A prefrontal-habenular circuitry regulates social fear behaviour.

The medial prefrontal cortex (mPFC) has been implicated in the pathophysiology of social impairments including social fear. However, the precise subcortical partners that mediate mPFC dysfunction on social fear behaviour have not been identified. Employing a social fear conditioning paradigm, we induced robust social fear in mice and found that the lateral habenula (LHb) neurons and LHb-projecting mPFC neurons are synchronously activated during social fear expression. Moreover, optogenetic inhibition of the mPFC-LHb projection significantly reduced social fear responses. Importantly, consistent with animal studies, we observed an elevated prefrontal-habenular functional connectivity in subclinical individuals with higher social anxiety characterized by heightened social fear. These results unravel a crucial role of the prefrontal-habenular circuitry in social fear regulation and suggest that this pathway could serve as a potential target for the treatment of social fear symptom often observed in many psychiatric disorders.

Highly Efficient Ultraviolet Third-Harmonic Generation in an Isolated Thin Si Meta-Structure.

Nonlinear nanophotonic devices have shown great potential for on-chip information processing, quantum source, 3D microfabrication, greatly promoting the developments of integrated optics, quantum science, nanoscience and technologies, etc. To promote the applications of nonlinear nanodevices, improving the nonlinear efficiency, expanding the spectra region of nonlinear response and reducing device thickness are three key issues. Herein, this study focuses on the nonlinear effect of third-harmonic generation (THG), and present a thin Si meta-sructure to improve the THG efficiency in the ultraviolet (UV) region. The measured THG efficiency is up to 10-5 at an emission wavelength of 309 nm. Also, the THG nanosystem is only 100 nm in thickness, which is two-five times thinner than previous all-dielectric nanosystems applied in THG studies. These findings not only present a powerful thin meta-structure with highly efficient THG emission in UV region, but also provide a constructive avenue for further understanding the light-matter interactions at subwavelength scales, guiding the design and fabricating of advanced photonic devices in future.

Identification of Parkinson's disease PACE subtypes and repurposing treatments through integrative analyses of multimodal data.

Parkinson's disease (PD) is a serious neurodegenerative disorder marked by significant clinical and progression heterogeneity. This study aimed at addressing heterogeneity of PD through integrative analysis of various data modalities. We analyzed clinical progression data (≥5 years) of individuals with de novo PD using machine learning and deep learning, to characterize individuals' phenotypic progression trajectories for PD subtyping. We discovered three pace subtypes of PD exhibiting distinct progression patterns: the Inching Pace subtype (PD-I) with mild baseline severity and mild progression speed; the Moderate Pace subtype (PD-M) with mild baseline severity but advancing at a moderate progression rate; and the Rapid Pace subtype (PD-R) with the most rapid symptom progression rate. We found cerebrospinal fluid P-tau/α-synuclein ratio and atrophy in certain brain regions as potential markers of these subtypes. Analyses of genetic and transcriptomic profiles with network-based approaches identified molecular modules associated with each subtype. For instance, the PD-R-specific module suggested STAT3, FYN, BECN1, APOA1, NEDD4, and GATA2 as potential driver genes of PD-R. It also suggested neuroinflammation, oxidative stress, metabolism, PI3K/AKT, and angiogenesis pathways as potential drivers for rapid PD progression (i.e., PD-R). Moreover, we identified repurposable drug candidates by targeting these subtype-specific molecular modules using network-based approach and cell line drug-gene signature data. We further estimated their treatment effects using two large-scale real-world patient databases; the real-world evidence we gained highlighted the potential of metformin in ameliorating PD progression. In conclusion, this work helps better understand clinical and pathophysiological complexity of PD progression and accelerate precision medicine.

YOLOC-tiny: a generalized lightweight real-time detection model for multiripeness fruits of large non-green-ripe citrus in unstructured environments.

