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1.
Phys Chem Chem Phys ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39145725

RESUMEN

Enhanced dielectric constant and high breakdown strength offers immense promise for excellent energy storage performance, which is of critical significance in modern electronics and power systems. However, polymer nanocomposites with traditional routes have to balance between dielectric constant and breakdown strength, hence hindering substantive increases in energy density. Herein, a sandwiched polymer nanocomposite film has been constructed to take full advantage of the individual component layers. BaTiO3 nanoparticles are coated with a fluoropolymer to form core-shell structures and then introduced into a polymer as the top and the bottom layers of a sandwich film for enhancing polarization. Moreover, boron nitride nanosheets (BNNSs) in the middle layer of the sandwich film exert positive effects on the inhibition of current leakage for high breakdown resistance. The breakdown strength increases from 480 MV m-1 of the neat polymer to 580 MV m-1 of the sandwiched film. Additionally, the film exhibits a higher dielectric constant in comparison with the neat polymer. The sandwiched film displays a superior energy density (15.75 J cm-3), which is about 1.9 times that of the neat polymer. This work proposes a feasible route to achieve excellent energy storage of polymer dielectrics by synergistically introducing insulating fillers and additional dipoles in a sandwiched polymer nanocomposite film.

2.
JGH Open ; 8(8): e70014, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39148512

RESUMEN

Background: Helicobacter pylori (H. pylori) infection is prevalent and associated with the development of various gastric diseases. On the other hand, inflammatory bowel disease (IBD) is an immune-related intestinal disorder influenced by factors like gut microbiota imbalance, genetic predisposition, and environmental influences. Despite extensive research on the H. pylori-IBD relationship, a comprehensive bibliometric analysis in this area is lacking. Therefore, this study aims to use bibliometric methods to explore research trends, hotspots, and frontiers in H. pylori and IBD-related research, offering valuable insights for future research and clinical practice. Methods: We retrieved relevant literature on H. pylori and IBD from the Web of Science Core Collection (WoSCC) and Scopus databases covering 2007 to 2024. We perform a comprehensive analysis within the WoSCC literature. We compare these findings with relevant results from Scopus. Results: Research on H. pylori and IBD has remained prominent in recent years. The United States leads in output, with strong contributions from authors, institutions, and journals. China, despite being a developing country, shows rapid article growth, signaling growing research potential. Key topics include Crohn's disease, gut microbiota, H. pylori infection, and ulcerative colitis. Newer interests include health, cancer prevention, and chronic gastritis. Conclusion: Over the past, research on H. pylori and IBD has primarily centered around epidemiology and clinical studies. The question of whether H. pylori definitively offers protective effects against IBD remains unresolved. Therefore, further investigation could explore the underlying mechanisms of their relationship or initiate long-term prospective cohort studies to gather more compelling evidence.

3.
Nanoscale ; 16(31): 14621-14639, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39023195

RESUMEN

Tumors have always been a major public health concern worldwide, and attempts to look for effective treatments have never ceased. Sialic acid is known to be a crucial element for tumor development and its receptors are highly expressed on tumor-associated immune cells, which perform significant roles in establishing the immunosuppressive tumor microenvironment and further boosting tumorigenesis, progression, and metastasis. Obviously, it is essential to consider sophisticated crosstalk between tumors, the immune system, and preparations, and understand the links between pharmaceutics and immunology. Sialic acid-based chemoimmunotherapy enables active targeting drug delivery via mediating the recognition between the sialic acid-modified nano-drug delivery system represented by liposomes and sialic acid-binding receptors on tumor-associated immune cells, which inhibit their activity and utilize their homing ability to deliver drugs. Such a "Trojan horse" strategy has remarkably improved the shortcomings of traditional passive targeting treatments, unexpectedly promoted tumor shedding, and persistently induced robust immunological memory, thus highlighting its prospective application potential for targeting various tumors. Herein, we review recent advances in sialic acid-based active targeting chemoimmunotherapy to promote tumor shedding, summarize the current viewpoints on the tumor shedding mechanism, especially the formation of durable immunological memory, and analyze the challenges and opportunities of this attractive approach.


