Picotesla-sensitivity microcavity optomechanical magnetometry.

Cavity optomechanical systems have enabled precision sensing of magnetic fields, by leveraging the optical resonance-enhanced readout and mechanical resonance-enhanced response. Previous studies have successfully achieved mass-produced and reproducible microcavity optomechanical magnetometry (MCOM) by incorporating Terfenol-D thin films into high-quality (Q) factor whispering gallery mode (WGM) microcavities. However, the sensitivity was limited to 585 pT Hz-1/2, over 20 times inferior to those using Terfenol-D particles. In this work, we propose and demonstrate a high-sensitivity and mass-produced MCOM approach by sputtering a FeGaB thin film onto a high-Q SiO2 WGM microdisk. Theoretical studies are conducted to explore the magnetic actuation constant and noise-limited sensitivity by varying the parameters of the FeGaB film and SiO2 microdisk. Multiple magnetometers with different radii are fabricated and characterized. By utilizing a microdisk with a radius of 355 µm and a thickness of 1 µm, along with a FeGaB film with a radius of 330 µm and a thickness of 1.3 µm, we have achieved a remarkable peak sensitivity of 1.68 pT Hz-1/2 at 9.52 MHz. This represents a significant improvement of over two orders of magnitude compared with previous studies employing sputtered Terfenol-D film. Notably, the magnetometer operates without a bias magnetic field, thanks to the remarkable soft magnetic properties of the FeGaB film. Furthermore, as a proof of concept, we have demonstrated the real-time measurement of a pulsed magnetic field simulating the corona current in a high-voltage transmission line using our developed magnetometer. These high-sensitivity magnetometers hold great potential for various applications, such as magnetic induction tomography and corona current monitoring.

ß-glucan improves intestinal health of pearl gentian grouper via activation of the p38 mitogen-activated protein kinase signaling pathway.

Our previous study has demonstrated that supplementation of yeast ß-glucan improves intestinal health in pearl gentian grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀), accompanied by the activation of the mitogen-activated protein kinase (MAPK) signaling pathway. In this study, we investigated the effects of perturbing p38 MAPK activity using an inhibitor on the intestinal health of ß-glucan-injected pearl gentian grouper to elucidate the potential molecular mechanism underlying the protective effects of ß-glucan on the fish gut. The pearl gentian grouper was categorized into four groups: PBS injected (CD group), ß-glucan injected at a dose of 80 mg/kg (ßG group), p38 MAPK inhibitor SB203580 injected at a dose of 1 mg/kg (SB203580 group), and a combination of ß-glucan (80 mg/kg) and SB203580 (1 mg/kg) injected together (ßG + SB203580 group). The results revealed that the introduction of SB203580 significantly suppressed the ß-glucan-induced increase in p38α and p38ß mRNA expression, as well as the phosphorylation of p38 MAPK. Both the ßG group and SB203580 group exhibited reduced plica height and muscularis thickness. The ßG + SB203580 group displayed a significant reduction in mucin cell level; interleukin 1ß (il1ß) mRNA expression; induced nitric oxide synthase, tumor necrosis factor α, and IL1ß concentration; catalase and total antioxidant capacity activities. Additionally, there was a significant increase in the levels of intestinal malondialdehyde in the ßG + SB203580 group compared to the ßG group. The inhibition of the p38 MAPK signaling halted the trend of apoptosis-related caspase molecular expression induced by ß-glucan. In conclusion, ß-glucan injection resulted in elevated levels of mucous cells, nonspecific immunity, antioxidant capacity, and anti-apoptosis in grouper by modulating the p38 MAPK pathway. This study offers insights into the potential molecular mechanism underlying the protective effects of ß-glucan on intestinal health in pearl gentian grouper.

Effect of Cooling Method on Physical and Mechanical Properties of PVA Fiber-Reinforced High-Strength Concrete Exposed to High Temperature.

