As an antioxidant widely used in tire rubber, (1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) has been recognized as an emerging contaminant with unclear neurotoxic potential. Using zebrafish (Danio rerio) as a model, we systematically evaluated the neurodevelopmental, behavioral, and molecular effects of 6PPD at environmentally relevant (5 μg/L) and sublethal (300 μg/L) concentrations. 6PPD exposure caused developmental abnormalities, including microphthalmia, exophthalmos, cardiac malformations, and hypopigmentation. Notably, benchmark dose (BMD) modeling identified the eye as a sensitive target, with microphthalmia likely impairing retinal development, photoreception, and circadian regulation. 6PPD increased neuronal apoptosis; impaired central nervous system and lateral line development; and, at high doses, reduced vitality, rhythmicity, and responsiveness. Corticotropin-releasing hormone receptor 1 (CRHR1), a synaptic receptor enhancing glutamatergic and suppressing GABAergic signaling, was identified as a potential target mediating neuronal hyperexcitability and hyperactivity at low doses. Consistently, behavioral tests confirmed a biphasic hormetic response: hyperactivity at low doses and hypoactivity at high doses. Furthermore, transcriptomic analysis, immunohistochemical staining, and xenograft tumor assays revealed a close association between 6PPD exposure and gliomagenesis, suggesting its potential risk of inducing glioma. Overall, these findings provide the first integrated phenotypic, behavioral, and molecular evidence of 6PPD-induced neurotoxicity and highlight CRHR1-mediated hormetic responses as critical considerations for risk assessment.

Hair cells are the sensory receptors of the auditory and vestibular systems in the inner ears of all vertebrates. Hair cells also serve to detect water flow in the lateral line system in amphibians and fish. The zebrafish lateral line serves as a well-established model for investigating hair cell development and function, including research on genetic mutations associated with deafness and environmental factors that cause hair cell damage. Rheotaxis, the ability to orient and swim in response to water flow, is a behavior mediated by multiple sensory modalities, including the lateral line organ. In this protocol, we describe a rheotaxis assay in which station holding behavior, which employs positive rheotaxis to maintain position in oncoming water flow, serves as a sensitive measure of lateral line function in larval zebrafish. This assay provides a valuable tool for researchers assessing the functional consequences of genetic or environmental disruptions of the lateral line system.Key features• Describes the method developed by Newton et al. [1] to assess lateral line function in larval zebrafish.• Provides instructions on building the micro flume apparatus with updated information from the WashU Neurotech Hub.• Uses DeepLabCut to track fish and SimBA to classify rheotaxis to compare lateral line–mediated behaviors in large cohorts of larval zebrafish.

Parafaveoloolithus is an oogenus within Faveoloolithidae, comprising oospecies with uncertain parataxonomic status due to ambiguous microstructures. The revision of problematic taxonomy and the identification of new materials in Parafaveoloolithus can make the classification of Parafaveoloolithus more accurate. Here, we described a new clutch containing 13 dinosaur eggs from the Upper Cretaceous Zhaoying Formation in the Xixia Basin, Henan Province, China by macroscopic measurement and microscopic observation (PLM, CL and SEM). Compared with other oogenera of Faveoloolithidae, these specimens could be assigned to Parafaveoloolithus based on the subspherical shape, columnar eggshell units and partially developed secondary eggshell units. A new oospecies of Parafaveoloolithus, Parafaveoloolithus xixiaensis, was further erected on the basis of the subspherical shape (average 84 in shape index), small size (average 132.4 mm in length and 111.3 mm in width), the parallelly arranged slender eggshell units with a width of 0.05–0.11 mm and wide pore canals with a width of 0.10–0.23 mm in the radial sections, as well as the honeycomb- like structure in the tangential sections. Radial sections of P. xixiaensis oosp. nov. show a single structural layer composed of columnar eggshell units and straight pore canals; some secondary eggshell units are present in the radial sections. The parataxonomy of Parafaveoloolithus guoqingsiensis is revised to Propagoolithus guoqingsiensis based on the branched eggshell unit and smaller pores near the outer surface of the radial section, and the smaller eggshell thickness. Duovallumoolithus is considered an invalid oogenus in Faveoloolithidae, and Duovallumoolithus shangdanensis is assigned to the new combination Parafaveoloolithus shangdanensis. The geographic distribution of Faveoloolithidae is mainly restricted to China, Mongolia and South Korea of East Asia, and P. xixiaensis oosp. nov. provides new material and a complete clutch of Parafaveoloolithus. The assignment of Parafaveoloolithus provides important references for the study of parataxonomy, geographical distribution and clutch structure in Faveoloolithidae.

