Search Results (303)

Dopaminergic amacrine cells (DACs) are a subclass of amacrine cells that modulate retinal processing and light adaptation by releasing dopamine. Although the role of dopamine is largely conserved, their retinal distribution across mammals remains incompletely characterized. In mice, rats, thirteen-lined ground squirrels (TLGSs), and macaques, we systematically compared the localization, number, and topography of DACs by their expression of tyrosine hydroxylase (TH), a crucial enzyme in the biosynthesis of dopamine. In all species examined, TH+ cells were primarily located in the inner nuclear layer; however, there was a species-dependent influence on their number and distribution. Mice exhibited the highest density of TH+cells but completely lacked displaced TH+cells (dTH+cells) in the ganglion cell layer. Despite interspecies variation in the total number of TH+cells in the retina, the overall density in rats, TLGSs, and macaques was similar. Most species displayed a higher density of DACs toward central retinal regions. However, rats exhibited a distinctive dorsal concentration, particularly among dTH+cells. Although most species examined exhibited a similar ratio of TH+cells to Brn3a+ retinal ganglion cells, TLGSs showed a marked reduction, indicating a potentially diminished dopaminergic modulatory role. Species-specific DAC topographies aligned with specialized visual regions, such as the visual streak in TLGS and the macula in macaques. These results reveal both conserved and divergent features of retinal dopamine circuitry, reflecting evolutionary adaptations to visual processing demands. Full article

The neurobiology of chronic pain is complex and multifaceted, intertwining with the mesocorticolimbic system to regulate the behavioral and perceptional response to adverse stimuli. Specifically, the ventral tegmental area (VTA), the dopaminergic hub of the reward pathways located deep within the midbrain, is crucial for regulating the release of dopamine (DA) throughout the central nervous system (CNS). To better understand the nuances among chronic pain, VTA response, and therapeutics, implementing progressive approaches for mapping and visualizing the deep brain in real time during nociceptive stimulation is crucial. In this study, we utilize a fluorescence imaging platform with a genetically encoded calcium indicator (GCaMP6s) to directly visualize activity in the VTA during acute nociceptive stimulation in both healthy adult mice and adult mice with partial nerve ligation (PNL)-induced neuropathic pain. We also investigate the visualization of the analgesic properties of morphine. Deep brain imaging using our self-fabricated µ-complementary metal–oxide–semiconductor (CMOS) imaging device allows the tracking of the VTA’s response to adverse stimuli. Our findings show that nociceptive stimulation is associated with a reduction in VTA fluorescence activity, supporting the potential of this platform for visualizing pain-related responses in the central nervous system. Additionally, treatment with morphine significantly reduces the neuronal response caused by mechanical stimuli and is observable using the CMOS imaging platform, demonstrating a novel way to potentially assess and treat neuropathic pain. Full article

This study develops and characterizes GelMA–dopamine conjugates as novel tissue adhesives, offering an alternative to sutures. GelMA was synthesized at 5%, 10%, and 15% (w/v) with medium and high dopamine (DOPA) conjugation. Adhesives were evaluated for swelling, degradation, mechanical strength, and cytocompatibility using AlamarBlue assays and F-actin staining to assess cell viability and adhesion. Our findings indicate that DOPA conjugation significantly reduced the swelling ratio while increasing the biodegradation rate, resulting in enhanced release of free methacrylate groups over time. The mechanical properties and adhesion capabilities showed a complex relationship with DOPA substitution. Notably, the formulation containing 10% GelMA with high dopamine conjugation (HD) exhibited superior adhesion and mechanical strength. All formulations demonstrated shear-thinning behavior and recovery, making them suitable for injection and bioprinting applications. Although increased DOPA levels negatively affected crosslinking, the optimal formulation achieved a balance between adhesion and gel concentration. Rapid crosslinking was achieved within five minutes, enhancing the material’s suitability for clinical applications. In vitro cell-based assays confirmed the non-cytotoxic nature of the optimal adhesives, with metabolic activity showing significant increases over a 7-day period. These advancements support the development of improved tissue adhesives, potentially reducing reliance on sutures and enhancing wound healing outcomes. Full article