Asunto(s)
Inmunoterapia , Ácido N-Acetilneuramínico , Neoplasias , Humanos , Ácido N-Acetilneuramínico/química , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Neoplasias/metabolismo , Neoplasias/inmunología , Microambiente Tumoral/efectos de los fármacos , Animales , Liposomas/química , Sistemas de Liberación de Medicamentos
4.
J Infect ; 89(2): 106190, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38834107

RESUMEN

OBJECTIVES: This study aimed to determine the association of early use of oral antiviral drugs (including nirmatrelvir-ritonavir and molnupiravir) with the risk of post COVID-19 condition (PCC) and compare the possible efficacy of nirmatrelvir-ritonavir and molnupiravir. METHODS: PubMed, Web of Science, Embase, Cochrane, MedRxiv, and Psycinfo were searched from inception until November 1, 2023. We included studies that assessed the effect of oral antiviral drugs on the incidence of PCC. Pairwise and network meta-analyses were conducted using a random-effects model. Risk ratios (RRs) for oral antiviral drugs were calculated with a confidence interval (CI). RESULTS: Nine observational studies containing 866,066 patients were included. Nirmatrelvir-ritonavir and molnupiravir were evaluated in eight and two studies respectively, with both drugs evaluated in one study. Pair-wise meta-analysis showed that early oral antiviral drugs reduced PCC risk (RR 0.77, 95% CI 0.68-0.88). Network meta-analysis showed that nirmatrelvir-ritonavir may perform better than molnupiravir (surface under the cumulative ranking curve: 95.5% vs. 31.6%) at reducing PCC risk. CONCLUSIONS: Early use of oral antiviral drugs may potentially protect against developing PCC in non-hospitalized patients with COVID-19. These findings support the standardized administration of oral antiviral drugs in patients during the acute phase of COVID-19 according to the guidelines.


Asunto(s)
Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Metaanálisis en Red , Ritonavir , SARS-CoV-2 , Humanos , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Ritonavir/uso terapéutico , Ritonavir/administración & dosificación , Administración Oral , COVID-19/epidemiología , Combinación de Medicamentos , Hidroxilaminas/uso terapéutico , Hidroxilaminas/administración & dosificación , Síndrome Post Agudo de COVID-19 , Lactamas , Citidina/análogos & derivados , Nitrilos , Prolina , Leucina
5.
Medicine (Baltimore) ; 103(21): e38257, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38788011

RESUMEN

BACKGROUND: Crohn's disease and ulcerative colitis are forms of inflammatory bowel disease affecting approximately 1% of the population. Their typical features include chronic diarrhea, abdominal pain, and weight loss. Extraintestinal manifestations may coincide with or precede the diagnosis of these diseases. Primary sclerosing cholangitis is one such extraintestinal manifestation. Although many papers on this field have been published, bibliometric analysis still needs to be conducted. This article summarizes the current research progress through a bibliometric study, provides an overview of the research status in this field, and analyzes recent research trends. METHODS: Publications on inflammatory bowel disease and primary sclerosing cholangitis from January 1, 2008, to August 31, 2023, were extracted from the Web of Science Core Collection. VOSviewer and CiteSpace were used to perform a bibliometric and visual study. RESULTS: There are 1499 relevant articles, and the number of articles in this field has been relatively stable in recent years. The results indicate that Karlson TH from the University of Oslo has the highest cumulative number of publications. The institution with the highest publication output is the Mayo Clinic, and the United States leads in article production, occupying a dominant position. Keyword analysis reveals 4079 keywords, with primary sclerosing cholangitis, inflammatory bowel disease, and ulcerative colitis being the most frequently occurring keywords. CONCLUSION: Research on the association between inflammatory bowel disease and primary sclerosing cholangitis is steadily advancing, with the United States leading in publication output globally. China needs to invest more in research in this area, and collaboration among institutions should be strengthened. The research hotspots revolve around the association between inflammatory bowel disease and primary sclerosing cholangitis, gut microbiota, and other fields.


