Search Results (3,177)

This study examines the interconnectedness of African stock markets during three major global crises: the 2008 Global Financial Crisis (GFC), the COVID-19 pandemic, and the Russia–Ukraine conflict. We use daily stock index data from 2007 to 2023 for ten African countries and apply a Time-Varying Parameter Vector Autoregressive (TVP-VAR) model. The results reveal that volatility connectedness among African markets intensified during all three crises, peaking during the COVID-19 pandemic followed by the 2008 GFC and the Russia–Ukraine conflict. Short-term connectedness consistently exceeded long-term connectedness across all crises. South Africa and Egypt acted as dominant transmitters of volatility, highlighting their systemic importance, while Morocco showed increased influence during the COVID-19 pandemic. These findings suggest that African markets are more globally integrated than previously assumed, making them vulnerable to external shocks. Policy implications include the need for stronger regional financial cooperation, the development of early warning systems, and enhanced intra-African investment to improve market resilience and reduce contagion risk. Full article

The present Perspective analyzes the remarkable evolution of the Amyloid Cascade Hypothesis 2.0 (ACH2.0) theory of Alzheimer’s disease (AD) since its inception a few years ago, as reflected in the diminishing role of amyloid-beta (Aβ) in the disease. In the initial iteration of the ACH2.0, Aβ-protein-precursor (AβPP)-derived intraneuronal Aβ (iAβ), accumulated to neuronal integrated stress response (ISR)-eliciting levels, triggers AD. The neuronal ISR, in turn, activates the AβPP-independent production of its C99 fragment that is processed into iAβ, which drives the disease. The second iteration of the ACH2.0 stemmed from the realization that AD is, in fact, a disease of the sustained neuronal ISR. It introduced two categories of AD—conventional and unconventional—differing mainly in the manner of their causation. The former is caused by the neuronal ISR triggered by AβPP-derived iAβ, whereas in the latter, the neuronal ISR is elicited by stressors distinct from AβPP-derived iAβ and arising from brain trauma, viral and bacterial infections, and various types of inflammation. Moreover, conventional AD always contains an unconventional component, and in both forms, the disease is driven by iAβ generated independently of AβPP. In its third, the current, iteration, the ACH2.0 posits that proteolytic production of Aβ is suppressed in AD-affected neurons and that the disease is driven by C99 generated independently of AβPP. Suppression of Aβ production in AD seems an oxymoron: Aβ is equated with AD, and the later is inconceivable without the former in an ingrained Amyloid Cascade Hypothesis (ACH)-based notion. But suppression of Aβ production in AD-affected neurons is where the logic leads, and to follow it we only need to overcome the inertia of the preexisting assumptions. Moreover, not only is the generation of Aβ suppressed, so is the production of all components of the AβPP proteolytic pathway. This assertion is not a quantum leap (unless overcoming the inertia counts as such): the global cellular protein synthesis is severely suppressed under the neuronal ISR conditions, and there is no reason for constituents of the AβPP proteolytic pathway to be exempted, and they, apparently, are not, as indicated by the empirical data. In contrast, tau protein translation persists in AD-affected neurons under ISR conditions because the human tau mRNA contains an internal ribosomal entry site in its 5′UTR. In current mouse models, iAβ derived from AβPP expressed exogenously from human transgenes elicits the neuronal ISR and thus suppresses its own production. Its levels cannot principally reach AD pathology-causing levels regardless of the number of transgenes or the types of FAD mutations that they (or additional transgenes) carry. Since the AβPP-independent C99 production pathway is inoperative in mice, the current transgenic models have no potential for developing the full spectrum of AD pathology. What they display are