductivity in these materials is still a subject of intense debate, and therefore, finding a new class of superconductors will help unravel the mysteries of their unconventional superconductivity. Here, we report the discovery of superconductivity at ∼6.3 K in our newly synthesized layered compound Na2CoSe2O, in which the edge-shared CoSe6 octahedra form [CoSe2] layers with a perfect triangular lattice of Co ions. It is the first 3d transition metal oxychalcogenide superconductor with distinct structural and chemical characteristics. Despite its relatively low TC, this material exhibits very high superconducting upper critical fields, µ0HC2(0), which far exceeds the Pauli paramagnetic limit by a factor of 3-4. First-principles calculations show that Na2CoSe2O is a rare example of a negative charge transfer superconductor. This cobalt oxychalcogenide with a geometrical frustration among Co spins shows great potential as a highly appealing candidate for the realization of unconventional and/or high-TC superconductivity beyond the well-established Cu- and Fe-based superconductor families and opens a new field in the physics and chemistry of low-dimensional superconductors.

6.
Heliyon ; 10(2): e24088, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38293534

ABSTRACT

Purpose: Malignant biliary obstruction (MBO) is common in patients with advanced malignant tumors, leading to poor prognosis and hindering antitumor therapy. The purpose of our study was to assess the survival outcomes for patients under therapy after percutaneous transhepatic biliary drainage (PTBD) and identify prognostic factors associated with survival in patients with MBO. Methods: From July 2010 to February 2021, 269 patients with MBO secondary to malignant tumor were divided into two groups (functional success and non-functional success). Survival time and prognostic factors were analyzed by Kaplan-Meier curves and the Cox model. Results: The overall median survival time after PTBD was 4.6 months (95 % IC:3.9-5.3). The 3- and 6-month survival rates were 68.0 % and 38.7 %, respectively. The median survival improved from 3.2 months to 8.4 months when the procedure achieved functional success. Multivariate analysis demonstrated that functionally successful drainage and antitumor treatment after PTBD were independent positive prognostic factors, but the total bilirubin after drainage and tumor size were independent negative predictive values. Conclusions: Functionally successful drainage could prolong survival time in patients with malignant biliary obstruction. Palliative care after drainage can prolong patient survival and improve their quality of life.

7.
J Cell Physiol ; 239(1): 124-134, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37942832

ABSTRACT

Studies regarding age-related erectile dysfunction (ED) based on naturally aging models are limited by their high costs, especially for the acquisition of primary cells from the corpus cavernosum. Herein, d-galactose ( d-gal) was employed to accelerate cell senescence, and the underlying mechanism was explored. As predominant functional cells involved in the erectile response, corpus cavernosum smooth muscle cells (CCSMCs) were isolated from 2-month-old rats. Following this, d-gal was introduced to induce cell senescence, which was verified via ß-galactosidase staining. The effects of d-gal on CCSMCs were evaluated by terminal deoxynucleoitidyl transferase dUTP nick-end labeling (TUNEL), immunofluorescence staining, flow cytometry, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, RNA interference (RNAi) was carried out for rescue experiments. Subsequently, the influence of senescence on the corpus cavernosum was determined via scanning electron microscopy, qRT-PCR, immunohistochemistry, TUNEL, and Masson stainings. The results revealed that the accelerated senescence of CCSMCs was promoted by d-gal. Simultaneously, smooth muscle alpha-actin (alpha-SMA) expression was inhibited, while that of osteopontin (OPN) and Krüppel-like factor 4 (KLF4), as well as fibrotic and apoptotic levels, were elevated. After knocking down KLF4 expression in d-gal-induced CCSMCs by RNAi, the expression level of cellular alpha-SMA increased. Contrastingly, the OPN expression, apoptotic and fibrotic levels declined. In addition, cellular senescence acquired partial remission. Accordingly, in the aged corpus cavernosum, the fibrotic and apoptotic rates were increased, followed by downregulation in the expression of alpha-SMA and the concurrent upregulation in the expression of OPN and KLF4. Overall, our results signaled that d-gal-induced accelerated senescence of CCSMCs could trigger fibrosis, apoptosis and phenotypic switch to the synthetic state, potentially attributed to the upregulation of KLF4 expression, which may be a multipotential therapeutic target of age-related ED.