High-strength concrete (HSC) boasts excellent compressive strength and durability, making it a popular choice in various engineering applications. However, under the impact of high temperatures, HSC tends to crack easily, so it is combined with polyvinyl alcohol fiber (PVA fiber) to explore its engineering application prospect. This paper investigated the physical and mechanical characteristics of HSC reinforced with PVA fibers subjected to different heating temperatures and cooling techniques. The experimental results reveal a correlation between rising temperatures and observable changes in the specimens: a progressively lighter surface hue, an augmented frequency of cracking, and a considerable escalation in the mass loss rate, particularly after the temperature exceeds 400 °C. Regarding mechanical properties, the dynamic elastic modulus and compressive and flexural strength all decrease as the heating temperature increases. As the amount of PVA fiber rises while maintaining a steady temperature, these measurements initially show an increase followed by a decrease. The fiber contents yielding the best compressive and flexural strength are 0.2% and 0.3%, in that order. Considering the influence of cooling methods, water spray cooling has a greater impact on physical and mechanical properties than natural cooling. Furthermore, SEM was employed to scrutinize the microstructure of HSC, enhancing comprehension of the alterations in its physical and mechanical characteristics. The findings of this research offer significant information regarding the high-temperature behavior of HSC, serving as a valuable resource for guiding the design, building, and upkeep of structures that incorporate HSC. Additionally, this study will aid in advancing the progress and utilization of HSC technology.

An Experimental Study on the Influence of Different Cooling Methods on the Mechanical Properties of PVA Fiber-Reinforced High-Strength Concrete after High-Temperature Action.

High-strength concrete (HSC) has a high compressive strength, high density, excellent durability, and seepage resistance, but its deformation ability is weak. Adding fibers can improve the physical and mechanical properties of HSC. Additionally, the HSC structure may face the threat of fire. In the process of fire extinguishing, the damage mechanism of high-temperature-resistant concrete is complicated due to the different contact conditions with water at different locations. Hence, it is essential to conduct pertinent research on the behavior of fiber-reinforced HSC with different cooling methods after high-temperature action. In this paper, polyvinyl alcohol fiber (PVA fiber) was selected to be added into the HSC to carry out high-temperature experimental research, so as to explore the apparent changes, failure pattern, and mass loss rate of the fiber-reinforced HSC using different cooling methods and analyze the influence of its residual compressive strength and flexural strength. The test results suggest that, with the increase in heating temperature, the color of the specimen's surface transitions from dark blue-gray to white, and the quantity of surface cracks on the specimen gradually rises. The mechanical strength gradually decreases as the heating temperature increases. At a consistent heating temperature, the mechanical strength initially rises, and then falls with an increase in fiber content. The maximum compressive strength and flexural strength were achieved at PVA fiber contents of 0.2% and 0.3%, respectively. For different temperatures and fiber contents, the mechanical strength after natural cooling is generally higher than that after immersion cooling. In addition, X-ray polycrystalline diffractometry (XRD) and scanning electron microscopy (SEM) tests were conducted to analyze the compositional alterations and microstructure of the fiber-reinforced HSC following high-temperature exposure, accompanied by an explanation of the factors influencing the alterations in the physical and mechanical properties. Therefore, the findings of this study can serve as a valuable reference for the utilization of HSC in engineering structures and contribute to the advancement of HSC technology.

Phenotypic characteristics and rehabilitation effect of children with regressive autism spectrum disorder: a prospective cohort study.

BACKGROUND: In this prospective cohort study, we determined the phenotypic characteristics of children with regressive autism spectrum disorder (ASD) and explored the effects of rehabilitation. METHODS: We recruited 370 children with ASD aged 1.5-7 years. Based on the Regression Supplement Form, the children were assigned to two groups: regressive and non-regressive. The core symptoms and neurodevelopmental levels of ASD were assessed before and after 1 year of behavioral intervention using the Autism Diagnostic Observation Schedule (ADOS), Social Response Scale (SRS), Children Autism Rating Scale (CARS), and Gesell Developmental Scale (GDS). RESULTS: Among the 370 children with ASD, 28.38% (105/370) experienced regression. Regression was primarily observed in social communication and language skills. Children with regressive ASD exhibited higher SRS and CARS scores and lower GDS scores than those with non-regressive ASD. After 1 year of behavioral intervention, the symptom scale scores significantly decreased for all children with ASD; however, a lesser degree of improvement was observed in children with regressive ASD than in those with non-regressive ASD. In addition, the symptom scores of children with regressive ASD below 4 years old significantly decreased, whereas the scores of those over 4 years old did not significantly improve. Children with regressive ASD showed higher core symptom scores and lower neurodevelopmental levels. Nevertheless, after behavioral intervention, some symptoms exhibited significant improvements in children with regressive ASD under 4 years of age. CONCLUSION: Early intervention should be considered for children with ASD, particularly for those with regressive ASD.