only effects of the AβPP-derived iAβ-elicited neuronal ISR. The paper describes strategies to construct adequate transgenic AD models. It also details the utilization of human neuronal cells as the only adequate model system currently available for conventional and unconventional AD. The final alteration of the ACH2.0, introduced in the present Perspective, is that AβPP, which supports neuronal functionality and viability, is, after all, potentially produced in AD-affected neurons, albeit not conventionally but in an ISR-driven and -compatible process. Thus, the present narrative begins with the “omnipotent” Aβ capable of both triggering and driving the disease and ends up with this peptide largely dislodged from its pedestal and retaining its central role in triggering the disease in only one, although prevalent (conventional), category of AD (and driving it in none). Among interesting inferences of the present Perspective is the determination that “sporadic AD” is not sporadic at all (“non-familial” would be a much better designation). The term has fatalistic connotations, implying that the disease can strike at random. This is patently not the case: The conventional disease affects a distinct subpopulation, and the basis for unconventional AD is well understood. Another conclusion is that, unless prevented, the occurrence of conventional AD is inevitable given a sufficiently long lifespan. This Perspective also defines therapeutic directions not to be taken as well as auspicious ways forward. The former category includes ACH-based drugs (those interfering with the proteolytic production of Aβ and/or depleting extracellular Aβ). They are legitimate (albeit inefficient) preventive agents for conventional AD. There is, however, a proverbial snowball’s chance in hell of them being effective in symptomatic AD, lecanemab, donanemab, and any other “…mab” or “…stat” notwithstanding. They comprise Aβ-specific antibodies, inhibitors of beta- and gamma-secretase, and modulators of the latter. In the latter category, among ways to go are the following: (1) Depletion of iAβ, which, if sufficiently “deep”, opens up a tantalizing possibility of once-in-a-lifetime preventive transient treatment for conventional AD and aging-associated cognitive decline, AACD. (2) Composite therapy comprising the degradation of C99/iAβ and concurrent inhibition of the neuronal ISR. A single transient treatment could be sufficient to arrest the progression of conventional AD and prevent its recurrence for life. Multiple recurrent treatments would achieve the same outcome in unconventional AD. Alternatively, the sustained reduction/removal of unconventional neuronal ISR-eliciting stressors through the elimination of their source would convert unconventional AD into conventional one, preventable/treatable by a single transient administration of the composite C99/iAβ depletion/ISR suppression therapy. Efficient and suitable ISR inhibitors are available, and it is explicitly clear where to look for C99/iAβ-specific targeted degradation agents—activators of BACE1 and, especially, BACE2. Directly acting C99/iAβ-specific degradation agents such as proteolysis-targeting chimeras (PROTACs) and molecular-glue degraders (MGDs) are also viable options. (3) A circumscribed shift (either upstream or downstream) of the position of transcription start site (TSS) of the human AβPP gene, or, alternatively, a gene editing-mediated excision or replacement of a small, defined segment of its portion encoding 5′-untranslated region of AβPP mRNA; targeting AβPP RNA with anti-antisense oligonucleotides is another possibility. If properly executed, these RNA-based strategies would not interfere with the protein-coding potential of AβPP mRNA, and each would be capable of both preventing and stopping the AβPP-independent generation of C99 and thus of either preventing AD or arresting the progression of the disease in its conventional and unconventional forms. The paper is interspersed with “validation” sections: every conceptually significant notion is either validated by the existing data or an experimental procedure validating it is proposed. Full article

