Search Results (452)

In the age of labor shortage, increasing the throughput of warehouses is a good issue. In the recent two decades, automatic warehouses designed to reduce human labor have therefore become a very hot research topic. Tricycle forklifts being able to carry heavy goods can play important roles in automatic warehouses. Meanwhile, Robot Operating System (ROS) is a very famous and popular platform for developing the software of robotics. Its powerful communication function makes lots of warehouse information exchange easy. Therefore, ROS installed as the communication backbone of warehouse is very popular. However, the software modules of ROS do not offer tricycle forklifts. Therefore, in this research, the model of a tricycle forklift developed for ROS systems in warehouse applications is constructed. In spite of the developed model, the existing software modules must be modified for compatible connection such that the tricycle forklift can be navigated and controlled by constructed ROS. For the function of Simultaneous Localization And Mapping (SLAM) and the control of self-guided navigation, the constructed system is verified by Gazebo simulation. In addition, the experiments of a real tricycle forklift to demonstrate the developed ROS for enough accuracy of warehouse application are also included. Full article

The escalating traffic violations associated with electric tricycles pose a critical challenge to urban traffic safety. It is important to automatically track the trajectories of electric tricycles and detect the multi-violations related to electric tricycles. This paper proposed an Electric Tricycle Object Detection (ETOD) model based on the custom-built dataset of electric tricycles. ETOD can successfully achieve real-time and accurate recognition and high-precision detection for electric tricycles. By integrating a multi-object tracking algorithm, an Electric Tricycle Violation Detection System (ETVDS) was developed. The ETVDS can detect and identify violations including speeding, passenger overloading, and illegal lane changes by plotting electric tricycle trajectories. The ETVDS can identify the conflicts related to electric tricycles in complex traffic scenarios. This work offers an effective technological solution for mitigating electric tricycle traffic violations in challenging urban environments. Full article

Background: Alzheimer’s disease (AD) is largely linked with oxidative stress, the accumulation of amyloid-β plaques, and hyperphosphorylated τ-protein aggregation. Alterations in dopaminergic and serotonergic neurotransmission have also been implicated in various AD-related symptoms. Methods: To explore new therapeutic agents, a series of bicyclic and tricyclic thieno-oxazepine derivatives were synthesized as potential acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The resultant compounds were purified via HPLC and characterized using spectral analysis techniques. Histopathological examinations, other antioxidants, and anti-inflammatory biomarkers were evaluated, and in silico ADMET calculations were performed for synthetic hybrids. Molecular docking was utilized to validate the new drugs’ binding mechanisms. Results: The most powerful AChE inhibitors were 14 and 16, with respective values of IC₅₀ equal to 0.39 and 0.76 µM. Derivative 15 demonstrated remarkable BChE-inhibitory efficacy, on par with tacrine, with IC₅₀ values of 0.70 µM. Hybrids 13 and 15 showed greater selectivity towards BChE, despite substantial inhibition of AChE. Compounds 13 and 15 reduced escape latency and raised residence time, with almost equal activity to donepezil. Conclusions: According to these findings, the designed hybrids constitute multipotent lead compounds that could be used in the creation of novel anti-AD medications. Full article