This study addresses the challenges of low detection precision and limited generalization across various ripeness levels and varieties for large non-green-ripe citrus fruits in complex scenarios. We present a high-precision and lightweight model, YOLOC-tiny, built upon YOLOv7, which utilizes EfficientNet-B0 as the feature extraction backbone network. To augment sensing capabilities and improve detection accuracy, we embed a spatial and channel composite attention mechanism, the convolutional block attention module (CBAM), into the head's efficient aggregation network. Additionally, we introduce an adaptive and complete intersection over union regression loss function, designed by integrating the phenotypic features of large non-green-ripe citrus, to mitigate the impact of data noise and efficiently calculate detection loss. Finally, a layer-based adaptive magnitude pruning strategy is employed to further eliminate redundant connections and parameters in the model. Targeting three types of citrus widely planted in Sichuan Province-navel orange, Ehime Jelly orange, and Harumi tangerine-YOLOC-tiny achieves an impressive mean average precision (mAP) of 83.0%, surpassing most other state-of-the-art (SOTA) detectors in the same class. Compared with YOLOv7 and YOLOv8x, its mAP improved by 1.7% and 1.9%, respectively, with a parameter count of only 4.2M. In picking robot deployment applications, YOLOC-tiny attains an accuracy of 92.8% at a rate of 59 frames per second. This study provides a theoretical foundation and technical reference for upgrading and optimizing low-computing-power ground-based robots, such as those used for fruit picking and orchard inspection.

Genome assembly of redclaw crayfish (Cherax quadricarinatus) provides insights into its immune adaptation and hypoxia tolerance.

BACKGROUND: The introduction of non-native species is a primary driver of biodiversity loss in freshwater ecosystems. The redclaw crayfish (Cherax quadricarinatus) is a freshwater species that exhibits tolerance to hypoxic stresses, fluctuating temperatures, high ammonia concentration. These hardy physiological characteristics make C. quadricarinatus a popular aquaculture species and a potential invasive species that can negatively impact tropical and subtropical ecosystems. Investigating the genomic basis of environmental tolerances and immune adaptation in C. quadricarinatus will facilitate the development of management strategies of this potential invasive species. RESULTS: We constructed a chromosome-level genome of C. quadricarinatus by integrating Nanopore and PacBio techniques. Comparative genomic analysis suggested that transposable elements and tandem repeats drove genome size evolution in decapod crustaceans. The expansion of nine immune-related gene families contributed to the disease resistance of C. quadricarinatus. Three hypoxia-related genes (KDM3A, KDM5A, HMOX2) were identified as being subjected to positive selection in C. quadricarinatus. Additionally, in vivo analysis revealed that upregulating KDM5A was crucial for hypoxic response in C. quadricarinatus. Knockdown of KDM5A impaired hypoxia tolerance in this species. CONCLUSIONS: Our results provide the genomic basis for hypoxic tolerance and immune adaptation in C. quadricarinatus, facilitating the management of this potential invasive species. Additionally, in vivo analysis in C. quadricarinatus suggests that the role of KDM5A in the hypoxic response of animals is complex.

Real-World Effectiveness of Nirmatrelvir in Protecting Long COVID for Outpatient Adult Patients - A Large-Scale Observational Cohort Study from the RECOVER Initiative.

Paxlovid has been approved for use in patients who are at high risk for severe acute COVID-19 illness. Evidence regarding whether Paxlovid protects against Post-Acute Sequelae of SARS-CoV-2 infection (PASC), or Long COVID, is mixed in high-risk patients and lacking in low-risk patients. With a target trial emulation framework, we evaluated the association of Paxlovid treatment within 5 days of SARS-CoV-2 infection with incident Long COVID and hospitalization or death from any cause in the post-acute period (30-180 days after infection) using electronic health records from the Patient-Centered Clinical Research Networks (PCORnet) RECOVER repository. The study population included 497,499 SARS-CoV-2 positive patients between March 1, 2022, to February 1, 2023, and among which 165,256 were treated with Paxlovid within 5 days since infection and 307,922 were not treated with Paxlovid or other COVID-19 treatments. Compared with the non-treated group, Paxlovid treatment was associated with reduced risk of Long COVID with a Hazard Ratio (HR) of 0.88 (95% CI, 0.87 to 0.89) and absolute risk reduction of 2.99 events per 100 persons (95% CI, 2.65 to 3.32). Paxlovid treatment was associated with reduced risk of all-cause death (HR, 0.53, 95% CI 0.46 to 0.60; risk reduction 0.23 events per 100 persons, 95% CI 0.19 to 0.28) and hospitalization (HR, 0.70, 95% CI 0.68 to 0.73; risk reduction 2.37 events per 100 persons, 95% CI 2.19 to 2.56) in the post-acute phase. For those without documented risk factors, the associations (HR, 1.03, 95% CI 0.95 to 1.11; risk increase 0.80 events per 100 persons, 95% CI -0.84 to 2.45) were inconclusive. Overall, high-risk, nonhospitalized adult patients with COVID-19 who were treated with Paxlovid within 5 days of SARS-CoV-2 infection had a lower risk of Long COVID and all-cause hospitalization or death in the post-acute period. However, Long COVID risk reduction with Paxlovid was not observed in low-risk patients.