Peripheral nerve regeneration requires precise selection of the appropriate targets of innervation, often in an environment that differs from that during the developmental wiring of the neural circuit. Severed axons of the zebrafish posterior lateral line nerve have the capacity to reinnervate mechanosensory hair cells clustered in neuromast organs. Regeneration represents a balance between fasciculated regrowth of the axonal bundle and defasciculation of individual axons into the epidermis where neuromasts reside. The cues that guide pathfinding during regeneration of the posterior lateral line nerve are unknown. Here, we show that regenerating axons selectively defasciculate through distinct gaps in the epidermal boundary layer. We found that the gene col18a1a, which encodes the secreted heparan sulfate proteoglycan collagen XVIII, is expressed by the neuromast and by a subset of Schwann cells that are located at the points of axonal defasciculation. Furthermore, we observed aberrant axonal branching at inappropriate locations during nerve regeneration in col18a1a mutants. We propose a model in which collagen XVIII patterns the basement membrane to affect the precision of axonal navigation.

ABSTRACTCohesinopathies and ciliopathies are congenital disorders affecting overlapping body systems. The extent to which these syndromes may be linked remains largely untested. Recently, reduced expression of a cohesin core subunit, Smc3, was found to result in abnormal otolith development in zebrafish embryos. This finding suggests that Smc3 may contribute to kinociliary development and function, which would represent a novel role for Smc3. Using hair cells found in neuromasts of the posterior lateral line, we found that Smc3 knockdown resulted in reduced kinociliary length. To address the role of Smc3 in kinocilial function, we monitored neomycin resistance of neuromasts (associated with several cilial gene mutants) and FM1-43X uptake in hair cells (associated with mechanotransduction). We found that Smc3 knockdown indeed led to neomycin resistance of the posterior lateral line neuromasts, suggesting impaired kinocilium function. However, neuromast hair cells did not have defects in FM1-43X uptake. We further demonstrated that hair cell number is reduced within neuromasts. This study suggests a significant influence of cohesin subunit Smc3 in ciliary structure and function and provides a preliminary link between cohesinopathy and ciliopathy etiologies.

Abstract Traditionally, the procedure for proximal interphalangeal (PIP) joint fusion has been described with an open approach using a dorsalcurvilinear incision. Due to the inherent risk of soft tissue complications with this technique, we propose a percutaneous technique for resecting bone cartilage and achieving a stable fusion angle with two mini-incisions, one lateral and one dorsal. The goal of all arthrodesis techniques is to create a stable joint fusion at the most functional angle for activities of daily living. A small, low speed high torque straight burr was introduced into the joint through a lateral joint line stab incision. The joint space was enlarged with manual traction, and chondral resection was performed under fluoroscopy. The PIP joint was then fused in adequate position with a headless compression screw through a dorsal stab incision. The joints were subsequently dissected to evaluate the degree of resection, the percentage of appropriately prepped joint surface, and any evidence of tissue damage. This study was conducted using 10 cadaver hands and included 39 joints. This study demonstrated that joint preparation and fusion angle can be reproducibly achieved while preserving a non-disrupted soft tissue envelope. Taken together, these findings suggest that the described percutaneous PIP arthrodesis technique has strong potential for achieving favorable clinical outcomes. Minimally invasive percutaneous PIP joint arthrodesis appears to be a feasible alternative technique that offers the advantage of minimal soft tissue disruption while achieving a stable construct for joint fusion.

