Targeting Myeloid Differentiation Primary Response Protein 88 (MyD88) and Galectin-3 to Develop Broad-Spectrum Host-Mediated Therapeutics against SARS-CoV-2.

Nearly six million people worldwide have died from the coronavirus disease (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although COVID-19 vaccines are largely successful in reducing the severity of the disease and deaths, the decline in vaccine-induced immunity over time and the continuing emergence of new viral variants or mutations underscore the need for an alternative strategy for developing broad-spectrum host-mediated therapeutics against SARS-CoV-2. A key feature of severe COVID-19 is dysregulated innate immune signaling, culminating in a high expression of numerous pro-inflammatory cytokines and chemokines and a lack of antiviral interferons (IFNs), particularly type I (alpha and beta) and type III (lambda). As a natural host defense, the myeloid differentiation primary response protein, MyD88, plays pivotal roles in innate and acquired immune responses via the signal transduction pathways of Toll-like receptors (TLRs), a type of pathogen recognition receptors (PRRs). However, recent studies have highlighted that infection with viruses upregulates MyD88 expression and impairs the host antiviral response by negatively regulating type I IFN. Galectin-3 (Gal3), another key player in viral infections, has been shown to modulate the host immune response by regulating viral entry and activating TLRs, the NLRP3 inflammasome, and NF-κB, resulting in the release of pro-inflammatory cytokines and contributing to the overall inflammatory response, the so-called "cytokine storm". These studies suggest that the specific inhibition of MyD88 and Gal3 could be a promising therapy for COVID-19. This review presents future directions for MyD88- and Gal3-targeted antiviral drug discovery, highlighting the potential to restore host immunity in SARS-CoV-2 infections.

Current trends and future perspective of probiotic yeasts research in Indonesia.

Indonesia is a mega biodiversity country with various local wisdom, including the enormous variety of fermented foods and beverages. Indonesian researchers have conducted an intensive study to understand the diversity of microbes on those fermented products, one of which shows probiotic properties. Compared to that lactic acid bacteria, the study on probiotic yeasts is less explored. Probiotic yeast isolates are commonly isolated from traditional Indonesian fermented products. Saccharomyces, Pichia, and Candida are among Indonesia's most popular genera of probiotic yeasts, primarily applied in poultry and human health. The exploration of functional probiotic characteristics, such as antimicrobial, antifungal, antioxidant, and immunomodulator, has been widely reported from these local probiotic yeast strains. In vivo studies in a model organism such as mice conclude the prospective functional probiotic characteristics of the yeast isolates. Employment of current technology, such as omics, is essential in elucidating those functional properties. Advanced research and development of probiotic yeasts in Indonesia are gaining significant attention currently. For instance, probiotic yeasts-mediated fermentation in the production of kefir and kombucha are among the trend with promising economic value. The future trends of probiotic yeasts research in Indonesia are discussed in this review to give valuable sight into the application of indigenous probiotic yeasts in various fields.

Development of Galectin-3 Targeting Drugs for Therapeutic Applications in Various Diseases.

Galectin-3 (Gal3) is one of the most studied members of the galectin family that mediate various biological processes such as growth regulation, immune function, cancer metastasis, and apoptosis. Since Gal3 is pro-inflammatory, it is involved in many diseases that are associated with chronic inflammation such as cancer, organ fibrosis, and type 2 diabetes. As a multifunctional protein involved in multiple pathways of many diseases, Gal3 has generated significant interest in pharmaceutical industries. As a result, several Gal3-targeting therapeutic drugs are being developed to address unmet medical needs. Based on the PubMed search of Gal3 to date (1987-2023), here, we briefly describe its structure, carbohydrate-binding properties, endogenous ligands, and roles in various diseases. We also discuss its potential antagonists that are currently being investigated clinically or pre-clinically by the public and private companies. The updated knowledge on Gal3 function in various diseases could initiate new clinical or pre-clinical investigations to test therapeutic strategies, and some of these strategies could be successful and recognized as novel therapeutics for unmet medical needs.

In Vitro Evaluation of Curcumin Encapsulation in Gum Arabic Dispersions under Different Environments.

