Search Results (554)

Cancer treatment has undergone a paradigm shift following the introduction of novel cancer treatment approaches that involve the host’s immune system in fighting established tumors. This new concept aids the immune system in identifying, attacking, and killing the tumor cells. However, although some encouraging results were observed clinically, this approach has its own limitations. For example, the benefits of certain anticancer drugs were only observed in some patients, off-target effects, immune evasion, and poor pharmacokinetics. Recently, several advancements have been made with the understanding and development of tumor-targeted drug delivery systems, which combine both effectiveness and patients’ safety during cancer treatment. In this review, we will focus on the latest progress in targeted drug delivery, particularly applying nanoparticles, liposomes, exosomes, and Wharton’s jelly-derived macrovesicles as immune cell enhancers, as well as overcoming therapeutic resistance. We also characterize major current problems, such as the biocompatibility and scalability of the delivered engineering systems, as well as the required regulations. Lastly, we will show some examples of effective approaches to resolve these issues for more efficient cancer therapy. The importance of this article lies in bridging two sides in a single framework perspective: the novel implementation of unique delivery systems and the latest advances in the field of cancer immunotherapy. Thus, this provides better insights for the future of cancer treatment. Full article

This paper explores the geometric interplay between the Levi–Civita connection and the quarter-symmetric metric connection on doubly warped product manifolds. We analyze the behavior of Ricci solitons on such manifolds, focusing on the influence of conformal and Killing vector fields within the framework of quarter-symmetric metric connections (QSMCs). Furthermore, we examine conditions under which the manifold exhibits Einstein properties, presenting new insights into Einstein-like structures in the context of doubly warped product manifolds endowed with a quarter-symmetric metric connection. Full article

Spiders and other arthropods can sometimes consume others of their kind, and this is most often associated with mating activity, whereby females cannibalize males during or after mating, or during mating attempts. Nonsexual cannibalism is less common but may be associated with food availability or territorial aggression. In the Southeastern United States, a non-native orb-weaving spider, Trichonephila clavata (the “jorō spider”), is expanding its range. Prior lab experiments indicated this species to be “shy” compared to other native spiders, based on behavioral reactions to stimuli. Here, we report descriptive observations and photo-documentation of nonsexual cannibalism by this species, including from anecdotal observations, plus findings from controlled pairings of spiders, both in the lab and in natural webs in the field. In the cases where cannibalism was witnessed, it involved one female biting and killing another, typically after a short fight. When two females of a similar size were placed together in a container (n = 25 trials), fights ensued 40% of the time. When females of different sizes were paired (n = 27 trials), fights happened 18% of the time, and the larger females were not always the aggressor. Across all the lab trials (n = 52), six bouts (9%) led to the direct killing of one female. In field trials where two females were placed on an empty web (n = 14 trials), we observed one fight (7%) where the aggressor ended up killing and wrapping the other spider in silk. Given that some of these instances happened away from any web, these observations imply that the aggression is not necessarily an act of territoriality. The intraspecific aggression could arise when females are provoked or stressed, which deserves more study. Full article

The subject of this study is almost contact complex Riemannian manifolds, also known as almost contact B-metric manifolds. The considerations are restricted to a special class of these manifolds, namely those of the Sasaki-like type, because of their geometric construction and the explicit expression of their classification tensor by the pair of B-metrics. Here, each of the two B-metrics is considered as an $\eta$-Ricci–Bourguignon almost soliton, where $\eta$ is the contact form. The soliton potential is chosen to be a conformal Killing vector field (in particular, concircular or concurrent) and then a generalization of the notion of conformality using contact conformal transformations of B-metrics. The resulting manifolds, equipped with the introduced almost solitons, are geometrically characterized. In the five-dimensional case, an explicit example on a Lie group depending on two real parameters is constructed, and the properties obtained in the theoretical part are confirmed. Full article