Type II polyketide synthases (PKSs) collectively generate polyketide intermediates of varying chain lengths, which undergo cyclization and further tailoring to produce structurally diverse aromatic polyketides. The length of the polyketide chain is a critical factor shaping the core scaffold of the final product. However, individual type II PKSs typically produce intermediates with a fixed chain length, thereby limiting the structural diversity accessible from a single biosynthetic system. In this study, we report the discovery of two pairs of novel tricyclic aromatic polyketides, varsomycin C/C′ and oxtamycin A/A′, along with two known analogues. These compounds are derived from the var and oxt gene clusters in Streptomyces varsoviensis/varR1, which primarily produce decaketide-derived tetracycline natural products, varsomycin A-B and oxytetracycline. Bioinformatic analysis combined with metabolite profiling of gene-disrupted mutants indicated that varsomycin C and C′ are co-produced by enzymes encoded in the var cluster, with contributions from oxtJ and oxtF in the oxt cluster, resulting in nonaketide-derived tricyclic scaffolds. Oxtamycin A and A′, along with the two analogues, are predicted to be biosynthesized by the oxt cluster. These results suggest that the minimal PKSs from both clusters possess intrinsic flexibility in controlling polyketide chain length, enabling the production of both decaketide and nonaketide intermediates, which represents a rare example of dual chain-length programming in type II PKSs. This flexibility reveals new natural sources of nonaketide biosynthetic enzymes and enriches the chemical diversity of tricyclic aromatic polyketides. Our findings deepen the understanding of type II PKS chain-length regulation and provide a foundation for future engineering of PKSs to produce customized bioactive aromatic polyketides. Full article

Background/Objectives: Pain—whether acute, chronic, or neuropathic—remains a leading cause of disability and reduced quality of life worldwide. Despite advances in pharmacologic options, interindividual variability in response and susceptibility to adverse effects continues to challenge clinicians. In recent years, pharmacogenetics has emerged as a promising approach to optimize analgesic selection and dosing based on patient-specific genetic profiles. This perspective examines current pharmacogenetic evidence in pain management, focusing on validated biomarkers and their clinical implications. Methods: A narrative review was conducted of recent literature addressing the impact of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of analgesic agents. Particular focus was given to genes involved in drug metabolism and transport as well as receptor signaling, along with the clinical applications of genotype-informed prescribing. Results: Substantial evidence indicates that genetic variants significantly influence patient responses to analgesics, contributing to both inadequate pain relief and heightened sensitivity to adverse effects. The main pharmacogenetic biomarkers appear to be CYP2C9 (for NSAIDs), CYP2D6 (for opioids and tricyclic antidepressants), CYP2C19 (for tricyclic antidepressants) and HLA-B*15:02 and HLA-A*31:01 for carbamazepine. PGx-informed strategies have shown promise in improving analgesic effectiveness, reducing opioid-related complications, and supporting opioid-sparing protocols. Conclusions: Pharmacogenetic screening represents a valuable tool for personalizing pain management. Incorporating validated pharmacogenetic biomarkers into clinical practice could improve treatment outcomes and patient safety. Further research, infrastructure development, and clinician education are essential for scaling PGx implementation in pain care. Full article

We report here two new series of designed PDE4 inhibitors, the first one showing the quinoline scaffold recently investigated by us through a fragment-based drug design strategy, and the second consisting of pyrazolo [1′,5′:1,6]pyrimido[4,5-d]pyridazine derivatives. Both the new series were subjected to biological studies to assess their inhibitory effect on PDE4 enzymes, supported by molecular modelling experiments, to rationalize the different activities recorded in the in vitro tests. Interesting results were achieved for two compounds belonging to the tricyclic series, namely 10a and 10e, exhibiting IC₅₀ = 62 and 175.5 nM, respectively. These results could represent the starting point for further studies with the aim of developing new and effective PDE4 inhibitors for biomedical investigations. Full article

Background: Post-traumatic trigeminal neuropathic pain (PTTNP) is a chronic condition often caused by dental procedures such as implant placement or tooth extraction. It involves persistent pain and sensory disturbances, negatively affecting the quality of life of patients. Methods: This retrospective observational study was conducted at Chosun University Dental Hospital and included 120 patients diagnosed with PTTNP involving the orofacial region. Patient data were collected between January 2014 and December 2023. Among them, 79 patients (65.8%) developed PTTNP following dental implant placement, with a total of 121 implants analyzed. The inferior alveolar nerve was most frequently involved. Clinical factors, including the time to treatment, removal of the causative factor, the Sunderland injury grade, and the type of treatment, were evaluated. Pain intensity and sensory changes were assessed using the visual analog scale (VAS). Results: Treatment initiated within the early post-injury period, commonly regarded as within three months, and implant removal tended to improve outcomes. Pharmacological therapy was the most commonly employed modality, particularly gabapentinoids (e.g., gabapentin, pregabalin) and tricyclic antidepressants such as amitriptyline. However, combined therapy, which included pharmacologic, physical, and surgical approaches, was associated with the greatest sensory improvement. Conclusions: Prompt, multidisciplinary intervention may enhance recovery in patients with PTTNP. Implant-related injuries require careful management, and multimodal strategies appear more effective than monotherapies. Full article