Biopolymers, especially polysaccharides (e.g., gum Arabic), are widely applied as drug carriers in drug delivery systems due to their advantages. Curcumin, with high antioxidant ability but limited solubility and bioavailability in the body, can be encapsulated in gum Arabic to improve its solubility and bioavailability. When curcumin is encapsulated in gum Arabic, it is essential to understand how it works in various conditions. As a result, in Simulated Intestinal Fluid and Simulated Gastric Fluid conditions, we investigated the potential of gum Arabic as the drug carrier of curcumin. This study was conducted by varying the gum Arabic concentrations, i.e., 5, 10, 15, 20, 30, and 40%, to encapsulate 0.1 mg/mL of curcumin. Under both conditions, the greater the gum Arabic concentration, the greater the encapsulation efficiency and antioxidant activity of curcumin, but the worse the gum Arabic loading capacity. To achieve excellent encapsulation efficiency, loading capacity, and antioxidant activity, the data advises that 10% is the best feasible gum Arabic concentration. Regarding the antioxidant activity of curcumin, the findings imply that a high concentration of gum Arabic was effective, and the Simulated Intestinal Fluid brought an excellent surrounding compared to the Simulated Gastric Fluid solution. Moreover, the gum Arabic releases curcumin faster in the Simulated Gastric Fluid condition.

Cellulose nanofibers of oil palm fronds as a filler in nanocomposite coating for corrosion protection of copper.

Cellulose nanofibers (CNF) create a physical barrier preventing contact with corrosive substances and improving corrosion prevention. Oil palm fronds (OPF), the primary source of underused biomass waste from plantations, were processed into CNF. The OPF-CNF, mixed with hydroxyethyl cellulose as the matrix, forms a nanocomposite. Corrosion analysis using electrochemical methods demonstrated that copper coated with cellulose-rich nanocomposite containing 5 % CNF had a significantly decreased corrosion rate with an efficiency of 97.92 %. This CNF-based coating, combining barrier and passivation mechanisms, enhances performance, providing a competitive, eco-friendly alternative to conventional coatings.

Prospect of Gum Arabic-Cocoliposome Matrix to Encapsulate Curcumin for Oral Administration.

Curcumin is an antioxidant that can effectively eliminate free radicals. However, as its oral bioavailability is low, an effective delivery method is required. Phospholipid-based liposomes can encapsulate lipophilic drugs, such as curcumin, while liposome, cholesterol, and gum Arabic (GA) can enhance the internal and external stability of drug membranes. This present study used concentrations of cholesterol (Cchol) and GA (CGA), ranging from 0 to 10, 20, 30, and 40% as well as 0 to 5, 10, 15, 20, 30, and 40%, respectively, to encapsulate curcumin in a GA-cocoliposome (CCL/GA) matrix and test its efficacy in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF). The absence of new characteristic peaks in the Fourier transform infrared (FTIR) spectra results indicate the presence of non-covalent interactions in the CCL/GA encapsulation. Furthermore, increasing the Cchol decreased the encapsulation efficiency (EE), loading capacity (LC), and antioxidant activity (IR) of the CCL/GA encapsulation but increased its release rate (RR). Conversely, increasing CGA increased its EE and IR but decreased its LC and RR. The two conditions applied confirmed this. Liposomal curcumin had the highest IR in SIF (84.081%) and the highest RR in SGF (0.657 ppm/day). Furthermore, liposomes loaded with 10% Cchol and 20% CGA performed best in SIF, while those loaded with 10% Cchol and 30% CGA performed best in SGF. Lastly, the CCL/GA performed better in SIF than SGF.

Random forest-based simultaneous and proportional myoelectric control system for finger movements.

A classification scheme for myoelectric control systems (MCS) cannot mimic complex hand movements. This paper presents simultaneous and proportional MCS by estimating the angles of fourteen finger joints using time-domain feature extraction and random forest. The experimental results show that the best feature was the root mean square (RMS). Furthermore, the random forest attained an average coefficient of determination (R2) of 0.85 compared to other regressors which perform below 0.75. The ANOVA tests indicated that the performance of the proposed system was significantly different. Therefore, the proposed system will be the best option for real-time MCS applications in the future.