Background: Shirakiopsis indica (Willd.) (Family: Euphorbiaceae), a mangrove species found in the Asian region, is a popular folkloric plant. Locally, the plant is traditionally used to treat various types of ailments, especially for pain relief. Therefore, the current study investigates the neuropharmacological, antipyretic, thrombolytic, and anthelmintic properties of the S. indica fruit methanolic extract (SIF-ME). Methods: The neuropharmacological activity was evaluated using several bioactive assays, and the antipyretic effect was investigated using the yeast-induced pyrexia method, both in Swiss albino mice models. Human blood clot lysis was employed to assess thrombolytic activity, while in vitro anthelmintic characteristics were tested on Tubifex tubifex. Insights into phytochemicals from SIF-ME have also been reported from a literature review, which were further subjected to molecular docking, pass prediction, and ADME/T analysis and validated the wet-lab outcomes. Results: In the elevated plus maze test, SIF-ME at 400 mg/kg demonstrated significant anxiolytic effects (200.16 ± 1.76 s in the open arms, p < 0.001). SIF-ME-treated mice exhibited increased head dipping behavior and spent a longer time in the light box, confirming strong anxiolytic activity in the hole board and light–dark box tests, respectively. It (400 mg/kg) also significantly reduced depressive behavior during forced swimming and tail suspension tests (98.2 ± 3.83 s and 126.33 ± 1.20 s, respectively). The extract induced strong locomotor activity, causing mice’s mobility to gradually decrease over time in the open field and hole cross tests. The antipyretic effect of SIF-ME (400 mg/kg) was minimal using the yeast-induced pyrexia method, while it (100 μg/mL) killed T. tubifex in 69.33 ± 2.51 min, indicating a substantial anthelmintic action. SIF-ME significantly reduced blood clots by 67.74% (p < 0.001), compared to the control group’s 5.56%. The above findings have also been predicted by in silico molecular docking studies. According to the molecular docking studies, the extract’s constituents have binding affinities ranging from 0 to −10.2 kcal/mol for a variety of human target receptors, indicating possible pharmacological activity. Conclusions: These findings indicate that SIF-ME could serve as a promising natural source of compounds with neuropharmacological, anthelmintic, thrombolytic, and antipyretic properties. Full article

Papapetrou showed that the covariant derivative of a Killing vector field satisfies Maxwell’s equations in vacuum. Papapetrou’s result is extended, in this article, and it is shown that the covariant derivative of a Killing vector field satisfies Maxwell’s equations in non-vacuum backgrounds as well if one allows electromagnetic currents of purely geometric origin. It is then postulated that every Killing vector field gives rise to a physical electromagnetic field and, in a non-vacuum background, a physical electromagnetic current—hereafter called Killing electromagnetic field and Killing electromagnetic current, respectively. It is shown that the Killing electromagnetic field of the flat FLRW (Friedmann–Lema$\hat{\mathrm{i}}$tre–Robertson–Walker) universe comprises a Killing magnetic field and a rotational Killing electric field; an upper bound on the Killing magnetic field is derived, and it is found that the upper bound is consistent with the current observational bounds on the cosmic magnetic field. Next, the time-like Killing vector of the Schwarzschild spacetime is shown to give rise to a radial Killing electric field. It is also shown that in the weak field regime—and far from the matter distribution—the back reaction of the radial Killing electric field changes the Schwarzschild metric to the Reissner–Nordström metric, establishing a partial converse of Wald’s result. Drawing upon Rainich’s work on Rainich–Riemann manifolds, the etiological question of how a physical electromagnetic field can arise out of geometry is discussed; it is also argued that detection of the Killing electric field of flat FLRW spacetime may be within the current experimental reach. Finally, this article discusses the relevance of Killing electromagnetic currents and the aforementioned transmutation of Schwarzschild spacetime to Reissner–Nordstrom spacetime, to Misner and Wheeler’s program of realizing “charge without charge”. Full article

