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1.
Skin Res Technol ; 30(4): e13679, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38616503

ABSTRACT

BACKGROUND: Injectable filler, a nonsurgical beauty method, has gained popularity in rejuvenating sagging skin. In this study, polydioxanone (PDO) was utilized as the main component of the ULTRACOL200 filler that helps stimulate collagenesis and provide skin radiant effects. The study aimed to evaluate and compare the effectiveness of ULTRACOL200 with other commercialized products in visually improving dermatological problems. METHODS: Herein, 31 participants aged between 20 and 59 years were enrolled in the study. 1 mL of the testing product, as well as the quantity for the compared groups was injected into each participants face side individually. Subsequently, skin texture and sunken volume of skin were measured using ANTERA 3D CS imaging technology at three periods: before the application, 4 weeks after the initial application, and 4 weeks after the 2nd application of ULTRACOL200. RESULTS: The final results of skin texture and wrinkle volume evaluation consistently demonstrated significant enhancement. Consequently, subjective questionnaires were provided to the participants to evaluate the efficacy of the testing product, illustrating satisfactory responses after the twice applications. CONCLUSION: The investigation has contributed substantially to the comprehension of a PDO-based filler (ULTRACOL200) for skin enhancement and provided profound insight for future clinical trials.


Subject(s)
Nasolabial Fold , Skin Transplantation , Humans , Young Adult , Adult , Middle Aged , Skin/diagnostic imaging , Imaging, Three-Dimensional , Technology
2.
EClinicalMedicine ; 71: 102578, 2024 May.
Article in English | MEDLINE | ID: mdl-38606167

ABSTRACT

Background: Constipation is prevalent worldwide, significantly increasing healthcare costs and diminishing the quality of life in children affected. Current studies have yielded mixed results regarding the factors associated with constipation, and mainly focusing on patients outside of Asia. Moreover, most of these studies lack focus on the paediatric population. This study aimed to identify the prevalence and associated factors of constipation among children in Asia. Methods: In this systematic review and meta-analysis, we systematically searched PubMed, Scopus, and Cochrane for cohort and cross-sectional studies published from database inception up to October 12, 2022, and continued with manual searching until September 2, 2023. Eligible studies were those that included children in Asia aged 0-18 years old suffering from idiopathic constipation, with prevalence value provided in the English abstract. The analysis included clinical and general population. Children with organic constipation, who had undergone gastrointestinal surgery, or with congenital defects were excluded, as these factors affect the incidence of constipation. Data included in the analysis were extracted from published reports only. The extracted data were pooled using random-effects model to analyse the prevalence of constipation in children in Asia. This study is registered with PROSPERO, CRD42022367122. Findings: Out of 4410 systematically searched studies and 36 manually searched ones, a total of 50 studies were included in the final analysis, encompassing data from 311,660 children residing in Asia. The pooled prevalence of constipation was 12.0% (95% CI 9.3-14.6%, I2 = 99.8%). There was no significant difference in constipation prevalence observed by sex and geographical location. Nonetheless, adolescents and children aged 1-9 years exhibited a significantly higher prevalence constipation compared to infants (p < 0.0001) Additionally, significant differences in constipation rates were observed across various diagnostic methods, population sources, and mental health conditions. Interpretation: Despite the high heterogeneity resulting from varying diagnostic tools or definitions used among studies, our review adds to the literature on constipation among children in Asia. It reveals a notably high prevalence of constipation in this demographic. Diagnostic methods, age, and compromised mental health emerged as significant influencers of constipation among children in Asia, highlighting potential strategies to mitigate constipation prevalence in children in Asia. Funding: The National Science and Technology Council, Taiwan.

