Selective serotonin reuptake inhibitor (SSRI)-associated bruxism is an increasingly recognized medication-associated phenomenon, although its incidence, neuropharmacologic mechanisms, and optimal management remain incompletely understood. This focused narrative review examines the clinical evidence, proposed mechanisms, and therapeutic implications of SSRI-associated bruxism. Available literature demonstrates recurring temporal associations between SSRI initiation or dose escalation and the emergence of jaw clenching, tooth grinding, pain, and related orofacial symptoms across multiple agents. Proposed mechanisms are multifactorial and may involve altered monoaminergic regulation within central motor networks, including serotonergic-dopaminergic interactions, 5-hydroxytryptamine (serotonin) receptor 1A (5-HT1A) signaling, and possible noradrenergic contributions; however, these mechanisms remain unconfirmed in affected patients. Adjunctive buspirone is the most consistently described pharmacologic strategy and may permit the continuation of an otherwise effective SSRI, although evidence for benefit remains primarily case-based. The literature is limited by heterogeneous bruxism definitions, inconsistent differentiation between awake and sleep manifestations, variable antidepressant exposures, and sparse objective physiologic assessment. Prospective studies using standardized assessment methods and controlled treatment designs are needed to clarify incidence, susceptibility, pathophysiology, and treatment response.

Current antibacterial therapies often suffer from limited bacterial selectivity, host-cell toxicity, and inflammation triggered by toxin release during bacterial killing. Here, we report a neutrophil extracellular traps (NETs)-mimetic, dopamine-incorporated DNA net, termed DANet-DA, enabling targeted bacterial eradication and concurrent toxin neutralization. Inspired by the trap-kill-neutralize function of NETs, DANet-DA selectively captures and traps bacteria, followed by in situ catalytic formation of polydopamine nanoshells on the trapped bacteria. This process enables efficient photothermal bacterial eradication while minimizing damage to host cells. Meanwhile, the nanoshells act as molecular sponges to sequester and neutralize bacterial toxins, thereby mitigating toxin-associated inflammation. These integrated functions endow DANet-DA with potent therapeutic efficacy in vivo, as demonstrated by markedly reduced bacterial burdens, toxin levels, tissue inflammation in both conventional and burn wound infection models. Moreover, the simultaneous clearance of bacteria and residual toxins alleviates pro-inflammatory macrophage polarization, thereby accelerating wound tissue regeneration. This work presents a NETs-mimetic antibacterial strategy that integrates pathogen clearance with toxin neutralization, offering a promising method for treating bacterial infection-associated diseases.

Despite growing evidence that dopamine acts as an innate immune inflammatory mediator, the molecular mechanisms by which dopamine modulates human immune function are incompletely defined. Here, we define the pathway in which dopamine induces robust IL-6 secretion in primary human monocyte-derived macrophages (hMDMs) through mitochondrial stress. Dopamine initiates a transient mitochondrial membrane depolarization that leads to sustained alterations in mitochondrial dynamics, including morphology and metabolism. These events promote the release of mtDNA into the cytoplasm, triggering the cGAS-STING pathway and NF-κB signaling. Pharmacological inhibition at multiple nodes of this pathway attenuates IL-6 secretion, establishing mitochondrial dysfunction and cGAS-STING signaling as central mediators of dopamine-driven IL-6 secretion. Variability in dopamine receptor expression across donors correlates with the magnitude of IL-6 responses. These findings highlight a potential link between dopamine signaling and systemic inflammation and suggest that differences in dopamine receptor expression may contribute to inter-individual variation in innate immune responses.

Silk fibroin is a highly promising biomaterial for wound dressings; however, its lack of inherent antibacterial activity limits broader clinical adoption. In this study, robust antibacterial properties were successfully conferred onto electrospun silk fibroin nanofiber mats using a mussel-inspired polydopamine (PDA) dip-coating strategy. Primary dip-coating deposited a uniform PDA nanolayer that served as an adhesive scaffold, enabling subsequent anchoring of dopamine nanoparticles during secondary coating. This hierarchical structure markedly increased surface roughness and reactive catechol density. Antibacterial evaluation against Staphylococcus aureus showed that secondary PDA-coated mats substantially reduced bacterial colonization relative to both primary-coated and unmodified controls. Secondary coating cycles further enhanced antibacterial performance. Cytocompatibility assessment performed according to ISO 10993-5 confirmed excellent biocompatibility of the modified mats, with no significant cytotoxicity observed. This simple, versatile, and antibiotic-free functionalization approach significantly improves the translational potential of silk fibroin nanofibers as next-generation antibacterial wound dressings.

