Search Results (12,560)

Canids act as a crucial intermediary in the transmission of rabies and Echinococcus granulosus, serving as co-infection hosts and pathogen carriers for both rabies and hydatid disease (HD) transmitted from animals to humans. Therefore, an effective and efficient bivalent oral vaccine for preventing HD and rabies is urgently required to reduce economic losses in husbandry resulting from rabies and HD. In this study, a full-length plasmid (pcDNA4-NPM+G_ΔCD+EgM123+eGFP+L) carrying the Echinococcus granulosus EgM123 gene and fluorescence reporter genes of eGFP and four auxiliary transfection plasmids of rabies virus SRV₉ (pcDNA4-N, pcDNA4-P, pcDNA4-G, pcDNA-L) were established by reverse genetics approaches and co-transfected to BSR cells by electrotransfection. The co-transfected BSR cells showed green fluorescence 48 h after electrotransfection. The recombinant virus was exposed to the sixth-generation blind passage, with the N, P, G, and EgM123 genes amplified via RT-PCR, yielding targeted strips. The rescued virus-infected BSR cells were characterized by TEM, and the results indicated that bullet-like viral particles with an average size of 148.47 nm and a cyst structure were present in the cytoplasm of BSR cells; the expression levels of continuously cultivated 9th-, 10th-, 11th-, 12th-, and 13th-generation viruses were quantified by qRT-PCR, and the results showed that mRNA expression of the virus was upregulated. The LD₅₀ titer of suckling rats was measured to be 10^−1.4. The synthesized EgM123 recombinant gene rabies virus SRV₉ can function as a vaccine strain for the development of the “Rabies-HD bivalent recombinant gene oral vaccine”, therefore aiding in the prevention and management of rabies and HD in animals. Full article

In this study, we aim to enhance the internal quantum efficiency (IQE) of AlGaN-based ultraviolet (UV) light-emitting diodes (LEDs) by using the short-period AlGaN/GaN superlattice as a tunnel junction (TJ) to construct polarized structures. We analyze in detail the effect of this polarized TJ on the carrier injection efficiency and investigate the increase in hole and electron density caused by the formation of 2D hole gas (2DHG) and 2D electron gas (2DEG) in the superlattice structure. In addition, a dielectric layer is introduced to evaluate the effect of stress changes on the tunneling probability and current spread in TJ. At a current of 140 mA, this method demonstrates effective current expansion. Our results not only improve the performance of UV LEDs but also provide an important theoretical and experimental basis for future research on UV LEDs based on superlattice TJ. In addition, our study also highlights the key role of group III nitride materials in achieving efficient UV luminescence, and the polarization characteristics and band structure of these materials are critical for optimizing carrier injection and recombination processes. Full article

Background/Objectives: Intranasal vaccination enhances protection against respiratory viruses by providing stimuli to the immune system at the primary site of infection, promoting a balanced and effective response. Influenza vectors with truncated NS1 are a promising vaccine approach that ensures a pronounced local CD8+ T-cellular immune response. Here, we describe the protective and immunomodulating properties of an influenza vector FluVec-N carrying the C-terminal fragment of the SARS-CoV-2 nucleoprotein within a truncated NS1 open reading frame. Methods: We generated several FluVec-N recombinant vectors by reverse genetics and confirmed the vector’s genetic stability, antigen expression in vitro, attenuation, and immunogenicity in a mouse model. We tested the protective potential of FluVec-N intranasal immunization in naïve mice and seropositive Th2-prone mice, primed with aluminium-adjuvanted inactivated SARS-CoV-2. Immune response in immunized and challenged mice was analyzed through serological methods and flow cytometry. Results: Double intranasal immunization of naïve mice with FluVec-N reduced weight loss and viral load in the lungs following infection with the SARS-CoV-2 beta variant. Mice primed with alum-adjuvanted inactivated coronavirus experienced substantial early weight loss and eosinophilia in the lungs during infection, demonstrating signs of enhanced disease. A single intranasal boost immunization with FluVec-N prevented the disease enhancement in primed mice by modulating the local immune response. Protection was associated with the formation of specific IgA and the early activation of virus-specific effector and resident CD8+ lymphocytes in mouse lungs. Conclusions: Our study supports the potential of immunization with influenza vector vaccines to prevent respiratory diseases and associated immunopathology. Full article

