This study investigated the impacts of students’ mood states and background sound levels on students’ sound perceptions and academic performance in four library rooms. The background sound level was measured for five days. Meanwhile, around 300 students were invited to participate in a survey of questions about their acoustic perceptions and mood states and a concentration test. Pearson correlation, one-way ANOVA, and two-way ANOVA were applied to establish the relationships between the LAeq, students’ mood states, acoustic perceptions, and concentration levels on both the individual level and the room level and to identify the interaction effect between the background sound levels and mood states on students’ acoustic perception and concentration. The results indicated that LAeq in learning spaces significantly impacted students’ acoustic satisfaction, but only at the room level. In contrast, mood states mainly influenced students’ sound perception and concentration at the individual level. Furthermore, this study reports significant interaction effects between mood state and LAeq on students’ sound perceptions and reveals different impacts of mood states due to different sound levels. These results could help improve occupants’ acoustic perceptions and performance in learning spaces in the future. Full article

Currently, in the digital era, critical infrastructure is increasingly exposed to cyber threats to their operation and security. This study explores the use of blockchain technology to address these challenges, highlighting its immutability, decentralization, and transparency as keys to strengthening the resilience of these vital structures. Through a methodology encompassing literature review, use-case analysis, and the development and evaluation of prototypes, the effective implementation of the blockchain in the protection of critical infrastructure is investigated. The experimental results reveal the positive impact of the blockchain on security and resilience, presenting a solid defense against cyber-attacks due to its immutable and decentralized structure, with a 40% reduction in security incidents. Despite the observed benefits, blockchain integration faces significant challenges in scalability, interoperability, and regulations. This work demonstrates the potential of the blockchain to strengthen critical infrastructure. It marks progress towards the blockchain’s practical adoption, offering a clear direction for future research and development in this evolving field. Full article

Human malignancies are one of the major health-related issues throughout the world and are anticipated to rise in the future. Despite huge investments made in anticancer drug development, limited success has been obtained and the average number of FDA approvals per year is declining. So, an increasing interest in drug repurposing exists. Metformin (MET) and aspirin (ASP) possess anticancer properties. This work aims to test the effect of these two drugs in combination on colorectal cancer (CRC) cells in vitro. The effects of MET and/or ASP on cell proliferation, viability, migratory ability, anchorage-independent growth ability (colony formation), and nutrient uptake were determined in two (HT-29 and Caco-2) human CRC cell lines. Individually, MET and ASP possessed antiproliferative, cytotoxic, and antimigratory effects and reduced colony formation in HT-29 cells (BRAF- and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PI3KCA)-mutant), although MET did not affect either ³H-deoxy-D-glucose or ¹⁴C-butyrate uptake and lactate production, and ASP caused only a small decrease in ¹⁴C-butyrate uptake. Moreover, in these cells, the combination of MET and ASP resulted in a tendency to an increase in the cytotoxic effect and in a potentiation of the inhibitory effect on colony formation, although no additive antiproliferative and antimigratory effects, and no effect on nutrient uptake and lactate production were observed. In contrast, MET and ASP, both individually and in combination, were almost devoid of effects on Caco-2 cells (BRAF- and PI3KCA-wild type). We suggest that inhibition of PI3K is the common mechanism involved in the anti-CRC effect of both MET, ASP and their combination and, therefore, that the combination of MET + ASP may especially benefit PI3KCA-mutant CRC cases, which currently have a poor prognostic. Full article

In the contemporary era, conventional energy sources like oil, coal, and natural gas overwhelmingly contribute 89.6% to global CO₂ emissions, intensifying environmental challenges. Recognizing the urgency of addressing climate concerns, a pivotal shift towards renewable energy, encompassing solar, wind, and biofuels, is crucial for bolstering environmental sustainability. Bioethanol, a globally predominant biofuel, offers a versatile solution, replacing gasoline or integrating into gasoline–ethanol blends while serving as a fundamental building block for various valuable compounds. This review investigates the dynamic landscape of biomass generations, drawing insightful comparisons between the first, second, third, and fourth generations. Amid the drive for sustainability, the deliberate focus on the initial generation of biomass, particularly corn, in bioethanol production is grounded in the current dependence on edible crops. The established utilization of first-generation biomass, exemplified by corn, underscores the necessity for a comprehensive examination of its advantages and challenges, allowing for a nuanced exploration of existing infrastructure and practices. To produce bioethanol from corn feedstock, various milling methods can be employed. Thus, this paper delves into a comparative assessment of dry-milling and wet-milling processes scrutinizing their efficiency, environmental impact, and economic feasibility. Full article

