Search Results (72)

Diseases associated with yeast pathogens have become an increasingly serious global health issue. The range of virulence factors and the development of mechanisms of resistance have posed a significant challenge in the fight against these types of infections. Lectins, proteins capable of reversibly binding to carbohydrates and glycoconjugates, have been assessed as antifungal agents. This review shows that lectins have demonstrated versatility and significant potential as therapeutic agents against Candida, Nakaseomyces and Cryptococcus. These molecules act through diverse mechanisms, including disruption of fungal cell membranes, induction of oxidative stress, inhibition of ergosterol biosynthesis, and interference with mitochondrial and lysosomal functions. Some lectins have been shown to inhibit yeast-to-hyphae morphological transitions and biofilm formation, which are critical virulence factors for pathogenic yeasts. Moreover, some lectins have shown potential to enhance the efficacy of conventional antifungal drugs through synergistic interactions, though these effects can depend on the fungal isolate. Beyond in vitro activity, translational considerations remain underdeveloped in the context of antifungal applications of lectins. Some lectins exhibit minimal toxicity, while others require careful dosing due to potential toxicity or undesired immunogenicity. Delivery and stability also present challenges, though strategies such as chemical modifications and topical, mucosal, or nanoparticle-based formulations show promise. Overall, the multifaceted antifungal activities of lectins highlight their promising role as innovative candidates in the development of novel therapies to address the growing challenge of yeast pathogen resistance. However, significant knowledge gaps persist, highlighting the urgent need for coordinated research that bridges in vitro findings with practical pharmacological applications. Full article

Abortive zoonoses represent a major public-health threat and a significant constraint on small-ruminant production in West Africa, particularly in Benin. Yet they remain largely undocumented from the perspective of frontline actors. This cross-sectional study assessed the levels of knowledge, attitude, and perception (KAP) of Beninese farmers, butchers, meat inspectors, and para-veterinary staff. A structured questionnaire containing 28 items (11 knowledge, 9 attitudes, 8 perception) was administered to four professional groups (small ruminant keeper, para-veterinarian, butcher and meat inspectors) from four communes in the South, Central, and North of Benin. The number of correct and desirable responses was evaluated on a 0–100% scale. Overall, respondents demonstrated limited knowledge (50.4 ± 25.2%), highly undesirable attitudes (71.0 ± 23.2%) (higher attitude score means risky practices), and likely desirable (65.0 ± 24.4%) toward abortive zoonoses. Mixed-effect linear regression revealed that knowledge was generally higher among trained professionals such as meat inspectors and para-veterinarians. On the other hand, farmers and butchers showed larger informational gaps and more frequent risky practices. Respondents with previous experience of livestock abortion tended to be more aware of zoonotic risks but did not consistently translate this awareness into safer behavior. Correlations between knowledge and perception were weak and non-significant (r = 0.14; p = 0.135). Psychometric analysis revealed that the Knowledge scale was robust and effectively discriminated between respondents, while the Attitude scale showed poor validity, likely due to social desirability bias. Most participants perceived abortive diseases as a serious threat, yet this awareness did not translate into safer practices. The findings highlight substantial cognitive gaps, persistent risky practices and an incomplete perception of danger among value-chain actors. They underscore the need for targeted, behavior-change interventions in Benin, prioritizing practical training for farmers and butchers and the scaling-up of flock vaccination within a strengthened One Health framework. Full article

Obesity is a chronic disorder associated with serious comorbidities such as diabetes, cardiovascular disease, and cancer. Conventional pharmacological treatments often suffer from limited efficacy, poor selectivity, and undesirable side effects, highlighting the need for more effective alternatives. Nanomedicine offers a promising approach by overcoming these limitations through targeted drug delivery and enhanced therapeutic precision. This review examines key nanotechnological strategies in obesity management, including targeting white adipose tissue (WAT) and the vascular marker prohibitin, promoting WAT browning, and utilizing photothermal therapy and magnetic hyperthermia as nanotheranostic tools. We discuss major nanomedicine platforms—such as liposomes, nanoemulsions, and polymeric nanoparticles—alongside emerging applications in gene nanotherapy and herbal formulations. Potential toxicity concerns are also addressed. In summary, nanomedicine holds substantial potential to revolutionize obesity treatment through targeted, effective, and multifunctional therapeutic strategies. Full article