Converting CO₂ greenhouse gases into high-value-added fuels via semiconductor photocatalysts is an ideal solution to address current environmental and energy issues. Due to its unique physicochemical traits and flexible structure, WO₃ is widely employed in photocatalysis. Nevertheless, it commonly faces problems such as limited light absorption and low reaction selectivity. Here, we effectively tackle the existing issue by introducing an oxygen defect strategy to synthesize two-dimensional WO_3−x nanosheets with rich oxygen vacancies. Due to localized surface plasmon resonance (LSPR), these nanosheets may exhibit broad light absorption and efficient CO₂ adsorption and activation. In the photocatalytic reduction of carbon dioxide (CO₂) to carbon monoxide (CO), WO_3−x nanosheets exhibited 100% selectivity and 16.1 μmol g⁻¹ h⁻¹ yield, 6.2 times higher than WO₃. Oxygen vacancies improve WO₃’s band structure and increase its capacity to absorb visible light. Based on electrochemical tests and fluorescence spectroscopy analysis, the outstanding functionality of WO_3−x nanosheets is related to the improved separation and transport of photocurrents and the restricted radiative recombination of the resulting electron pairs and holes. Full article

The green unicellular algae Chlamydomonas reinhardtii contains 12–13 carbonic anhydrases (CAs). For a long time, the two closely related α-CAs of the periplasmic membrane CAH1 and CAH2 were considered to be the CAs with the highest CO₂ hydration activity. The recombinant protein α-CA CAH3 (rCAH3) from the thylakoid lumen obtained in the present study showed more than three times higher activity compared to CAH1 and more than 11 times higher compared to previous studies with rCAH3. Long-term sustainability of the enzyme was observed at alkaline pH (>8), with maintenance of half of its activity at 4 °C for up to 50 days. Thermostability of rCAH3 indicated the retention of the activity at 20 °C for one hour at pH 9–10 with its ~50% decrease at pH 6–7. However, the residual activity of rCAH3 after incubation at an extremely high temperature (75 °C) for 15 min led to the formation of the double-hump graph with maxima at pH 6 and 9. The enzyme demonstrated high sensitivity to ethoxyzolamide and acetazolamide at nM concentrations, to Zn²⁺ and Cu²⁺ cations at 1 mM concentrations, and L-cysteine was able to completely inhibit CA activity of rCAH3 through reduction of sulfhydryl groups. Esterase activity of rCAH3 was well detected with values comparable to those of bovine CAII, but with a maximum at pH 8 instead of pH 9, which is usual for bovine CAII. The results indicated that CAH3 may be the most active CA of C. reinhardtii and that its role in the photosynthetic apparatus function could have been underestimated in previous works. Full article

Yield-related traits have higher heritability and lower genotype-by-environment interaction, making them more suitable for genetic studies in comparison with the yield per se. Different populations have been developed and employed in QTL mapping; however, the use of reciprocal SSSLs is limited. In this study, three kinds of bi-parental populations were used to investigate the stable and novel QTLs on six yield-related traits, i.e., plant height (PH), heading date (HD), thousand-grain weight (TGW), effective tiller number (ETN), number of spikelets per panicle (NSP), and seed set percentage (SS). Two parental lines, i.e., japonica Asominori and indica IR24, their recombinant inbred lines (RILs), and reciprocal single-segment substitution lines (SSSLs), i.e., AIS and IAS, were genotyped by SSR markers and phenotyped in four environments with two replications. Broad-sense heritability of the six traits ranged from 0.67 to 0.94, indicating their suitability for QTL mapping. In the RIL population, 18 stable QTLs were identified for the six traits, 4 for PH, 6 for HD, 5 for TGW, and 1 each for ETN, NSP, and SS. Eight of them were validated by the AIS and IAS populations. The results indicated that the allele from IR24 increased PH, and the alternative allele from Asominori reduced PH at qPH3-1. AIS18, AIS19, and AIS20 were identified to be the donor parents which can be used to increase PH in japonica rice; on the other hand, IAS14 and IAS15 can be used to reduce PH in indica rice. The allele from IR24 delayed HD, and the alternative allele reduced HD at qHD3-1. AIS14 and AIS15 were identified to be the donor parents which can be used to delay HD in japonica rice; IAS13 and IAS14 can be used to reduce HD in indica rice. Reciprocal SSSLs not only are the ideal genetic materials for QTL validation, but also provide the opportunity for fine mapping and gene cloning of the validated QTLs. Full article