IntroductionGuideline-based prophylaxis prevents most vomiting during highly emetogenic chemotherapy (HEC), but nausea remains incompletely controlled, especially where NK1 receptor antagonists and olanzapine are inaccessible or ineffective. Amisulpride, a dopamine D2/D3 antagonist, may add benefit with less sedation than olanzapine.MethodsAdults receiving cisplatin-based or anthracycline-cyclophosphamide HEC were studied during a single cycle in this randomized, double-blind, placebo-controlled group sequential trial. All received intravenous ondansetron and dexamethasone on day 1 plus oral dexamethasone 8 mg twice daily on days 2-4, with oral amisulpride (25 mg before chemotherapy, then 12.5 mg nightly for 3 days) or placebo. The primary endpoint was the 4-day (0-96 h) no-nausea responder rate; the planned sample size of 94 targeted an 18 percentage-point improvement. Two interim and one final analysis used O'Brien-Fleming efficacy and futility boundaries.ResultsThe trial stopped for futility at the second interim analysis (70 participants; 35 per arm). No-nausea response was 65.7% with amisulpride versus 57.1% with placebo (risk difference 8.6 percentage points; 95% CI -14.2 to 31.3; p = 0.461). Complete response (no emesis or rescue medication) was 80.0% versus 68.6% (p = 0.274). VAS, FLIE, rescue medication use, and adverse-event frequency were similar, apart from more frequent constipation with amisulpride.ConclusionsThe 8.6 percentage-point difference favored amisulpride but fell short of the 18-point practice-changing MCID, in a well-controlled placebo arm. Without an olanzapine- or NK1-containing comparator, the trial cannot position amisulpride against those regimens, nor exclude a smaller benefit worth having where they are inaccessible.

Severe spinal cord injury (SCI) frequently causes persistent neurological deficits, and its repair is constrained by multiple pathological factors including deterioration of the microenvironment following secondary injury, massive neuronal loss, interruption of electrical signal conduction, and insufficient endogenous regenerative capacity. Although electroacupuncture (EA) participates in the rehabilitation of SCI by regulating inflammatory responses and promoting the secretion of neurotrophic factors, standalone EA therapy can hardly fully reverse oxidative stress, ferroptosis and neural circuit destruction following severe SCI. Accordingly, this study constructs a conductive anti-ferroptosis hydrogel system (HBP@BMSCs), which utilizes dopamine-grafted hyaluronic acid (HADA) as the bionic matrix, baicalin-polypyrrole (BA-PPy) as the functional component, and is loaded with bone marrow mesenchymal stem cells (BMSCs). This hydrogel system is combined with EA for the repair of severe SCI. The results demonstrate that the HBP hydrogel exhibits favorable cytocompatibility, which can support the survival of BMSCs and maintain their typical mesenchymal stem cell phenotype. In vitro experiments demonstrate that HBP hydrogel effectively alleviates TBHP-induced oxidative stress injury and Erastin-induced ferroptosis-related injury, and exerts a protective effect on BMSCs and PC12 cells. In vivo experiments further confirmed that the combination therapy of HBP@BMSCs with EA significantly downregulated the expression levels of 4HNE, COX2, NOX2, FTH, FTL and TFR after SCI, and restored the expression levels of XCT, GPX4, SOD1 and FPN, thereby alleviating ROS accumulation, lipid peroxidation, iron overload and ferroptosis. With the alleviation of oxidative stress and ferroptosis-related secondary damage, the combination therapy further downregulates the expression of Bax and C-caspase3, upregulates Bcl-2 levels, and significantly inhibits neuronal apoptosis. In addition, the BA-PPy conductive network can synergize with EA to enhance electrical stimulation conduction, upregulate NGF/NGFR and BDNF neurotrophic signaling pathways, and promote the neural lineage differentiation of BMSCs, axon regeneration, corticospinal tract (CST) remodeling, and the recovery of motor function. In conclusion, HBP@BMSCs combined with EA exerts multiple synergistic effects including microenvironment remodeling, anti-ferroptosis protection, stem cell delivery and electroactive neural regeneration, providing a comprehensive therapeutic strategy with translational potential for severe SCI repair.

Early differentiation between Parkinson's disease (PD) and multiple system atrophy-parkinsonian type (MSA-P) remains clinically challenging because of overlapping motor symptoms and subtle imaging abnormalities.

Making choices about whether and when to engage cognitive effort is a common feature of human everyday experience with important consequences for academic, career, and health outcomes. Yet, despite its importance, little is understood about the neurochemical mechanisms that underlie individual differences in the willingness to engage in cognitively effortful activities. To examine this question, we employed a multi-modal neuroimaging approach in which participants performed the Cognitive Effort Discounting paradigm (Cog-ED) while simultaneous PET-fMRI was acquired. We assessed both individual differences in dopamine-D2 receptor availability and brain activity during decision-making. In addition, the same participants performed a parametric working memory task (N-Back) and reported the cognitive effort associated with their daily life activities through a seven-day Ecological Momentary Assessment (EMA) protocol. The findings suggest a central role for caudate dopamine-D2 receptors in modulating cognitive effort-related motivation. People with higher caudate dopamine-D2 receptor availability had better working memory function, heightened sensitivity to effort costs, and greater modulation of brain activity during effort valuation. These laboratory findings also translated directly to daily life: higher levels of caudate dopamine-D2 receptors were associated with greater engagement in cognitively effortful activities. Together, the results suggest that how individuals determine the motivational value of cognitively effortful activities strongly depends on the dopamine system.