Ignoring the presence of non-performing assets makes efficiency measurement inappropriate and incomplete. Thus, the present study considers non-performing assets as an undesirable output and applies the slack-based efficiency model to measure the efficiency of public sector banks in India during 2004–2005 to 2018–2019. A two-metric performance assessment of sample banks is carried out using mean efficiency and the non-performing assets management ratio. This study is extended to investigate determinants of bank efficiency using a fixed effects model and dynamic panel data regression on the contextual variables. Results show that profitability as measured by return on equity (ROE) and priority sector exposure have had no impact on efficiency. However, cost of deposits and capital adequacy ratio have a significant negative impact on the efficiency of public sector banks in India. Most importantly, the study finds a decline in efficiency in recent years, indicating a necessity of serious efforts for revamping these state-owned banks. Full article

The interpretation of the biochemistry of immune metabolism could be considered an attractive scientific field of biomedicine research. In this review, the role of glycolysis in macrophage polarization is discussed together with mitochondrial metabolism in cancer cells. In the first part, the focus is on the Warburg effect and redox metabolism during macrophage polarization, cancer development, and management of the immune response by the cancer cells. The second part addresses the possibility of impacts on the Warburg effect through targeting peroxisome proliferator-activated receptors (PPARs). This could be an activator of native immune responses. Because of the reported serious adverse effects of using synthetic ligands for PPARs in combination with chemotherapeutics, searches for less toxic and more active PPAR inhibitors, as well as blocking undesirable cellular PPAR-dependent processes, are in progress. On the other hand, recent research in modern immunotherapy has focused on the search for gentle immune-modulating natural compounds with harmless synergistic chemotherapeutic efficacy that can be used as an adjuvant. It is a well-known fact that the plant kingdom is a source of important therapeutic agents with multifaceted effectiveness. One of these is the known association with PPAR activities. In this regard, the secondary metabolites extracted from plants could change the game. Full article

Distal radius fractures (DRF) are one of the most prevalent injuries a person may sustain. The current treatment of DRF involves the use of casts made from Plaster of Paris or fiberglass. The application of these materials is a serious endeavor that influences their intended use, and should be conducted by specially trained personnel. In this research, with the use of the full-body 3D scanner Vitus Smart, 3D modelling software Rhinoceros 3D, and 3D printer Creality CR-10 max, an easy, yet effective workflow of orthosis fabrication was developed. Furthermore, samples that represent segments of the orthosis were subjected to static loading. Lastly, fragments that occurred due to excessive force were characterized with the use of a digital microscope. It was observed that with the implementation of the designed workflow, a faster 3D printing process was present. Samples subjected to mechanical loading had values that exceeded those of conventional Plaster of Paris; the minimum recorded value was 681 N, while the highest was 914 N. Microscopic characterization enabled a clear insight into the occurrence of fragments, as well as their potential risk. Therefore, in this research, an insight into different stages of fabrication, characterization of undesirable events, as well as the risks they may pose were presented. Full article

Due to the inherent broadcasting nature and openness of wireless transmission channels, wireless communication systems are vulnerable to the eavesdropping of malicious attackers and usually encounter undesirable situations of information leakage. The problem may be more serious when a passive eavesdropping device is directly connected to the transmitter of a single-input single-output (SISO) system. To deal with this urgent situation, a novel IRS-assisted physical-layer secure transmission scheme based on joint transmitter perturbation and IRS reflection (JPR) is proposed, such that the secrecy of wireless SISO systems can be comprehensively guaranteed regardless of whether the reflection-based jamming from the IRS to the eavesdropper is blocked or not. Moreover, to develop a trade-off between the achievable performance and implementation complexity, we propose both element-wise and group-wise reflected perturbation alignment (ERPA/GRPA)-based IRS reflection strategies, respectively. In order to evaluate the achievable performance, we analyze the ergodic secrecy rate (ESR) and secrecy outage probability (SOP) of the SISO secure systems with the ERPA/GRPA-based JPRs, respectively. Finally, by characterizing the simulated and numerical ESR and SOP performance results, our proposed scheme is compared with the benchmark scheme of random phase-based reflection, which strongly demonstrates the effectiveness of our proposed scheme. Full article