A randomized controlled trial on hair follicular-derived microtissue for promoting wound healing and alleviating postoperative complications after hair transplantation.

BACKGROUND: Hair transplantation, particularly through follicular unit extraction (FUE), can lead to postoperative complications, such as numbness, itching, and pain in donor areas, primarily because of delayed wound healing. Efficient management of donor-site healing is crucial to mitigate these complications and improve overall patient outcomes. OBJECTIVE: This study aimed to assess the efficacy of hair follicular-derived microtissue (HFMT) in promoting wound healing and alleviating postoperative complications in donor areas after FUE hair transplantation. METHODS: Perifollicular tissue obtained during the trimming phase of hair transplantation was processed into HFMT and analyzed for its properties using histological and molecular techniques. In a single-blind, split-scalp study involving 98 participants, Group A received HFMT or mupirocin, whereas Group B received HFMT or no treatment. Dermatoscopic images were captured postoperatively, and visual analog scale scores were used to evaluate pain, itching, and numbness. RESULTS: HFMT-treated donor sites in Group A demonstrated a significantly higher wound closure ratio on postoperative day 3 than mupirocin-treated sites. Pain scores for HFMT-treated sites were consistently lower on postoperative days 3, 5, and 7. Similar trends were observed for itching scores. Group B exhibited outcomes comparable with Group A. CONCLUSION: The application of HFMT homogenates effectively accelerated wound healing and alleviated donor-site complications after FUE hair transplantation.

SANTO: a coarse-to-fine alignment and stitching method for spatial omics.

With the flourishing of spatial omics technologies, alignment and stitching of slices becomes indispensable to decipher a holistic view of 3D molecular profile. However, existing alignment and stitching methods are unpractical to process large-scale and image-based spatial omics dataset due to extreme time consumption and unsatisfactory accuracy. Here we propose SANTO, a coarse-to-fine method targeting alignment and stitching tasks for spatial omics. SANTO firstly rapidly supplies reasonable spatial positions of two slices and identifies the overlap region. Then, SANTO refines the positions of two slices by considering spatial and omics patterns. Comprehensive experiments demonstrate the superior performance of SANTO over existing methods. Specifically, SANTO stitches cross-platform slices for breast cancer samples, enabling integration of complementary features to synergistically explore tumor microenvironment. SANTO is then applied to 3D-to-3D spatiotemporal alignment to study development of mouse embryo. Furthermore, SANTO enables cross-modality alignment of spatial transcriptomic and epigenomic data to understand complementary interactions.

Evaluating the necessity of lymph node sampling in lung adenocarcinoma with ground glass opacities.

BACKGROUND: Ground glass opacity is observed frequently in the early stages of lung adenocarcinoma and is associated with a favorable prognosis and a low incidence of lymph node metastasis. However, the necessity of lymph node sampling in these patients is questionable, although current guidelines still recommend it. METHODS: Radiologic and clinical data were retrospectively collected and analyzed for 2,298 patients with lung cancer who underwent surgical resection for lesions ≤15 mm during 2022. Based on the consolidation tumor ratios, patients were categorized into 4 groups (pure ground glass opacity, ground glass opacity-predominant, solid-predominant, and pure solid). The incidence of lymph node metastasis in each group was examined. RESULTS: A total of 2,298 patients with a median age of 54.0 years were enrolled in this study. Tumors were categorized into 4 types: 1,427 (62.1%) were pure ground glass opacity, which constituted the majority, while 421 (18.3%) were ground glass opacity-predominant, 330 (14.4%) were solid-predominant, and the remaining 120 (5.2%) were pure solid. Significant positive correlations were revealed between the consolidation tumor ratio group and pathologic grade (P < .001, ρ = 0.307), T stage (P < .001, ρ = 0.270), and N stage (P < .001, ρ = 0.105). Among the included cases, only 7 cases with metastasis were in the pure solid group. Within this group, 113 cases (94.2%) were N0, 5 cases (4.2%) were N1, and 2 cases (1.7%) were N2. CONCLUSION: Lymph node metastasis exclusively occurred in the pure solid group, suggesting that for nodules <15 mm, lymph node sampling may be crucial for pure solid nodules but less so for those containing ground glass opacities.