Dental implant papilla (DIP) is susceptible to bacterial adhesion and biofilm formation, and oral pathogenic biofilms can cause persistent oral infections. Enrichment of bacterial biofilms on implants can lead to soft tissue irritation and adjacent bone resorption, severely compromising dental health and potentially leading to periodontitis, implant loss and costly follow-up care. Nanozymes (NZs) are recently used in biofilm removal as they can induce the production of reactive oxygen species (ROS), which can kill bacteria. However, the short lifespan of ROS limits their diffusion distance, and affects their therapeutic efficacy. In this study, we prepared Fe₃O₄ nanoparticles (NZs) with different morphologies: flower-like (F-Fe₃O₄), hollow spherical (M-Fe₃O₄), octahedral (O-Fe₃O₄), and conventional nanoparticles (N-Fe₃O₄). The ferromagnetic properties of Fe₃O₄ NZs allow them to move and penetrate the biofilm under the action of a magnetic field. The saturation magnetic intensities of the four samples were as follows: F-Fe₃O₄ (23.1 emu g⁻¹), M-Fe₃O₄ (73.34 emu g⁻¹), O-Fe₃O₄ (96.06 emu g⁻¹), and N-Fe₃O₄ (52.15 emu g⁻¹). The synergistic combination of photothermal action and catalytic sterilization can effectively remove the biofilm. In addition, the prepared Fe₃O₄ nanozymes were able to maintain high biological activity on the implant surface with some osteogenic effect. Full article

Bispecific antibodies (BsAbs) have shown potential in cancer treatment and have become a rapidly growing field in cancer immunotherapy. Unlike monoclonal antibodies with two identical binding sites, BsAbs simultaneously bind two distinct epitopes on the same or different antigens, allowing for a range of mechanisms of action, including engaging immune cells to kill cancer cells and blocking signaling pathways. Despite regulatory approvals for hematological malignancies in the last decade, their clinical success in solid malignancies has been lacking until recently. There are currently five BsAbs approved by the FDA in the United States for solid tumors—amivantamab, tarlatamab, tebentafusp, zanidatamab and zenocutuzumab—and two BsAbs approved in China—cadonilimab and ivonescimab. Currently, several BsAbs are under clinical development for solid tumors, but are mostly in early phase I and II trials. This review provides an overview of the basic mechanism of action of BsAbs, current FDA-approved BsAbs, and current BsAbs under clinical development, their challenges in clinical use, the management of toxicities, and future directions. Full article

Background: Glioblastoma (GBM) resists current therapies due to its rapid proliferation, diffuse invasion, and heterogeneous cell populations. We previously showed that a single cold atmospheric plasma discharge tube (DT) reduces GBM viability via broad-spectrum electromagnetic (EM) emissions. Here, we tested whether two DTs arranged in a helmet configuration could generate overlapping EM fields to amplify the anti-tumor effects without thermal injury. Methods: The physical outputs of the single- and dual-DT setups were characterized by infrared thermography, broadband EM field probes, and oscilloscope analysis. Human U87-MG cells were exposed under the single or dual configurations. The viability was quantified with WST-8 assays mapped across 96-well plates; the intracellular reactive oxygen species (ROS), membrane integrity, apoptosis, and mitochondrial potential were assessed by multiparametric flow cytometry. Our additivity models compared the predicted versus observed dual-DT cytotoxicity. Results: The dual-DT operation produced constructive EM interference, elevating electric and magnetic field amplitudes over a broader area than either tube alone, while temperatures remained <39 °C. The single-DT exposure lowered the cell viability by ~40%; the dual-DT treatment reduced the viability by ~60%, exceeding the additive predictions. The regions of greatest cytotoxicity co-localized with the zones of highest EM field overlap. The dual-DT exposure doubled the intracellular ROS compared with single-DT and Annexin V positivity, confirming oxidative stress-driven cell death. The out-of-phase operation of the discharge tubes enabled the localized control of the treatment regions, which can guide future treatment planning. Conclusions: Two synchronously operated plasma discharge tubes synergistically enhanced GBM cell killing through non-thermal mechanisms that coupled intensified overlapping EM fields with elevated oxidative stress. This positions modular multi-DT arrays as a potential non-invasive adjunct or alternative to existing electric-field-based therapies for glioblastoma. Full article