Asunto(s)
Bibliometría , Colangitis Esclerosante , Enfermedades Inflamatorias del Intestino , Colangitis Esclerosante/epidemiología , Colangitis Esclerosante/complicaciones , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/epidemiología , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/complicaciones
6.
Small ; : e2401308, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773889

RESUMEN

Incorporating ultralow loading of nanoparticles into polymers has realized increases in dielectric constant and breakdown strength for excellent energy storage. However, there are still a series of tough issues to be dealt with, such as organic solvent uses, which face enormous challenges in scalable preparation. Here, a new strategy of dual in situ synthesis is proposed, namely polymerization of polyethylene terephthalate (PET) synchronizes with growth of calcium borate nanoparticles, making polyester nanocomposites from monomers directly. Importantly, this route is free of organic solvents and surface modification of nanoparticles, which is readily accessible to scalable synthesis of polyester nanocomposites. Meanwhile, uniform dispersion of as ultralow as 0.1 wt% nanoparticles and intense bonding at interfaces have been observed. Furthermore, the PET-based nanocomposite displays obvious increases in both dielectric constant and breakdown strength as compared to the neat PET. Its maximum discharged energy density reaches 15 J cm-3 at 690 MV m-1 and power density attains 218 MW cm-3 under 150 Ω resistance at 300 MV m-1, which is far superior to the current dielectric polymers that can be produced at large scales. This work presents a scalable, safe, low-cost, and environment-friendly route toward polymer nanocomposites with superior capacitive performance.

7.
Adv Mater ; 36(23): e2313219, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38597361

RESUMEN

The development of novel materials and structures for efficient second-order nonlinear micro/nano devices remains a significant challenge. In this study, the remarkable enhancement of second-harmonic generation (SHG) and cascaded sum frequency generation in whispering gallery mode microspheres made of surface-crystallized glass with a 6-µm Ba2TiSi2O8 crystal layer are demonstrated. Attributed to the core-shell design, the Ba2TiSi2O8 located on the surface can be efficiently coupled with whispering gallery modes, resulting in a highly efficient micron-scale cavity-enhanced second-order optical nonlinearity. Greatly enhanced SHG of the microcavity is observed, which is up to 80 times stronger than that of a non-resonant sample. Furthermore, owing to the wavelength non-selectivity of random quasi-phase matching, ultra-wideband SHG with a strong response ranging from 860 to 1600 nm and high-contrast polarization characteristics is demonstrated. The glass-ceramic-based microsphere cavity also boosts the cascading optical nonlinearity, manifested by a two-magnitude enhancement of cascaded sum frequency generation. This work delineates an efficient strategy for boosting nonlinear optical response in glass ceramics, which will open up new opportunities for applications in photonics and optical communications.

8.
Food Chem ; 446: 138806, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38402767

RESUMEN

High pressure processing (HPP) juice often experiences cloud loss during storage, caused by the activity of pectin methylesterase (PME). The combination of HPP with natural pectin methylesterase inhibitor (PMEI) could improve juice stability. However, extracting natural PMEI is challenging. Gene recombination technology offers a solution by efficiently expressing recombinant PMEI from Escherichia coli and Pichia pastoris. Experimental and molecular dynamics simulation were conducted to investigate changes in activity, structure, and interaction of PME and recombinant PMEI during HPP. The results showed PME retained high residual activity, while PMEI demonstrated superior pressure resistance. Under HPP, PMEI's structure remained stable, while the N-terminus of PME's α-helix became unstable. Additionally, the helix at the junction with the PME/PMEI complex changed, thereby affecting its binding. Furthermore, PMEI competed with pectin for active sites on PME, elucidating. The potential mechanism of PME inactivation through the synergistic effects of HPP and PMEI.