3.
J Nutr Biochem ; 129: 109640, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38583497

ABSTRACT

Midlife overweight and obesity are risk factors of cognitive decline and Alzheimer' s disease (AD) in late life. In addition to increasing risk of obesity and cognitive dysfunction, diets rich in fats also contributes to an imbalance of gut microbiota. Xylo-oligosaccharides (XOS) are a kind of prebiotic with several biological advantages, and can selectively promote the growth of beneficial microorganisms in the gut. To explore whether XOS can alleviate cognitive decline induced by high-fat diet (HFD) through improving gut microbiota composition, mice were fed with normal control or 60% HFD for 9 weeks to induce obesity. After that, mice were supplemented with XOS (30 g or 60 g/kg-diet) or without, respectively, for 12 weeks. The results showed that XOS inhibited weight gain, decreased epidydimal fat weight, and improved fasting blood sugar and blood lipids in mice. Additionally, XOS elevated spatial learning and memory function, decreased amyloid plaques accumulation, increased brain-derived neurotrophic factor levels, and improved neuroinflammation status in hippocampus. Changes in glycerolipids metabolism-associated lipid compounds caused by HFD in hippocampus were reversed after XOS intervention. On the other hand, after XOS intervention, increase in immune-mediated bacteria, Faecalibacterium was observed. In conclusion, XOS improved gut dysbiosis and ameliorated spatial learning and memory dysfunction caused by HFD by decreasing cognitive decline-associated biomarkers and changing lipid composition in hippocampus.

4.
Front Oncol ; 14: 1341794, 2024.
Article in English | MEDLINE | ID: mdl-38515575

ABSTRACT

Background: Large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of prostate cancer. The pathogenesis, clinical manifestation, treatment options, and prognosis are uncertain and underreported. Materials and methods: A systematic search was conducted in April 2022 through PubMed, Embase, and Cochrane. We reviewed cases of LCNEC developed either from de novo or transformation from prostate adenocarcinoma and summarized the relevant pathophysiological course, treatment options, and outcomes. Results: A total of 25 patients with a mean age of 70.4 (range 43 87 years old) from 18 studies were included in this review. 13 patients were diagnosed with de novo LCNEC of the prostate. 12 patients were from the transformation of adenocarcinoma post-hormonal therapy treatment. Upon initial diagnosis, patients diagnosed with de novo prostatic LCNEC had a mean serum PSA value of 24.6 ng/ml (range: 0.09-170 ng/ml, median 5.5 ng/ml), while transformation cases were significantly lower at 3.3 ng/ml (range: 0-9.3 ng/ml, median 0.05 ng/ml). The pattern of metastasis closely resembles prostate adenocarcinoma. Six out of twenty-three cases displayed brain metastasis matching the correlation between neuroendocrine tumors and brain metastasis. Three notable paraneoplastic syndromes included Cushings syndrome, dermatomyositis, and polycythemia. Most patients with advanced metastatic disease received conventional platinum-based chemotherapy with a mean survival of 5 months. There was one exception in the transformation cohort with a somatic BRCA2 mutation who was treated with a combination of M6620 and platinum-based chemotherapy with an impressive PFS of 20 months. Patients with pure LCNEC phenotype have worse survival outcomes when compared to those with mixed LCNEC and adenocarcinoma phenotypes. It is unclear whether there is a survival benefit to administering ADT in pure pathologies. Conclusion: LCNEC of the prostate is a rare disease that can occur de novo or transformation from prostatic adenocarcinoma. Most patients present at an advanced stage with poor prognosis and are treated with conventional chemotherapy regimens. Patients who had better outcomes were those who were diagnosed at an early stage and received treatment with surgery or radiation and androgen deprivation therapy (ADT). There was one case with an exceptional outcome that included a treatment regimen of M6620 and chemotherapy.