Conventional filters for air filtration typically feature compact nonwoven structures, which not only lead to high pressure drop, significant energy consumption, and a decay in filtration efficacy, but are also uncleanable, resulting in substantial pollution upon disposal. In this study, filters with high-voltage electrostatic loading capability were developed with a dopamine binding layer to facilitate the establishment of an Ag conductive layer on the surface of ultraloose woven structure fabrics (pore size: 73.7 μm). The high-voltage-loaded woven structure filtration (VLWF) system was constructed with a negative-ion zone, a high-voltage filtration zone, and a grounded filter. The morphological, chemical, and electrical properties of the filters and the filtration performance of the VLWF system were evaluated. The single-pass filtration efficiencies for PM_2.5 and E. coli were 67.4% and 97.0%, respectively. Notably, the pressure drop was reduced to 6.2 Pa, and the quality factor reached 0.1810 Pa⁻¹ with no detectable ozone release. After three cycles of ultrasonic cleaning, approximately 58.4% of filtration efficiency was maintained without any increase in air resistance. The removal of PM_2.5 and microorganisms by this system was not solely reliant on blocking and electrostatic attraction but may also involve induced repulsion and biostructure inactivation. By integrating the ultraloose woven structure with high-voltage assistance, this VLWF system effectively balanced the requirements for high filtration efficacy and low air resistance. More importantly, this VLWF system provided a cleanable filter model that reduced the pollution associated with conventional disposable filters and lowered costs for customers. Full article

To address the dual clinical challenges of poor osseointegration and inadequate analgesia caused by postoperative infections in traditional titanium implants, this study proposes a multifunctional synergistic strategy based on metal—organic frameworks (MOFs). By integrating drug-controlled release and ionic microenvironment regulation, it constructs a titanium-based implant coating system with antibacterial and bone-regenerative properties. Ketoprofen, a drug with excellent analgesic properties, was loaded into MgCu-MOF74 powder, and the Ket@MgCu-MOF74 powder was successfully anchored onto the surface of the titanium alloy through dopamine-mediated adhesion. The maximum load of ketoprofen to MgCu-MOF74 is 18.55%, and it has a good controllable release effect. The results showed that MgCu-MOF74/Ti and Ket@MgCu-MOF74/Ti coatings enhanced osteogenic performance by promoting alkaline phosphatase activity, collagen secretion, and extracellular matrix mineralization. Additionally, the release of Mg²⁺ and Cu²⁺ created an alkaline environment, providing antibacterial properties. In summary, the MOF enabled the controlled release of ketoprofen, and the composite coating can improve osteogenic differentiation of osteoblasts and enhance the antibacterial properties of titanium alloy implants. Full article

Medical titanium alloy Ti-6Al-4V (TC4) is widely used as a surgical implant material in biomedical fields owing to its superior biocompatibility, corrosion resistance, and mechanical performance, particularly for osseous integration applications. However, long-term contact of medical titanium-based implants with human soft tissues may induce infection and inflammation. To address these limitations, a drug-loading gel was designed to be synthesized on a TC4 surface to improve biointegration. Considering the critical regulatory roles of temperature and pH in physiological environments, this study synthesized a dual-responsive hydrogel using the temperature-sensitive monomers 2-(2-methoxyethoxy)ethyl methacrylate (MEO₂MA) and oligoethylene glycol methacrylate (OEGMA) and the pH-sensitive monomer diethylaminoethyl methacrylate (DEAEMA), employing stereocomplexed polylactic acid as a physical crosslinker and N,N′-methylenebisacrylamide (MBA) as a chemical crosslinker. A polydopamine-based initiator was synthesized via dopamine functionalization with 2-bromoisobutyryl bromide (BIBB). The amphiphilic co-network hydrogel was grafted onto a modified TC4 surface through atom transfer radical polymerization (ATRP). Integration of the drug-loading gel and TC4 gives the implant an “active therapeutic” function by localized drug release. The results demonstrated that the energy storage modulus of the double-crosslinked gel matched that of human soft tissues. The gels exhibited efficient drug release. Full article