An Empirical Study on the Use of Digital Technologies to Achieve Cost-Effectiveness in Healthcare Management.

Objectives: Healthcare cost reduction is one of the major challenges of the current era. This study was based on the general system theory-based view to assess the significance of sensing communication technologies and processing actuation technologies in improving healthcare quality, leading to cost reduction. Moreover, the contingent rule of healthcare supply chain management in enhancing the influence of improved quality on healthcare cost reduction was also empirically tested. Methods: The sample of the study comprised 337 middle and senior healthcare managers employed in various government and private hospitals and health institutions in Jakarta, Indonesia. The administrative departments of each hospital and health institution was visited to take their consent to conduct this survey at their clinical and non-clinical departments. The data collected was analyzed using SmartPLS ver. 4 software. Results: Results reveal a significant direct and indirect influence of sensing communication technologies and processing actuation technologies on achieving cost-effectiveness in the healthcare sector, in the presence of perceived quality improvement as a mediator. However, the strength of the associations varied and was based on highly reliable and familiar nature of sensing communication technologies compared to processing actuation technologies which were emerging and gaining popularity in recent years. Conclusion: Considering the healthcare cost as a critical factor based on limited resources in emerging economies, healthcare institutions/centers should use digital technologies to achieve cost-effectiveness for providing healthcare facilities in the industry 4.0 era.

SARS-CoV-2 Antibody Neutralization Assay Platforms Based on Epitopes Sources: Live Virus, Pseudovirus, and Recombinant S Glycoprotein RBD.

The high virulent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that emerged in China at the end of 2019 has generated novel coronavirus disease, coronavirus disease 2019 (COVID-19), causing a pandemic worldwide. Every country has made great efforts to struggle against SARS-CoV-2 infection, including massive vaccination, immunological patients' surveillance, and the utilization of convalescence plasma for COVID-19 therapy. These efforts are associated with the attempts to increase the titers of SARS-CoV-2 neutralizing Abs (nAbs) generated either after infection or vaccination that represent the body's immune status. As there is no standard therapy for COVID-19 yet, virus eradication will mainly depend on these nAbs contents in the body. Therefore, serological nAbs neutralization assays become a requirement for researchers and clinicians to measure nAbs titers. Different platforms have been developed to evaluate nAbs titers utilizing various epitopes sources, including neutralization assays based on the live virus, pseudovirus, and neutralization assays utilizing recombinant SARS-CoV-2 S glycoprotein receptor binding site, receptor-binding domain. As a standard neutralization assay, the plaque reduction neutralization test (PRNT) requires isolation and propagation of live pathogenic SARS-CoV-2 virus conducted in a BSL-3 containment. Hence, other surrogate neutralization assays relevant to the PRNT play important alternatives that offer better safety besides facilitating high throughput analyses. This review discusses the current neutralization assay platforms used to evaluate nAbs, their techniques, advantages, and limitations.

A Novel Mechanism for Nitrosative Stress Tolerance Dependent on GTP Cyclohydrolase II Activity Involved in Riboflavin Synthesis of Yeast.

The biological functions of nitric oxide (NO) depend on its concentration, and excessive levels of NO induce various harmful situations known as nitrosative stress. Therefore, organisms possess many kinds of strategies to regulate the intracellular NO concentration and/or to detoxify excess NO. Here, we used genetic screening to identify a novel nitrosative stress tolerance gene, RIB1, encoding GTP cyclohydrolase II (GTPCH2), which catalyzes the first step in riboflavin biosynthesis. Our further analyses demonstrated that the GTPCH2 enzymatic activity of Rib1 is essential for RIB1-dependent nitrosative stress tolerance, but that riboflavin itself is not required for this tolerance. Furthermore, the reaction mixture of a recombinant purified Rib1 was shown to quench NO or its derivatives, even though formate or pyrophosphate, which are byproducts of the Rib1 reaction, did not, suggesting that the reaction product of Rib1, 2,5-diamino-6-(5-phospo-D-ribosylamino)-pyrimidin-4(3 H)-one (DARP), scavenges NO or its derivatives. Finally, it was revealed that 2,4,5-triamino-1H-pyrimidin-6-one, which is identical to a pyrimidine moiety of DARP, scavenged NO or its derivatives, suggesting that DARP reacts with N2O3 generated via its pyrimidine moiety.