The pyrrolo[2,3-d]pyrimidine (7-deazapurine) scaffold is a unique heterocyclic system included in the composition of most nucleotides. In this study, series of the pyrrolo[2,3-d]pyrimidine-imines and 3-halo-substituted pyrrolo[2,3-d]pyrimidines were designed and prepared in high yields. Condensed pyrimidines are obtained via carbonyl-amine condensation and carbon-halogen bond formation. Pyrrolo[2,3-d]pyrimidine-imines containing a bromine substituent at position C-4 of the phenyl ring and azepine side-ring exhibited superior antitumor activity on the colon cancer HT-29 cell line; IC₅₀ values were 4.55 and 4.01 µM, respectively. These results revealed an interesting pattern, where condensed pyrimidinones containing an azepine ring demonstrated selective antitumor activity on the colon cancer cell line HT-29. In addition, the molecular docking results suggest that compound 8g provided a thorough understanding of its interactions with the DDR2 active site. This could pave the way for further development and optimization of DDR-targeting drugs, contributing to advancements in cancer therapeutics. This lead compound may serve as design templates for further studies. Full article

Oximes have been reported to exhibit useful pharmaceutical properties, including compounds with anticancer, anti-arthritis, antibacterial, and neuroprotective activities. Many oximes are kinase inhibitors and have been shown to inhibit various kinases. Herein, a panel of oxime derivatives of tricyclic isatins was synthesized and evaluated for inhibition of cellular inflammatory responses and binding affinity to several kinases. Compounds 5a and 5d (a.k.a. NS-102), which have an unsubstituted oxime group, inhibited lipopolysaccharide (LPS)-induced nuclear factor-κB/activating protein 1 (NF-κB/AP-1) transcriptional activity in human THP-1Blue monocytic cells and interleukin-6 (IL-6) production in human MonoMac-6 monocytic cells, with IC₅₀ values in the micromolar range. These compounds also inhibited LPS-induced production of several other proinflammatory cytokines, including IL-1α, IL-1β, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF) in MonoMac-6 cells. Compounds 5a and 5d exhibited nanomolar/submicromolar binding affinity toward several kinase targets. The most potent inhibitor, 5d (3-(hydroxyimino)-5-nitro-1,3,6,7,8,9-hexahydro-2H-benzo[g]indol-2-one), demonstrated high binding affinity for 12 kinases, including DYRK1A, DYRK1B, PIM1, Haspin, HIPK1-3, IRAK1, NEK10, and DAPK1-3. Molecular modeling suggested modes of binding interaction of selected compounds in the DYRK1A and PIM1 catalytic sites that agreed with the experimental binding data. Our results demonstrate that tricyclic isatin oximes could be potential candidates for developing anti-inflammatory drugs with neuroprotective effects for treating neurodegenerative diseases. Full article