Studies in animals and humans suggested that the tonic dopamine inhibition of prolactin release may be estimated by submaximal prolactin stimulation by thyrotropin-releasing hormone (TRH), the mini-TRH test. Because patients with schizophrenia may be more vulnerable to stress-induced elevations of prolactin, great care was taken to avoid stress-induced increases in prolactin, including applying local anaesthesia before blood extraction in our psychotic patients. Basal prolactin levels were in the reference range in all psychotic patients studied by us and were not higher in male patients than in normal men. Results of the mini-TRH test suggested that in acute patients with non-affective psychoses, everyday memory problems, non-paranoid delusions, and first-rank symptoms, but not other Comprehensive Psychopathological Rating Scale (CPRS) positive symptoms, could correlate with decreasing dopamine transmission in lactotrophs. In acute patients with first-episode schizophrenia, increasing negative disorganisation symptoms might correlate with increasing dopamine transmission. In first-episode patients, a hypersensitivity of the TRH response was detected, which could indicate that variability in the basal prolactin levels may confound the interpretation of the mini-TRH response. To avoid that, a smaller dose of TRH was recommended in first-episode patients. Studies using other estimates of basal dopamine release suggested that striatal dopamine transmission reflected delusions and hallucinations but not other Positive and Negative Symptom Scale (PANSS) positive symptoms. Including a wide range of symptoms in the PANSS positive scale may reduce its specificity for assessing basal dopamine transmission, although the scale remains useful for tracking treatment response. Full article

Glucagon-like peptide-1 receptor agonists, originally developed for the treatment of metabolic disorders, have recently emerged as promising candidates for the management of substance use disorders. This review synthesizes preclinical, clinical, and translational evidence on the effects of glucagon-like peptide-1 receptor agonists across addiction models involving alcohol, nicotine, psychostimulants, and opioids. In animal studies, glucagon-like peptide-1 receptor agonists consistently reduce drug intake, attenuate dopamine release in reward circuits, and decrease relapse-like behavior. Clinical and observational studies provide preliminary support for these findings, particularly among individuals with comorbid obesity or insulin resistance. However, several translational barriers remain, including limited blood–brain barrier penetration, species differences in pharmacokinetics, and variability in treatment response due to genetic and metabolic factors. Ethical considerations and methodological heterogeneity further complicate clinical translation. Future directions include the development of central nervous system penetrant analogues, personalized medicine approaches incorporating pharmacogenomics, and rigorously designed trials in diverse populations. Glucagon-like peptide-1 receptor agonists may offer a novel therapeutic strategy that addresses both metabolic and neuropsychiatric dimensions of addiction, warranting further investigation to define their role in the evolving landscape of substance use disorder treatment. Full article

Objective: This narrative review aims to analyze physical activity as a central pillar of lifestyle modification in the management of chronic musculoskeletal pain by examining its effects on pain modulation as well as related lifestyle domains, including sleep, stress regulation, dietary habits, and smoking behavior. Methods: A narrative structured review was conducted. We searched MEDLINE/PubMed, Embase, and Cochrane Reviews using terms related to chronic pain and lifestyle. Randomized controlled trials, observational studies, systematic reviews, and narrative reviews reporting on the concepts of interest were included. The results were synthesized and described narratively. Results: Through the release of neuromodulatory compounds such as endorphins, endocannabinoids, dopamine, and serotonin, exercise improves analgesia, promotes emotional resilience, and reduces the reward response associated with addictive behaviors such as smoking. Its effects on the hypothalamic–pituitary–adrenal axis reduce cortisol levels, while melatonin regulation promotes circadian synchronization and deeper sleep stages. In addition, exercise modulates appetite by increasing insulin sensitivity and altering hormones such as leptin and ghrelin, contributing to appetite control and energy balance. These mechanisms support a comprehensive approach to chronic pain management. Conclusions: Physical activity is a core component of lifestyle-based chronic pain management, not only because of its analgesic effects, but also because of its positive influence on sleep, stress regulation, dietary habits, and smoking reduction. Although the available evidence is promising, more randomized controlled trials are needed to examine the effects of exercise on other healthy lifestyle behaviors, such as stress reduction, dietary modification, and smoking cessation, to consolidate its role in the comprehensive prevention and management of chronic pain. Full article