The role of immune cell signatures in the pathogenesis of ovarian-related diseases: a causal inference based on mendelian randomization.

BACKGROUND: Immune cells play a pivotal role in maintaining ovarian function. However, the specific contributions of different immune cell phenotypes to the pathogenesis of specific ovarian-related diseases remain poorly understood. We aim to investigate the correlation between 731 immunophenotypes and ovarian-related diseases. MATERIALS AND METHODS: Utilizing publicly available genetic data, we undertook a series of quality control measures to identify instrumental variables (IVs) associated with exposure. Subsequently, we conducted two-sample Mendelian randomization (MR) using inverse variance weighting to explore the causal relationships between 731 immune cell features and six ovarian-related diseases: ovarian cysts, ovarian dysfunction, premature ovarian failure (POF), polycystic ovary syndrome (PCOS), benign neoplasm of ovary, and malignant neoplasm of ovary at the genetic level. Sensitivity analyses, including leave-one-out and other MR analysis models, were performed. Finally, Bayesian colocalization (COLOC) analysis was employed to identify specific co-localized genes, thereby validating the MR results. RESULTS: At the significance level corrected by Bonferroni, four immune phenotypes, including CD25 on IgD- CD38- B cells, were associated with ovarian cysts; four immune phenotypes, including CD39+ CD4+ T cell Absolute Count, were associated with ovarian dysfunction; eight immune phenotypes, including SSC-A on HLA DR+ CD8+ T cells, were associated with POF; five immune phenotypes, including CD20- CD38- B cell Absolute Count, were associated with PCOS; five immune phenotypes, including CD4+ CD8dim T cell Absolute Count, were associated with benign ovarian tumors; and three immune phenotypes, including BAFF-R on IgD- CD38+ B cells, were associated with malignant ovarian tumors. Sensitivity analysis indicated robust results. COLOC analysis identified four immune cell co-localized variants (rs150386792, rs117936291, rs75926368, rs575687159) with ovarian diseases. CONCLUSION: Our study elucidates the close genetic associations between immune cells and six ovarian-related diseases, thereby providing valuable insights for future research endeavors and clinical applications.

Purification and Structural Analyses of Sulfated Polysaccharides from Low-Value Sea Cucumber Stichopus naso and Anticoagulant Activities of Its Oligosaccharides.

Three polysaccharides (SnNG, SnFS and SnFG) were purified from the body wall of Stichopus naso. The physicochemical properties, including monosaccharide composition, molecular weight, sulfate content, and optical rotation, were analyzed, confirming that SnFS and SnFG are sulfated polysaccharides commonly found in sea cucumbers. The highly regular structure {3)-L-Fuc2S-(α1,}n of SnFS was determined via a detailed NMR analysis of its oxidative degradation product. By employing ß-elimination depolymerization of SnFG, tri-, penta-, octa-, hendeca-, tetradeca-, and heptadeca-saccharides were obtained from the low-molecular-weight product. Their well-defined structures confirmed that SnFG possessed the backbone of {D-GalNAc4S6S-ß(1,4)-D-GlcA}, and each GlcA residue was branched with Fuc2S4S. SnFS and SnFG are both structurally the simplest version of natural fucan sulfate and fucosylated glycosaminoglycan, facilitating the application of low-value sea cucumbers S. naso. Bioactivity assays showed that SnFG and its derived oligosaccharides exhibited potent anticoagulation and intrinsic factor Xase (iXase) inhibition. Moreover, a comparative analysis with the series of oligosaccharides solely branched with Fuc3S4S showed that in oligosaccharides with lower degrees of polymerization, such as octasaccharides, Fuc2S4S led to a greater increase in APTT prolongation and iXase inhibition. As the degree of polymerization increases, the influence from the sulfation pattern diminishes, until it is overshadowed by the effects of molecular weight.