Electric-field control of nonvolatile resistance state of perpendicular magnetic tunnel junction via magnetoelectric coupling.

Magnetic tunnel junctions (MTJs) are the core elements of spintronic devices. Now, the mainstream writing operation of MTJs mainly relies on electric current with high energy dissipation, which can be greatly reduced if an electric field is used instead. In this regard, strain-mediated multiferroic heterostructure composed of MTJ and ferroelectrics are promising with the advantages of room temperature and magnetic field-free as already demonstrated by MTJ with in-plane magnetic anisotropy. However, there is no such report on the perpendicular MTJs (p-MTJs), which have been commercialized. Here, we investigate electric-field control of resistance state of MgO-based p-MTJs in multiferroic heterostructures. A remarkable and nonvolatile manipulation of resistance is demonstrated at room temperature without magnetic field assistance. Through various characterizations and micromagnetic simulation, the manipulation mechanism is uncovered. Our work provides an effective avenue for manipulating p-MTJ resistance by electric fields and is notable for high density and ultralow power spintronic devices.

QKL injection ameliorates Alzheimer's disease-like pathology by regulating expression of RAGE.

The onset of Alzheimer's disease is related to neuron damage caused by massive deposition of Aß in the brain. Recent studies suggest that excessive Aß in the brain mainly comes from peripheral blood, and BBB is the key to regulate Aß in and out of the brain. In this study, we explored the pathogenesis of AD from the perspective of Aß transport through the BBB and the effect of QKL injection in AD mice. The results showed that QKL could improve the cognitive dysfunction of AD mice, decrease the level of Aß and Aß transporter-RAGE, which was supported by the results of network pharmacology, molecular docking and molecular dynamics simulation. In conclusion, RAGE is a potential target for QKL's therapeutic effect on AD.

Electric field control of perpendicular magnetic tunnel junctions with easy-cone magnetic anisotropic free layers.

Magnetic tunnel junctions (MTJs) are the core element of spintronic devices. Currently, the mainstream writing operation of MTJs is based on electric current with high energy dissipation, and it can be notably reduced if an electric field is used instead. In this regard, it is promising for electric field control of MTJ in the multiferroic heterostructure composed of MTJ and ferroelectrics via strain-mediated magnetoelectric coupling. However, there are only reports on MTJs with in-plane anisotropy so far. Here, we investigate electric field control of the resistance state of MgO-based perpendicular MTJs with easy-cone anisotropic free layers through strain-mediated magnetoelectric coupling in multiferroic heterostructures. A remarkable, nonvolatile, and reversible modulation of resistance at room temperature is demonstrated. Through local reciprocal space mapping under different electric fields for Pb(Mg1/3Nb2/3)0.7Ti0.3O3 beneath the MTJ pillar, the modulation mechanism is deduced. Our work represents a crucial step toward electric field control of spintronic devices with non-in-plane magnetic anisotropy.

Railway wagon bearing fault diagnosis method based on improved sparrow search algorithm optimizing variational mode decomposition and multi-level convolutional neural network.

Ensuring the safe operation of trains hinges on precise bearing condition monitoring, given the pivotal role bearings play in railway wagons. The status and maintenance of wagon bearings are of paramount concern, necessitating a shift from traditional maintenance approaches reliant on schedules and experience, which often lack real-time precision and efficiency. To address this challenge, our research focuses on enhancing the sparrow search algorithm by incorporating logistic chaos mapping and the levy flight strategy. This enhanced algorithm optimizes variational mode decomposition parameters, utilizing intrinsic mode components' average dispersion entropy as the fitness function. This optimization is integrated with a multi-level convolutional neural network for bearing fault diagnosis. Our findings demonstrate the improved algorithm's enhanced spatial search capabilities and reduced modal aliasing in the frequency components. Experimental validation on public datasets and the group's experimental platform for railway wagons shows that multi-level convolutional neural networks have higher diagnostic accuracy and faster convergence speeds than traditional models such as LeNet-5, AlexNet, and convolutional neural network. Our research introduces a highly accurate and widely applicable methodology for mechanical equipment fault diagnosis, aligning with the requirements of the "smart" era.

