COVID-19 abatement strategies have risks and uncertainties which could lead to repeating waves of infection. We show-as proof of concept grounded on rigorous mathematical evidence-that periodic, ...high-frequency alternation of into, and out-of, lockdown effectively mitigates second-wave effects, while allowing continued, albeit reduced, economic activity. Periodicity confers (i) predictability, which is essential for economic sustainability, and (ii) robustness, since lockdown periods are not activated by uncertain measurements over short time scales. In turn-while not eliminating the virus-this fast switching policy is sustainable over time, and it mitigates the infection until a vaccine or treatment becomes available, while alleviating the social costs associated with long lockdowns. Typically, the policy might be in the form of 1-day of work followed by 6-days of lockdown every week (or perhaps 2 days working, 5 days off) and it can be modified at a slow-rate based on measurements filtered over longer time scales. Our results highlight the potential efficacy of high frequency switching interventions in post lockdown mitigation. All code is available on Github at https://github.com/V4p1d/FPSP_Covid19. A software tool has also been developed so that interested parties can explore the proof-of-concept system.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Short-chain fatty acids (SCFAs), especially acetate, propionate and butyrate, are the end products from the intestinal microbial fermentation of dietary fibers and resistant starch. It has been well ...documented that plasma and colonic SCFAs are associated with metabolic syndromes. Recently, the involvement of SCFAs in energy homeostasis regulation has been extensively studied. The importance of SCFAs on energy metabolism has highlighted the potential of modulating SCFAs as a nutritional target to prevent and counteract metabolism disorders and its associated diseases such as obesity and type 2 diabetes. Here, we summarize the current knowledge about the biological properties of SCFAs with their impact on the energy homeostasis.
Lentinan, a
β-(1 → 3)-
d-glucan isolated from a common edible mushroom,
Lentinus edodes, is known as a biologically active macromolecules with very strong host-mediated anti-cancer activity, via ...activation of the human immune system. However, its widespread medicinal application is hindered by some technical difficulties in its extraction and purification, as well as a lack of thorough understanding of the structure-and-function relationship of this polysaccharide. This review aims at highlighting the different areas of research conducted on lentinan in the past 40 years, including its extraction and purification processes, the analysis of structure, the determination of its chain conformation and conformation transition in solution, as well as its rheological properties and bioactivities especially on anti-cancer treatment. About 156 literatures were cited to summarize the advancement of lentinan in the review paper.
Display omitted This review aims at highlighting the different areas of research conducted on lentinan in the past 40 years, including its extraction and purification processes, the analysis of structure, the determination of its chain conformation and conformation transition in solution, as well as its rheological properties and bioactivities especially on anti-cancer treatment.
Deep neural networks have proven to be particularly effective in visual and audio recognition tasks. Existing models tend to be computationally expensive and memory intensive, however, and so methods ...for hardware-oriented approximation have become a hot topic. Research has shown that custom hardware-based neural network accelerators can surpass their general-purpose processor equivalents in terms of both throughput and energy efficiency. Application-tailored accelerators, when co-designed with approximation-based network training methods, transform large, dense, and computationally expensive networks into small, sparse, and hardware-efficient alternatives, increasing the feasibility of network deployment. In this article, we provide a comprehensive evaluation of approximation methods for high-performance network inference along with in-depth discussion of their effectiveness for custom hardware implementation. We also include proposals for future research based on a thorough analysis of current trends. This article represents the first survey providing detailed comparisons of custom hardware accelerators featuring approximation for both convolutional and recurrent neural networks, through which we hope to inspire exciting new developments in the field.