The search for life beyond Earth currently hinges on the detection of biosignatures that are indicative of current or past life, with terrestrial life being the sole known example. Deoxyribonucleic acid (DNA), which acts as the long-term storage of genetic information in all known organisms, is considered a biosignature of life. Techniques like the Polymerase Chain Reaction (PCR) are particularly useful as they allow for the amplification of DNA fragments, allowing the detection of even trace amounts of genetic material. This study aimed to detect DNA extracted from colonies of an Antarctic black fungus both when (i) alone and (ii) mixed with a Sulfatic Mars Regolith Simulant (S-MRS), after exposure to increasing doses of Fe ions (up to 1 kGy). PCR-based amplification methods were used for detection. The findings of this study revealed no DNA amplification in samples mixed with Sulfatic Mars Regolith Simulant, providing important insights into the potential application of these techniques for in situ DNA detection during future space exploration missions or for their application on the Mars sample return program; it also gives input in the planetary protection discussions. Full article

Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid malignancy, and its progression is closely associated with patient outcomes. This study investigated the role of the long non-coding RNA LINC02560 in the pathogenesis and aggressiveness of PTC through cell culture, transfection, RT-qPCR, Western blot analysis, and various functional assays, such as MTT, EdU, colony formation, wound healing, and Transwell migration assays. Our results revealed a significant upregulation of LINC02560 in PTC tissues, correlating with poor prognosis in affected patients. Functional analyses demonstrated that silencing of LINC02560 markedly inhibited the proliferation, migration, and invasion of the PTC cell lines, KTC-1, and BCPAP, whereas overexpression promoted these aggressive traits. Mechanistically, LINC02560 acted as a competitive endogenous RNA, sponging miR-505-5p and alleviating its suppression on PDE4C degradation, thereby activating the P-AKT and epithelial–mesenchymal transition (EMT) signaling pathways. Additionally, HNF4α was identified as a transcription factor capable of enhancing the expression of LINC02560. In conclusion, our findings elucidate the critical HNF4α/LINC02560/miR-505-5p/PDE4C axis in PTC pathology, presenting this regulatory network as a promising biomarker combination and potential therapeutic target to improve patient outcomes and survival rates, warranting further clinical investigation to validate these insights and support the development of targeted therapies in PTC management. Full article

Purpose: Dirofilariasis is a zoonotic infectious disease caused by a species belonging to the Dirofilaria genus. Human dirofilariasis cases have increased in Europe in the last few decades. Dogs and wild canids represent the definitive hosts and principal reservoirs of Dirofilaria repens, while mosquito species are biological vectors. Humans act as accidental hosts, and clinical manifestations depend on the location of the worm in the organs or tissues. We described the first case of ocular dirofilariasis in the Aosta Valley region (Italy). Case description: a 62-year-old Italian woman complained of recurrent ocular redness, pain and discomfort, accompanied by itching and foreign body sensation in the right eye. The slit lamp biomicroscopic examination revealed conjunctival congestion on the temporal region of bulbar conjunctiva, and a long whitish vermiform mobile mass was detected under the conjunctiva. The anterior chamber showed no flare or cells in either eye, and the dilated fundus examination was normal. The worm was immediately surgically removed to prevent further migration, and was diagnosed morphologically and molecularly as D. repens. Following surgical removal, the symptoms resolved completely and rapidly, with no recurrence of ocular symptoms recorded during 12-month follow-up visits. Conclusions: Ocular dirofilariasis can lead to misdiagnosis due to its rare ocular manifestations, and it is considered an emergent zoonosis in European countries. Accurate diagnosis and control of ocular dirofilariasis by D. repens require a multidisciplinary approach under the One Health framework to effectively address this emergent zoonosis. Full article

Background: Esketamine is a rapidly acting antidepressant with robust efficacy in treatment-resistant depression (TRD). Diminishing therapeutic effects and attenuated side effects have been reported after long-term use. This study aimed to investigate its long-term pharmacokinetics and factors that may contribute to reduced efficacy over time in patients with TRD by evaluating the potential role of auto-induction. Methods: Pharmacokinetic data were collected from 18 patients receiving oral esketamine for six weeks. A pharmacokinetic model was developed to predict esketamine and noresketamine plasma concentrations. Observed esketamine and noresketamine plasma concentrations were compared to model-predicted concentrations to assess deviations suggestive of auto-induction. Results: On day 39, plasma concentrations of esketamine and noresketamine were 59% and 35% lower than predicted, respectively, indicative of auto-induction of CYP3A4 and CYP2B6. Conclusions: Auto-induction appears to occur in oral esketamine treatment, which may contribute to reduced therapeutic efficacy and side effects in long-term treatment. Identifying auto-induction as a mechanism of tolerance potentially has important clinical implications. Further studies are warranted to confirm these findings and evaluate strategies to maintain therapeutic efficacy. Full article