Asunto(s)
Hidrolasas de Éster Carboxílico , Proteínas de Plantas , Proteínas de Plantas/metabolismo , Hidrolasas de Éster Carboxílico/metabolismo , Dominio Catalítico , Alimentos
9.
Foods ; 12(16)2023 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-37628094

RESUMEN

Apple cultivars exhibit significant diversity in fruit quality traits, creating distinct consumption scenarios. This study aimed to assess the physicochemical parameters and sensory attributes differences among fifteen apple cultivars and identify characteristic qualities suitable for various processed apple products using chemometric analysis. Relatively large differences were registered between cultivars for deflection, peel color, titratable acidity (TA), the ratio of total soluble solid to titratable acidity (TSS/TA), hardness, soluble sugar, and volatile organic compound contents. Sensory results showed significant differences existed among the preferences for different processed products. Based on the above results, all cultivars could be distinguished into three main clusters. Cluster I (i.e., Aziteke, Bakeai, Magic Flute, Royal Gala, Red General, Red Delicious, and Zhongqiuwang) demonstrated favorable appearance, high sensory scores, and rich aroma volatile compounds, making them suitable for direct consumption. Cluster II (i.e., Fuburuisi, Sinike, Honglu, and Huashuo) exhibited a higher sugar and acid content, making them suitable for apple juice production. Cluster III (i.e., Miqila, Honey Crisp, Shandong Fuji, and Yanfu 3) were more suitable for fresh-cut apples due to their good flavor and undesirable appearance. Several chemometric analyses effectively assessed differences among apple cultivars.

10.
Angew Chem Int Ed Engl ; 62(42): e202309619, 2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37610742

RESUMEN

In this work, a facile and versatile strategy for the synthesis of contorted polycyclic aromatic hydrocarbons (PAHs) starting from the functionalized pentacene was established. A series of novel PAHs 1-4 and their derivatives were synthesized through a simple two-step synthesis procedure involving an intramolecular reductive Friedel-Crafts cyclization of four newly synthesized pentacene aldehydes 5-8 as a key step. All the molecules were confirmed by single-crystal X-ray diffraction and their photophysical and electrochemical properties were studied in detail. Interestingly, the most striking feature of 1-4 is their highly contorted carbon structures and the accompanying helical chirality. In particular, the optical resolution of 2 was successfully achieved by chiral-phase HPLC, and the enantiomers were characterized by circular dichroism and circularly polarized luminescence spectroscopy. Despite the highly nonplanar conformations, these contorted PAHs exhibited emissive properties with moderate-to-good fluorescence quantum yields, implying the potential utility of this series PAHs as high-quality organic laser dyes. By using a self-assembly method with the help of epoxy resin, a bottle microlaser based on 3 a was successfully illustrated with a lasing wavelength of 567.8 nm at a threshold of 0.3 mJ/cm2 . We believe that this work will shed light on the chemical versatility of pentacene and its derivatives in the construction of novel functionalized PAHs.

11.
Molecules ; 28(9)2023 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-37175250

RESUMEN

Skeletal muscle is closely linked to energy metabolism, but it is inevitably deprived of energy. Cellular differentiation is an essential and energy-demanding process in skeletal muscle development. Much attention has been paid to identifying beneficial factors that promote skeletal muscle satellite cell differentiation and further understanding the underlying regulatory mechanisms. As a critical metabolic substrate or regulator, α-ketoglutarate (AKG) has been recognized as a potential nutritional supplement or therapeutic target for skeletal muscle. We have previously found beneficial effects of AKG supplementation on the proliferation of C2C12 myoblasts cultured under both normal and energy-deficient conditions and have further elucidated the underlying metabolic mechanisms. However, it remains unclear what role AKG plays in myotube formation in different energy states. In the present study, we investigated the effects of AKG supplementation on the differentiation of C2C12 myoblasts cultured in normal medium (Nor myotubes) and low glucose medium (Low myotubes) and performed NMR-based metabonomic profiling to address AKG-induced metabolic changes in both Nor and Low myotubes. Significantly, AKG supplementation promoted myotube formation and induced metabolic remodeling in myotubes under normal medium and low glucose medium, including improved energy metabolism and enhanced antioxidant capacity. Specifically, AKG mainly altered amino acid metabolism and antioxidant metabolism and upregulated glycine levels and antioxidase expression. Our results are typical for the mechanistic understanding of the effects of AKG supplementation on myotube formation in the two energy states. This study may be beneficial for further exploring the applications of AKG supplementation in sports, exercise, and therapy.