The analysis of urban sewerage system components reveals varying reliability levels and criticality. Descriptive statistics show that the Pump Station has the highest variability, with an MTBF of 185.58 hours, a standard deviation of 112.54, and a CV of 0.606, alongside a relatively high failure rate (0.0066), indicating a greater likelihood of operational interruptions. Conversely, the Lateral Line and Manhole Line demonstrate higher reliability and operational consistency. Correlation analysis indicates that total operational time is strongly positively correlated with total failures (r = 0.903), while average MTBF is negatively correlated with failures and operational time, confirming that components with longer intervals between failures experience fewer breakdowns. Performance scoring, based on combined CVs of MTBF and failure rate, ranks the Sewer Chamber as the most reliable component, followed by the Lateral Line. The Pump Station requires focused maintenance due to its higher variability, whereas the Manhole shows the lowest stability. Risk-based factor assessment identifies Sewage System Design and Construction Quality as the most critical factor (composite score = 4.037), followed by Condition Assessment and Corrosion Resistance. Normalised scores highlight Ageing Infrastructure, Pumping and Flow Control Mechanisms, and Risk Transfer Mechanisms as high-impact factors, while Material Durability, Hydraulic Capacity, Peak Load Management, and System Complexity are lower impact. FMECA analysis confirms Pumping and Flow Control as the component with the highest RPN (100), representing the greatest risk of leaks, contamination, and collapse. Design and Construction Quality (RPN = 75) and Ageing Infrastructure (RPN = 40) also pose significant risks. These results emphasise that proactive maintenance, robust design, and continuous condition monitoring are essential for improving the reliability and operational performance of urban sewerage systems.

Myofascial continuity: Review of anatomical and functional evidence.

Closing the flexion gap: Differences in femoral sizes, level of constraint, and joint anatomy between robotic assisted and conventional high volume orthopedic surgeons.

Expression analysis of the adaptor proteins Sh2b family during zebrafish embryonic development.

Since human inner ear hair cells do not regenerate, the current treatments of hereditary deafness depend on hearing aids or cochlear implant. However, uncovering the functions of genes responsible for hereditary hearing loss is not only useful for their diagnosis but also for developing therapies. The pathogenetic mechanism of human non-syndromic deafness DFNB77 without morphological defects in the inner year caused by LOXHD1 mutations is not fully understood. We introduced zebrafish because the lateral line hair cells are structurally and physiologically similar to the human inner ear hair cells and mutations involved in non-symptomatic hearing loss can be assessed by their swimming behavior. The knock-out (KO) of LOXHD1b gene which is expressed in the lateral line hair cells was generated using the CRISPR-Cas9 system in zebrafish, and its morphological and functional changes were evaluated. As with human patients the LOXHD1b KO zebrafish larvae did not exhibit detectable morphological defects, but showed prolonged water flow sensing time. These results suggest that LOXHD1b plays pivotal roles for the hair cell neural activity and its KO zebrafish mutant serves as a useful model for revealing the molecular mechanisms linking LOXHD with hair cell function and for a drug screening to rescue the swimming phenotype.

This study reports the first records of Sphyraena arabiansis in the Korean waters. The two specimens were collected from the coastal waters of Yeosu (1164 mm TL) and Jeju Island (1187 mm TL), Korea, on 31 July and 24 October 2025, respectively. This species is characterized by the posterior end of the upper jaw not extending vertically below the eye, the lateral line curving anterior to the first dorsal fin, the lower part of the branchiostegal membrane being whitish, dark transverse bands on the upper side of the body crossing the lateral line but not reaching the abdomen, no black spots on the body side, 118 and 121 lateral line scales, and 14 scales below the lateral line. To confirm the accuracy of species identification, the mitochondrial DNA cytochrome c oxidase subunit I sequences were obtained from the samples and compared with those of seven sphyraenid species recorded in the NCBI GenBank database. As a result, they matched well with S. arabiansis but differed from those of S. barracuda. The new Korean name, “Jjal-beun-ip-keun-kko-chi-go-gi,” is proposed for the species.