Background and Objectives: This study aimed to evaluate the mid-term effectiveness and safety of a combined ultrasound (US) and fluoroscopy (FL)-guided approach in comparison to US-guided and FL-guided caudal epidural steroid injections (CESI) for treating unilateral lower lumbar radicular pain. Materials and Methods: A total of 154 patients who underwent CESI between 2018 and 2022 were included. Patients were categorized into three groups based on the guidance method: combined US and FL (n = 51), US-guided (n = 51), and FL-guided (n = 52). The study design was retrospective case-controlled, utilizing patient charts and standardized forms to assess clinical outcomes, adverse events, complications during the procedures. Results: In all groups, Oswestry Disability Index and Verbal Numeric Scale scores improved at 1, 3, and 6 months after the last injection, with no significant differences between groups (p < 0.05). The treatment success rate at all time points was also similar among the groups. Logistic regression analysis showed that injection method, cause, sex, age, number of injections, and pain duration did not independently predict treatment success. Blood was aspirated before injection in 2% (n = 1), 13.5% (n = 7), and 4% (n = 2) of patients in the combined US and FL groups, FL-guided groups, and US-guided groups, respectively. Intravascular contrast spread was detected in one patient in the combined method groups and seven in the FL-guided groups. Conclusions: When comparing pain reduction and functional improvement, there was no significant difference between the three methods. The combined method took less time compared to using FL alone. The combined approach also showed a lower occurrence of intravascular injection compared to using FL alone. Moreover, blood vessels at the injection site can be identified with an ultrasound using the combined method. Given these advantages, it might be advisable to prioritize the combined US- and FL-guided therapy when administering CESI for patients with unilateral lumbar radicular pain. Full article

Patient-Reported Outcome Measures (PROMs), such as the six-item International Knee Documentation Committee Subjective Knee Form (IKDC-6), play a crucial role in assessing health conditions and guiding clinical decisions. Latent Growth Modeling (LGM) can be employed to understand recovery trajectories in patients post-operatively. Therefore, the purpose of this study was to assess LGM properties of the IKDC-6 in patients with knee pathologies that require surgical intervention and to assess differences between subgroups (i.e., sex and age). A cross-sectional study was conducted using the Surgical Outcome System (SOS) database with patients who had undergone knee arthroscopy. Our results found that preoperative scores did not influence the rate of change overtime. Perceived knee health improved over time, with varying rates among individuals. The adolescent age subgroup and male subgroup exhibited faster recovery rates compared to the older age subgroup and female subgroup. While initial hypotheses suggested IKDC-6 could serve as a prognostic tool, results did not support this. However, results indicated favorable outcomes irrespective of preoperative perceived knee impairment levels. This study provides valuable insights into recovery dynamics following knee surgery, emphasizing the need for personalized rehabilitation strategies tailored to individual patient characteristics. Full article

Peptides possessing antihypertensive attributes via inhibiting the angiotensin-converting enzyme (ACE) were derived through the enzymatic degradation of Trichiurus lepturus (ribbonfish) using alkaline protease. The resulting mixture underwent filtration using centrifugation, ultrafiltration tubes, and Sephadex G-25 gels. Peptides exhibiting ACE-inhibitory properties and DPPH free-radical-scavenging abilities were isolated and subsequently purified via LC/MS-MS, leading to the identification of over 100 peptide components. In silico screening yielded five ACE inhibitory peptides: FAGDDAPR, QGPIGPR, IFPRNPP, AGFAGDDAPR, and GPTGPAGPR. Among these, IFPRNPP and AGFAGDDAPR were found to be allergenic, while FAGDDAPRR, QGPIGPR, and GPTGPAGP showed good ACE-inhibitory effects. IC₅₀ values for the latter peptides were obtained from HUVEC cells: FAGDDAPRR (IC₅₀ = 262.98 μM), QGPIGPR (IC₅₀ = 81.09 μM), and GPTGPAGP (IC₅₀ = 168.11 μM). Peptide constituents derived from ribbonfish proteins effectively modulated ACE activity, thus underscoring their therapeutic potential. Molecular docking and modeling corroborated these findings, emphasizing the utility of functional foods as a promising avenue for the treatment and prevention of hypertension, with potential ancillary health benefits and applications as substitutes for synthetic drugs. Full article