Asunto(s)
Antioxidantes , Ácidos Cetoglutáricos , Antioxidantes/metabolismo , Ácidos Cetoglutáricos/farmacología , Ácidos Cetoglutáricos/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Suplementos Dietéticos , Glucosa
12.
J Endod ; 49(7): 880-888, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37211311

RESUMEN

INTRODUCTION: Augmented reality (AR) is a novel visualization technique in which pregenerated virtual 3D content is superimposed on surgical sites. This study aimed to validate the viability of AR-guided endodontic microsurgery (ARG) and compare the changes in objective and subjective outcomes of surgical simulation using ARG and freehand (FH) endodontic microsurgery on customized 3D-printed models. METHODS: We created and printed a customized 3D alveolar bone model with artificial periapical lesions (APLs) based on cone-beam computed tomography. Eight models with 96 APLs were equally divided into ARG and FH groups. We planned surgical trajectories on rescanned printed models. Four inexperienced residents (IRs) performed ARG and FH on the models and completed pre and intraoperative confidence questionnaires for the subjective outcome. Postoperative cone-beam computed tomography scans of the models were reconstructed and analyzed, and all procedures were timed. We used pairwise Wilcoxon rank sum tests to compare objective outcomes. Kruskal-Wallis tests and post hoc pairwise Wilcoxon rank sum tests were used to compare subjective outcomes. RESULTS: Compared to the FH group, the ARG group significantly reduced deviation of the volume of bone removal, root-end resection, and deviation of bevel angle, with improved confidence of the IRs (P < .05); it also significantly increased surgical time and volume of unremoved APL (P < .05). CONCLUSIONS: We customized an APL model through 3D printing and developed and validated a low-cost AR application framework, based on free AR software, for endodontic microsurgery. ARG allowed IRs to perform more conservative and precise surgical procedures with enhanced confidence.


Asunto(s)
Realidad Aumentada , Microcirugia , Microcirugia/métodos , Osteotomía/métodos , Simulación por Computador , Impresión Tridimensional , Tomografía Computarizada de Haz Cónico
13.
Foods ; 12(3)2023 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-36766110

RESUMEN

This study investigated the prospect of producing cloud-stable orange-based juice by combining high-pressure processing (HPP) with a natural kiwifruit pectin methylesterase inhibitor (PMEI) during chilled storage. Kiwifruit is rich in a PMEI, which greatly improves the cloud loss caused by the pectin methylesterase (PME) demethylation of pectin. The results show that the cloud loss of orange juice occurred after 3 days, while the orange-kiwifruit mixed juice and kiwifruit puree were cloud stable during 28 days' storage. Although, the kiwifruit puree contained larger particles compared to the orange juice, its higher viscosity and solid-like behavior were dominant, improving the cloud stability of the juice systems. In addition, the particle size distribution and rheological properties were highly related to PME activity, PMEI activity, and pectin characterization. The kiwifruit PMEI showed higher resistance to HPP and storage time than PME. More water-solubilized pectin fractions with a high molecular mass were found in the kiwifruit puree, leading to its high viscosity and large particle size, but a more chelator-solubilized pectin fraction with a low esterification degree was observed in the orange juice, resulting in its cloud loss. In general, the outcome of this work provides a novel strategy to improve the cloud stability of orange-based juices using natural PMEIs and nonthermal processing technologies.