5.
Chemosphere ; 355: 141748, 2024 May.
Article in English | MEDLINE | ID: mdl-38521109

ABSTRACT

Sugarcane bagasse is one of the most common Vietnamese agricultural waste, which possesses a large percentage of cellulose, making it an abundant and environmentally friendly source for the fabrication of cellulose carbon aerogel. Herein, waste sugarcane bagasse was used to synthesize cellulose aerogel using different crosslinking agents such as urea, polyvinyl alcohol (PVA) and sodium alginate (SA). The 3D porous network of cellulose aerogels was constructed by intermolecular hydrogen bonding, which was confirmed by Fourier transform infrared (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and nitrogen adsorption/desorption. Among the three cellulose aerogel samples, cellulose - SA aerogel (SB-CA-SA) has low density of 0.04 g m-3 and high porosity of 97.38%, leading to high surface area of 497.9 m2 g-1 with 55.67% micropores of activated carbon aerogel (SB-ACCA-SA). The salt adsorption capacity was high (17.87 mg g-1), which can be further enhanced to 31.40 mg g-1 with the addition of CNT. Moreover, the desalination process using the SB-ACCA-SA-CNT electrode was stable even after 50 cycles. The results show the great combination of cellulose from waste sugarcane bagasse with sodium alginate and carbon nanotubes in the fabrication of carbon materials as the CDI-utilized electrodes with high desalination capability and good durability.


Subject(s)
Nanotubes, Carbon , Saccharum , Cellulose/chemistry , Saccharum/chemistry , Alginates
6.
AIDS Patient Care STDS ; 38(3): 115-122, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38471090

ABSTRACT

Long-acting cabotegravir/rilpivirine (LA-CAB/RPV) is the first complete injectable antiretroviral for patients living with HIV. To facilitate patient access to long-acting injectable treatment, a system-wide, pharmacist-led, LA-CAB/RPV transition program was developed at four health system-based New York clinics. Provider referrals were received across four clinics between January 22nd, 2021, and December 31st, 2022. All referrals were evaluated by a pharmacist for clinical eligibility and medication access. The primary outcome was the treatment retention rate defined as the percentage of patients who remained on LA-CAB/RPV at 3 months post-transition. A total of 171 referrals were received, with 73 patients (43%) initiating LA-CAB/RPV. Baseline demographics included a median age of 38 years, 81% patients were male, 41% were African American, and 49% had commercial insurance coverage. The treatment retention rate was 90% at 3 months post-transition. By the end of the study period, 84% of patients who transitioned remained on LA-CAB/RPV. Treatment was discontinued due to reasons such as viral breakthrough (4%), emergence of mutations (4%), and intolerable side effects (4%). Injection site reactions were commonly reported (51%), but only resulting in treatment discontinuation for one patient. A pharmacist-led program can transition a diverse population of patients living with HIV to LA-CAB/RPV. Results from this study further add to clinical experiences with LA-CAB/RPV, demonstrating real-world treatment retention despite more frequent clinic visits for patients.


Subject(s)
Anti-HIV Agents , Diketopiperazines , HIV Infections , HIV Seropositivity , HIV-1 , Pyridones , Humans , Male , Adult , Female , Rilpivirine/adverse effects , HIV-1/genetics , Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , New York , Pharmacists , Anti-Retroviral Agents/therapeutic use , HIV Seropositivity/drug therapy
7.
Semin Musculoskelet Radiol ; 28(2): 180-192, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38484770

ABSTRACT

Increase in youth sports participation, longer duration of play, and earlier starting points have increased the prevalence of acute and repetitive overuse musculoskeletal injuries. This rise in injury rates has led to increased efforts to better understand the susceptible sites of injury that are unique to the growing immature skeleton. Upper extremity injuries are currently the best studied, particularly those that occur among pediatric baseball players and gymnasts. The weak link in skeletally immature athletes is the growth plate complex that includes those injuries located at the epiphyseal and apophyseal primary physes and the peripherally located secondary physes. This article reviews the anatomy and function of these growth plate complexes, followed by a discussion of the pathophysiologic mechanisms, spectrum of imaging findings, and existing evidence-based guidelines for injury prevention and return to play.