The delivery of therapeutical molecules through the skin, particularly to its deeper layers, is impaired due to the stratum corneum layer, which acts as a barrier to foreign substances. Thus, for the past years, scientists have focused on the development of more efficient methods to deliver molecules to skin distinct layers. Microneedles, as a new class of biomedical devices, consist of an array of microscale needles. This particular biomedical device has been drawing attention due to its ability to breach the stratum corneum, forming micro-conduits to facilitate the passage of therapeutical molecules. The microneedle device has several advantages over conventional methods, such as better medication adherence, easiness, and painless self-administration. Moreover, it is possible to deliver the molecules swiftly or over time. Microneedles can vary in shape, size, and composition. The design process of a microneedle device must take into account several factors, like the location delivery, the material, and the manufacturing process. Microneedles have been used in a large number of fields from drug and vaccine application to cosmetics, therapy, diagnoses, tissue engineering, sample extraction, cancer research, and wound healing, among others. Full article

The study of extreme events (EEs) in photonics has expanded significantly due to straightforward implementation conditions. EEs have not been discussed systematically, to the best of our knowledge, in the chaotic dynamics of a Fabry–Perot laser with optical feedback, so we address this in the current contribution. Herein, we not only find EEs in all modes but also divide the EEs in total output into two categories for further discussion. The two types of EEs have similar statistical features to conventional rogue waves. The occurrence probability of EEs undergoes a saturation effect as the feedback strength increases. Additionally, we analyze the influence of feedback strength, feedback delay, and pump current on the probability of EEs defined by two criteria of EEs and find similar trends. We hope that this work contributes to a deep understanding and serves as inspiration for further research into various multimode semiconductor laser systems. Full article

The aim of this paper is to analyze the formative and evaluative activities involving statistical graphs in the new textbooks for Chilean rural multigrade education. The methodology is qualitative, at a descriptive level and uses the content analysis technique. The sample is made up of the six primary education textbooks distributed by the Ministry of Education for rural multigrade schools. The results show the predominance of the bar chart, semiotic level 3, the task of calculating and the personal context in both types of activities, although with respect to the reading level, it is evident that level 4 predominates in the formative activities and level 2 in the evaluative ones. According to the results, it is recommended to incorporate graphs proposed by the curricular guidelines of the Ministry of Education, which are absent in textbooks as well as to include evaluative activities that require reflection on the nature of the data, context, representation and conclusions obtained from them. Full article

Background: The diagnosis of depression in dementia patients leads to an increase in the burden of the disease. To treat depression in this patient group, antidepressants are frequently used; however, there is not any proof of their therapeutic effectiveness, and their use may be potentially harmful. This narrative review aims to summarize the existing evidence regarding the role of antidepressants in treating depression in dementia patients. Main text: A search was conducted in the PubMed, Excerpta Medica database (EMBASE), and Cochrane databases for randomized controlled trials and meta-analyses wherein antidepressants were given to dementia sufferers to address depression. Fifteen randomized controlled trials and seven meta-analyses were identified. Most well-designed blinded placebo-controlled trials reported a lack of effectiveness of antidepressants in treating depression in dementia patients. Among the seven metanalyses, two reported good efficacy of Selective serotonin reuptake inhibitors (SSRIs). However, two major Cochrane reviews reported little or no effectiveness and increased side effects of antidepressants in dementia patients. Conclusion: There is robust evidence regarding the lack of efficacy of antidepressants in treating depression in dementia patients. However, further well-designed Randomized controlled trials (RCTs,) using scales with good validity and reliability to diagnose depression in dementia patients, sufficient sample sizes, and detailed adverse effect profiles may help determine the rationale for their use. Full article