TLR4 is the prototype immune receptor and central to infection defense via detecting lipopolysaccharide (LPS). Surprisingly, the impacts of LPS upon the TLR4 homologs in zebrafish, an important animal model, are equivocal and the function of TLR4 homologs across all fishes remains debatable. Recent work suggests zebrafish Tlr4 mediates ototoxic responses to a platinum-based chemotherapeutic. This prompts our hypothesis that Tlr4 detects group IX/X transition metals and thus has conserved roles with human TLR4 mediating allergic responses to nickel. Here, we use the larval zebrafish lateral line model to demonstrate (sub-)micromolar Ni, Co and Pt are ototoxic in a dose-dependent manner. TLR4 homologs are required for this toxicity because Tlr4 knockdown via CRISPR significantly reduced the metals’ impacts by ~50%. Moreover, zebrafish Tlr4 was sufficient to mediate inflammatory responses to metals when expressed in a human cell line. These data show zebrafish TLR4 homologs are necessary and sufficient to mediate responses to metals, however, direct biophysical binding of metals to zebrafish TLR4 homologs remains uninvestigated. These data are consistent with the notion that mediating responses to transition metals was a function of TLR4 homologs in the last common ancestor of fish and mammals, and begins to resolve the function(s) of TLR4 homologs in the zebrafish animal model of disease.

SummaryAn animal’s ability to interact with its environment relies on the brain’s capacity to distinguish between patterns of sensory information. To investigate this, we used the posterior lateral line system of larval zebrafish, composed of mechanosensory neuromasts innervated by neurons from the posterior lateral line ganglion. Using single-neuromast optogenetic stimulation and whole-brain calcium imaging, we developed a precise and flexible approach to examine sensory processing. Stimulating individual neuromasts revealed that second-order circuits show diverse selectivity despite lacking topographic organization. We further show that complex combinations of neuromast stimulation are encoded by sparse neuronal ensembles within the medial octavolateralis nucleus (MON) and that neuromast input integrates nonlinearly. This approach provides a powerful method for spatiotemporal interrogation of the zebrafish lateral line, sheds light on how neuromast input is integrated in the brain, and positions this system as a valuable model for studying whole-brain sensory encoding.

In fishes and aquatic-stage amphibians, mechanosensory neuromasts are arranged in characteristic lines in the skin of the head and trunk, with afferent innervation from anterior or posterior lateral line nerves. In electroreceptive non-teleost jawed fishes and amphibians, fields of electrosensory ampullary organs flank some or all of the cranial neuromast lines, innervated by the anterior lateral line nerve. Like the mechanosensory hair cells found in neuromasts and the inner ear, electroreceptor cells in ampullary organs across vertebrates form specialised ribbon synapses with afferent nerve terminals. Ribbon synapses in hair cells are distinct from other glutamatergic synapses, including the ribbon synapses in photoreceptors: In hair cells, synaptic vesicles are loaded with glutamate by vGlut3 and otoferlin is the Ca2+ sensor for synaptic vesicle exocytosis. We previously showed that the genes encoding vGlut3 and otoferlin are expressed by ampullary organs as well as neuromasts in a chondrostean ray-finned fish, the Mississippi paddlefish (Polyodon spathula), suggesting that electroreceptor ribbon synapses are very similar to those in hair cells. In this study, we selected additional synapse-related candidate genes from our previously published dataset of putatively lateral line organ-enriched genes from late-larval paddlefish, and examined their expression in developing lateral line organs in a more experimentally tractable chondrostean, the sterlet sturgeon (Acipenser ruthenus). We found that sterlet ampullary organs express genes encoding vGlut3 (as expected from paddlefish) and the high-affinity glutamate re-uptake transporter EAAT1 (GLAST). Sterlet ampullary organs also express Otof (also expected from paddlefish, though we identified one Otof transcript variant maintained in ampullary organs but not neuromasts) and two other hair cell synapse-associated genes, Apba1 (Mint1) and Rab3a. Genes encoding the presynaptic cell adhesion molecule Nrxn3, the calcium-independent synaptotagmin Syt14, the calmodulin regulator protein PCP4 (PEP-19) and cell adhesion molecule DSCAML1 were expressed in both neuromasts and ampullary organs. In contrast, Cbln18, encoding a secreted trans-synaptic scaffolding protein, was only expressed in neuromasts and Tulp1, encoding tubby-related protein 1 (required for the development and function of photoreceptor ribbon synapses), was only expressed in ampullary organs. Overall, our results support electroreceptor ribbon synapses in non-teleost ray-finned bony fish being glutamatergic and suggest further commonalities, but also some differences, with hair cell ribbon synapses.