Subject(s)
Erectile Dysfunction , Galactose , Myocytes, Smooth Muscle , Animals , Male , Rats , Erectile Dysfunction/metabolism , Erectile Dysfunction/therapy , Galactose/pharmacology , Galactose/metabolism , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/metabolism , Penis , Phenotype , Rats, Sprague-Dawley , Actins
8.
Chem Res Toxicol ; 37(1): 117-125, 2024 01 15.
Article in English | MEDLINE | ID: mdl-38146714

ABSTRACT

Ammonia (NH3) is a commonly used industrial chemical to which exposure at high concentrations can result in severe skin damage. Moreover, high levels of ammonia in the human body can lead to hyperammonemia conditions and enhanced cancer metabolism. In this work, the toxicity mechanism of NH3 has been studied against human dermal fibroblast (HDF) cells using surface-enhanced Raman spectroscopy (SERS). For this purpose, gold nanoparticles of size 50 nm have been prepared and used as probes for Raman signal enhancement, after being internalized inside HDF cells. Following the exposure to ammonia, HDF cells showed a significant variation in the protein ternary structure's signals, demonstrating their denaturation and oxidation process, together with early signs of apoptosis. Meaningful changes were observed especially in the Raman vibrations of sulfur-containing amino acids (cysteine and methionine) together with aromatic residues. Fluorescence microscopy revealed the formation of reactive oxygen and nitrogen species in cells, which confirmed their stressed condition and to whom the causes of protein degradation can be attributed. These findings can provide new insights into the mechanism of ammonia toxicity and protein oxidation at a single-cell level, demonstrating the high potential of the SERS technique in investigating the cellular response to toxic compounds.


Subject(s)
Metal Nanoparticles , Neoplasms , Humans , Gold/chemistry , Ammonia/toxicity , Spectrum Analysis, Raman/methods , Metal Nanoparticles/chemistry
9.
Int J Mol Sci ; 24(21)2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37958551

ABSTRACT

Raman spectroscopy was applied to study the structural differences between herpes simplex virus Type I (HSV-1) and Epstein-Barr virus (EBV). Raman spectra were first collected with statistical validity on clusters of the respective virions and analyzed according to principal component analysis (PCA). Then, average spectra were computed and a machine-learning approach applied to deconvolute them into sub-band components in order to perform comparative analyses. The Raman results revealed marked structural differences between the two viral strains, which could mainly be traced back to the massive presence of carbohydrates in the glycoproteins of EBV virions. Clear differences could also be recorded for selected tyrosine and tryptophan Raman bands sensitive to pH at the virion/environment interface. According to the observed spectral differences, Raman signatures of known biomolecules were interpreted to link structural differences with the viral functions of the two strains. The present study confirms the unique ability of Raman spectroscopy for answering structural questions at the molecular level in virology and, despite the structural complexity of viral structures, its capacity to readily and reliably differentiate between different virus types and strains.


Subject(s)
Epstein-Barr Virus Infections , Herpes Simplex , Herpesvirus 1, Human , Humans , Herpesvirus 4, Human , Multiomics
10.
bioRxiv ; 2023 Oct 28.
Article in English | MEDLINE | ID: mdl-37961137

ABSTRACT

Mutations in microRNA-96 ( MIR96 ) cause dominant delayed onset hearing loss DFNA50 without treatment. Genome editing has shown efficacy in hearing recovery by intervention in neonatal mice, yet editing in the adult inner ear is necessary for clinical applications. Here, we developed an editing therapy for a C>A point mutation in the seed region of the Mir96 gene, Mir96 14C>A associated with hearing loss by screening gRNAs for genome editors and optimizing Cas9 and sgRNA scaffold for efficient and specific mutation editing in vitro. By AAV delivery in pre-symptomatic (3-week-old) and symptomatic (6-week-old) adult Mir96 14C>A mutant mice, hair cell on-target editing significantly improved hearing long-term, with an efficacy inversely correlated with injection age. We achieved transient Cas9 expression without the evidence of AAV genomic integration to significantly reduce the safety concerns associated with editing. We developed an AAV-sgmiR96-master system capable of targeting all known human MIR96 mutations. As mouse and human MIR96 sequences share 100% homology, our approach and sgRNA selection for efficient and specific hair cell editing for long-term hearing recovery lays the foundation for future treatment of DFNA50 caused by MIR96 mutations.