Depression, anxiety, and perceived stress are common comorbidities in patients with inflammatory bowel disease (IBD) and may negatively influence the disease course. Likewise, severe IBD may contribute to the development or worsening of psychiatric symptoms. Despite the established relevance of the gut–brain axis and frequent use of psychotropic medications in IBD patients, limited evidence exists regarding the effects of psychiatric treatments on gastrointestinal disease activity. Therefore, the aim of this systematic review is to evaluate the effectiveness of psychiatric therapies on gastrointestinal symptoms and disease activity in patients with IBD. The work was conducted in accordance with PRISMA guidelines. Searches were performed across PubMed, Web of Science, and Scopus up to July 2024. Eligible studies evaluated the effectiveness of psychiatric medications—including antidepressants, antipsychotics, anxiolytics, sedative-hypnotics, mood stabilizers, anticonvulsants, and others—on at least one gastrointestinal outcome in patients with IBD. Outcomes included changes in commonly used clinical and endoscopic scores for Crohn’s disease (CD) and ulcerative colitis (UC), number of bowel movements, stool consistency, presence of blood in stool, severity of abdominal pain, as well as in surrogate markers of disease activity following treatment. Out of 8513 initially identified articles, 22 studies involving 45,572 IBD patients met the inclusion criteria. Antidepressants, particularly bupropion, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), venlafaxine, and duloxetine, were associated with improvements in IBD activity scores, including Crohn’s Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD, Mayo score and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) for UC. Case reports highlighted potential benefits of pregabalin and lithium carbonate, respectively, showed by the reduction in clinical and endoscopic score of disease activity for pregabalin and improvement of UC symptoms for lithium carbonate, while topiramate showed limited efficacy. Clonidine and naltrexone determined the reductions in clinical and endoscopic score of disease activity, including CDAI and Crohn’s disease endoscopy index severity score (CDEIS) for CD and Disease Activity Index (DAI) for UC. Despite the limited data and study heterogeneity, antidepressants, naltrexone, and clonidine were associated with improvements in IBD activity. Larger, prospective studies are needed to confirm the therapeutic potential of psychiatric medications in modulating IBD activity and to guide integrated clinical management. Full article

Saxitoxin (STX) is a potent toxin produced by marine dinoflagellates and freshwater or brackish water cyanobacteria, and is a member of the paralytic shellfish toxins (PSTs). As a highly specific blocker of voltage-gated sodium channels (NaVs), STX blocks sodium ion influx, thereby inhibiting nerve impulse transmission and leading to systemic physiological dysfunctions in the nervous, respiratory, cardiovascular, and digestive systems. Severe exposure can lead to paralysis, respiratory failure, and mortality. STX primarily enters the human body through the consumption of contaminated shellfish, posing a significant public health risk as the causative agent of paralytic shellfish poisoning (PSP). Beyond its acute toxicity, STX exerts cascading impacts on food safety, marine ecosystem integrity, and economic stability, particularly in regions affected by harmful algal blooms (HABs). Moreover, the complex molecular structure of STX—tricyclic skeleton and biguanide group—and its diverse analogs (more than 50 derivatives) have made it the focus of research on natural toxins. In this review, we traced the discovery history, chemical structure, molecular biosynthesis, biological enrichment mechanisms, and toxicological actions of STX. Moreover, we highlighted recent advancements in the potential for detection and treatment strategies of STX. By integrating multidisciplinary insights, this review aims to provide a holistic understanding of STX and to guide future research directions for its prevention, management, and potential applications. Full article

Metabolic syndrome has emerged as a significant global public health concern worldwide, characterized by a cluster of interrelated risk factors such as hypertension, hyperlipidemia, hyperglycemia, and abdominal obesity. In recent years, functional foods containing bioactive phytochemicals have attracted considerable scientific interest as potential therapeutic approaches for metabolic syndrome management. Xanthones, a class of naturally occurring tricyclic phenolic compounds abundant in various fruits and medicinal plants, demonstrate diverse biological activities relevant to metabolic health. This comprehensive review examines the dietary sources of xanthones, their bioactivity, and their promising role as functional food components for mitigating metabolic syndrome. The underlying mechanisms of action include modulation of lipid metabolism, improvement of insulin signaling pathways, potent anti-inflammatory and antioxidant effects, and modulation of glucose metabolism. Additionally, we discuss the stability and processing considerations of xanthones in food products. These findings highlight the development of xanthone-enriched functional foods and nutraceuticals as dietary interventions for metabolic syndrome prevention and management. This review comprehensively covers all relevant studies published up to the present without time restrictions. Full article