This study examines Türkiye’s compliance with the Paris Agreement by comparing its climate policy framework with those of Germany and Spain—two EU countries with absolute, legally binding emission reduction targets. Despite ratifying the Paris Agreement in 2021 and declaring a net-zero target for 2053, Türkiye’s Nationally Determined Contribution (NDC) lacks absolute reduction commitments and a comprehensive Climate Act. This gap is particularly critical given the EU’s implementation of the Carbon Border Adjustment Mechanism (CBAM), which links climate action to trade competitiveness. Using a comparative policy analysis approach, this study evaluates official emission data, legal documents, and EU climate progress reports to assess the coherence of Türkiye’s climate strategy. The findings indicated that Türkiye’s emissions continue to rise in the presence of fossil fuel domination and the absence of binding targets. Conversely, Germany and Spain have reduced emissions through robust legislation, functioning Emissions Trading Systems, and long-term investment in renewables. This study offers policy recommendations tailored to Türkiye’s context, including the adoption of absolute and binding targets, acceleration of renewable energy—especially solar—and the promotion of community-based energy models, inspired by Spain’s approach. Additionally, mechanisms to balance energy security, local acceptance, and decarbonization are discussed, drawing from Germany’s phased fossil fuel exit. The results indicate that Türkiye’s ability to align with EU climate targets and the Paris Agreement without compromising its development priorities or energy supply security can only be achieved with a realistic roadmap and specific reforms. Full article

The Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) is a conservation and trade convention regulating international trade in wild species listed under its various appendices. Party nations are required to have designated scientific and management authorities to administer CITES and, ideally, domestic enabling legislation for proper implementation. However, the complexity of the convention makes it difficult to implement in resource-constrained nations that lack expertise and commitment. Apart from the lack of resources and expertise in much of the global south, hurdles to CITES implementation arise from delays in the formation of necessary legislation, apathy in enforcing the legislation, and the gatekeeping of resources by leading government agencies. Nepal has a long and well-documented history of wildlife conservation and is party to most major global environmental conventions, although it has frequently lacked the ability to implement them fully. Recently, Nepal has formulated domestic policies and developed institutions supporting biodiversity conservation but still refrains from formulating and implementing some provisions. After a long history of only partial (at best) compliance, Nepal enacted domestic CITES-implementing legislation, the CITES Act of 2017, with progressive provisions for enforcement, wildlife farming, and resource utilization and conservation. Here, we used a mixed methods research approach involving published and gray literature reviews and key informant interviews with concerned stakeholders to understand the workings and modality of authorities under the 2017 Act. We explore its nuances and discuss potential challenges for its implementation over time. Though the new policy has many positive aspects in that it is progressive in shifting away from more classical, strict protection, we found that there are still shortcomings within national administrative structures and a lack of policy that coordinates and informs different government offices of their responsibilities and how they interface under the current federal system. This has resulted in ongoing obstacles to achieving fuller CITES implementation to date and, in some cases, also inhibits sustainable uses of biodiversity. Full article

Long non-coding RNAs (lncRNAs) have been defined as non-coding transcripts exceeding 200 nucleotides, which play essential roles during transcriptional and post-transcriptional regulation in multiple biological processes. Understanding R. delavayi lncRNAs is of great significance as it is profoundly influenced by heat stress. In this research, a total of 1145 differentially expressed lncRNAs (DE-lncRNAs) and 9447 differentially expressed genes (DEGs) (log₂|FC| > 1, p < 0.05) were characterized between heat-stress-treated groups and control groups. Further analysis showed that 229 DE-lncRNAs (144 upregulated and 85 downregulated) were commonly distributed in two comparisons (CK_vs._H3 and CK_vs._H6). We further investigated the cis- and trans-acting genes of the upregulated DE-lncRNAs, and found that 142 upregulated DE-lncRNAs corresponded to 1565 cis-acting DEGs, and 143 upregulated DE-lncRNAs corresponded to 3417 trans-acting DEGs. KEGG enrichment analysis of these target genes revealed that cis- and trans-acting DEGs of upregulated DE-lncRNA were primarily enriched in five and twelve KEGG pathways, respectively. Co-expression network analysis of upregulated DE-lncRNAs and DEGs enriched in the common KEGG pathways revealed 57 co-expression relationships between 28 DE-lncRNAs and 43 cis-acting DEGs and 554 co-expression relationships between 26 DE-lncRNAs and 90 trans-acting DEGs. Six DE-lncRNAs and six of their target DEGs were used as candidate genes to verify the RNA-seq data using qRT-PCR. Further analysis revealed three target genes (TrxG, PEPC, and CCR) out of six candidate DEGs that were selected as candidate genes for subsequent research. This study examined the relationship between DE-lncRNAs and DEGs and further screened out candidate DE-lncRNAs that can potentially provide an important theoretical basis and experimental data for the genetic improvement of heat tolerance in R. delavayi. Full article