Cats are different from dogs, and many questions remain open concerning the establishment of pregnancy. In cats, as in dogs, no feto-maternal signaling leading to establishment of pregnancy is known. But as opposed to dogs, the placenta is a source of steroid hormones and corticotropin-releasing hormone (CRH). Scarce information is available on physiological mechanisms at the uterine level during early gestation; more studies are needed on lymphocyte subsets, feto-maternal crosstalk and other mechanisms leading to local immunosuppression, allograft acceptance and embryo nidation and invasion. Recent studies investigate the function of extracellular vesicles (EVs); however, there is no study on embryo- or endometrium-derived EV. During pregnancy, anti-Müllerian hormone (AMH) serum concentrations were found to be higher than in non-pregnant cats, and a recent study found that supraphysiological levels may lead to pregnancy loss; the function of AMH during pregnancy warrants investigation. Most information is available on corpus luteum development and function, showing some similarities to dogs. Some information on maintenance of feline pregnancy was obtained by ovariectomy (OE) or the use of endocrine disruptors, showing that OE does not lead to pregnancy loss in all cases, especially when performed after day 35; the variable effect is still not fully understood. Antiprogesterone, dopamine agonists and prostaglandins were used in different dosages and treatment schemes and showed variable effect during the second half of gestation, highlighting progesterone and prolactin as key hormones for the maintenance of gestation. Some events during early gestation are comparable with the canine species, even though they appear earlier, like the entrance of the zygote into the uterus and implantation; however, significant differences are present concerning the histomorphology of the placenta and, in a few cases, even the gross morphology as in some cats, where the zonary placenta does not completely surround the fetus. Sonographical monitoring of feline pregnancy requires knowledge of species-specific developmental steps and the differential appearance of fetal and maternal structures in comparison with dogs. Full article

Both a shortage and an excess of dopamine (DA) in the prefrontal cortex and striatum result in their decreased functions, and the relationship between the DA levels and their functions exhibits an inverted-U shape. Increased DA transmission via dose reduction in the currently used antipsychotics may improve the activation of DA-related symptoms in schizophrenia; these include delusions and auditory hallucinations caused by increased DA release. In this case, reducing the dose of the antipsychotic may be a treatment option for relapse in patients with schizophrenia who are already on high doses of antipsychotics and find it difficult to further increase the dose. A total of 54 inpatients with schizophrenia receiving high-dose antipsychotic therapy were randomly assigned to either the halved-dose group or the high-dose group (symptomatic treatment). The study compared the time from relapse to improvement between the two groups. In the halved-dose group, the period until relapse improvement ranged from 1 to 3 weeks, while the high-dose group experienced improvement in 4 to 9 weeks, and a significant difference was observed between the two groups using Kaplan–Meier survival analysis (p < 0.001). Full article

Dysregulated dopamine (DA) release in the mesocorticolimbic circuit is noted in Parkinson’s disease (PD) patients with impulsive and compulsive behaviors (ICBs). However, the effect of acute DA release on mood, the localization of this process, and the phenotypic differences in patients with ICB remain unknown. We applied a placebo-controlled dextro-amphetamine (dAMPH) study in 20 PD patients: 10 with ICBs (PD-ICB) and 10 without (PD-C). Subjective mood experiences were measured with well-described self-reported measures including the Positive and Negative Affect Scale (PANAS), Drug Effects Questionnaire (DEQ), and Amphetamine Interview Rating Scale (AIRS). D2-like receptor availability was measured as non-displaceable binding potential (BP_ND) using PET imaging with the high-affinity D2/3 receptor ligand [¹⁸F]-fallypride. Among all the subjects, dAMPH increased the PANAS positive, DEQ feel, DEQ high, and AIRS total scores. Increases in the PANAS positive and AIRS total scores were greater in the PD-ICB cohort. A mixed-effects model correlated these questionnaire changes with dAMPH-induced reductions in BP_ND in the ventral striatum (VS), caudate, amygdala, and caudo-medial orbitofrontal cortex. The baseline caudate, VS, and amygdala BP_ND positively correlated with lower on-dAMPH PANAS positive scores. Elevated mood symptoms of acute dAMPH administration in PD are linked to DA release in the mesocorticolimbic regions. Distinctions in behavioral effects among PD-ICB subjects emphasize that dysregulated striatal and extra-striatal DA-ergic networks alter mood responses to stimulated DA release and may also contribute to behavioral changes resulting from DA-targeting therapies in PD. Full article