Kynurenic acid (KYNA) derivatives condensed with an aromatic ring (tricyclic KYNA derivatives) have been successfully synthesized, and the reactivity of these analogues has been investigated in the modified Mannich reaction resulting in new Mannich bases. The N,N-dimethyl-ethylenediamine analogues of the tricyclic KYNA derivatives have also been successfully synthesized, and their reactivity in the modified Mannich reaction was investigated. The synthesized ring systems bear resemblance to molecules previously investigated as G-quadruplex binding agents. Based on this similarity, the synthesized tricyclic KYNA derivatives could be investigated as potential antiviral and anticancer molecules. Full article

Pyridine derivatives are widely distributed in nature and have valuable pharmacological properties. The pyridine core can be found in drugs such as sorafenib, zapiclone or prothipendyl. Dipyridothiazines are derivatives of phenothiazines that exhibit valuable anticancer, antioxidant and immunomodulatory activities. In this study, we present the synthesis and preliminary in vitro analysis of anticancer activity towards melanotic (COLO829, G361) and amelanotic (A375, C32) melanoma cells and normal human fibroblasts (HDF) of a series of new tricyclic diazaphenothiazines containing a pyridine scaffold in their structure. The structures of these new molecules was confirmed using spectral techniques, including ¹H NMR, ¹³C NMR, 2D NMR and HRMS. An in vitro panel of experiments was assessed using the WST-1 assay and cytometric techniques. The two most promising compounds were analyzed for their effect on intracellular GSH levels, mitochondrial membrane potential and their ability to initiate DNA fragmentation to determine the potential mechanism of both cytotoxic and proapoptotic activity. The conducted studies confirmed the ability of the new 3-methyl-1,6-diazaphenothiazines to induce apoptosis in cancer cells, especially in terms of inducing initial as well as late-phase apoptosis. Moreover, the studied compounds were found to induce redox imbalance (evidenced by GSH depletion) in the analyzed melanoma cells, which may be an important factor that directs melanoma cells towards cell death signaling pathways. Full article

Background/Objectives: The joint presence of chronic pain (CP) and depression is frequent, exacerbating symptoms of both conditions. Although tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors are effective treatments, they are frequently not well tolerated, and selective serotonin reuptake inhibitors are not useful for controlling CP. This study investigated vortioxetine’s effectiveness in relieving CP in patients with any degree of depression. Methods: Patient data with any degree of depression and with CP (Visual Analog Scale [VAS] score ≥ 4) were collected and analyzed. Included patients (n = 142) were initially treated with vortioxetine 10 mg/day for 3 months. Improvement of patients’ pain and condition was measured with the VAS, Patient Global Impression (PGI), and Clinical Global Impression (CGI) scales at 1 and 3 months. Brief Pain Inventory (BPI) was measured at baseline and 3 months. Additionally, at baseline and after 3 months of treatment, the Satisfaction with Medicines Questionnaire (SATMED-Q) and 9-item Patient Health Questionnaire (PHQ-9) were evaluated. Adverse Events (AEs) were recorded. Results: Patients showed significant improvement (p < 0.001) in VAS from baseline to 1 and 3 months (mean [SD]: 7.19 [0.62], 6.23 [0.80], and 5.41 [1.15], respectively). BPI and PHQ-9 scores also showed a significant decrease from baseline (mean [SD] of 6.05 [0.75] and 11.73 [4.89], respectively) to 3 months (5.11 [1.04] and 6.95 [2.52], respectively). Clinical improvement with the CGI and PGI scales were reported. According to the SATMED-Q, patients were satisfied with the treatment. Only a few mild EAs were recorded. Conclusions: Vortioxetine can improve both the severity and intensity of CP in patients with any degree of depression. Full article