Subject-independent Classification on Brain-Computer Interface using Autonomous Deep Learning for finger movement recognition.

The degradation of the subject-independent classification on a brain-computer interface is a challenging issue. One method mostly taken to overcome this problem is by collecting as many subjects as possible and then training the system across all subjects. This article introduces streaming online learning called autonomous deep learning (ADL) to classify five individual fingers based on electroencephalography (EEG) signals to overcome the issue above. ADL is a deep learning architecture that can construct its structure by itself through streaming learning and adapt its structure to the changes occurring in the input. In this article, the input of ADL is a common spatial pattern (CSP) extracted from the EEG signal of healthy subjects. The experimental results on the subject-dependence classification across four subjects using 5fold cross-validation show that that ADL achieved the classification accuracy of around 77%. This performance was excellent compared to a random forest (RF) and a convolutional neural network (CNN). They achieved accuracies of about 53% and 72%, respectively. On the subject-independent classification, ADL outperforms CNN by resulting stable accuracies for both training and testing, different from CNN that experience accuracy degradation to approximately 50%. These results imply that ADL is a promising machine learning in dealing with the issue in the subject-independent classification.

Extracorporeal shock wave therapy suppresses the early proinflammatory immune response to a severe cutaneous burn injury.

Following severe burn injury, persistent inflammation perpetuated by surface eschar, bacterial colonisation and neutrophil proteolytic activity can impede normal healing and result in further tissue damage. Extracorporeal shock wave treatment (ESWT) has been shown in the clinical setting to promote the healing of burn and difficult-to-heal wounds; however, the mechanism is unclear. We investigated the role of ESWT on the early proinflammatory response using a severe, full-thickness and highly inflammatory cutaneous burn wound in a murine model. Various wound-healing parameters were measured and leukocyte infiltration quantitated. A panel of 188 candidate genes known to be involved in acute inflammation and wound healing was screened. We show that ESWT of burn wounds 1 hour postwounding significantly blunts polymorphonuclear neutrophil and macrophage infiltration into the wound. ESWT treatment potently attenuates both CC- and CXC-chemokine expression, acute proinflammatory cytokine expression and extracellular matrix proteolytic activity at the wound margin. Given these findings and the clinical success of ESWT, we speculate that ESWT may be a potential therapeutic modality to treat severe wounds wherein excessive inflammatory responses involving increased levels of inflammatory cells, proinflammatory cytokines and proteases may become self-resolving allowing wound healing to progresses by way of normal physiological repair processes.

Angiogenic response to extracorporeal shock wave treatment in murine skin isografts.

Skin grafts are commonly utilized and proven effective methods of open wound coverage. Revascularization through neoangiogenesis is a pivotal mechanism for skin graft integration and durability. Extracorporeal shock-wave treatment (ESWT) has been demonstrated to accelerate wound repair; however, its mechanism-of-action is unclear. We investigated the role of ESWT in early revascularization of full-thickness skin isografts in a murine model. Cohorts of mice were euthanized and skin grafts were harvested 6 h, 2, 4, and 7 days post grafting +/- ESWT. Various aspects of graft neovascularization were measured including gross morphology, quantitative microscopy (vessel number, density), immunohistochemistry (CD31), cDNA SuperArrays for 84 angiogenesis-specific genes, and custom-designed 'Wound Repair' TaqMan Low Density Array (TLDA) cards to assess expression of 188 wound repair genes. We demonstrate that a single administration of ESWT immediately following skin grafting significantly enhances recipient graft revascularization (increased vessel number, size, and density). An augmented early pro-angiogenic and suppressed delayed pro-inflammatory response to ESWT was accompanied by significantly increased expression of both skin graft CD31 and angiogenesis pathway-specific genes, including ELR-CXC chemokines (CXCL1, CXCL2, CXCL5), CC chemokines (CCL2, CCL3, CCL4), cytokines (IL-1 beta, IL-6, G-CSF, VEGF-A), matrix metalloproteinases (MMP3, MMP9, MMP13), hypoxia-inducible factors (HIF-1 alpha), and vascular remodeling kinase (Mst1), as early as 6 h and up to 7 days post grafting and treatment. These findings suggest that early pro-angiogenic and anti-inflammatory effects of ESWT promote tissue revascularization and wound healing by augmenting angiogenesis and dampening inflammation.