Subject(s)
Athletic Injuries , Baseball , Humans , Adolescent , Child , Athletic Injuries/diagnostic imaging , Return to Sport , Upper Extremity/diagnostic imaging , Upper Extremity/injuries , Athletes , Radiologists , Baseball/injuries
8.
Nat Commun ; 15(1): 2139, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38459016

ABSTRACT

The pressing demand for sustainable energy storage solutions has spurred the burgeoning development of aqueous zinc batteries. However, kinetics-sluggish Zn2+ as the dominant charge carriers in cathodes leads to suboptimal charge-storage capacity and durability of aqueous zinc batteries. Here, we discover that an ultrathin two-dimensional polyimine membrane, featured by dual ion-transport nanochannels and rich proton-conduction groups, facilitates rapid and selective proton passing. Subsequently, a distinctive electrochemistry transition shifting from sluggish Zn2+-dominated to fast-kinetics H+-dominated Faradic reactions is achieved for high-mass-loading cathodes by using the polyimine membrane as an interfacial coating. Notably, the NaV3O8·1.5H2O cathode (10 mg cm-2) with this interfacial coating exhibits an ultrahigh areal capacity of 4.5 mAh cm-2 and a state-of-the-art energy density of 33.8 Wh m-2, along with apparently enhanced cycling stability. Additionally, we showcase the applicability of the interfacial proton-selective coating to different cathodes and aqueous electrolytes, validating its universality for developing reliable aqueous batteries.

9.
bioRxiv ; 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38405985

ABSTRACT

A central problem in cancer immunotherapy with immune checkpoint blockade (ICB) is the development of resistance, which affects 50% of patients with metastatic melanoma1,2. T cell exhaustion, resulting from chronic antigen exposure in the tumour microenvironment, is a major driver of ICB resistance3. Here, we show that CD38, an ecto-enzyme involved in nicotinamide adenine dinucleotide (NAD+) catabolism, is highly expressed in exhausted CD8+ T cells in melanoma and is associated with ICB resistance. Tumour-derived CD38hiCD8+ T cells are dysfunctional, characterised by impaired proliferative capacity, effector function, and dysregulated mitochondrial bioenergetics. Genetic and pharmacological blockade of CD38 in murine and patient-derived organotypic tumour models (MDOTS/PDOTS) enhanced tumour immunity and overcame ICB resistance. Mechanistically, disrupting CD38 activity in T cells restored cellular NAD+ pools, improved mitochondrial function, increased proliferation, augmented effector function, and restored ICB sensitivity. Taken together, these data demonstrate a role for the CD38-NAD+ axis in promoting T cell exhaustion and ICB resistance, and establish the efficacy of CD38 directed therapeutic strategies to overcome ICB resistance using clinically relevant, patient-derived 3D tumour models.

10.
Tissue Eng Part A ; 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38205627

ABSTRACT

Tissue engineering scaffolds are often made from the decellularization of tissues. The decellularization of tissues caused by prolonged contact with aqueous detergents might harm the microstructure and leave cytotoxic residues. In this research, we developed a new technique to use supercritical carbon dioxide (Sc-CO2)-based decellularization for porcine nerve tissue. The effect of decellularization was analyzed by histological examination, including Hematoxylin and Eosin, Masson's Trichrome staining, and 4',6-diamidino-2-phenylindole staining. Moreover, biochemical analysis of the decellularized tissues was also performed by measuring DNA content, amount of collagen, and glycosaminoglycans (GAGs) after decellularization. The results showed that the tissue structure was preserved, cells were removed, and the essential components of extracellular matrix, such as collagen fibers, elastin fibers, and GAG fibers, remained after decellularization. In addition, the DNA content was decreased compared with native tissue, and the concentration of collagen and GAGs in the decellularized nerve tissue was the same as in native tissue. The in vivo experiment in the rat model showed that after 6 months of decellularized nerve implantation, the sciatic function index was confirmed to recover in decellularized nerve. Morphological analysis displayed a range of infiltrated cells in the decellularized nerve, similar to that in native tissue, and the number of Schwann cells that play essential for motor function and sensory in the decellularized nerve was confirmed. These findings indicate that tissue decellularization using Sc-CO2 has been successfully used in tissue engineering.