11.
Stem Cell Reports ; 18(12): 2344-2355, 2023 12 12.
Article in English | MEDLINE | ID: mdl-37995700

ABSTRACT

Immune rejection has long hindered allogeneic cell transplantation therapy. Current genetic modification approaches, including direct targeting of major histocompatibility complex or constitutive expression of immune inhibitory molecules, exhibit drawbacks such as severe adverse effects or elevated tumorigenesis risks. To overcome these limitations, we introduce an innovative approach to induce cell-type-specific immune tolerance in differentiated cells. By engineering human embryonic stem cells, we ensure the exclusive production of the immune inhibitory molecules PD-L1/CTLA4Ig in differentiated cells. Using this strategy, we generated hepatocyte-like cells expressing PD-L1 and CTLA4Ig, which effectively induced local immunotolerance. This approach was evaluated in a humanized mouse model that mimics the human immune system dynamics. We thus demonstrate a robust and selective induction of immunotolerance specific to hepatocytes, improving graft survival without observed tumorigenesis. This precise immune tolerance strategy holds great promise for advancing the development of stem cell-based therapeutics in regenerative medicine.


Subject(s)
Hematopoietic Stem Cell Transplantation , Animals , Humans , Mice , Abatacept , B7-H1 Antigen/genetics , Carcinogenesis , Graft Survival , Immune Tolerance , Immunosuppression Therapy
12.
Adv Mater ; 35(52): e2307141, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37929924

ABSTRACT

Stent implantation is a commonly used palliative treatment for alleviating stenosis in advanced esophageal cancer. However, tissue proliferation induced by stent implantation and continuous tumor growth can easily lead to restenosis. Therefore, functional stents are required to relieve stenosis while inhibiting tissue proliferation and tumor growth, thereby extending the patency. Currently, no ideal functional stents are available. Here, iodine-125 (125 I) nuclides are encapsulated into a nickel-titanium alloy (NiTi) tube to develop a novel temperature-memory spiral radionuclide stent (TSRS). It has the characteristics of temperature-memory, no cold regions at the end of the stent, and a uniform spatial dose distribution. Cell-viability experiments reveal that the TSRS can reduce the proliferation of fibroblasts and tumor cells. TSRS implantation is feasible and safe, has no significant systemic radiotoxicity, and can inhibit in-stent and edge stenosis caused by stent-induced tissue proliferation in healthy rabbits. Moreover, TSRS can improve malignant stenosis and luminal patency resulting from continuous tumor growth in a VX2 esophageal cancer model. As a functional stent, the TSRS combines the excellent properties of NiTi with brachytherapy of the 125 I nuclide and will make significant contributions to the treatment of malignant esophageal stenosis.


Subject(s)
Esophageal Neoplasms , Stents , Animals , Rabbits , Constriction, Pathologic , Temperature , Esophageal Neoplasms/radiotherapy , Esophageal Neoplasms/pathology , Radioisotopes
13.
Nat Commun ; 14(1): 7012, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37919285

ABSTRACT

The search for topological superconductivity (TSC) is currently an exciting pursuit, since non-trivial topological superconducting phases could host exotic Majorana modes. However, the difficulty in fabricating proximity-induced TSC heterostructures, the sensitivity to disorder and stringent topological restrictions of intrinsic TSC place serious limitations and formidable challenges on the materials and related applications. Here, we report a new type of intrinsic TSC, namely intrinsic surface topological superconductivity (IS-TSC) and demonstrate it in layered AuSn4 with Tc of 2.4 K. Different in-plane and out-of-plane upper critical fields reflect a two-dimensional (2D) character of superconductivity. The two-fold symmetric angular dependences of both magneto-transport and the zero-bias conductance peak (ZBCP) in point-contact spectroscopy (PCS) in the superconducting regime indicate an unconventional pairing symmetry of AuSn4. The superconducting gap and surface multi-bands with Rashba splitting at the Fermi level (EF), in conjunction with first-principle calculations, strongly suggest that 2D unconventional SC in AuSn4 originates from the mixture of p-wave surface and s-wave bulk contributions, which leads to a two-fold symmetric superconductivity. Our results provide an exciting paradigm to realize TSC via Rashba effect on surface superconducting bands in layered materials.