Photodynamic therapy (PDT) is a light-activated treatment that generates reactive oxygen species (ROS) to induce microbial cell death. As resistance to traditional antibiotics intensifies globally, PDT has emerged as a promising alternative or adjunctive antimicrobial strategy. Among various photosensitizers, Hypocrellin, a perylenequinone compound, has shown high ROS yield and broad-spectrum activity against bacteria and fungi. This systematic review evaluated the efficacy, safety, and therapeutic potential of Hypocrellin-mediated antimicrobial photodynamic therapy. Following PRISMA 2020 guidelines, a comprehensive literature search was conducted in PubMed, Embase, Scopus, and the Cochrane Library for studies published between 2015 and 2025. Eligible studies included in vitro and preclinical in vivo research using Hypocrellin as a photosensitizer. Quality and risk of bias were assessed using a structured nine-item checklist. Ten eligible studies, all conducted in China, were included. Hypocrellin-mediated aPDT significantly reduced microbial loads in both planktonic and biofilm states of resistant pathogens such as Candida albicans, Candida auris, Cutibacterium acnes, and Staphylococcus aureus. The treatment acted via ROS-mediated apoptosis, membrane disruption, and mitochondrial dysfunction, with minimal cytotoxicity to mammalian cells. Studies also reported enhanced efficacy when Hypocrellin was incorporated into nanocarriers, polymeric scaffolds, or combined with chemodynamic or photothermal therapies. However, substantial heterogeneity was observed in Hypocrellin concentrations, irradiation parameters, and outcome measures. Hypocrellin-based PDT exhibits potent antimicrobial activity and favorable safety in preclinical settings, supporting its potential as an alternative to conventional antibiotics. However, standardized treatment protocols and robust clinical trials are urgently needed to validate long-term safety and translational feasibility. These findings underscore the broader promise of PDT in addressing drug-resistant infections through a mechanism unlikely to induce resistance. Full article

Background/Objectives: Enterobacteriaceae, including pathogenic Shigella (S.) flexneri and Escherichia (E.) coli, cause severe gastrointestinal infections through toxins like Shiga and Shiga-like toxins. Antibiotic use is often discouraged due to its potential to increase toxin effects or contribute to the development of resistance. The host protease furin is capable of activating several viral glycoproteins and bacterial toxins, thus enhancing pathogen infectivity. Methods: To assess the therapeutic potential of furin inhibitors, cultured epithelial cell models (IPEC-J2 and MDCK) were used. The effects of MI-1851 and MI-2415 were evaluated after short-term (2 h) and long-term (6 h) exposure to S. flexneri, enterohemorrhagic E. coli (EHEC), and enteropathogenic E. coli (EPEC). Cytotoxicity was determined using the CCK-8 assay, and the inflammatory response was assessed by measuring interleukin (IL)-6 and IL-8 levels. Additionally, extracellular hydrogen peroxide production was monitored in IPEC-J2 cells to evaluate the potential alterations in redox status. Results: Infections with EHEC, EPEC, and S. flexneri significantly reduced the viability of epithelial cells after 6 h of incubation. Furin inhibitors MI-1851 and MI-2415 decreased cytotoxicity and compensated for IL-6 and IL-8 overproduction in cells during infection with EHEC and S. flexneri, but not in cells exposed to EPEC. In addition, they alleviated oxidative stress, particularly during S. flexneri addition. Conclusions: The development of new antimicrobial drugs that act via alternative mechanisms and effectively manage life-threatening enterobacterial infections is of key importance. Targeting furin with inhibitors MI-1851 and MI-2415, thus blocking toxin activation, could prevent the development of antimicrobial resistance, reduce the need for antibiotics and enhance overall treatment outcomes. Full article