The treatment of patients diagnosed with hematologic malignancies typically includes hematopoietic stem cell transplantation (HSCT) as part of a therapeutic standard of care. The primary graft source of hematopoietic stem and progenitor cells (HSPCs) for HSCT is mobilized from the bone marrow into the peripheral blood of allogeneic donors or patients. More recently, these mobilized HSPCs have also been the source for gene editing strategies to treat diseases such as sickle-cell anemia. For a HSCT to be successful, it requires the infusion of a sufficient number of HSPCs that are capable of adequate homing to the bone marrow niche and the subsequent regeneration of stable trilineage hematopoiesis in a timely manner. Granulocyte-colony-stimulating factor (G-CSF) is currently the most frequently used agent for HSPC mobilization. However, it requires five or more daily infusions to produce an adequate number of HSPCs and the use of G-CSF alone often results in suboptimal stem cell yields in a significant number of patients. Furthermore, there are several undesirable side effects associated with G-CSF, and it is contraindicated for use in sickle-cell anemia patients, where it has been linked to serious vaso-occlusive and thrombotic events. The chemokine receptor CXCR4 and the cell surface integrin α4β1 (very late antigen 4 (VLA4)) are both involved in the homing and retention of HSPCs within the bone marrow microenvironment. Preclinical and/or clinical studies have shown that targeted disruption of the interaction of the CXCR4 or VLA4 receptors with their endogenous ligands within the bone marrow niche results in the rapid and reversible mobilization of HSPCs into the peripheral circulation and is synergistic when combined with G-CSF. In this review, we discuss the roles CXCR4 and VLA4 play in bone marrow homing and retention and will summarize more recent development of small-molecule CXCR4 and VLA4 inhibitors that, when combined, can synergistically improve the magnitude, quality and convenience of HSPC mobilization for stem cell transplantation and ex vivo gene therapy after the administration of just a single dose. This optimized regimen has the potential to afford a superior alternative to G-CSF for HSPC mobilization. Full article

Bacteria are capable of remarkable adaptations to their environment, including undesirable bacterial resistance to antibacterial agents. One of the most serious cases is an infection caused by multidrug-resistant Staphylococcus aureus, which has unfortunately also spread outside hospitals. Therefore, the development of new effective antibacterial agents is extremely important to solve the increasing problem of bacterial resistance. The bacteriolytic enzyme autolysin E (AtlE) is a promising new drug target as it plays a key role in the degradation of peptidoglycan in the bacterial cell wall. Consequently, disruption of function can have an immense impact on bacterial growth and survival. An in silico and in vitro evaluation of iminosugar derivatives as potent inhibitors of S. aureus (AtlE) was performed. Three promising hit compounds (1, 3 and 8) were identified as AtlE binders in the micromolar range as measured by surface plasmon resonance. The most potent compound among the SPR response curve hits was 1, with a K_D of 19 μM. The K_D value for compound 8 was 88 μM, while compound 3 had a K_D value of 410 μM. Full article

The objective of the present study was to assess the effect of intra-articular Hyaluronic acid (HA) and Chondroitin sulfate (CS) supplementation (Hialurom^® Hondro (HH)) on pain symptoms and joint mobility. In total, 60 mg/mL sodium hyaluronate and 90 mg/mL CS were administered to 21 patients (17 females and 4 males) respecting the in-force requirements, excluding patients with some specific comorbidities. In addition to the clinical study (where the pain intensity (severity) and joint mobility were assessed), rheological characterization was conducted evaluating the following parameters: elastic modulus (G′), loss modulus (G″) oscillatory frequency (fc) at 0.5 Hz and 2.5 Hz, crossover frequency (fc), relaxation time (λ) where it was noticed that the addition of chondroitin sulfate (CS) to sodium hyaluronate (SH) significantly enhances and improves the viscoelastic properties, particularly at higher shear frequencies. A significant decrease in pain intensity felt by the subjects was found, from 7.48 (according to Wong–Baker scale)—pain close to 8 (the patient is unable to perform most activities), to more reduced values of 5.86—at 6 weeks after injection, 4.81—at 3 months after injection, and 5.24—at 6 months after injection, improvements in symptoms was fast and durable. Data related to the evolution of joint mobility show that at 6 weeks after injection, the mobility of joints increased by 17.8% and at 6 months by 35.61%. No serious adverse events were reported with undesired effects so that they would impose additional measures. Better resistance to enzymatic degradation and free radicals could be expected from the synergic combination of sodium hyaluronate and chondroitin sodium sulfate, this having a special importance for the patients, granting them the ability to perform more ample movements and reducing dependency on attendants, thus increasing quality of life. Full article