In this work, the mechanisms for creating a combined electronic–radiative local state beneath the conduction band, consisting of intrinsic and activator electron–hole states, are experimentally substantiated. In the first part of this work, the mechanisms of the formation of intrinsic and activator electron–hole trapping centers are experimentally demonstrated in all four matrices with activators. Intrinsic electronic states are localized on activators and anions of the matrix, forming intrinsic and activator electronic states. The hole component of the electron–hole pairs is localized near the activators. Thus, the energy of intrinsic electronic excitations localized in the matrix in the form of combined electronic–radiative states is observed at 3.06–3.1 eV and 2.92–2.95 eV. Radiative states are excited by photon energies of ~4.5 eV and ~4.0 eV, resulting in recombination emissions at 3.06–3.1 eV and 2.92–2.95 eV, as well as activator emissions at 2.06 eV for Mn2+, 2.5 eV for Tb3+, and 2.56 eV and 2.16 eV for Dy3+. Energy transfer from the matrix to emitters or activators occurs during the decay of the combined radiative state. Upon heating, electrons localized on anions and activators delocalize at temperatures of 200–350 K. The energy released during the recombination of an electron with a hole near the activators is transferred to the activators. This process facilitates energy transfer to activators in dosimeters and detectors. Full article

Coupling superconducting (SC) contacts to light-emitting layers can lead to remarkable effects, as seen in inorganic quantum-well LEDs with superconducting contacts, where an enhancement in radiative recombination was observed. Additional dramatic effects were theorized if both electrodes are SC, such as correlated emission and 2-photon entanglement. Motivated by this and by the question of whether proximity induced SC is possible in organic light-emitting materials, we studied the electronic properties of stacked SC–organic–SC devices. Our structures consisted of Nb (bottom) and NbN (top) SC electrodes and a spin-coated light-emitting semiconductor polymer, MEH-PPV. Sputtering the SC directly on the polymer causes pinholes, which we prevent by ultra-slow deposition of a 5 nm aluminum film, before depositing the top SC in situ. The Al protects the organic film from damage and pinhole formation, while preserving SC in the top electrodes due to the proximity effect between Al and NbN. Electrical transport measurements of the completed junctions indicate that indeed, the top and bottom contacts are superconducting and the protected MEH-PPV layer is pinhole-free, as supported by HR-TEM and EDS. Most importantly, we find that as the temperature is decreased below the critical temperature of the SCs, the device shows evidence for the proximity effect in the MEH-PPV. Full article

Air pollution caused by fine particles known as PM2.5 is a significant health concern worldwide, contributing to illnesses like asthma, heart disease, and lung cancer. To address this issue, this study focused on improving air purification systems using negative ions, which can attach to these harmful particles and help remove them from the air. This paper developed a novel mathematical model based on linear differential equations to study how PM2.5 particles interact with negative ions, making it easier to design more effective purification systems. The proposed model was validated in a small, controlled space, using common urban pollutants such as cigarette smoke, incense, coal, and gasoline. These tests were conducted at different temperatures and under two levels of ion generation. The results showed that the system could remove over 99% of PM2.5 particles in five minutes when temperatures were low or moderate. However, at higher temperatures, the system’s performance dropped significantly. This research goes beyond earlier studies by examining how temperature affects the process, which had not been fully explored before. Furthermore, this approach aligns with global sustainability goals by promoting public health, reducing healthcare costs, and providing scalable solutions for sustainable urban living. Full article