11.
J Immunother Cancer ; 12(1)2024 01 17.
Article in English | MEDLINE | ID: mdl-38233101

ABSTRACT

BACKGROUND: Immune-related adverse events (irAEs) are major barriers of clinical management and further development of immune checkpoint inhibitors (ICIs) for cancer therapy. Therefore, biomarkers associated with the onset of severe irAEs are needed. In this study, we aimed to identify immune features detectable in peripheral blood and associated with the development of severe irAEs that required clinical intervention. METHODS: We used a 43-marker mass cytometry panel to characterize peripheral blood mononuclear cells from 28 unique patients with melanoma across 29 lines of ICI therapy before treatment (baseline), before the onset of irAEs (pre-irAE) and at the peak of irAEs (irAE-max). In the 29 lines of ICI therapy, 18 resulted in severe irAEs and 11 did not. RESULTS: Unsupervised and gated population analysis showed that patients with severe irAEs had a higher frequency of CD4+ naïve T cells and lower frequency of CD16+ natural killer (NK) cells at all time points. Gated population analysis additionally showed that patients with severe irAEs had fewer T cell immunoreceptor with Ig and ITIM domain (TIGIT+) regulatory T cells at baseline and more activated CD38+ CD4+ central memory T cells (TCM) and CD39+ and Human Leukocyte Antigen-DR Isotype (HLA-DR)+ CD8+ TCM at peak of irAEs. The differentiating immune features at baseline were predominantly seen in patients with gastrointestinal and cutaneous irAEs and type 1 diabetes. Higher frequencies of CD4+ naïve T cells and lower frequencies of CD16+ NK cells were also associated with clinical benefit to ICI therapy. CONCLUSIONS: This study demonstrates that high-dimensional immune profiling can reveal novel blood-based immune signatures associated with risk and mechanism of severe irAEs. Development of severe irAEs in melanoma could be the result of reduced immune inhibitory capacity pre-ICI treatment, resulting in more activated TCM cells after treatment.


Subject(s)
Melanoma , T-Lymphocytes, Regulatory , Humans , Immune Checkpoint Inhibitors/adverse effects , Leukocytes, Mononuclear , Melanoma/drug therapy , Killer Cells, Natural
12.
J Oleo Sci ; 73(1): 65-71, 2024.
Article in English | MEDLINE | ID: mdl-38171732

ABSTRACT

Lyotropic liquid crystals (LLCs) are interesting wall-materials for encapsulation technology, in which monoacylglycerols (MAGs) are considered as potential ingredient for LLC formulation. This study, therefore, applied palm oil-based MAGs to encapsulate Gac fruit oils and compared the effect of two drying methods (freeze-drying and spray-drying) on the quality of products during storage. Wall-materials were prepared by ultrasound dispersing MAGs/water mixtures (40/60, w/w) into Pluronic solution (2%, w/w) to formulate LLC dispersions. Then, Gac fruit oils were encapsulated by freeze-drying and spray-drying. Various technologies were applied to characterize the properties of dispersions, the encapsulated powder morphology and the loading capacity. Obtained results showed that LLC dispersions made of palm oilbased MAG were micro- and nano-emulsions which were very convenient for encapsulating Gac fruit oils. For both drying methods, ß-carotene of Gac fruit oils was successfully entrapped by MAGs with a high loading capacity (200 µg ß-carotene/g powder). The degradation of encapsulated ß-carotene after four storage weeks was 10 - 40% and freeze-dried samples showed a better protection effect in comparison to spray-dried samples.


Subject(s)
Fruit , beta Carotene , Fruit/chemistry , beta Carotene/analysis , Palm Oil/analysis , Monoglycerides , Powders , Oils/chemistry , Freeze Drying
13.
Plant Biotechnol J ; 22(1): 19-36, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37794706