The high power-conversion efficiencies of hybrid perovskite solar cells encourage many researchers. However, their limited photostability represents a serious obstacle to the commercialization of this promising technology. Herein, we present an efficient method for improving the intrinsic photostability of a series of commonly used perovskite material formulations such as MAPbI₃, FAPbI₃, Cs_0.12FA_0.88PbI₃, and Cs_0.10MA_0.15FA_0.75PbI₃ through modification with octenidine dihydroiodide (OctI₂), which is a widely used antibacterial drug with two substituted pyridyl groups and two cationic centers in its molecular framework. The most impressive stabilizing effects were observed in the case of FAPbI₃ and Cs_0.12FA_0.88PbI₃ absorbers that were manifested in significant suppression or even blocking of the undesirable perovskite films’ recrystallization and other decomposition pathways upon continuous 110 mW/cm² light exposure. The achieved material photostability—within 9000 h for the Oct(FA)_n−1Pb_nI_3n+1 (n = 40–400) and 20,000 h for Oct(Cs_0.12FA_0.88)_n−1Pb_nI_3n+1 (where n = 40–400) formulations—matches the highest values ever reported for complex lead halides. It is important to note that the stabilizing effect is maintained when OctI₂ is used only as a perovskite surface-modifying agent. Using a two-cation perovskite composition as an example, we showed that the performances of the solar cells based on the developed Oct(Cs_0.12FA_0.88)₃₉₉Pb₄₀₀I₁₂₀₁ absorber material are comparable to that of the reference devices based on the unmodified perovskite composition. These findings indicate a great potential of the proposed approach in the design of new highly photostable and efficient light absorbers. We believe that the results of this study will also help to establish important guidelines for the rational material design to improve the operational stability of perovskite solar cells. Full article

China’s rapid economic growth has inevitably led to serious resource depletion, environmental degradation, and a decline in social welfare. As such, establishing total-factor energy green efficiency (TFEGE) and exploring its factors are of paramount importance to bolster comprehensive energy efficiency and foster sustainable development. In this research, we deployed the spatial lag model (SLM) and data envelopment analysis (DEA), using energy, capital and labor as input indicators, GDP and social dimension metrics as desirable outputs, and “three wastes” as undesirable outputs, to assess the TFEGE across 30 provinces in China from 2001 to 2020. Employing the exploratory spatial data analysis (ESDA) method, we analyzed the spatial autocorrelation of TFEGE at national and provincial levels. Simultaneously, we examined the influencing factors of TFEGE using a spatial econometric model. Our study reveals that, throughout the examined period, the TFEGE in China has generally shown a steady decline. The TFEGE dropped from 0.630 to 0.553. The TFEGE of all regions in China also showed a downward trend, but the rate of decrease varied significantly across different regions. Among them, the TFEGE of the eastern region fluctuated between 0.820 and 0.778. The TFEGE of the northeast region decreased significantly from 0.791 to 0.307. The TFEGE of the western region decreased from 0.512 to 0.486. The TFEGE of the central region decreased from 0.451 to 0.424. Beijing, Guangdong, Hainan, Qinghai, and Ningxia showed an effective TFEGE, while for other provinces, it was ineffective. The TFEGE in all four major regions failed to achieve effectiveness. Its distribution pattern was east > west > northeast > central. The TFEGE across the 30 provinces showed positive spatial autocorrelation, indicating a strong spatial clustering trend. We found that while transportation infrastructure and technological progression exert a positive impact on TFEGE, elements such as industrial structure, energy composition, and foreign direct investment negatively influence TFEGE. Full article