Astragalus polysaccharide (APS) derived from A. membranaceus plays a crucial role in traditional Chinese medicine. These polysaccharides have shown antitumor effects and are considered safe. Thus, they have become increasingly important in cancer immunotherapy. APS can limit the spread of cancer by influencing immune cells, promoting cell death, triggering cancer cell autophagy, and impacting the tumor microenvironment. When used in combination with other therapies, APS can enhance treatment outcomes and reduce toxicity and side effects. APS combined with immune checkpoint inhibitors, relay cellular immunotherapy, and cancer vaccines have broadened the application of cancer immunotherapy and enhanced treatment effectiveness. By summarizing the research on APS in cancer immunotherapy over the past two decades, this review elaborates on the anticancer mechanism of APS and its use in cancer immunotherapy and clinical trials. Considering the multiple roles of APS, this review emphasizes the importance of using APS as an adjunct to cancer immunotherapy and compares other polysaccharides with APS. This discussion provides insights into the specific mechanism of action of APS, reveals the molecular targets of APS for developing effective clinical strategies, and highlights the wide application of APS in clinical cancer therapy in the future. Full article

The article describes the selection of a permanent magnet synchronous machine design that could be implemented in a small wind turbine designed by the GUST student organization together with researchers working at the Technical University of Lodz. Based on measurements of the characteristics of available machines, eight initial designs of machines with different rotor designs were proposed. The size of the stator, the number of pairs of poles, and the dimensions of the magnets were used as initial parameters of the designed machines. The analysis was carried out about the K-index, the so-called index of benefits. The idea was to make the selected design as efficient as possible while keeping production costs and manufacturing time low. This paper describes how to select the best design of a permanent magnet synchronous generator intended to work with a small wind turbine. All generator parameters were selected keeping in mind the competition requirements, as the designed generator will be used in the author’s wind turbine. Based on the determined characteristics of the generator variants and the value of the K-index, a generator with a latent magnet rotor was selected as the best solution. The aforementioned K-index is a proprietary concept developed for the selection of the most suitable generator design. This paper did not use optimization methods; the analysis was only supported by the K-index. Full article

African American (AA) populations present with notably higher incidence and mortality rates from lung cancer in comparison to other racial groups. Here, we elucidated the contribution of long non-coding RNAs (lncRNAs) in the racial disparities and their potential clinical applications in both diagnosis and therapeutic strategies. AA patients had elevated plasma levels of MALAT1 and PVT1 compared with cancer-free smokers. Incorporating these lncRNAs as plasma biomarkers, along with smoking history, achieved 81% accuracy in diagnosis of lung cancer in AA patients. We observed a rise in MALAT1 expression, correlating with increased levels of monocyte chemoattractant protein-1 (MCP-1) and CD68, CD163, CD206, indicative of tumor-associated macrophages in lung tumors of AA patients. Forced MALAT1 expression led to enhanced growth and invasiveness of lung cancer cells, both in vitro and in vivo, accompanied by elevated levels of MCP-1, CD68, CD163, CD206, and KI67. Mechanistically, MALAT1 acted as a competing endogenous RNA to directly interact with miR-206, subsequently affecting MCP-1 expression and macrophage activity, and enhanced the tumorigenesis. Targeting MALAT1 significantly reduced tumor sizes in animal models. Therefore, dysregulated MALAT1 contributes to lung cancer disparities in AAs by modulating the tumor immune microenvironment through its interaction with miR-206, thereby presenting novel diagnostic and therapeutic targets. Full article

Life Cycle Assessment (LCA) and Life Cycle Cost Assessment (LCCA) are essential tools for environmental and economic assessment and decision-making in an evolving world with continuous climate change. In the same conditions, one of the most used and assessed solutions for facing climate change is using pervious pavements, with many papers proving its benefits. However, the literature has shown a need for more research on the LCA methodological aspects in the context of new green infrastructure. This research aims to review pervious pavements, LCA and LCCA combined, while discussing possible differences in boundaries, functional units, and other parameters. Thus, a string search was performed, leading to 89 documents. The main results indicate LCA is usually scope-bounded in the field of pervious pavements, with different benefits and characteristics, such as traffic impact, urban heat island effects, and carbonation. As for LCCA, private and public cost differentiation provide a scope definition and monetisation difficulties. In conclusion, both tools offer promising applications in pervious pavements. As a significant deliverable and recommendation of this paper, both LCA and LCCA theoretical frameworks were provided based on the benefits and specific characteristics included in the literature. These frameworks introduce novel ideas and perspectives, inviting further exploration and discussion. Full article