ABSTRACT

Prime editing (PE) technology utilizes an extended prime editing guide RNA (pegRNA) to direct a fusion peptide consisting of nCas9 (H840) and reverse transcriptase (RT) to a specific location in the genome. This enables the installation of base changes at the targeted site using the extended portion of the pegRNA through RT activity. The resulting product of the RT reaction forms a 3' flap, which can be incorporated into the genomic site through a series of biochemical steps involving DNA repair and synthesis pathways. PE has demonstrated its effectiveness in achieving almost all forms of precise gene editing, such as base conversions (all types), DNA sequence insertions and deletions, chromosomal translocation and inversion and long DNA sequence insertion at safe harbour sites within the genome. In plant science, PE could serve as a groundbreaking tool for precise gene editing, allowing the creation of desired alleles to improve crop varieties. Nevertheless, its application has encountered limitations due to efficiency constraints, particularly in dicotyledonous plants. In this review, we discuss the step-by-step mechanism of PE, shedding light on the critical aspects of each step while suggesting possible solutions to enhance its efficiency. Additionally, we present an overview of recent advancements and future perspectives in PE research specifically focused on plants, examining the key technical considerations of its applications.


Subject(s)
Chromosome Inversion , RNA, Guide, CRISPR-Cas Systems , Alleles , DNA Repair , Gene Editing , DNA , CRISPR-Cas Systems
14.
Chemosphere ; 349: 140797, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38016526

ABSTRACT

Arsenic (As) turnover in rice paddy agro-ecosystems has received much attention because As can enter the food chain through its accumulation in rice, thereby affecting human health. Returning straw to soil is a common practice to retain nutrients for soil and crops, but it also cycles As within the rice paddy field ecosystems. However, there is still a lack of detailed understanding of the fate of As in rice straw, and how or to what extent it is recycled back into the soil environment. This study aims to elucidate the relationship between the microstructure of rice straw and the release of As during rice straw decomposition. The microstructure of rice straw was found to comprise both organic and silica (phytolith) components. These two constituents are inter-embedded to form a composite-like structure that contains up to 6.48 mg As Kg-1. The 30-day batch experiments revealed that the biochemical release of As simultaneously depends upon the decomposition of the organic component and the desilicification of the silica component. Accompanying the release of As was the release of other elements such as Fe, Al, P and S. These elements can further interact with As to form less mobile compounds. The introduction of either Trichoderma harzianum or Bacillus velezensis was expected to accelerate the decomposition of rice straw, and enhance the silica dissolution, hence contributing to an increase in the As release. Despite these expectations, our observations showed the opposite effects. Microorganisms presumably have facilitated the change in solution chemistry or the inclusion of As into the newly-formed precipitates. The biochemical decomposition process can reduce straw particle size, while the negatively-charge surface will involve microsized straw particles in the electrostatic interaction, thereby favoring the dispersibility state. Therefore, the co-transport of micro-sized straw particles with As under field conditions should not be neglected.


Subject(s)
Arsenic , Oryza , Humans , Oryza/chemistry , Ecosystem , Soil/chemistry , Silicon Dioxide
15.
Adv Healthc Mater ; 13(7): e2301679, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37931928

ABSTRACT

The regulation of proinflammatory mediators has been explored to promote natural healing without abnormal inflammation or autoimmune response induced by their overproduction. However, most efforts to control these mediators have relied on pharmacological substances that are directly engaged in biological cycles. It is believed that functional porous materials removing target mediators provide a new way to promote the healing process using their adsorption mechanisms. In this study, the Zr-based metal-organic frameworks (MOF)-808 (Zr6 O4 (OH)4 (BTC)2 (HCOO)6 ) crystals are found to be effective at removing proinflammatory mediators, such as nitric oxide (NO), cytokines, and reactive oxygen species (ROS) in vitro and in vivo, because of their porous structure and surface affinity. The MOF-808 crystals are applied to an in vivo skin wound model as a hydrogel dispersion. Hydrogel containing 0.2 wt% MOF-808 crystals shows significant improvement in terms of wound healing efficacy and quality over the corresponding control. It is also proven that the mode of action is to remove the proinflammatory mediators in vivo. Moreover, the application of MOF-808-containing hydrogels promotes cell activation, proliferation and inhibits chronic inflammation, leading to increased wound healing quality. These findings suggest that Zr-based MOFs may be a promising drug-free solution for skin problems related to proinflammatory mediators.


