Examining the Roles of GABAA Receptor Subtypes in Anxiety and Anxiolysis: Focusing on the Basolateral Amygdala

The investigation of the differential roles GABAA receptor (GABAAR) subtypes play in mediating various behaviors such as fear and anxiety was an intriguing research topic over the past decade. At present, most evidence suggests that benzodiazepine (BZ)-induced anxiolysis is primarily mediated by GABAARs containing the α2-subunit (α2-subtype). However, there is conflicting evidence as to whether α1- and α3-subtypes might also be involved in BZ-induced anxiolysis. In an attempt to further discern the role played by different α-subtype GABAARs in BZ-induced anxiolysis both systemically and within the basolateral amygdala (BLA), a brain region crucial for anxiety-like behaviors, we examined the anxiolytic-like effects, as measured by elevated-plus maze test (EPM), of several subtype selective and non-selective GABAAR positive allosteric modulators (PAMs) both in wild type mice and in mutant mice that express BZ-insensitive GABAARs of specific α-subtypes. In our experiments, systemic injections of the α1-selective PAM zolpidem in WT mice produced slight anxiolytic-like effects with a narrow therapeutic window that overlapped with prominent motor-inhibiting effects. Systemic injection of the α3-selective PAM TP003 produced marked anxiolytic-like effects in WT mice that were accompanied by motor-stimulating effects. Systemic injection of the α2-, α3-, and α5-selective PAM L-838417 elicited significant anxiolytic-like effects in WT, and the effects were weakened in the α3(H126R) mice. Similarly, anxiolytic-like effects were observed when these selective PAMs were administered via microinjection into the BLA; however, these local injections did not significantly affect motor activity at the doses tested. In the experiment examining systemic injections of the non-selective BZ chlordiazepoxide (CDP), we found that CDP induced robust anxiolytic-like effects in both male and female WT mice. These effects were potentiated in female α1(H101R) mice, and were reduced in α2(H101R) mice of both sexes, as well as male α3(H126R) mice. Interestingly, intra-BLA microinjection of CDP produced few effects in WT, α1(H101R), or α2(H101R) mice, but showed some anxiolytic-like effects in α3(H126R) mice. Taken together, our results suggests (i) all three (α1-, α2-, and α3-) GABAAR subtypes are involved in BZ-induced anxiolysis, but subtle differences do exist; (ii) augmentation of the α1-subtype GABAARs exerts anxiolytic-like effects; however, the therapeutic window is narrow; (iii) augmentation of the α2-, α3-, (and α5-) subtype GABAARs exerts anxiolytic-like effects and motor-stimulating effects, and these effects are weakened in α3(H126R) mice at doses tested, (iv) augmentation of the α3-subtype GABAARs exerts anxiolytic-like effects, accompanied by motor-stimulating effects; (v) BLA is an important brain region that is sufficient to mediate the anxiolytic-like effects, but not the motor-stimulating or inhibiting effects of subtype selective GABAAR PAMs; and (vi) intra-BLA microinjection of CDP yielded an inconclusive behavioral outcome, possibly due to the complex GABAergic intra-amygdaloidal microcircuitries which might antagonize each other when multiple subtypes of GABAARs are simultaneously modulated by BZs. Taken together, our results provide novel evidence that may benefit the current development of subtype selective drugs for treating clinical anxiety disorders

CosAvatar: Consistent and Animatable Portrait Video Tuning with Text Prompt

Recently, text-guided digital portrait editing has attracted more and more attentions. However, existing methods still struggle to maintain consistency across time, expression, and view or require specific data prerequisites. To solve these challenging problems, we propose CosAvatar, a high-quality and user-friendly framework for portrait tuning. With only monocular video and text instructions as input, we can produce animatable portraits with both temporal and 3D consistency. Different from methods that directly edit in the 2D domain, we employ a dynamic NeRF-based 3D portrait representation to model both the head and torso. We alternate between editing the video frames' dataset and updating the underlying 3D portrait until the edited frames reach 3D consistency. Additionally, we integrate the semantic portrait priors to enhance the edited results, allowing precise modifications in specified semantic areas. Extensive results demonstrate that our proposed method can not only accurately edit portrait styles or local attributes based on text instructions but also support expressive animation driven by a source video.Comment: Project page: https://ustc3dv.github.io/CosAvatar

A Dual Stealthy Backdoor: From Both Spatial and Frequency Perspectives

Backdoor attacks pose serious security threats to deep neural networks (DNNs). Backdoored models make arbitrarily (targeted) incorrect predictions on inputs embedded with well-designed triggers while behaving normally on clean inputs. Many works have explored the invisibility of backdoor triggers to improve attack stealthiness. However, most of them only consider the invisibility in the spatial domain without explicitly accounting for the generation of invisible triggers in the frequency domain, making the generated poisoned images be easily detected by recent defense methods. To address this issue, in this paper, we propose a DUal stealthy BAckdoor attack method named DUBA, which simultaneously considers the invisibility of triggers in both the spatial and frequency domains, to achieve desirable attack performance, while ensuring strong stealthiness. Specifically, we first use Discrete Wavelet Transform to embed the high-frequency information of the trigger image into the clean image to ensure attack effectiveness. Then, to attain strong stealthiness, we incorporate Fourier Transform and Discrete Cosine Transform to mix the poisoned image and clean image in the frequency domain. Moreover, the proposed DUBA adopts a novel attack strategy, in which the model is trained with weak triggers and attacked with strong triggers to further enhance the attack performance and stealthiness. We extensively evaluate DUBA against popular image classifiers on four datasets. The results demonstrate that it significantly outperforms the state-of-the-art backdoor attacks in terms of the attack success rate and stealthinessComment: 10 pages, 7 figures. Submit to ACM MM 202

Is Underwater Image Enhancement All Object Detectors Need?