In testing for main effects, the use of orthogonal contrasts for balanced designs with the factor levels not ordered is well known. Here, we consider two-factor fixed-effects ANOVA with the levels of one factor ordered and one not ordered. The objective is to extend the idea of decomposing the main effect to decomposing the interaction. This is achieved by defining level–degree coefficients and testing if they are zero using permutation testing. These tests give clear insights into what may be causing a significant interaction, even for the unbalanced model. Full article

In a screen of over 200 novel pyrazole compounds, ethyl 1-(2-hydroxypentyl)-5-(3-(3-(trifluoromethyl) phenyl)ureido)-1H-pyrazole-4-carboxylate (named GeGe-3) has emerged as a potential anticancer compound. GeGe-3 displays potent anti-angiogenic properties through the presumptive targeting of the protein kinase DMPK1 and the Ca2⁺-binding protein calreticulin. We further explored the anticancer potential of GeGe-3 on a range of established cancer cell lines, including PC3 (prostate adenocarcinoma), SKMEL-28 (cutaneous melanoma), SKOV-3 (ovarian adenocarcinoma), Hep-G2 (hepatocellular carcinoma), MDA-MB231, SKBR3, MCF7 (breast adenocarcinoma), A549 (lung carcinoma), and HeLa (cervix epithelioid carcinoma). At concentrations in the range of 10 μM, GeGe-3 significantly restricted cell proliferation and metabolism. GeGe-3 also reduced PC3 cell migration in a standard wound closure and trans-well assay. Together, these results confirm the anticancer potential of GeGe-3 and underline the need for more detailed pre-clinical investigations into its molecular targets and mechanisms of action. Full article

The development of fully biobased hydrogels obtained by simple routes and in the absence of toxic or environmentally harmful reagents is a major challenge in meeting new societal demands. In this work, we discuss the development of hydrogels made from cellulose nanocrystals (CNCs) and xyloglucan (XG), two non-toxic, renewable, and biobased components. We present three strategies to fine-tune the functional properties. The first one consists in varying the XG/CNC ratio that leads to the modulation of the mechanical properties of hydrogels as well as a better comprehension of the gel mechanism formation. The second relies on tuning the XG chains’ interaction by enzymatic modification to achieve thermoresponsive systems. Finally, the third one is based on the increase in the hydrogel solid content by osmotic concentration. The high-solid-content gels were found to have very high mechanical properties and self-healing properties that can be used for molding materials. Overall, these approaches are a case study of potential modifications and properties offered by biobased nanocolloidal hydrogels. Full article

Polymerase I (Pol I) is at the epicenter of ribosomal RNA (rRNA) synthesis. Pol I is a target for the treatment of cancer. Given the many cellular commonalities between cancer and neurodegeneration (i.e., different faces of the same coin), it seems rational to consider targeting Pol I or, more generally, rRNA synthesis for the treatment of disorders associated with the death of terminally differentiated neurons. Principally, ribosomes synthesize proteins, and, accordingly, Pol I can be considered the starting point for protein synthesis. Given that cellular accumulation of abnormal proteins such as α-synuclein and tau is an essential feature of neurodegenerative disorders such as Parkinson disease and fronto-temporal dementia, reduction of protein production is now considered a viable target for treatment of these and closely related neurodegenerative disorders. Abnormalities in polymerase I activity and rRNA production may also be associated with nuclear and nucleolar stress, DNA damage, and childhood-onset neuronal death, as is the case for the UBTF E210K neuroregression syndrome. Moreover, restraining the activity of Pol I may be a viable strategy to slow aging. Before starting down the road of Pol I inhibition for treating non-cancerous disorders of the nervous system, many questions must be answered. First, how much Pol I inhibition can neurons tolerate, and for how long? Should inhibition of Pol I be continuous or pulsed? Will cells compensate for Pol I inhibition by upregulating the number of active rDNAs? At present, we have no effective and safe disease modulatory treatments for Alzheimer disease, α-synucleinopathies, or tauopathies, and novel therapeutic targets and approaches must be explored. Full article