14.
Biomater Sci ; 11(8): 2787-2808, 2023 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-36825722

RESUMEN

The recent approvals for antibody-drug conjugates (ADCs) in multiple malignancies in the past few years have fueled the ongoing development of this class of drug. However, the limitation of ADCs is selectivity toward cancer cells especially overexpressing the antigen of interest. To broaden the anti-cancer spectrum of ADCs, combinatorial strategies of ADCs with chemotherapy have become a central focus of the current preclinical and clinical research. Here, we used the microtubule stabilizer paclitaxel and enfortumab vedotin-ejfv (EV), an ADC carrying the microtubule inhibitor payload monomethyl auristatin E (MMAE), for co-administration under the consideration of their mechanism of action associated with microtubules. We designed a sialic acid-cholesterol (SA-CH) conjugate-modified cationic liposome platform loaded with PTX (PTX-SAL) for efficiently targeting tumor-associated immune cells. Compared with monotherapy, PTX-SAL-mediated combination therapy with ADCs significantly inhibited S180 tumor growth in mice, with complete tumor regression occurring. The formation of a durable tumor-specific immunological memory response in mice that experienced complete tumor regression was assessed by secondary tumor cell rechallenge, and the production of memory T cells in the spleen was detected as related to the increased CD4+T memory cells and the enhanced serum IFN-γ. All our preliminary results throw light on the tremendous application potential for the application of this combination therapy regimen capable of mounting a durable immune response and stimulating a robust T cell-mediated tumor-specific immunological memory.


Asunto(s)
Inmunoconjugados , Paclitaxel , Ratones , Animales , Liposomas , Ácido N-Acetilneuramínico , Memoria Inmunológica , Línea Celular Tumoral
15.
Curr Microbiol ; 79(10): 293, 2022 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-35972650

RESUMEN

Ursolic acid (UA) exists in a variety of medicinal plants. UA exhibits antimicrobial activity against several microorganisms; however, little is known regarding the potential antifungal effect of UA on Cryptococcus neoformans (C. neoformans). The antifungal and antibiofilm activities of UA on C. neoformans H99 were evaluated in this study. Minimum inhibitory concentration (MIC) of UA against C. neoformans H99 was determined by microdilution technique, and its action mode was elucidated by clarifying the variations in cell membrane integrity, capsule, and melanin production. Moreover, the inhibition and dispersal effects of UA on biofilm formation and mature biofilms by C. neoformans H99 were evaluated using crystal violet (CV) assay, optical microscopy, field emission scanning electron microscopy and confocal laser scanning microscopy. The results indicated that the MIC value of UA against C. neoformans H99 was 0.25 mg/mL. UA disrupted the cell membrane integrity, inhibited the capsule and melanin production of C. neoformans H99 in a concentration-dependent manner. Further, UA presented the inhibitory effect on biofilm formation and dispersed mature biofilms, as well as compromised the cell membrane integrity of C. neoformans H99 cells within biofilms. Together, these results indicate that UA might be a potential therapeutic option for the treatment of C. neoformans-related infections.


Asunto(s)
Criptococosis , Cryptococcus neoformans , Antifúngicos/metabolismo , Antifúngicos/farmacología , Biopelículas , Criptococosis/tratamiento farmacológico , Cryptococcus neoformans/metabolismo , Melaninas/metabolismo , Melaninas/farmacología , Pruebas de Sensibilidad Microbiana , Triterpenos , Ácido Ursólico
16.
Omega ; 110: 102617, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35185262

RESUMEN

This work investigates a new multi-period vaccination planning problem that simultaneously optimizes the total travel distance of vaccination recipients (service level) and the operational cost. An optimal plan determines, for each period, which vaccination sites to open, how many vaccination stations to launch at each site, how to assign recipients from different locations to opened sites, and the replenishment quantity of each site. We formulate this new problem as a bi-objective mixed-integer linear program (MILP). We first propose a weighted-sum and an ϵ -constraint methods, which rely on solving many single-objective MILPs and thus lose efficiency for practical-sized instances. To this end, we further develop a tailored genetic algorithm where an improved assignment strategy and a new dynamic programming method are designed to obtain good feasible solutions. Results from a case study indicate that our methods reduce the operational cost and the total travel distance by up to 9.3% and 36.6%, respectively. Managerial implications suggest enlarging the service capacity of vaccination sites can help improve the performance of the vaccination program. The enhanced performance of our heuristic is due to the newly proposed assignment strategy and dynamic programming method. Our findings demonstrate that vaccination programs during pandemics can significantly benefit from formal methods, drastically improving service levels and decreasing operational costs.