Silver nanoparticles, with various uses in pharmacy, cosmetics, sanitation, textiles, optoelectronics, photovoltaics, etc., that are provided by worldwide industrial production, estimated to hundreds of tons annually, are finally released in the environment impacting randomly the biosphere. An alternative synthesis approach could be implemented by replacing chemical reductants of silver with natural antioxidants ensuring production and utilization sustainability with focus on environmental pollution diminishing. We synthesized silver nanoparticles by using plant extracts, aiming to offer antimicrobial products with reduced impact on the environment through sustainable green-chemistry. Fresh extracts of lemon pulp, blueberry and blackberry fruits as well as of green tea dry leaves were the sources of the natural antioxidants able to ensure ionic silver reduction and silver nanoparticle formation in the form of colloidal suspensions. The four samples were characterized by UV–Vis spectrophotometry, scanning electron microscopy, dark field optical microscopy, X-ray diffractometry, dynamic light scattering, which evidenced specific fine granularity, plasmonic features, standard crystallinity, and good stability in water suspension. Antimicrobial activity was assayed using the agar diffusion method and the bacteria kill-time technique against Staphylococcus aureus and Escherichia coli. In both cases, all silver nanoparticles revealed their adequacy for the aimed purposes, the sample synthesized with green tea showing the best efficiency, which is in concordance with its highest contents of polyphenols, flavones and best total antioxidant activity. Various applications could be safely designed based on such silver nanoparticles for sustainable chemistry development. Full article

Nucleopolyhedroviruses of lepidopteran larvae (Alphabaculovirus, Baculoviridae) form the basis for effective and highly selective biological insecticides for the control of caterpillar pests of greenhouse and field crops and forests. Horizontal transmission is usually achieved following the release of large quantities of viral occlusion bodies (OBs) from virus-killed insects. In the present review, I examine the evidence for productive midgut infection in different host species and the resulting transmission through the release of OBs in the feces (frass) of the host. This has been a neglected aspect of virus transmission since it was initially studied over six decades ago. The different host–virus pathosystems vary markedly in the quantity of OBs released in feces and in their ability to contaminate the host’s food plant. The release of fecal OBs tends to increase over time as the infection progresses. Although based on a small number of studies, the prevalence of transmission of fecal inoculum is comparable with that of recognized alternative routes for transmission and dissemination, such as cannibalism and interactions with predators and parasitoids. Finally, I outline a series of predictions that would affect the importance of OBs in feces as a source of inoculum in the environment and which could form the basis for future lines of research. Full article

Since the first observations of biofilm formation by microorganisms on various surfaces more than 50 years ago, it has been shown that most “unicellular” microorganisms prefer to grow in multicellular communities that often adhere to surfaces. The microbes in these communities adhere to each other, produce an extracellular matrix (ECM) that protects them from drugs, toxins and the host’s immune system, and they coordinate their development and differentiate into different forms via signaling molecules and nutrient gradients. Biofilms are a serious problem in industry, agriculture, the marine environment and human and animal health. Many researchers are therefore investigating ways to disrupt biofilm formation by killing microbes or disrupting adhesion to a surface, quorum sensing or ECM production. This review provides an overview of approaches to altering various surfaces through physical, chemical or biological modifications to reduce/prevent microbial cell adhesion and biofilm development and maintenance. It also discusses the advantages and disadvantages of each approach and the challenges faced by researchers in this field. Full article