To create a radiogenomics map and evaluate the correlation between molecular and imaging phenotypes in localized prostate cancer (PCa), using radical prostatectomy histopathology as a reference standard. Radiomic features were extracted from T2-weighted (T2WI) and Apparent Diffusion Coefficient (ADC) images of clinically localized PCa patients (n = 15) across different Gleason score-based risk categories. DNA extraction was performed on formalin-fixed, paraffin-embedded (FFPE) samples. Gene expression analysis of androgen receptor expression, apoptosis, and hypoxia was conducted using the Chromosome Analysis Suite (ChAS) application and OSCHIP files. The relationship between gene expression alterations and textural features was assessed using Pearson’s correlation analysis. Receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive accuracy of the model. A significant correlation was observed between radiomic texture features and copy number variation (CNV) of genes associated with apoptosis, hypoxia, and androgen receptor (p-value ≤ 0.05). The identified radiomic features, including Sum Entropy ADC, Inverse Difference ADC, Sum Variance T2WI, Entropy T2WI, Difference Variance T2WI, and Angular Secondary Moment T2WI, exhibited potential for predicting cancer grade and biological processes such as apoptosis and hypoxia. Incorporating radiomics and genomics into a prediction model significantly improved the prediction of prostate cancer grade (clinically significant prostate cancer), yielding an AUC of 0.95. Radiomic texture features significantly correlate with genotypes for apoptosis, hypoxia, and androgen receptor expression in localised prostate cancer. Integration of these into the prediction model improved prediction accuracy of clinically significant prostate cancer. Full article

Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as well as on inflammatory cells (e.g., tumor-infiltrating T cells, TILs) in the tumor microenvironment. Expressional changes of chemokines and their receptors in solid cancers are common and well known, especially in affecting colorectal cancer patient outcomes. Therefore, the aim of this current systematic review and meta-analysis was to classify chemokines as a prognostic biomarker in colorectal cancer patients. A systematic literature search was conducted in PubMed, CENTRAL and Web of Science. Information on the chemokine expression of 25 chemokines in colorectal cancer tissue and survival data of the patients were investigated. The hazard ratio of overall survival and disease-free survival with chemokine expression was examined. The risk of bias was analyzed using Quality in Prognosis Studies. Random effects meta-analysis was performed to determine the impact on overall respectively disease survival. For this purpose, the pooled hazard ratios (HR) and their 95% confidence intervals (CI) were used for calculation. Twenty-five chemokines were included, and the search revealed 5556 publications. A total of thirty-one publications were included in this systematic review and meta-analysis. Overexpression of chemokine receptor CXCR4 was associated with both a significantly reduced overall survival (HR = 2.70, 95%-CI: 1.57 to 4.66, p = 0.0003) as well as disease-free survival (HR = 2.68, 95%-CI: 1.41 to 5.08, p = 0.0026). All other chemokines showed either heterogeneous results or few studies were available. The overall risk of bias for CXCR4 was rated low. At the current level of evidence, this study demonstrates that CXCR4 overexpression in patients with colorectal cancer is associated with a significantly diminished overall as well as disease-free survival. Summed up, this systematic review and meta-analysis reveals CXCR4 as a promising prognostic biomarker. Nevertheless, more evidence is needed to evaluate CXCR4 and its antagonists serving as new therapeutic targets. Full article

Alzheimer’s disease (AD) remains a significant health challenge, with an increasing prevalence globally. Recent research has aimed to deepen the understanding of the disease pathophysiology and to find potential therapeutic interventions. In this regard, G protein-coupled receptors (GPCRs) have emerged as novel potential therapeutic targets to palliate the progression of neurodegenerative diseases such as AD. Orexin and cannabinoid receptors are GPCRs capable of forming heteromeric complexes with a relevant role in the development of this disease. On the one hand, the hyperactivation of the orexins system has been associated with sleep–wake cycle disruption and Aβ peptide accumulation. On the other hand, cannabinoid receptor overexpression takes place in a neuroinflammatory environment, favoring neuroprotective effects. Considering the high number of interactions between cannabinoid and orexin systems that have been described, regulation of this interplay emerges as a new focus of research. In fact, in microglial primary cultures of APPSw/Ind mice model of AD there is an important increase in CB₂R–OX₁R complex expression, while OX₁R antagonism potentiates the neuroprotective effects of CB₂R. Specifically, pretreatment with the OX₁R antagonist has been shown to strongly potentiate CB₂R signaling in the cAMP pathway. Furthermore, the blockade of OX₁R can also abolish the detrimental effects of OX₁R overactivation in AD. In this sense, CB₂R–OX₁R becomes a new potential therapeutic target to combat AD. Full article