14.
ACS Infect Dis ; 9(11): 2226-2251, 2023 11 10.
Article in English | MEDLINE | ID: mdl-37850869

ABSTRACT

The latest RNA genomic mutation of SARS-CoV-2 virus, termed the Omicron variant, has generated a stream of highly contagious and antibody-resistant strains, which in turn led to classifying Omicron as a variant of concern. We systematically collected Raman spectra from six Omicron subvariants available in Japan (i.e., BA.1.18, BA.2, BA.4, BA.5, XE, and BA.2.75) and applied machine-learning algorithms to decrypt their structural characteristics at the molecular scale. Unique Raman fingerprints of sulfur-containing amino acid rotamers, RNA purines and pyrimidines, tyrosine phenol ring configurations, and secondary protein structures clearly differentiated the six Omicron subvariants. These spectral characteristics, which were linked to infectiousness, transmissibility, and propensity for immune evasion, revealed evolutionary motifs to be compared with the outputs of genomic studies. The availability of a Raman "metabolomic snapshot", which was then translated into a barcode to enable a prompt subvariant identification, opened the way to rationalize in real-time SARS-CoV-2 activity and variability. As a proof of concept, we applied the Raman barcode procedure to a nasal swab sample retrieved from a SARS-CoV-2 patient and identified its Omicron subvariant by coupling a commercially available magnetic bead technology with our newly developed Raman analyses.


Subject(s)
COVID-19 , Humans , SARS-CoV-2/genetics , Spectrum Analysis, Raman , RNA
15.
Foods ; 12(20)2023 Oct 13.
Article in English | MEDLINE | ID: mdl-37893662

ABSTRACT

This study exploits quantitative algorithms of Raman spectroscopy to assess, at the molecular scale, the nutritional quality of individual kernels of the Japanese short-grain rice cultivar Koshihikari in terms of amylose-to-amylopectin ratio, fractions of phenylalanine and tryptophan aromatic amino acid residues, protein-to-carbohydrate ratio, and fractions of protein secondary structures. Statistical assessments on a large number of rice kernels reveal wide distributions of the above nutritional parameters over nominally homogeneous kernel batches. This demonstrates that genetic classifications cannot catch omic fluctuations, which are strongly influenced by a number of extrinsic factors, including the location of individual grass plants within the same rice field and the level of kernel maturation. The possibility of collecting nearly real-time Raman "multi-omic snapshots" of individual rice kernels allows for the automatic (low-cost) differentiation of groups of kernels with restricted nutritional characteristics that could be used in the formulation of functional foods for specific diseases and in positively modulating the intestinal microbiota for protection against bacterial infection and cancer prevention.

16.
Int J Mol Sci ; 24(17)2023 Aug 28.
Article in English | MEDLINE | ID: mdl-37686157

ABSTRACT

The aim of this study was to elucidate the chemistry of cellular degeneration in human neuroblastoma cells upon exposure to outer-membrane vesicles (OMVs) produced by Porphyromonas gingivalis (Pg) oral bacteria by monitoring their metabolomic evolution using in situ Raman spectroscopy. Pg-OMVs are a key factor in Alzheimer's disease (AD) pathogenesis, as they act as efficient vectors for the delivery of toxins promoting neuronal damage. However, the chemical mechanisms underlying the direct impact of Pg-OMVs on cell metabolites at the molecular scale still remain conspicuously unclear. A widely used in vitro model employing neuroblastoma SH-SY5Y cells (a sub-line of the SK-N-SH cell line) was spectroscopically analyzed in situ before and 6 h after Pg-OMV contamination. Concurrently, Raman characterizations were also performed on isolated Pg-OMVs, which included phosphorylated dihydroceramide (PDHC) lipids and lipopolysaccharide (LPS), the latter in turn being contaminated with a highly pathogenic class of cysteine proteases, a key factor in neuronal cell degradation. Raman characterizations located lipopolysaccharide fingerprints in the vesicle structure and unveiled so far unproved aspects of the chemistry behind protein degradation induced by Pg-OMV contamination of SH-SY5Y cells. The observed alterations of cells' Raman profiles were then discussed in view of key factors including the formation of amyloid ß (Aß) plaques and hyperphosphorylated Tau neurofibrillary tangles, and the formation of cholesterol agglomerates that exacerbate AD pathologies.