Integrating biophysical, computational, in situ, and in vivo approaches with selective heteromer-disrupting transmembrane peptides, this study demonstrates that µ-opioid receptors (MORs) and dopamine D1 receptors (D1Rs) assemble into functional heteromers. Furthermore, real-time in vivo fiber photometry using a genetically encoded cAMP biosensor directly demonstrates that MORs regulate striatal D1Rs via heteromerization in the intact mouse brain. Our findings support a tetrameric structure composed of Gi-coupled MOR and Gs-coupled D1R homodimers, which enables both canonical Gi-Gs antagonistic interaction at the level of adenylyl cyclase and receptor-level cross-antagonism, by which MOR agonists and antagonists counteract D1R agonist-induced signaling. Located predominantly within striosomal GABAergic projection neurons, MOR-D1R heteromers constitute mechanistically defined signaling units that integrate dopaminergic and opioid neurotransmission governing motor control and reward processing. Collectively, these findings establish MOR-D1R heteromers as a previously unrecognized therapeutic target for the treatment of opioid withdrawal-associated restlessness and restless legs syndrome.

Dopamine in the nucleus accumbens Core powerfully influences motivation and learning, yet the information encoded by Core dopamine remains unresolved. Competing theories typically assume a spatially uniform signal, and standard recording methods average dopamine over substantial tissue volumes. Using two-photon imaging through microprisms in behaving mice, we reveal a pronounced spatial organization of Core dopamine dynamics. Posterior Core showed phasic dopamine increases to both rewards and aversive stimuli, with transfer to a predictive cue after learning. Anterior Core showed phasic decreases to aversive stimuli, weaker increases to reward, and higher tonic dopamine that was further amplified by cocaine. Rather than uniform or highly fragmented signals, the Core contains a smoothly graded mixture between two distinct sets of dopamine dynamics, neither matching canonical reward prediction errors.

Adverse childhood experiences like social isolation (SI) contribute to long term negative health outcomes and the development of severe psychiatric disorder. Adolescence is a unique period of coordinated social and motivational system development driven by dopamine (DA) signaling. Microglia, immune cells of the brain, may play a unique role in regulating SI-induced DA system changes and associated behavioral dysfunction. Male microglia refine dopamine D1 receptors (D1rs) in the nucleus accumbens (NAc) of adolescent male rats shaping play behavior. Here we characterized the molecular developmental impacts of postweaning SI from P21-P38, with a resocialization period to P54. We tested the role of microglial engulfment of D1rs in mediating behavioral consequences of SI using neutrophil inhibitory factor (NIF) to block complement-mediated engulfment required for D1r pruning. We found sex specific impacts of SI on brain development and the DA system. In SI males, microglia engulf more NAc D1rs than group housed (GH) controls. Within GH animals, NAc D1r density is positively correlated to play and allogrooming. In SI animals, NAc D1r density is negatively correlated to biting behavior, and is not correlated to play or allogrooming. Pharmacologically inhibiting microglial engulfment of D1r via bilateral NAc NIF injection prevents observed D1r:behavior correlations in GH and SI animals. NIF treatment interacts with SI, exaggerating aggressive-like behavior, showing a role for microglia in regulating aggressive-like behavior via complement pruning in adolescence. Microglia may play a unique role in regulating behavior that drive negative health outcomes in the face of developmental stress, including SI.

Binge drinking is characterized by an initial bout of rapid, high-vigor alcohol intake (front-loading) followed by a prolonged period of lower-rate "maintenance" drinking, yet the circuit mechanisms that generate and regulate these phases remain unclear. Here, we develop a systems-level computational model that links the structure of binge drinking to interactions among medial prefrontal cortex (mPFC), insula, striatum, and ventral tegmental area (VTA). The model consists of cortical Seek (mPFC) and Go (insula) populations that form a mutually excitatory loop, a SetPoint population that integrates striatal activity as an internal estimate of effort/consumption, ventral (nucleus accumbens, NAc) and dorsal (dorsolateral striatum, DLS) striatal populations, and a dopaminergic VTA population providing transient reward-prediction signaling. Using a firing-rate formalism with noisy dynamics, we reproduce the canonical two-phase binge pattern and show that: (i) the PFC-insula loop acts as a bistable module that initiates and sustains front-loading; (ii) striato-cortical feedback to the Setpoint population controls the timing of the transition from front-loading to maintenance without altering its vigor; and (iii) the amplitude of the VTA dopamine transient selectively scales front-loading intensity. Sensitivity analyses identify PFC-insula connectivity, VTA-to-NAc modulation, and striato-cortical feedback as key parameters that bifurcate two-phase drinking into regimes with abolished or persistent front-loading. These findings provide a mechanistic framework for interpreting binge-like alcohol intake in terms of identifiable circuit motifs and generate testable predictions for targeting mPFC-insula-striatal- VTA interactions in alcohol use disorder.