HELM-GPT: de novo macrocyclic peptide design using generative pre-trained transformer.

MOTIVATION: Macrocyclic peptides hold great promise as therapeutics targeting intracellular proteins. This stems from their remarkable ability to bind flat protein surfaces with high affinity and specificity while potentially traversing the cell membrane. Research has already explored their use in developing inhibitors for intracellular proteins, such as KRAS, a well-known driver in various cancers. However, computational approaches for de novo macrocyclic peptide design remain largely unexplored. RESULTS: Here, we introduce HELM-GPT, a novel method that combines the strength of the hierarchical editing language for macromolecules (HELM) representation and generative pre-trained transformer (GPT) for de novo macrocyclic peptide design. Through reinforcement learning (RL), our experiments demonstrate that HELM-GPT has the ability to generate valid macrocyclic peptides and optimize their properties. Furthermore, we introduce a contrastive preference loss during the RL process, further enhanced the optimization performance. Finally, to co-optimize peptide permeability and KRAS binding affinity, we propose a step-by-step optimization strategy, demonstrating its effectiveness in generating molecules fulfilling both criteria. In conclusion, the HELM-GPT method can be used to identify novel macrocyclic peptides to target intracellular proteins. AVAILABILITY AND IMPLEMENTATION: The code and data of HELM-GPT are freely available on GitHub (https://github.com/charlesxu90/helm-gpt).

Si-Miao-Yong-An Decoction alleviates thromboangiitis obliterans by regulating miR-548j-5p/IL-17A signaling pathway.

Thromboangiitis obliterans (TAO) is a rare, chronic, progressive, and segmental inflammatory disease characterized by a high rate of amputation, significantly compromising the quality of life of patients. Si-Miao-Yong-An decoction (SMYA), a traditional prescription, exhibits anti-inflammatory, anti-thrombotic, and various other pharmacological properties. Clinically, it was fully proved to be effective for TAO therapy, but the specific therapeutic effect of SMYA on TAO has been unknown. Thus, deep unveiling the mechanism of SMYA in TAO for identifying clinical therapeutic targets is extremely important. In this study, we observed elevated levels of IL-17A in the peripheral blood mononuclear cells (PBMCs) of TAO patients, whereas the expression of miR-548j-5p was significantly decreased. A negative correlation between the levels of miR-548j-5p and IL-17A was also demonstrated. In vitro experiments showed that overexpression of miR-548j-5p led to a decrease in IL-17A levels, whereas downregulation of miR-548j-5p showed the opposite effect. Using a dual luciferase assay, we confirmed that miR-548j-5p directly targets IL-17A. Furthermore, serum containing SMYA effectively decreased IL-17A levels by increasing the expression of miR-548j-5p. More importantly, the results of in vivo tests indicated that SMYA mitigated the development of TAO by inhibiting IL-17A through the upregulation of miR-548j-5p in vascular tissues. In conclusion, SMYA significantly enhances the expression of miR-548j-5p, thereby reducing the levels of the target gene IL-17A and alleviating TAO. Our research not only identifies novel targets and pathways for the clinical diagnosis and treatment of TAO but also advances the innovation in traditional Chinese medicine through the elucidation of the SMYA/miR-548j-5p/IL-17A regulatory axis in the pathogenesis of TAO.

A facile synthesis of water-soluble copper nanoclusters as label-free fluorescent probes for rapid, selective and sensitive determination of alizarin red.