PurposeLarge and balanced datasets are required to train artificial intelligence (AI) algorithms but are often difficult to acquire using clinical dermatologic photographs. We aimed to develop a new diffusion-based generative AI algorithm that generates patient photographs with modifiable details, thereby creating large and balanced datasets for neural network training. The newly developed model was tested using lateral canthal lines, a common patient’s reason for seeking treatment.Patients and MethodsFive hundred and sixty-six photographs of the lateral oblique face of graded by certified dermatologists according to the severity of lateral canthal lines. We developed a zero-shot and few-shot image generation model that adds structured compositional labels as control variables to the diffusion model. This allows us to create synthetic images from original photos while adjusting the severity of lateral canthal lines with only a few examples. The generated images were used to train a convolutional neural network (CNN) with ResNet-34 backbone for classifying the grade of lateral canthal lines.ResultsWe successfully generated 10,500 patient images similar to the original photographs with different grades of lateral canthal lines. The accuracy (82% vs 91%) and the area under the receiver operating characteristic curve (0.935 vs 0.981) of the classification CNN remarkably improved after training with the new dataset containing generated images.ConclusionThe compositional zero-shot and few-shot generation model is able to generate images similar to original clinical photographs, and the features of the images can be modified to match the needs of the specific task, allowing researchers to create a larger and more balanced dataset to improve neural network training outcomes. This is especially important in dermatology, where large-scale clinical photographs are difficult to acquire for machine learning. The results of this study are limited by low patient diversity and a lack of external validation.

ABSTRACTThe extensive limestone landscapes of southwestern China form one of the world's largest karst regions, providing ideal conditions for cavefish evolution. Within this region, Sinocyclocheilus, the most speciose cavefish genus globally, comprises 84 species adapted to dark environments. Despite the many species, the region is still poorly explored, with new species currently being added to the total. Here, using integrative taxonomic methods involving morphological and molecular analyses, we describe Sinocyclocheilus changlensis, a new troglobitic species discovered in a cave in central Guangxi, China. This species is characterized by the absence of eyes, an unpigmented and complete scaled body, and a forked, horn‐like structure at the dorsal posterior edge of the head. Morphologically, S. changlensis differs from its congeners by having pelvic‐fin rays that do not reach the anus when extended, 42–46 lateral line scales, and a posterior operculum margin reaching the base of the pectoral fin at vertical. Molecular phylogenetic analyses using mitochondrial markers (cytb and ND4), genetic distances, and geometric morphometric analysis further confirmed S. changlensis as a distinct species. The description of this new species contributes to the understanding of cave‐dwelling fish diversity in China and underscores the importance of further exploration of stygomorphic species across this poorly explored karstic landscape.