Evaluation of feature extraction techniques and classifiers for finger movement recognition using surface electromyography signal.

Electromyography (EMG) in a bio-driven system is used as a control signal, for driving a hand prosthesis or other wearable assistive devices. Processing to get informative drive signals involves three main modules: preprocessing, dimensionality reduction, and classification. This paper proposes a system for classifying a six-channel EMG signal from 14 finger movements. A feature vector of 66 elements was determined from the six-channel EMG signal for each finger movement. Subsequently, various feature extraction techniques and classifiers were tested and evaluated. We compared the performance of six feature extraction techniques, namely principal component analysis (PCA), linear discriminant analysis (LDA), uncorrelated linear discriminant analysis (ULDA), orthogonal fuzzy neighborhood discriminant analysis (OFNDA), spectral regression linear discriminant analysis (SRLDA), and spectral regression extreme learning machine (SRELM). In addition, we also evaluated the performance of seven classifiers consisting of support vector machine (SVM), linear classifier (LC), naive Bayes (NB), k-nearest neighbors (KNN), radial basis function extreme learning machine (RBF-ELM), adaptive wavelet extreme learning machine (AW-ELM), and neural network (NN). The results showed that the combination of SRELM as the feature extraction technique and NN as the classifier yielded the best classification accuracy of 99%, which was significantly higher than those from the other combinations tested. Graphical abstract Mean of classification accuracies for 14 finger movements obtained with various pairs of SRELM and classifier.

Evaluation of extreme learning machine for classification of individual and combined finger movements using electromyography on amputees and non-amputees.

The success of myoelectric pattern recognition (M-PR) mostly relies on the features extracted and classifier employed. This paper proposes and evaluates a fast classifier, extreme learning machine (ELM), to classify individual and combined finger movements on amputees and non-amputees. ELM is a single hidden layer feed-forward network (SLFN) that avoids iterative learning by determining input weights randomly and output weights analytically. Therefore, it can accelerate the training time of SLFNs. In addition to the classifier evaluation, this paper evaluates various feature combinations to improve the performance of M-PR and investigate some feature projections to improve the class separability of the features. Different from other studies on the implementation of ELM in the myoelectric controller, this paper presents a complete and thorough investigation of various types of ELMs including the node-based and kernel-based ELM. Furthermore, this paper provides comparisons of ELMs and other well-known classifiers such as linear discriminant analysis (LDA), k-nearest neighbour (kNN), support vector machine (SVM) and least-square SVM (LS-SVM). The experimental results show the most accurate ELM classifier is radial basis function ELM (RBF-ELM). The comparison of RBF-ELM and other well-known classifiers shows that RBF-ELM is as accurate as SVM and LS-SVM but faster than the SVM family; it is superior to LDA and kNN. The experimental results also indicate that the accuracy gap of the M-PR on the amputees and non-amputees is not too much with the accuracy of 98.55% on amputees and 99.5% on the non-amputees using six electromyography (EMG) channels.

Low dose busulfan facilitates chimerism and tolerance in a murine model.

T cell depletion, sirolimus and "mega" dose donor specific bone marrow (DSBM) infusion promotes stable multilineage chimerism and indefinite survival of skin allografts in completely mismatched mice. The purpose of this study is to determine whether the addition of low dose busulfan can reduce the amount of DSBM required while preserving efficacy. C57BL/6 recipients of BALB/c skin allografts were treated with alphaCD4 and alphaCD8 monoclonal antibodies, DSBM, sirolimus and various doses of busulfan. The kinetics and phenotype of chimerism and the presence of clonal deletion of alloreactive T-cells were defined using flow cytometry. In vitro reactivity was determined using mixed lymphocyte culture. Second skin grafts confirmed the presence of tolerance. All doses of busulfan resulted in engraftment when combined with this regimen using a reduced dose of donor marrow. The level, kinetics and character of chimerism observed were dose related. Chimerism was associated with indefinite allograft acceptance (>200 days). Tolerance was documented both in vitro/in vivo and was associated with clonal deletion. Addition of a single low dose of busulfan to an established tolerance protocol reduced the required DSBM dose by over 80% while still promoting comparable levels of donor chimerism and donor-specific tolerance.