Subject(s)
Alzheimer Disease , Neuroblastoma , Humans , Porphyromonas gingivalis , Amyloid beta-Peptides , Lipopolysaccharides , Inclusion Bodies , Blister
17.
Int J Mol Sci ; 24(16)2023 Aug 10.
Article in English | MEDLINE | ID: mdl-37628838

ABSTRACT

Hydrolytic reactions taking place at the surface of a silicon nitride (Si3N4) bioceramic were found to induce instantaneous inactivation of Human herpesvirus 1 (HHV-1, also known as Herpes simplex virus 1 or HSV-1). Si3N4 is a non-oxide ceramic compound with strong antibacterial and antiviral properties that has been proven safe for human cells. HSV-1 is a double-stranded DNA virus that infects a variety of host tissues through a lytic and latent cycle. Real-time reverse transcription (RT)-polymerase chain reaction (PCR) tests of HSV-1 DNA after instantaneous contact with Si3N4 showed that ammonia and its nitrogen radical byproducts, produced upon Si3N4 hydrolysis, directly reacted with viral proteins and fragmented the virus DNA, irreversibly damaging its structure. A comparison carried out upon testing HSV-1 against ZrO2 particles under identical experimental conditions showed a significantly weaker (but not null) antiviral effect, which was attributed to oxygen radical influence. The results of this study extend the effectiveness of Si3N4's antiviral properties beyond their previously proven efficacy against a large variety of single-stranded enveloped and non-enveloped RNA viruses. Possible applications include the development of antiviral creams or gels and oral rinses to exploit an extremely efficient, localized, and instantaneous viral reduction by means of a safe and more effective alternative to conventional antiviral creams. Upon incorporating a minor fraction of micrometric Si3N4 particles into polymeric matrices, antiherpetic devices could be fabricated, which would effectively impede viral reactivation and enable high local effectiveness for extended periods of time.


Subject(s)
Herpesvirus 1, Human , Humans , Silicon Compounds/pharmacology , Antiviral Agents/pharmacology , DNA, Viral
18.
Nat Commun ; 14(1): 4928, 2023 08 15.
Article in English | MEDLINE | ID: mdl-37582836

ABSTRACT

Mutations in Atp2b2, an outer hair cell gene, cause dominant hearing loss in humans. Using a mouse model Atp2b2Obl/+, with a dominant hearing loss mutation (Oblivion), we show that liposome-mediated in vivo delivery of CRISPR-Cas9 ribonucleoprotein complexes leads to specific editing of the Obl allele. Large deletions encompassing the Obl locus and indels were identified as the result of editing. In vivo genome editing promotes outer hair cell survival and restores their function, leading to hearing recovery. We further show that in a double-dominant mutant mouse model, in which the Tmc1 Beethoven mutation and the Atp2b2 Oblivion mutation cause digenic genetic hearing loss, Cas9/sgRNA delivery targeting both mutations leads to partial hearing recovery. These findings suggest that liposome-RNP delivery can be used as a strategy to recover hearing with dominant mutations in OHC genes and with digenic mutations in the auditory hair cells, potentially expanding therapeutics of gene editing to treat hearing loss.


Subject(s)
Deafness , Hearing Loss , Humans , CRISPR-Cas Systems/genetics , Ribonucleoproteins/genetics , Liposomes , RNA, Guide, CRISPR-Cas Systems , Hearing Loss/genetics , Hearing Loss/therapy , Deafness/genetics
19.
Sensors (Basel) ; 23(14)2023 Jul 24.
Article in English | MEDLINE | ID: mdl-37514941

ABSTRACT

To make unmanned surface vehicles that are better applied to the field of environmental monitoring in inland rivers, reservoirs, or coasts, we propose a global path-planning algorithm based on the improved A-star algorithm. The path search is carried out using the raster method for environment modeling and the 8-neighborhood search method: a bidirectional search strategy and an evaluation function improvement method are used to reduce the total number of traversing nodes; the planned path is smoothed to remove the inflection points and solve the path folding problem. The simulation results reveal that the improved A-star algorithm is more efficient in path planning, with fewer inflection points and traversing nodes, and the smoothed paths are more to meet the actual navigation demands of unmanned surface vehicles than the conventional A-star algorithm.

20.
ACS Omega ; 8(17): 14944-14951, 2023 May 02.
Article in English | MEDLINE | ID: mdl-37151518

ABSTRACT

In this paper, Raman and X-ray photoelectron spectroscopies were applied to analyze compositional and structural variations of the generated activated carbon (AC), as induced by changing carbonate source in three different types of systems, PVDF/M2CO3 (M = Li, Na, and K). According to the variations of I D/I G and sp2/sp3 ratios, a strong dependence of the AC structure on the type and content of the initial carbonate was found, determined by practical dehydrofluorination reactions associated with oxygen incorporation in AC and side reactions, because of the property variation induced by the difference in the cation of the carbonate sources. This procedure clarified the process of PVDF dehydrofluorination and the formation of activated carbon, which helps to optimize the material performance of the percolative composite for flexible energy storage applications.

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