Underwater object detection is a crucial and challenging problem in marine engineering and aquatic robot. The difficulty is partly because of the degradation of underwater images caused by light selective absorption and scattering. Intuitively, enhancing underwater images can benefit high-level applications like underwater object detection. However, it is still unclear whether all object detectors need underwater image enhancement as pre-processing. We therefore pose the questions "Does underwater image enhancement really improve underwater object detection?" and "How does underwater image enhancement contribute to underwater object detection?". With these two questions, we conduct extensive studies. Specifically, we use 18 state-of-the-art underwater image enhancement algorithms, covering traditional, CNN-based, and GAN-based algorithms, to pre-process underwater object detection data. Then, we retrain 7 popular deep learning-based object detectors using the corresponding results enhanced by different algorithms, obtaining 126 underwater object detection models. Coupled with 7 object detection models retrained using raw underwater images, we employ these 133 models to comprehensively analyze the effect of underwater image enhancement on underwater object detection. We expect this study can provide sufficient exploration to answer the aforementioned questions and draw more attention of the community to the joint problem of underwater image enhancement and underwater object detection. The pre-trained models and results are publicly available and will be regularly updated. Project page: https://github.com/BIGWangYuDong/lqit/tree/main/configs/detection/uw_enhancement_affect_detection.Comment: 17 pages, 9 figure

Effects of Litchi chinensis fruit isolates on prostaglandin E2 and nitric oxide production in J774 murine macrophage cells

<p>Abstract</p> <p>Background</p> <p><it>Litchi chinensis </it>is regarded as one of the 'heating' fruits in China, which causes serious inflammation symptoms to people.</p> <p>Methods</p> <p>In the current study, the effects of isolates of litchi on prostaglandin E₂(PGE₂) and nitric oxide (NO) production in J774 murine macrophage cells were investigated.</p> <p>Results</p> <p>The AcOEt extract (EAE) of litchi was found effective on stimulating PGE₂production, and three compounds, benzyl alcohol, hydrobenzoin and 5-hydroxymethyl-2-furfurolaldehyde (5-HMF), were isolated and identified from the EAE. Benzyl alcohol caused markedly increase in PGE₂and NO production, compared with lipopolysaccharide (LPS) as positive control, and in a dose-dependent manner. Hydrobenzoin and 5-HMF were found in litchi for the first time, and both of them stimulated PGE₂and NO production moderately in a dose-dependent manner. Besides, regulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) mRNA expression and NF-κB (p50) activation might be involved in mechanism of the stimulative process.</p> <p>Conclusion</p> <p>The study showed, some short molecular compounds in litchi play inflammatory effects on human.</p

Marked methylation changes in intestinal genes during the perinatal period of preterm neonates

BACKGROUND: The serious feeding- and microbiota-associated intestinal disease, necrotizing enterocolitis (NEC), occurs mainly in infants born prematurely (5-10% of all newborns) and most frequently after formula-feeding. We hypothesized that changes in gene methylation is involved in the prenatal maturation of the intestine and its response to the first days of formula feeding, potentially leading to NEC in preterm pigs used as models for preterm infants. RESULTS: Reduced Representation Bisulfite Sequencing (RRBS) was used to assess if changes in intestinal DNA methylation are associated with formula-induced NEC outbreak and advancing age from 10 days before birth to 4 days after birth. Selected key genes with differentially methylated gene regions (DMRs) between groups were further validated by HiSeq-based bisulfite sequencing PCR and RT-qPCR to assess methylation and expression levels. Consistent with the maturation of many intestinal functions in the perinatal period, methylation level of most genes decreased with advancing pre- and postnatal age. The highest number of DMRs was identified between the newborn and 4 d-old preterm pigs. There were few intestinal DMR differences between unaffected pigs and pigs with initial evidence of NEC. In the 4 d-old formula-fed preterm pigs, four genes associated with intestinal metabolism (CYP2W1, GPR146, TOP1MT, CEND1) showed significant hyper-methylation in their promoter CGIs, and thus, down-regulated transcription. Methylation-driven down-regulation of such genes may predispose the immature intestine to later metabolic dysfunctions and severe NEC lesions. CONCLUSIONS: Pre- and postnatal changes in intestinal DNA methylation may contribute to high NEC sensitivity in preterm neonates. Optimizing gene methylation changes via environmental stimuli (e.g. diet, nutrition, gut microbiota), may help to make immature newborn infants more resistant to gut dysfunctions, both short and long term. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-716) contains supplementary material, which is available to authorized users