Mycobacterium tuberculosis (Mtb) is one of the most successful bacterial pathogens in human history. Even in the antibiotic era, Mtb is widespread and causes millions of new cases of tuberculosis each year. The ability to disrupt the host’s innate and adaptive immunity, as well as natural persistence, complicates disease control. Tuberculosis traditional therapy involves the long-term use of several antibiotics. Treatment failures are often associated with the development of resistance to one or more drugs. The development of medicines that act on new targets will expand treatment options for tuberculosis caused by multidrug-resistant or extensively drug-resistant Mtb. Therefore, the development of drugs that target virulence factors is an attractive strategy. Such medicines do not have a direct bacteriostatic or bactericidal effect, but can disarm the pathogen so that the host immune system becomes able to eliminate it. Although cell wall-associated targets are being actively studied for anti-TB drug development, other virulence factors important for adaptation and host interaction are also worth comprehensive analysis. In this review, specific Mtb virulence factors (such as secreted phosphatases, regulatory systems, and the ESX-1 secretion system) are identified as promising targets for novel anti-virulence drug development. Additionally, models for the search of virulence inhibitors are discussed, such as virtual screening in silico, in vitro enzyme inhibition assay, the use of recombinant Mtb strains with reporter constructs, phenotypic analysis using in vitro cell infection models and specific environments. Full article

Ovarian aging significantly impacts female fertility, with mitochondrial dysfunction emerging as a key factor. This study investigated the effects of recombinant follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on mitochondrial function and metabolism in aging female reproductive cells. Human granulosa cells (HGL5) were treated with FSH/LH or not. Mitochondrial function was assessed through various assays, including mitochondrial mass, membrane potential, ROS levels, and ATP production. Mitochondrial dynamics and morphology were analyzed using MitoTracker staining. Cellular respiration was measured using a Seahorse Bioenergetics Analyzer. Metabolic reprogramming was evaluated through gene expression analysis and metabolite profiling. In vivo effects were studied using aging mouse oocytes. FSH/LH treatment significantly improved mitochondrial function in aging granulosa cells, increasing mitochondrial mass and membrane potential while reducing ROS levels. Mitochondrial dynamics showed a shift towards fusion and elongation. Cellular respiration, ATP production, and spare respiratory capacity were enhanced. FSH/LH-induced favorable alterations in cellular metabolism, favoring oxidative phosphorylation. In aging mouse oocytes, FSH/LH treatment improved in vitro maturation and mitochondrial health. In conclusion, FSH/LH supplementation ameliorates age-related mitochondrial dysfunction and improves cellular metabolism in aging female reproductive cells. Full article

Background: Vaccination is the main control measure to prevent Lumpy skin disease (LSD), and Neethling-based homologous vaccines have been shown to be safe and effective against infection with classical clade 1.2 strains. In 2017, recombinant clade 2 LSDV strains originating from a badly produced and insufficiently controlled vaccine were first detected in Russia. A clade 2.5 recombinant strain spread from Russia throughout Southeast Asia and caused a massive epidemic. In this study, the efficacy of three different Neethling strain-based vaccines against the recombinant clade 2.5 LSDV strain was evaluated. Methods: For each vaccine, seven bulls were vaccinated and followed for three weeks to evaluate vaccine safety. Thereafter, vaccinated animals and non-vaccinated controls were challenged with a virulent clade 2.5 strain and followed for three more weeks to evaluate vaccine efficacy. Results: Only limited adverse effects were observed after vaccination, and all vaccinated animals seroconverted and showed an LSDV-specific cellular immune response after vaccination. After the challenge, the vaccinated animals developed almost no clinical signs, and no viremia or nasal excretion was detected. This was in sharp contrast with the non-vaccinated controls, where 8 out of 13 animals developed clinical disease with clear nodules. Most of these animals also had a prolonged period of fever, a clear viremia and excreted virus. Conclusions: Neethling-based LSDV vaccines can thus be considered safe and are effective not only against clade 1.2 LSDV strains, as was proven earlier, but also against a clade 2.5 recombinant strain. Full article