Sodium Butyrate Ameliorates Atopic Dermatitis-Induced Inflammation by Inhibiting HDAC3-Mediated STAT1 and NF-κB Pathway.

A topic dermatitis (AD) is a common chronic and recurrent skin disorder. The protective effects of sodium butyrate (NaB), a metabolite of short-chain fatty acid breakdown by the gut microbiota, have been widely reported in numerous inflammatory diseases. However, the effect of NaB treatment alone on AD has not been reported. In the current study, AD was induced in BALB/c mice with 2,4-dinitrochlorobenzene (DNCB) for 28 days with NaB (200 mg/kg) treatment by gavage. NaB attenuated AD-induced skin bleeding, scarring, dryness, abrasions and erosions. In addition, NaB inhibited inflammatory cells infiltration and attenuated the expression of inflammatory cytokines and chemokines. Mechanistically, NaB reduced histone deacetylase 3 (HDAC3) expression and NF-κB p65 nuclear translocation by increasing the lysine acetylation levels of STAT1 and NF-κB p65 in AD. Taken together, our study suggests that NaB inhibits inflammatory mediators and ameliorates AD by inhibiting HDAC3 expression, thereby upregulating STAT1 and NF-κB p65 lysine acetylation levels and reducing NF-κB p65 nuclear translocation. Therefore, this study provides a new theoretical basis for NaB in the treatment of AD.

Transcriptomic analysis reveals the early body wall regeneration mechanism of the sea cucumber Holothuria leucospilota after artificially induced transverse fission.

BACKGROUND: Sea cucumbers exhibit a remarkable ability to regenerate damaged or lost tissues and organs, making them an outstanding model system for investigating processes and mechanisms of regeneration. They can also reproduce asexually by transverse fission, whereby the anterior and posterior bodies can regenerate independently. Despite the recent focus on intestinal regeneration, the molecular mechanisms underlying body wall regeneration in sea cucumbers still remain unclear. RESULTS: In this study, transverse fission was induced in the tropical sea cucumber, Holothuria leucospilota, through constrainment using rubber bands. Histological examination revealed the degradation and loosening of collagen fibers on day-3, followed by increased density but disorganization of the connective tissue on day-7 of regeneration. An Illumina transcriptome analysis was performed on the H. leucospilota at 0-, 3- and 7-days after artificially induced fission. The differential expression genes were classified and enriched by GO terms and KEGG database, respectively. An upregulation of genes associated with extracellular matrix remodeling was observed, while a downregulation of pluripotency factors Myc, Klf2 and Oct1 was detected, although Sox2 showed an upregulation in expression. In addition, this study also identified progressively declining expression of transcription factors in the Wnt, Hippo, TGF-ß, and MAPK signaling pathways. Moreover, changes in genes related to development, stress response, apoptosis, and cytoskeleton formation were observed. The localization of the related genes was further confirmed through in situ hybridization. CONCLUSION: The early regeneration of H. leucospilota body wall is associated with the degradation and subsequent reconstruction of the extracellular matrix. Pluripotency factors participate in the regenerative process. Multiple transcription factors involved in regulating cell proliferation were found to be gradually downregulated, indicating reduced cell proliferation. Moreover, genes related to development, stress response, apoptosis, and cell cytoskeleton formation were also involved in this process. Overall, this study provides new insights into the mechanisms of whole-body regeneration and uncover potential cross-species regenerative-related genes.

Research on fault diagnosis of rolling bearing based on multi-sensor bi-layer information fusion under small samples.