Subject(s)
Metal-Organic Frameworks , Humans , Metal-Organic Frameworks/chemistry , Zirconium/chemistry , Hydrogels/chemistry , Adsorption , Wound Healing , Inflammation
16.
ACS Appl Mater Interfaces ; 15(51): 59103-59116, 2023 Dec 27.
Article in English | MEDLINE | ID: mdl-38073418

ABSTRACT

How endothelial cells sense and respond to dynamic changes in their biophysical surroundings as we age is not fully understood. Vascular stiffness is clearly a contributing factor not only in several cardiovascular diseases but also in physiological processes such as aging and vascular dementia. To address this gap, we utilized a microfluidic model to explore how substrate stiffness in the presence of shear stress affects endothelial morphology, senescence, proliferation, and inflammation. We also studied the role of mechanosensitive ion channel Piezo1 in endothelial responses under the combined effect of shear stress and substrate stiffness. To do so, we cultured endothelial cells inside microfluidic channels covered with fibronectin-coated elastomer with elastic moduli of 40 and 200 kPa, respectively, mimicking the stiffness of the vessel walls in young and aged arteries. The endothelial cells were exposed to atheroprotective and atherogenic shear stress levels of 10 and 2 dyn/cm2, respectively. Our findings show that substrate stiffness affects senescence under atheroprotective flow conditions and cytoskeleton remodeling, senescence, and inflammation under atherogenic flow conditions. Additionally, we found that the expression of Piezo1 plays a crucial role in endothelial adaptation to flow and regulation of inflammation under both atheroprotective and atherogenic shear stress levels. However, Piezo1 contribution to endothelial senescence was limited to the soft substrate and atheroprotective shear stress level. Overall, our study characterizes the response of endothelial cells to the combined effect of shear stress and substrate stiffness and reveals a previously unidentified role of Piezo1 in endothelial response to vessel stiffening, which potentially can be therapeutically targeted to alleviate endothelial dysfunction in aging adults.


Subject(s)
Atherosclerosis , Vascular Stiffness , Humans , Aged , Biomechanical Phenomena , Endothelial Cells/metabolism , Mechanotransduction, Cellular/physiology , Atherosclerosis/metabolism , Inflammation/metabolism , Stress, Mechanical
17.
Front Microbiol ; 14: 1269869, 2023.
Article in English | MEDLINE | ID: mdl-38075878

ABSTRACT

Scytovirin (SVN) is a lectin from cyanobacteria which has a strong inhibitory activity against Ebola virus infection. We engineered scytovirin as the inhibitor for surface display of lactic acid bacteria to block Ebola virus infection. Two different bacterial strains (Lactobacillus casei and Lactococcus lactis) were successfully engineered for scytovirin expression on the bacterial surface. These bacteria were found to be effective at neutralizing pseudotyped Ebolavirus in a cell-based assay. This approach can be utilized for prophylactic prevention, as well as for treatment. Since lactic acid bacteria can colonize the human body, a long-term efficacy could be achieved. Furthermore, this approach is also simple and cost-effective and can be easily applied in the regions of Ebola outbreaks in the developing countries.

18.
Nat Commun ; 14(1): 8313, 2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38097633

ABSTRACT

Controlling site-selectivity and reactivity in chemical reactions continues to be a key challenge in modern synthetic chemistry. Here, we demonstrate the discovery of site-selective chemical reactions on the water surface via a sequential assembly approach. A negatively charged surfactant monolayer on the water surface guides the electrostatically driven, epitaxial, and aligned assembly of reagent amino-substituted porphyrin molecules, resulting in a well-defined J-aggregated structure. This constrained geometry of the porphyrin molecules prompts the subsequent directional alignment of the perylenetetracarboxylic dianhydride reagent, enabling the selective formation of a one-sided imide bond between porphyrin and reagent. Surface-specific in-situ spectroscopies reveal the underlying mechanism of the dynamic interface that promotes multilayer growth of the site-selective imide product. The site-selective reaction on the water surface is further demonstrated by three reversible and irreversible chemical reactions, such as imide-, imine-, and 1, 3-diazole (imidazole)- bonds involving porphyrin molecules. This unique sequential assembly approach enables site-selective chemical reactions that can bring on-water surface synthesis to the forefront of modern organic chemistry.