17.
Comput Oper Res ; 141: 105704, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35095172

RESUMEN

The outbreak of COVID-19 dramatically impacts the global economy. Mass COVID-19 vaccination is widely regarded as the most promising way to fight against the pandemic and help return to normal. Many governments have authorized certain types of vaccines for mass vaccination by establishing appointment platforms. Mass vaccination poses a vital challenge to decision-makers responsible for scheduling a large number of appointments. This paper studies a vaccination site selection, appointment acceptance, appointment assignment, and scheduling problem for mass vaccination in response to COVID-19. An optimal solution to the problem determines the open vaccination sites, the set of accepted appointments, the assignment of accepted appointments to open vaccination sites, and the vaccination sequence at each site. The objective is to simultaneously minimize 1) the fixed cost for operating vaccination sites; 2) the traveling distance of vaccine recipients; 3) the appointment rejection cost; and 4) the vaccination tardiness cost. We formulate the problem as a mixed-integer linear program (MILP). Given the NP-hardness of the problem, we then develop an exact logic-based Benders decomposition (LBBD) method and a matheuristic method (MH) to solve practical-sized problem instances. We conduct numerical experiments on small- to large-sized instances to demonstrate the performance of the proposed model and solution methods. Computational results indicate that the proposed methods provide optimal solutions to small-sized instances and near-optimal solutions to large ones. In particular, the developed matheuristic can efficiently solve practical-sized instances with up to 500 appointments and 50 vaccination sites. We discuss managerial implications drawn from our results for the mass COVID-19 vaccination appointment scheduling, which help decision-makers make critical decisions.

18.
Molecules ; 26(7)2021 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-33805924

RESUMEN

α-Ketoglutarate (AKG) is attracting much attention from researchers owing to its beneficial effects on anti-aging and cancer suppression, and, more recently, in nutritional supplements. Given that glucose is the main source of energy to maintain normal physiological functions of skeletal muscle, the effects of AKG supplementation for improving muscle performance are closely related to the glucose level in skeletal muscle. The differences of AKG-induced effects in skeletal muscle between two states of normal energy and energy deficiency are unclear. Furthermore, AKG-induced metabolic changes in skeletal muscles in different energy states also remain elusive. Here, we assessed the effects of AKG supplementation on mouse C2C12 myoblast cells cultured both in normal medium (Nor cells) and in low-glucose medium (Low cells), which were used to mimic two states of normal energy and energy deficiency, respectively. We further performed NMR-based metabolomic analysis to address AKG-induced metabolic changes in Nor and Low cells. AKG supplementation significantly promoted the proliferation and differentiation of cells in the two energy states through glutamine metabolism, oxidative stress, and energy metabolism. Under normal culture conditions, AKG up-regulated the intracellular glutamine level, changed the cellular energy status, and maintained the antioxidant capacity of cells. Under low-glucose culture condition, AKG served as a metabolic substrate to reduce the glutamine-dependence of cells, remarkably enhanced the antioxidant capacity of cells and significantly elevated the intracellular ATP level, thereby ensuring the normal growth and metabolism of cells in the state of energy deficiency. Our results provide a mechanistic understanding of the effects of AKG supplements on myoblasts in both normal energy and energy deficiency states. This work may be beneficial to the exploitation of AKG applications in clinical treatments and nutritional supplementations.


Asunto(s)
Metabolismo Energético/efectos de los fármacos , Ácidos Cetoglutáricos/farmacología , Espectroscopía de Resonancia Magnética , Metabolómica , Mioblastos Esqueléticos/metabolismo , Animales , Línea Celular , Ratones
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