Adaptive myoelectric pattern recognition for arm movement in different positions using advanced online sequential extreme learning machine.

The performance of the myoelectric pattern recognition system sharply decreases when working in various limb positions. The issue can be solved by cumbersome training procedure that can anticipate all possible future situations. However, this procedure will sacrifice the comfort of the user. In addition, many unpredictable scenarios may be met in the future. This paper proposed a new adaptive myoelectric pattern recognition using advance online sequential extreme learning (AOS-ELM) for classification of the hand movements to five different positions. AOS-ELM is an improvement of OS-ELM that can verify the adaptation validity using entropy. The proposed adaptive MPR was able to classify eight different classes from eleven subjects by accuracy of 95.42 % using data from one position. After learning the data from whole positions, the performance of the proposed system is 86.13 %. This performance was better than the MPR that employed original OS-ELM, but it was worse than the MPR that utilized the batch classifiers. Nevertheless, the adaptation mechanism of AOS-ELM is preferred in the real-time application.

A robust myoelectric pattern recognition using online sequential extreme learning machine for finger movement classification.

A robust myoelectric pattern-recognition-system requires a system that should work in the real application as good as in the laboratory. However, this demand should be handled properly and rigorously to achieve a robust myoelectric system. Electrode shift is an issue that usually emerges when dealing with robustness issue. In daily life, the placement of electrodes becomes a significant issue that can downgrade the performance of the system. This paper proposed a new way to overcome the robustness issue by conducting an update to the system to anticipate changes in the future such as electrode shift, improvement in muscle strength or any other issue. Such update will be used to generate an adaptation. The adaptation is done according to the user's need by employing an online sequential extreme learning (OS-ELM) to learn the training data chunk by chunk. OS-ELM enables the myoelectric system to learn from a small number of data to avoid cumbersome training process. The day-to-day experiment shows that the proposed system can maintain its performance on average accuracy around 85% whereas the non-adaptive system could not.

Targeted T-cell depletion or CD154 blockade generates mixed hemopoietic chimerism and donor-specific tolerance in mice treated with sirolimus and donor bone marrow.

BACKGROUND: The administration of donor specific bone marrow (DSBM) to mice conditioned with antilymphocyte serum (ALS) and sirolimus can result in stable multilineage mixed chimerism and long-term graft survival. This study seeks to determine if either the targeted depletion of CD4 and/or CD8 pos T cells or costimulation blockade can substitute for ALS and preserve the efficacy of this regimen. METHODS: C57BL/6 recipients of BALB/c skin allografts were treated with DSBM (150 x 10(6) cells), sirolimus (24 mg/kg intraperitonealy), and either ALS or various monoclonal antibodies (alphaCD4, alphaCD8, alphaCD154 alone or in combination). Recipient peripheral blood mononuclear cell (PBMC) depletion, donor chimerism, and deletion of donor reactive T cells were assessed using flow cytometry. The specificity of immunologic nonreactivity and the presence of immunoregulatory activity were assessed through a mixed lymphocyte reaction assay. RESULTS: The administration of ALS, sirolimus, and DSBM resulted in sustained recipient PBMC depletion, transient chimerism, and prolonged graft survival. The substitution of an equivalent degree and duration of targeted depletion of either CD4 or CD8 pos T cells alone for ALS failed to produce chimerism or prolonged graft survival. In contrast, depletion of both CD4 and CD8 pos T cells resulted in durable multilineage chimerism, indefinite allograft acceptance (>350 days), and donor-specific tolerance to secondary skin grafts. Substitution of alphaCD154 monoclonal antibody for ALS also resulted in a state of mixed chimerism and donor specific tolerance. This tolerant state appears to be maintained at least partially through clonal deletion and suppression. CONCLUSION: Either combined CD4 and CD8 T-cell depletion or alphaCD154 blockade can effectively substitute for ALS in producing chimerism and tolerance in this model.