To address the challenge of low fault diagnosis accuracy due to insufficient bearing fault data collected by single-sensor, a rolling bearing fault diagnosis method based on multi-sensor bi-layer information fusion under small samples is proposed. In the first-layer feature fusion, first, aiming at the problem that the number of intrinsic mode functions (IMFs) and the penalty factor in the variational mode decomposition (VMD) is challenging to determine, the Aquila optimizer algorithm is introduced to search for the optimal solution independently. Decomposition of bearing vibration signals acquired by multiple sensors using a parameter optimized the VMD method to obtain IMFs. The 12 time-domain features are then extracted for each IMF, and the maximum information coefficient (MIC) between each IMF time-domain feature and raw signal time-domain features is calculated. Finally, the feature fusion composition ratio is calculated according to the MIC mean of each. In the second layer of data fusion, the fusion composition ratio calculated in the first layer is used as a weight-to-weight and reconstructs the signals of each sensor to constitute a fused signal. Then, the fused signals are input into the fault diagnostic model, and fault pattern recognition and fault severity recognition are performed at the same time. The results show that the accuracy of the method proposed in this paper is higher than that of the comparison method on both the public dataset and the self-built experimental bench dataset, and it is an accurate, stable, and efficient fault diagnosis method.

Decomposition and comparative analysis of depressive symptoms between older adults living alone and with others in China.

Objective: This research dealt with investigating and measuring the contribution of the factors that impact depression in older adults living alone vs. those living with others (hereafter referred to as "not alone") in China. Design: This investigation adopts a cross-sectional research design. The dataset employed for this study comprises data from 2018 the Chinese Longitudinal Health Longevity Survey (CLHLS). Setting: The research involved data sourced from China, specifically from 23 of its provinces. From the 8th CLHLS, 12,197 older adults were selected who met the study requirements. Measures: Binary logistic regression models were established to delve into the primary factors impacting the depressive symptoms of the individuals. Furthermore, Fairlie models were employed to assess these factors between older adults living alone and those not living alone. This approach facilitated an in-depth analysis of their respective contributions. Results: It was observed that the demographic of Chinese older adults exhibited depressive symptoms at a rate of 11.92%. Older adults who resided alone (15.76%) exhibited a higher prevalence of depressive symptoms in comparison to their counterparts living in not-alone settings (11.15%). Employing Fairlie decomposition analysis, it was determined that this observed disparity in depressive symptoms, amounting to 55.33% of the overall difference, could be primarily attributed to distinct factors. This encompassed variance in marital status (20.55%), years of school (4.63%), self-reported local income status (7.25%), self-reported sleep status (17.56%), and self-reported health status (4.24%). Conclusion: The resulting data indicated that depressive symptoms exhibited an elevated prevalence in older adults living alone than in those living not alone. This discrepancy was predominantly attributed to variance in socioeconomic marital status, years of school, self-reported local income status, self-reported sleep status, and self-reported health status by living alone vs. not alone. Mitigating these influential factors could help develop targeted and meticulous intervention strategies, precisely tailored to improve the mental well-being of older adults at high risk.

Metabolome and Transcriptome Association Analysis Reveals the Link Between Pigmentation and Nutrition Utilization in the Juveniles of Sea Cucumber Holothuria leucospilota.

The sea cucumber Holothuria leucospilota is an economically and ecologically important tropical species. Following development into juveniles, H. leucospilota undergoes a color change from white to black, involving a pigmentation process for over a period of several months. In this study, a combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and Next-Generation sequencing (NGS) were employed to investigate the changes in metabolomic and transcriptomic profiles during pigmentation in H. leucospilota juveniles. The metabolomic analysis identified a total of 341 metabolites, of which 52 were found to be differentially regulated (P < 0.05 and VIP > 1), with 27 being upregulated in white individuals and 25 in black individuals. Additionally, 632 differentially expressed genes (DEGs) were identified, with 380 genes upregulated in white samples and 252 genes upregulated in black samples. Interestingly, the melanin content and tyrosinase transcript levels did not display significant differences between the two groups. Metabolomic data suggested the involvement of the linoleic acid metabolic pathway in pigmentation. Transcriptomic analysis, coupled with realtime PCR validation, revealed a decrease in the transcript levels of digestive enzymes like α-amylase, maltase-glucoamylase, and trehalase after the juveniles changed to black. Furthermore, the mRNA expressions of major yolk proteins showed a decline, indicating a shift in the accumulation of protein nutrient sources. Overall, our findings suggest that during the pigmentation process in H. leucospilota, no significant changes were observed in the classical melanin pathway, while notable alterations were observed in their nutritional status. This study provides valuable insights into the regulatory mechanisms of pigmentation in marine organisms.