Melanoma is a serious and aggressive type of skin cancer with growing incidence, and it is the leading cause of death among those affected by this disease. Although surgical resection has been employed as a first-line treatment for the early stages of the tumor, noninvasive topical treatments might represent an alternative option. However, they can be irritating to the skin and result in undesirable side effects. In this context, the potential of topical polymeric hydrogels has been investigated for biomedical applications to overcome current limitations. Due to their biocompatible properties, hydrogels have been considered ideal candidates to improve local therapy and promote wound repair. Moreover, drug combinations incorporated into the polymeric-based matrix have emerged as a promising approach to improve the efficacy of cancer therapy, making them suitable vehicles for drug delivery. In this work, we demonstrate the synthesis and characterization of Pluronic F-127 hydrogels (PL) containing the nitric oxide donor S-nitrosoglutathione (GSNO) and copper oxide nanoparticles (CuO NPs) against melanoma cells. Individually applied NO donor or metallic oxide nanoparticles have been widely explored against various types of cancer with encouraging results. This is the first report to assess the potential and possible underlying mechanisms of action of PL containing both NO donor and CuO NPs toward cancer cells. We found that PL + GSNO + CuO NPs significantly reduced cell viability and greatly increased the levels of reactive oxygen species. In addition, this novel platform had a huge impact on different organelles, thus triggering cell death by inducing nuclear changes, a loss of mitochondrial membrane potential, and lipid peroxidation. Thus, GSNO and CuO NPs incorporated into PL hydrogels might find important applications in the treatment of skin cancer. Full article

Strict adherence to data integrity and quality standards is crucial for the pharmaceutical industry to minimize undesired effects and ensure that medicines are of the required quality and safe for patients. A common data quality standard in the pharmaceutical industry is ALCOA+, which is a set of guiding principles for ensuring data integrity. Failure to comply with ALCOA+ guidelines, usually detected after audit inspections, may result in serious consequences for pharmaceutical manufacturers, such as the incurrence of fines, increase in costs, and production delays. It is, therefore, imperative to devise methods able to monitor ALCOA+ compliance and detect decreasing trends in data quality automatically. In this paper we present ALCOAi, a deep learning model based on the transformer architecture, which is able to process large quantities of non-homogeneous data and compute current and future ALCOA+ compliance. The proposed model can estimate trends concerning most ALCOA+ principles. The model was tested on a real dataset comprising raw sensor data, machine-provided values, and human-entered free-text data from two pharmaceutical manufacturing lines. The performed tests led to promising results in forecasting ALCOA+ compliance. Full article

The spoilage of juices by Alicyclobacillus spp. remains a serious problem in industry and leads to economic losses. Compounds such as guaiacol and halophenols, which are produced by Alicyclobacillus, create undesirable flavors and odors and, thus, decrease the quality of juices. The inactivation of Alicyclobacillus spp. constitutes a challenge because it is resistant to environmental factors, such as high temperatures, and active acidity. However, the use of bacteriophages seems to be a promising approach. In this study, we aimed to isolate and comprehensively characterize a novel bacteriophage targeting Alicyclobacillus spp. The Alicyclobacillus phage strain KKP 3916 was isolated from orchard soil against the Alicyclobacillus acidoterrestris strain KKP 3133. The bacterial host’s range and the effect of phage addition at different rates of multiplicity of infections (MOIs) on the host’s growth kinetics were determined using a Bioscreen C Pro growth analyzer. The Alicyclobacillus phage strain KKP 3916, retained its activity in a wide range of temperatures (from 4 °C to 30 °C) and active acidity values (pH from 3 to 11). At 70 °C, the activity of the phage decreased by 99.9%. In turn, at 80 °C, no activity against the bacterial host was observed. Thirty minutes of exposure to UV reduced the activity of the phages by almost 99.99%. Based on transmission-electron microscopy (TEM) and whole-genome sequencing (WGS) analyses, the Alicyclobacillus phage strain KKP 3916 was classified as a tailed bacteriophage. The genomic sequencing revealed that the newly isolated phage had linear double-stranded DNA (dsDNA) with sizes of 120 bp and 131 bp and 40.3% G+C content. Of the 204 predicted proteins, 134 were of unknown function, while the remainder were annotated as structural, replication, and lysis proteins. No genes associated with antibiotic resistance were found in the genome of the newly isolated phage. However, several regions, including four associated with integration into the bacterial host genome and excisionase, were identified, which indicates the temperate (lysogenic) life cycle of the bacteriophage. Due to the risk of its potential involvement in horizontal gene transfer, this phage is not an appropriate candidate for further research on its use in food biocontrol. To the best of our knowledge, this is the first article on the isolation and whole-genome analysis of the Alicyclobacillus-specific phage. Full article