19.
Commun Chem ; 6(1): 280, 2023 Dec 16.
Article in English | MEDLINE | ID: mdl-38104228

ABSTRACT

The water surface provides a highly effective platform for the synthesis of two-dimensional polymers (2DP). In this study, we present an efficient on-water surface synthesis of crystalline monolayer 2D polyimide (2DPI) through the imidization reaction between tetra (4-aminophenyl) porphyrin (M1) and perylenetracarboxylic dianhydride (M2), resulting in excellent stability and coverage over a large area (tens of cm2). We further fabricate innovative organic-inorganic hybrid van der Waals heterostructures (vdWHs) by combining with exfoliated few-layer molybdenum sulfide (MoS2). High-resolution transmission electron microscopy (HRTEM) reveals face-to-face stacking between MoS2 and 2DPI within the vdWH. This stacking configuration facilitates remarkable charge transfer and noticeable n-type doping effects from monolayer 2DPI to MoS2, as corroborated by Raman spectroscopy, photoluminescence measurements, and field-effect transistor (FET) characterizations. Notably, the 2DPI-MoS2 vdWH exhibits an impressive electron mobility of 50 cm2/V·s, signifying a substantial improvement over pristine MoS2 (8 cm2/V·s). This study unveils the immense potential of integrating 2D polymers to enhance semiconductor device functionality through tailored vdWHs, thereby opening up exciting new avenues for exploring unique interfacial physical phenomena.

20.
Sci Rep ; 13(1): 19720, 2023 11 13.
Article in English | MEDLINE | ID: mdl-37957217

ABSTRACT

Lymphedema is a disease that refers to tissue swelling caused by an accumulation of protein-rich fluid that is usually drained through the lymphatic system. Detection of lymphedema is often based on expensive diagnoses such as bioimpedance spectroscopy, shear wave elastography, computed tomography, etc. In current machine learning models for lymphedema prediction, reliance on observable symptoms reported by patients introduces the possibility of errors in patient-input data. Moreover, these symptoms are often absent during the initial stages of lymphedema, creating challenges in its early detection. Identifying lymphedema before these observable symptoms manifest would greatly benefit patients by potentially minimizing the discomfort caused by these symptoms. In this study, we propose to use new data, such as complete blood count, serum, and therapy data, to develop predictive models for lymphedema. This approach aims to compensate for the limitations of using only observable symptoms data. We collected data from 2137 patients, including 356 patients with lymphedema and 1781 patients without lymphedema, with the lymphedema status of each patient confirmed by clinicians. The data for each patient included: (1) a complete blood count (CBC) test, (2) a serum test, and (3) therapy information. We used various machine learning algorithms (i.e. random forest, gradient boosting, decision tree, logistic regression, and artificial neural network) to develop predictive models on the training dataset (i.e. 80% of the data) and evaluated the models on the external validation dataset (i.e. 20% of the data). After selecting the best predictive models, we created a web application to aid medical doctors and clinicians in the rapid screening of lymphedema patients. A dataset of 2137 patients was assembled from Seoul National University Bundang Hospital. Predictive models based on the random forest algorithm exhibited satisfactory performance (balanced accuracy = 87.0 ± 0.7%, sensitivity = 84.3 ± 0.6%, specificity = 89.1 ± 1.5%, precision = 97.4 ± 0.7%, F1 score = 90.4 ± 0.4%, and AUC = 0.931 ± 0.007). We developed a web application to facilitate the swift screening of lymphedema among medical practitioners: https://snubhtxt.shinyapps.io/SNUBH_Lymphedema . Our study introduces a novel tool for the early detection of lymphedema and establishes the foundation for future investigations into predicting different stages of the condition.


Subject(s)
Algorithms , Lymphedema , Humans , Neural Networks, Computer , Software , Hematologic Tests , Lymphedema/diagnosis , Lymphedema/therapy
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