The α7 nicotinic acetylcholine receptor (α7-nAChR) is a pivotal regulator of neurotransmission, neuroprotection, and immune modulation in the central nervous system. This review explores its structural and functional attributes, highlighting its therapeutic potential in neurodegenerative disorders, particularly Parkinson’s disease (PD). α7-nAChRs mediate synaptic plasticity, modulate inflammatory responses, and influence dopamine release, positioning them as a promising pharmacological target. Positive allosteric modulators (PAMs) enhance α7-nAChR activity mainly by reducing desensitization, offering a superior therapeutic approach compared with direct agonists. Emerging preclinical studies suggest that α7-nAChR activation mitigates dopaminergic neurodegeneration, improves L-dopa-induced dyskinesia, and reduces neuroinflammation. Despite promising findings, clinical trials have yielded mixed results, necessitating further research into optimizing α7-targeted therapies. This review underscores the significance of α7-nAChRs in PD pathophysiology and highlights future directions for their translational potential in neuroprotection and symptomatic relief. Full article

The widespread adoption of background music in workplaces contrasts with the inconsistent empirical evidence regarding its cognitive effects, particularly concerning how music types influence the sequential pathway from flow states to work engagement and task performance. While prior research identifies flow and engagement as potential mediators, theoretical conflicts persist regarding their temporal dynamics and susceptibility to auditory habituation. This study tested three hypotheses: (1) music type indirectly affects performance through flow–engagement mediation, (2) high-arousal music impairs while structured compositions (e.g., Mozart’s K448) enhance this pathway, and (3) repeated exposure diminishes music’s efficacy. A two-phase longitudinal experiment with 428 Chinese undergraduates employed structural equation modeling (SEM) to analyze data from randomized groups (control, high-arousal, low-arousal, and Mozart K448), completing Backward Digit Span tasks under controlled auditory conditions. The results confirmed Mozart K448’s superior immediate mediation effect (β = 0.118, 95% CI [0.072, 0.181]) compared to high-arousal music’s detrimental impact (β = −0.112, 95% CI [−0.182, −0.056]), with flow fully mediating engagement’s influence on performance. A longitudinal analysis revealed a 53% attenuation in Mozart’s flow-enhancing effect after a 30-day familiarization (B = 0.150 vs. baseline 0.321), though residual benefits persisted. These findings reconcile the cognitive tuning and arousal–mood hypotheses by proposing a hybrid model where music initially operates through a novelty-driven dopamine release before transitioning to schema-based cognitive priming. Practically, the results advocate tiered auditory strategies: deploying structured music during skill acquisition phases while rotating selections to counter habituation. The study highlights the cultural specificity in auditory processing, challenging universal prescriptions and underscoring the need for localized music policies. By integrating flow theory with neurocognitive habituation models, this research advances evidence-based guidelines for optimizing workplace auditory environments. Full article

Unsaturated polyester (UP) resin is widely utilized in the construction and automotive industries. The flammable nature of UP must be constrained when its products are manufactured. A novel organic flame retardant has been synthesized from 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) and triallyl isocyanate (TAIC). This DOPO-TAIC additive has been used to reduce the flammability of a matrix. Additionally, this flame retardant was then combined with dopamine-modified silicon carbide (M-SiC) to further diminish the flammability of UP. The limiting oxygen index (LOI) value combustion of a UP/DOPO-TAIC/M-SiC blend was 30.8% when the filler contents of DOPO-TAIC and M-SiC was 15 wt.% and 30 wt.%, respectively. These materials exhibited a UL 94 V-0 rating for combustion. Compared to the values for combustion of the neat UP, the peak heat release rate (Pk-HRR) and total heat release rate (THR) for this blend were reduced by 51% and 35%, respectively. The mode of action for flame retardant of UP blends containing DOPO-TAIC and M-SiC has been composed. The presence of a flame retardant containing P-Si elements can significantly reduce flammability compared to that of unmodified resin. Full article