Background: Clinical data indicate that at least half of patients with malignancies receive radiotherapy. While radiotherapy effectively kills tumor cells, it is also associated with significant ionizing radiation (IR) damage. Moreover, the increasing emissions of nuclear pollutants raise concerns about the potential exposure of more individuals to the risks associated with IR. The Chinese term for amniotic fluid (AF) is rooted in the Yin–Yang theory of traditional Chinese medicine, where it symbolizes the inception of human life. Chick early AF (ceAF), a natural product, has shown promise in the field of regenerative medicine. There have been no studies investigating the potential efficacy of ceAF in the treatment of IR-induced damage. This study aims to assess the therapeutic potential of ceAF in alleviating IR-induced damage and elucidate its potential molecular mechanism. Methods: In vivo experiments were conducted on 8-week-old male C57BL/6J mice to investigate the effects of ceAF in a radiation injury model induced by whole-body irradiation with X-rays (6 Gy) for 5 min. The ceAF was extracted from chicken embryos aged 7–9 days. Results: We found that the supplementation of ceAF reduces mortality induced by IR, improves exercise capacity in IR mice, and reverses IR-induced skin damage. IR leads to varying degrees of volume atrophy and weight loss in the major internal organs of mice. However, ceAF intervention effectively mitigates IR-induced organ damage, with a notable impact on the spleen. The supplementation of ceAF enhances spleen hematopoietic and immune functions by reducing oxidative stress, alleviating inflammatory responses, and preventing splenic DNA damage from IR exposure, ultimately leading to an overall improvement in health. Conclusions: ceAF effectively alleviates body damage induced by IR, and our findings provide new perspectives and therapeutic strategies for mitigating IR-induced damage. Full article

The conservation of biodiversity and the balance between ecological and societal needs are critical but often contested global issues. Wildlife-vehicle collision (WVC) on vital infrastructure, especially linear infrastructure, remains a persistent challenge from policy to practice and poses a serious life-threatening implication to humans and other non-human lives. Addressing this issue effectively requires solutions that provide win-win outcomes from both ecological and societal perspectives. This study critically analyzes a decade of roadkill incidents along Nepal’s longest East-West national highway, which passes through a biologically diverse national park in the western Terai Arc Landscape Area (TAL). Findings are drawn from field-based primary data collection of the period 2012–2022, secondary literature review, key informant interviews, and spatial analysis. The study reveals significant variations in roadkill incidence across areas and years. Despite Bardia National Park being larger and having a higher wildlife density, Banke National Park recorded higher roadkill rates. This is attributed to insufficient mitigation measures and law enforcement, more straight highway segments, and the absence of buffer zones between the core park and adjacent forest areas—only a road separates them. Wild boars (Sus scrofa) and spotted deer (Axis axis), the primary prey of Bengal tigers (Panthera tigris tigris), were the most frequently road-killed species. This may contribute to human-tiger conflicts, as observed in the study areas. Seasonal trends showed that reptiles were at higher risk during the wet season and mammals during winter. Hotspots were often located near checkpoints and water bodies, highlighting the need for targeted mitigation efforts such as wildlife crossings and provisioning wildlife requirements such as water, grassland, and shelter away from the regular traffic roads. Roadkill frequency was also influenced by forest cover and time of day, with more incidents occurring at dawn and dusk when most of the herbivores become more active in search of food, shelter, water, and their herds. The findings underscore the importance of road characteristics, animal behavior, and landscape features in roadkill occurrences. Effective mitigation strategies include wildlife crossings, speed limits, warning signs, and public education campaigns. Further research is needed to understand the factors in driving variations between parks and to assess the effectiveness of mitigation measures. Full article

This paper explores the geometry of 3-dimensional quasi Sasakian manifolds under CL-transformations. We construct both infinitesimal and $CL$-transformation and demonstrate that the former does not necessarily yield projective killing vector fields. A novel invariant tensor, termed the $CL$-curvature tensor, is introduced and shown to remain invariant under $CL$-transformations. Utilizing this tensor, we characterize $CL$-flat, $CL$-symmetric, $CL$-$\phi$ symmetric and $CL$-$\phi$ recurrent structures on such manifolds by mean of differential equations. Furthermore, we investigate conditions under which a Ricci soliton exists on a CL-transformed quasi Sasakian manifold, revealing that under flat curvature, the structure becomes Einstein. These findings contribute to the understanding of curvature dynamics and soliton theory within the context of contact metric geometry. Full article