Hypoxia improves self-renew and migration of urine-derived stem cells by upregulating autophagy and mitochondrial function through ERK signal pathway.

Urine-derived stem cells (USCs) are autologous stem cells with self-renewal ability and multi-lineage differentiation potential. Our previous studies have shown that hypoxia preconditioning can improve self-renewal and migration abilities of USCs by up-regulating autophagy. The purpose of this study was to investigate the specific mechanism by which hypoxia treatment promotes the biological function of USCs. We found that hypoxia treatment upregulated the expression of phosphralated ERK protein without affecting the expression of total ERK protein. Inhibiting ERK signaling with the PD98059 inhibitor decreased cell proliferation, migration and colony formation during hypoxia treatment. Hypoxia increased ATP production, mitochondrial membrane potential and mt-DNA copy number, which were reversed by inhibiting the ERK signal. Additionally, the number of autophagosomes and autophagic lysosomes was significantly lower in PD98059 group than in the hypoxia group. PD98059 treatment inhibited the up-regulation of autophagy related proteins induced by hypoxia. Therefore, this study suggests that hypoxia improves the self-renewal and migration abilities of USCs by upregulating autophagy and mitochondrial function through ERK signaling pathway. This finding may provide a new therapeutic mechanism for hypoxia pretreated USCs as a source of stem cell transplantation.

Applications of Environmental DNA (eDNA) in Monitoring the Endangered Status and Evaluating the Stock Enhancement Effect of Tropical Sea Cucumber Holothuria Scabra.

The tropical sea cucumber Holothuria scabra is naturally found in the Indo-West Pacific. However, due to their commercial value, natural H. scabra populations have declined significantly in recent years, resulting in its status as an endangered species. Surveys of H. scabra resource pose a challenge due to its specific characteristics, such as sand-burrowing behavior. To overcome this problem, our study established a convenient and feasible method for assessing H. scabra resources using environmental DNA (eDNA) monitoring technology. First, H. scabra-specific TaqMan primers and probe were designed based on its cox1 gene, followed by the development of an eDNA monitoring method for H. scabra in two separate sea areas (Xuwen and Daya Bay). The method was subsequently employed to investigate the distribution of H. scabra and assess the effects of aquaculture stock enhancement through juvenile releasing in the Weizhou Island sea area. The H. scabra eDNA monitoring approach was found to be more appropriate and credible than traditional methods, and a positive impact of stocking on H. scabra populations was observed. In summary, this is the first report to quantify eDNA concentration in a Holothuroidea species, and it provides a convenient and accurate method for surveying H. scabra resources. This study introduces novel concepts for eDNA-based detection of endangered marine benthic animals and monitoring their population distribution and abundance.

A novel rolling bearing fault diagnosis method based on parameter optimization variational mode decomposition with feature weighted reconstruction and multi-target attention convolutional neural networks under small samples.

To enhance the precision of rolling bearing fault diagnosis, an intelligent hybrid approach is proposed in this paper for signal processing and fault diagnosis in small samples. This approach is based on advanced techniques, combining parameter optimization variational mode decomposition weighted by multiscale permutation entropy (MPE) with maximal information coefficient and multi-target attention convolutional neural networks (MTACNN). First, an improved variational mode decomposition (VMD) is developed to denoise the raw signal. The whale optimization algorithm was used to optimize the penalty factor and mode component number in the VMD algorithm to obtain several intrinsic mode functions (IMFs). Second, separate MPE calculations are performed for both the raw signal and each of the IMF components obtained from the VMD decomposition; the results are used to calculate the maximum information coefficient (MIC). Subsequently, each MIC is normalized and converted to a weight coefficient for signal reconstruction. Ultimately, the reconstructed signals serve as input to the MTACNN for diagnosing rolling bearing faults. Results demonstrate that the signal processing approach exhibits superior noise reduction capability through simple processing. Furthermore, compared to several similar approaches, The method proposed for fault diagnosis achieves superior performance levels in the fault pattern recognition target and the fault severity recognition target.