Burst firing is an important property of neuronal activity, thought to enhance sensory encoding. While previous studies show significant differences in burst firing between in vivo and in vitro conditions, how burst firing contributes to neural coding in vivo and how it is modulated by underlying biophysical mechanisms when neurons are under active synaptic bombardments remains poorly understood. Here, we combined intracellular recordings and computational modeling to investigate how cellular and synaptic mechanisms can explain the in vivo firing activity of electrosensory lateral line lobe (ELL) pyramidal cells in Apteronotus leptorhynchus. We developed a biophysically detailed compartmental model incorporating voltage-gated currents, NMDA receptor-mediated calcium (Ca2 + ) influx, Ca2 + -activated SK channels, Ca2 + mobilization, and stochastic synaptic inputs to reproduce in vivo firing activities of ELL pyramidal cells. Specifically, using bifurcation analysis, we identified dynamical transitions between quiescent, tonic, and bursting regimes, governed by interactions among SK conductance, NMDA receptor activation, and applied current. Model parameters were optimized against in vivo data, accurately reproducing action potential waveforms and temporal dynamics, including characteristic bimodal interspike interval distributions reflecting intra- and inter-burst intervals. We further developed a modified Hindmarsh-Rose model incorporating dual adaptation variables and stochastic noise. This simplified phenomenological model successfully captured burst firing comparable to that observed in the biophysical model and recorded data, while replicating diverse firing patterns observed across the population. Finally, parameter sensitivity analysis revealed slow adaptation dynamics and noise intensity as key determinants of spiking variability within cells. Overall, our modeling results demonstrate that in vivo bursting arises from synergistic interactions between intrinsic conductances (e.g., NMDA-SK coupling), Ca2 + mobilization, and synaptic stochasticity, offering a potential reconciliation for discrepancies with in vitro firing activity. The models provide mechanistic insights into how background synaptic activity modulates burst firing.

Burst firing is an important property of neuronal activity, thought to enhance sensory encoding. While previous studies show significant differences in burst firing between in vivo and in vitro conditions, how burst firing contributes to neural coding in vivo and how it is modulated by underlying biophysical mechanisms when neurons are under active synaptic bombardments remains poorly understood. Here, we combined intracellular recordings and computational modeling to investigate how cellular and synaptic mechanisms can explain the in vivo firing activity of electrosensory lateral line lobe (ELL) pyramidal cells in Apteronotus leptorhynchus. We developed a biophysically detailed compartmental model incorporating voltage-gated currents, NMDA receptor-mediated calcium (Ca2 + ) influx, Ca2 + -activated SK channels, Ca2 + mobilization, and stochastic synaptic inputs to reproduce in vivo firing activities of ELL pyramidal cells. Specifically, using bifurcation analysis, we identified dynamical transitions between quiescent, tonic, and bursting regimes, governed by interactions among SK conductance, NMDA receptor activation, and applied current. Model parameters were optimized against in vivo data, accurately reproducing action potential waveforms and temporal dynamics, including characteristic bimodal interspike interval distributions reflecting intra- and inter-burst intervals. We further developed a modified Hindmarsh-Rose model incorporating dual adaptation variables and stochastic noise. This simplified phenomenological model successfully captured burst firing comparable to that observed in the biophysical model and recorded data, while replicating diverse firing patterns observed across the population. Finally, parameter sensitivity analysis revealed slow adaptation dynamics and noise intensity as key determinants of spiking variability within cells. Overall, our modeling results demonstrate that in vivo bursting arises from synergistic interactions between intrinsic conductances (e.g., NMDA-SK coupling), Ca2 + mobilization, and synaptic stochasticity, offering a potential reconciliation for discrepancies with in vitro firing activity. The models provide mechanistic insights into how background synaptic activity modulates burst firing.

In this study, we describe a newly recognized croaker (Sciaenidae), Johnius javaensis sp. nov. based on five specimens (87-121 mm in standard length) from the southern coast of Java, Indonesia. Specifically, taxonomic reassessment of sciaenids collected from fish markets on the islands of Java, Bali, and Lombok of Indonesia has revealed that specimens previously identified as Johnius heterolepis represent this new species. Johnius javaensis sp. nov. is characterized by five vesicular mental barbels on the chin, 30-32 dorsal-fin rays, seven or eight scale rows below the lateral line; 11 or 12 lower gill rakers, 11 or 12 swim-bladder appendages, and ventral margin of the sagitta head expanded into a distinct convexity. Historically, four Johnius species (J. amblycephalus, J. fuscolineatus, J. macropterus and J. mannarensis) were reported to have one mental barbel on the chin. The new species is readily distinguished from all other 33 described Johnius species by possessing five vesicular mental barbels on the chin. A phylogenetic analysis of 21 Johnius species based on the 521-bp COI gene confirms that the new species is placed as a sister species of J. macropterus, based on an average of dissimilarity 8.16%.