Aspect-based sentiment triplet extraction tasks remain a long-standing challenge, which aim to achieve aspect, opinion, and sentiment polarity from sentences. Most existing methods achieve excellent performance by exploring the interactions between aspect and opinion terms. However, few studies focus on the positive impact of sentiment on triplet extraction. As sentiment acts as a key cue in triplet extraction, its role is often overlooked, thereby limiting extraction performance. This paper proposes a novel framework, duality-driven aspect sentiment triplet extraction with a large language model and iterative reinforcement, which integrates duality-driven with a large language model for the aspect sentiment triplet task. This study employs a duality-driven strategy based on symmetry to extract aspect-based sentiment triplets, fully taking into account sentiment polarity during the interaction between aspects and opinions. Moreover, this study devises a two-view prompt template for prior knowledge fusion based on large language models and employs confidence cycle iteration strategies to alleviate cascading errors. Extensive experiments show that the framework outperforms the previous state-of-the-art model. These findings demonstrate that the proposed model makes a positive impact on the aspect sentiment triplet extraction task overall. Full article

The effects of climate change are particularly pronounced in cities, where urban green infrastructure—such as trees, parks, and green spaces—plays a vital role in both climate adaptation and mitigation. This study assesses the carbon sequestration potential of urban forests in Budapest, the capital city of Hungary, which lies at the intersection of the Great Hungarian Plain and the Buda Hills, and is traversed by the Danube River. The city is characterized by a temperate climate with hot summers and cold winters, and a diverse range of soil types, including shallow Leptosols and Cambisols in the limestone and dolomite hills of Buda, well-developed Luvisols and Regosols in the valleys, Fluvisols and Arenosols in the flood-affected areas of Pest, and Technosols found on both sides of the city. The assessment utilizes data from the National Forestry Database and the Copernicus Land Monitoring Service High Resolution Layer Tree Cover Density. The results show that Budapest’s urban forests and trees contribute an estimated annual carbon offset of −41,338 tCO₂, approximately 1% of the city’s total emissions. The urban forests on the Buda and Pest sides of the city exhibit notable differences in carbon sequestration and storage, age class structure, tree species composition, and naturalness. On the Buda side, older semi-natural forests dominated by native species primarily act as in situ carbon reservoirs, with limited additional sequestration capacity due to their older age, slower growth, and longer rotation periods. In contrast, the Pest-side forests, which are primarily extensively managed introduced forests and tree plantations, contain a higher proportion of non-native species such as black locust (Robinia pseudoacacia) and hybrid poplars (Populus × euramericana). Despite harsher climatic conditions, Pest-side forests perform better in carbon sink capacity compared to those on the Buda side, as they are younger, with lower carbon stocks but higher sequestration rates. Our findings provide valuable insights for the development of climate-resilient urban forestry and planning strategies, emphasizing the importance of enhancing the long-term carbon sequestration potential of urban forests. Full article

To extend food shelf life and reduce plastic pollution, halloysite nanotubes (HNTs) were employed as a carrier to load cinnamon essential oils (CEOs), and the nanotubes were blended with polybutylene adipate co-terephthalate (PBAT) resin to fabricate the film with non-contact antimicrobial activity. The results showed that the HNTs had a high loading efficiency (about 11%) for CEOs. The retention rate of CEOs in HNTs was still 33% after twenty days later, which indicated that the CEOs/HNTs nanoparticles had a long-acting controlled-released effect. The composite films represented excellent mechanical properties and antibacterial effects against Staphylococcus aureus and Escherichia coli due to the non-contact antimicrobial activity of CEOs. The strawberries remained fresh after five days when the composite film was applied in the packaging of strawberries, which proves that composite films can extend the shelf life of food. Therefore, it has potential application prospects in the food industry. Full article

Tennessee is in the southern region of the United States and has not yet fully benefitted from HIV pre-exposure prophylaxis (PrEP). Relatively little research has focused on pivotal roles of PrEP navigators. This study examined PrEP navigator perceptions of implementing long-acting injectable (LAI) PrEP in Tennessee. Semi-structured interviews with state-funded navigators were audio-recorded, transcribed, and systematically coded using a hierarchical system. Coded transcripts were aggregated, sorted, and analyzed using an iterative inductive/deductive qualitative approach. Using the Consolidated Framework for Implementation Research (CFIR), institutional, individual, and modifying factors to initiating and transitioning to LAI PrEP were identified. Most navigators initially had limited training and experience with LAI PrEP. Navigators reported systemic barriers associated with accessibility to LAI PrEP such as health insurance, pharmaceutical policies, and cost policies. While navigators noted the continued support of the state health department, strategies for circumventing individual and structural barriers are needed for universally implementing injectable PrEP. Full article