Retinoic acid supplementation ameliorates motor incoordination via RARα-CBLN2 in the cerebellum of a prenatal valproic acid-exposed rat autism model.

In addition to their core symptoms, most individuals with autism spectrum disorder (ASD) also experience motor impairments. These impairments are often linked to the cerebellum, which is the focus of the current study. Herein, we utilized a prenatal valproic acid (VPA)-induced rat model of autism and performed RNA sequencing in the cerebellum. Relative to control animals, the VPA-treated offspring demonstrated both abnormal motor coordination and impaired dendritic arborization of Purkinje cells (PCs). Concurrently, we observed a decrease in the cerebellar expression of retinoic acid (RA) synthesis enzymes (RDH10, ALDH1A1), metabolic enzyme (CYP26A2), and lower levels of RA, retinoic acid receptor α (RARα), and Cerebellin2 (CBLN2) in the VPA-treated offspring. However, RA supplementation ameliorated these deficits, restoring motor coordination, normalizing PCs dendritic arborization, and increasing the expression of RA, RARα, and CBLN2. Further, ChIP assays confirmed that RA supplementation enhanced RARα's binding capacity to CBLN2 promoters. Collectively, these findings highlight the therapeutic potential of RA for treating motor incoordination in VPA-induced autism, acting through the RARα-CBLN2 pathway.

The Holothuria leucospilota genome elucidates sacrificial organ expulsion and bioadhesive trap enriched with amyloid-patterned proteins.

Some tropical sea cucumbers of the family Holothuriidae can efficiently repel or even fatally ensnare predators by sacrificially ejecting a bioadhesive matrix termed the Cuvierian organ (CO), so named by the French zoologist Georges Cuvier who first described it in 1831. Still, the precise mechanisms for how adhesiveness genetically arose in CO and how sea cucumbers perceive and transduce danger signals for CO expulsion during defense have remained unclear. Here, we report the first high-quality, chromosome-level genome assembly of Holothuria leucospilota, an ecologically significant sea cucumber with prototypical CO. The H. leucospilota genome reveals characteristic long-repeat signatures in CO-specific outer-layer proteins, analogous to fibrous proteins of disparate species origins, including spider spidroin and silkworm fibroin. Intriguingly, several CO-specific proteins occur with amyloid-like patterns featuring extensive intramolecular cross-ß structures readily stainable by amyloid indicator dyes. Distinct proteins within the CO connective tissue and outer surface cooperate to give the expelled matrix its apparent tenacity and adhesiveness, respectively. Genomic evidence offers further hints that H. leucospilota directly transduces predator-induced mechanical pressure onto the CO surface through mediation by transient receptor potential channels, which culminates in acetylcholine-triggered CO expulsion in part or in entirety. Evolutionarily, innovative events in two distinct regions of the H. leucospilota genome have apparently spurred CO's differentiation from the respiratory tree to a lethal defensive organ against predators.

Prenatally VPA exposure is likely to cause autistic-like behavior in the rats offspring via TREM2 down-regulation to affect the microglial activation and synapse alterations.

Microglial dysfunction has been reported in the valproic acid (VPA)-induced autism spectrum disorder (ASD) rat models. However, how does prenatal VPA exposure affect microglia remains to be elucidated. The triggering receptor expressed on myeloid cells 2 (TREM2) is revealed to be implicated in a range of microglia functions. However, reports on the association between TREM2 and VPA-induced ASD rat models are scarce. Our results showed that prenatal VPA exposure induced autistic-like behaviors, downregulated the levels of TREM2, up-regulated microglial activation, dysregulated microglial polarization, and altered synapse in offspring. TREM2 overexpression partly ameliorated microglia dysfunction and autistic-like behaviors in prenatal VPA-exposed rats. Our findings demonstrated that prenatally VPA exposure is likely to cause autistic-like behavior in the rat offspring via TREM2 down-regulation to affect the microglial activation, microglial polarization and synaptic pruning of microglia for the first time.