AbstractObjectiveTo evaluate the effectiveness of heterologous and homologous covid-19 vaccine regimens with and without boosting in preventing covid-19 related infection, hospital admission, and ...death.DesignLiving systematic review and network meta-analysis.Data sourcesWorld Health Organization covid-19 databases, including 38 sources of published studies and preprints.Study selectionRandomised controlled trials, cohort studies, and case-control studies.Methods38 WHO covid-19 databases were searched on a weekly basis from 8 March 2022. Studies that assessed the effectiveness of heterologous and homologous covid-19 vaccine regimens with or without a booster were identified. Studies were eligible when they reported the number of documented, symptomatic, severe covid-19 infections, covid-19 related hospital admissions, or covid-19 related deaths among populations that were vaccinated and unvaccinated. The primary measure was vaccine effectiveness calculated as 1−odds ratio. Secondary measures were surface under the cumulative ranking curve (SUCRA) scores and the relative effects for pairwise comparisons. The risk of bias was evaluated by using the risk of bias in non-randomised studies of interventions (ROBINS-I) tool for all cohort and case-control studies. The Cochrane risk of bias tool (version 2; ROB-2) was used to assess randomised controlled trials.ResultsThe first round of the analysis comprised 53 studies. 24 combinations of covid-19 vaccine regimens were identified, of which a three dose mRNA regimen was found to be the most effective against asymptomatic and symptomatic covid-19 infections (vaccine effectiveness 96%, 95% credible interval 72% to 99%). Heterologous boosting using two dose adenovirus vector vaccines with one mRNA vaccine has a satisfactory vaccine effectiveness of 88% (59% to 97%). A homologous two dose mRNA regimen has a vaccine effectiveness of 99% (79% to 100%) in the prevention of severe covid-19 infections. Three dose mRNA is the most effective in reducing covid-19 related hospital admission (95%, 90% to 97%). The vaccine effectiveness against death in people who received three doses of mRNA vaccine remains uncertain owing to confounders. In the subgroup analyses, a three dose regimen is similarly effective in all age groups, even in the older population (≥65 years). A three dose mRNA regimen works comparably well in patients who are immunocompromised and those who are non-immunocompromised. Homologous and heterologous three dose regimens are effective in preventing infection by covid-19 variants (alpha, delta, and omicron).ConclusionAn mRNA booster is recommended to supplement any primary vaccine course. Heterologous and homologous three dose regimens work comparably well in preventing covid-19 infections, even against different variants. The effectiveness of three dose vaccine regimens against covid-19 related death remains uncertain.Systematic review registrationThis review was not registered. The protocol is included in the supplementary document.Readers’ noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.
•β-glucans can be specifically recognized by immune cells like macrophages.•Cancer immunotherapy based on TAMs profile in TME is an emerging strategy with its unique merits.•β-glucans have the ...potential use as nano-carrier for drug delivery targeting TAMs.
Use of polysaccharides as carriers in drug delivery system is a hot topic, especially those with specific recognition of immune cells, enabling them to be applied in targeting delivery system. β-d-glucans are naturally occurring non-digestible polysaccharides with immunomodulatory activities that have attracted increasing attention to serve as therapeutic agents or immune-adjuvants. Being able to be specifically recognized by immune cells like macrophages, β-d-glucans can be developed as promising carriers for targeting delivery with stability, biocompatibility and specificity when applied in immunotherapy. Targeting tumor associated macrophages (TAMs) is an emerging strategy for cancer immunotherapy since it exerts anti-cancer effects based on modulating body immunity in tumor microenvironment (TME). This new strategy does not require high concentration of drugs to kill cancer cells directly and lessen tumor recurrence by creating unique immune memory for malignant cells. In this review, construction strategies of polysaccharide-based drug delivery system of three types of β-d-glucan including non-yeast and yeast β-d-glucans as well as hyper-branched β-d-glucan are discussed with reference to their branching characteristics and conformation. The applications of these β-d-glucans as nano-carrier for drug delivery targeting TAMs are also discussed.
•Natural hyperbranched polysaccharides (HBPSs) possess unique structural features.•HBPSs could be isolated from plant, animal, microbial and fungal origins.•Many HBPSs exhibit compelling biological ...activities.•HBPSs have versatile applications in food, medicine, cosmetic, and nanomaterials.
In recent years, hyperbranched polymers, especially the natural hyperbranched polysaccharides (HBPSs), are receiving much attention due to their diverse biological activities and applications. With high degree of branching (DB), HBPSs mainly exist in the form of either a comb-brush shape, dendrimer-like particulate, or globular particle. HBPSs also possess some unique properties, such as high density, large spatial cavities, and numerous terminal functional groups, which distinguish them from other polymers. As a natural biopolymer, HBPS has excellent bioavailability, biocompatibility, and biodegradability, which have versatile applications in the fields of food, medicine, cosmetic, and nanomaterials. In this review, the source and structure of HBPSs from plant, animal, microbial and fungal origins as well as their biological functions and applications are covered, with the aim of further advancing the research of their structure and bioactivity.