Background: Identifying patients with gBRCAm is crucial to facilitate screening strategies, preventive measures and the usage of targeted therapeutics in their management. This review examines the evidence for the latest predictive and therapeutic approaches in BRCA-associated cancers. Clinical Description: Data supports the use of adjuvant olaparib in patients with gBRCAm high-risk HER2-negative breast cancer. In advanced gBRCAm HER2-negative breast cancer, the PARPis talazoparib and olaparib have demonstrated benefit over standard chemotherapy. In ovarian cancer, olaparib, niraparib or rucaparib can be used as monotherapy in frontline maintenance. Olaparib and bevacizumab as a combination can also be used as frontline maintenance. In the relapsed platinum-sensitive setting, olaparib, niraparib and rucaparib are effective maintenance options in BRCAm patients who are PARPi naive. Both olaparib and rucaparib are effective options in BRCAm metastatic castrate-resistant prostate cancer (mCRPC). Evidence also exists for the benefit of PARPi combinations in mCRPC. In metastatic pancreatic cancer, olaparib can be used in gBRCAm patients who are responding to platinum chemotherapy. However, there may be a development of PARPi resistance. Understanding the pathophysiology that contributes to such resistance may allow the development of novel therapeutics. Combination therapy appears to have promising results in emerging trials. Seeking avenues for subsidised genetic testing can reduce the total costs of cancer management, leading to improve detection rates. Conclusion: Identifying breast, ovarian, pancreatic and prostate cancer patients with gBRCAm plays a crucial predictive role in selecting those who will benefit significantly from PARPi therapy. The use of PARPi in gBRCAm HBOC-related cancers has resulted in significant survival benefits. Beyond BRCA1/2, HRR gene assessment and the consideration of other cancer predisposition syndromes may allow more patients to be eligible for and benefit from targeted therapies. Full article

Background/Objectives: Adenoviral vector-based vaccines against COVID-19 rarely cause vaccine-induced immune thrombocytopenia and thrombosis (VITT), a severe adverse reaction caused by IgG antibodies against platelet factor 4 (PF4). To study VITT, patient samples are crucial but have become a scarce resource. Recombinant antibodies (rAbs) derived from VITT patient characteristic amino acid sequences of anti-PF4 IgG are an alternative to study VITT pathophysiology. Methods: Amino acid sequences of the variable region of immunoglobulin light and heavy chain of anti-PF4 IgG derived from VITT patients were obtained by mass spectrometry sequencing and rAbs were synthetized by reverse-engineering. Six different rAbs were produced: CR23003, CR23004, and CR23005 (from a patient vaccinated with Jcovden, Johnson & Johnson-Janssen (Beerse, Belgium)), CR22046, and CR22050 and CR22066 (from two different patients vaccinated with Vaxzevria, AstraZeneca (Cambridge, UK)). These rAbs were further characterized using anti-PF4 and anti-PF4/heparin IgG ELISAs, rapid anti-PF4 and anti-PF4/polyanion chemiluminescence assays, and PF4-induced platelet activation assay (PIPA) and their capacity to induce procoagulant platelets. Results: rAbs bound to PF4 alone, but not to PF4/polyanion complexes in rapid chemiluminescence assays. Chemiluminescence assays and both anti-PF4 IgG and anti-PF4 IgG/heparin ELISA showed concentration-dependent PF4 binding of all six rAbs, however, with different reactivities among them. PIPA showed a similar, concentration-dependent platelet activation pattern. rAbs varied in their reactivity and the majority of the tested rAbs were able to induce procoagulant platelets. Conclusions: The six rAbs derived from VITT patients reflect VITT-typical binding capacities and the ability to activate platelets. Therefore, these rAbs offer an attractive new option to study VITT pathophysiology. Full article

Cathelicidins are a group of cationic, amphipathic peptides that play a vital role in the innate immune response of many vertebrates, including humans. Produced by immune and epithelial cells, they serve as natural defenses against a wide range of pathogens, including bacteria, viruses, and fungi. In humans, the cathelicidin LL-37 is essential for wound healing, maintaining skin barrier integrity, and combating infections. Cathelicidins of different origins have shown potential in treating various skin conditions, including melanoma, acne, and diabetic foot ulcers. Despite their promising therapeutic potential, cathelicidins face significant challenges in clinical application. Many peptide-based therapies have failed in clinical trials due to unclear efficacy and safety concerns. Additionally, the emergence of bacterial resistance, which contradicts initial claims of non-resistance, further complicates their development. To successfully translate cathelicidins into effective clinical treatments, therefore, several obstacles must be addressed, including a better understanding of their mechanisms of action, sustainable large-scale production, optimized formulations for drug delivery and stability, and strategies to overcome microbial resistance. This review examines the current knowledge of cathelicidins and their therapeutic applications and discusses the challenges that hinder their clinical use and must be overcome to fully exploit their potential in medicine. Full article