A novel water-soluble polysaccharide–protein complex (PRW1) isolated from the sclerotia of an edible mushroom Polyporus rhinocerus which was purified by membrane ultrafiltration could significantly ...activate murine macrophages RAW264.7 in vitro. PRW1 had a molecular weight of less than 50 kDa and was found to be a highly branched heteropolysaccharide–protein complex composed of 45.7 ± 0.97% polysaccharide and 44.2 ± 0.41% protein. Based on the results of total acid hydrolysis, methylation analysis, and Fourier transform infrared spectroscopy, the carbohydrate moiety of PRW1 was found to be a β-d-mannoglucan with its backbone containing →1)-d-Glcp-(4→, →1)-d-Glcp-(6→, and →1)-d-Manp-(2→ residues (molar ratio of 5:4:6) and having terminal d-Glcp as side chain (degree of branching of 0.62). In vitro studies showed that PRW1 significantly induced NO production and enhanced the release of a variety of cytokines including G-CSF, GM-CSF, IL-6, IL12p40/70, MCP-1, MCP-5, MIP-1-α, MIP-2, RANTES, sTNFRI, and TNF-α. Mechanistically, PRW1 treatment triggered ERK phosphorylation to activate macrophages within 15 min and significantly increased the expression level of inducible NOS after 6 h. In summary, this study indicates that PRW1 derived from the sclerotia of P. rhinocerus is a potential immunomodulatory agent for cancer immunotherapy.
In this study, an immunologically active novel microparticulate mushroom β-glucan (PRA-1p) was prepared using an alkali-soluble glucan PRA-1 by an emulsification and cross-linking method. PRA-1 was a ...hyperbranched (1→3),(1→6)-β-d-glucan with a degree of branching of 0.89, isolated from the sclerotia of Polyporus rhinocerus. PRA-1 had a rod-like conformation, while PRA-1p exhibited a monodisperse and homogeneous spherical conformation with a diameter ranging from 0.3 to 2.0 μm in water. PRA-1p significantly induced nitric oxide and reactive oxygen species production as well as morphological changes of murine macrophages (RAW 264.7 cells) and upregulated their phagocytic activity. Furthermore, PRA-1p treatment markedly enhanced the secretion of cytokines, including cutaneous T cell-attracting chemokine 27, granulocyte-colony-stimulating factor, monocyte chemoattractant protein 1, macrophage inflammatory protein 1α, macrophage inflammatory protein 2, regulated on activation, normal T cell expressed and secreted, soluble tumor necrosis factor receptor 1, and tissue inhibitors of metalloproteinases. Activation of RAW 264.7 cells triggered by PRA-1p was associated with activation of inducible nitric oxide synthase, nuclear factor κB, extracellular signal-regulated kinase, and protein kinase B. This work suggests that novel PRA-1p derived from the mushroom sclerotia of P. rhinocerus has potential application as an immunostimulatory agent.
This study evaluated the immunomodulatory effects of two high-molecular-weight and structurally different mushroom polysaccharides, an alkali-soluble polysaccharide (mPRSon) and a water-soluble ...polysaccharide–protein complex (PRW), isolated previously from the sclerotia of Pleurotus rhinocerus, on the maturation of murine bone-marrow-derived dendritic cells (BMDCs). The effects of mPRSon and PRW on the expression of morphological change, surface molecules, phagocytic activity, and cytokine release in BMDCs were determined by flow cytometry and a mouse cytokine array. The results showed that both mPRSon and PRW could induce phenotypic and functional maturation of BMDCs. At the same time, mPRSon upregulated the expression of membrane phenotypic marker CD86 and PRW markedly upregulated CD40, CD80, and CD86. In addition, mPRSon could bind to the dectin-1 receptor and stimulate the release of MIP-1α, MIP-2, and IL-2, while PRW could bind to complement receptor 3 and toll-like receptor 2 with an upregulation of the expression of IL-2, IL-6, MIP-1α, MIP-2, RANTES, IL-12p40p70, IL-12p70, TIMP-1, IFN-γ, KC, MCP-1, and GCSF. The study provides additional information on how structural differences in sclerotial polysaccharides influence their immunomodulatory activities on BMDCs involving different PAMP receptors. It is anticipated that more understanding of the interactions between the sclerotial polysaccharides and their receptors in immune cells can facilitate their future application for cancer immunotherapy.
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