Copper nanoclusters (FA@CuNCs) emitting blue fluorescence were successfully developed via a one-pot technique. In this method, the copper chloride, folic acid and hydrazine hydrate were applied as a precursor, protective agent and reducing agent, respectively. The absorption, fluorescence excitation and emission spectra of FA@CuNCs were carried out by using ultraviolet-visible and fluorescence spectrometry, respectively. The morphology, particle size, functional groups, oxidation states of elements of FA@CuNCs were discussed via using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS). The stability of FA@CuNCs was studied under various conditions, such as storage time at 25 ℃, ultraviolet radiation time, sodium chloride solutione and pH. The FA@CuNCs displayed blue fluorescence under the excitation wavelength of 361 nm, and the fluorescence quantum yield was 7.45 %. As a result of the inner filter effect, the alizarin red could significantly weaken the blue fluorescence of FA@CuNCs. Thus, the as-prepared FA@CuNCs could be utilized as fluorescence nanosensors for the trace determination of alizarin red. This platform suggested an excellent linear range for alizarin red varying from 0.5 to 200 µM with a fitting coefficient of 0.9955. The detection limit was calculated to be 0.064 µM in the light of the 3b/k (b and k refer to the standard deviation and slope of fitted curve, respectively). Furthermore, the as-developed FA@CuNCs could be used to detect the alizarin red in real samples and for the sensing of temperature.

Mechanism of Zhishi Xiebai Guizhi decoction to treat atherosclerosis: Insights into experiments, network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhishi Xiebai Guizhi Decoction (ZSXBGZD) is a traditional herbal manuscript used to treat cardiovascular disease, including atherosclerosis and coronary heart disease. The decoction has demonstrated its capability to protect arteries and resist atherosclerosis. Its mechanisms for anti-atherosclerosis effect, nevertheless, remain unknown. AIMS OF THE STUDY: The goal of the present study is to explore the effectiveness of ZSXBGZD acting on atherosclerosis and its key components based on experimental verification and network pharmacology analysis. MATERIALS AND METHODS: The ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and databases were used to identify chemical components in ZSXBGZD. Network pharmacological analysis and molecular docking were implemented in order to reveal the possible therapeutic targets of ZSXBGZD. To form the model of atherosclerosis, we gave Apolipoprotein E knocked out mice a high-fat diet. H&E staining was performed to observe the effects of ZSXBGZD on atherosclerosis. Immunofluorescence and Western blot were used to investigate whether ZSXBGZD could affect autophagy, apoptosis, AGE-RAGE signaling pathway and other related mechanisms. RESULTS: In total, 30 core compounds were screened through intersecting UPLC-Q-TOF-MS and the databases. The anti-atherosclerotic effect of ZSXBGZD might relate to the AGE-RAGE signaling pathway via network pharmacology analysis. ZSXBGZD could inhibit apoptosis, activate autophagy and ease inflammation by modifying AGE-RAGE signaling pathway to reduce the area of atherosclerotic plaque. CONCLUSION: ZSXBGZD could treat atherosclerosis by regulating autophagy and apoptosis via adjusting the AGE-RAGE signaling pathway.

Atomic-level polarization reversal in sliding ferroelectric semiconductors.

Intriguing "slidetronics" has been reported in van der Waals (vdW) layered non-centrosymmetric materials and newly-emerging artificially-tuned twisted moiré superlattices, but correlative experiments that spatially track the interlayer sliding dynamics at atomic-level remain elusive. Here, we address the decisive challenge to in-situ trace the atomic-level interlayer sliding and the induced polarization reversal in vdW-layered yttrium-doped γ-InSe, step by step and atom by atom. We directly observe the real-time interlayer sliding by a 1/3-unit cell along the armchair direction, corresponding to vertical polarization reversal. The sliding driven only by low energetic electron-beam illumination suggests rather low switching barriers. Additionally, we propose a new sliding mechanism that supports the observed reversal pathway, i.e., two bilayer units slide towards each other simultaneously. Our insights into the polarization reversal via the atomic-scale interlayer sliding provide a momentous initial progress for the ongoing and future research on sliding ferroelectrics towards non-volatile storages or ferroelectric field-effect transistors.

KaryoXpert: An accurate chromosome segmentation and classification framework for karyotyping analysis without training with manually labeled metaphase-image mask annotations.

Automated karyotyping is of great importance for cytogenetic research, as it speeds up the process for cytogeneticists through incorporating AI-driven automated segmentation and classification techniques. Existing frameworks confront two primary issues: Firstly the necessity for instance-level data annotation with either detection bounding boxes or semantic masks for training, and secondly, its poor robustness particularly when confronted with domain shifts. In this work, we first propose an accurate segmentation framework, namely KaryoXpert. This framework leverages the strengths of both morphology algorithms and deep learning models, allowing for efficient training that breaks the limit for the acquirement of manually labeled ground-truth mask annotations. Additionally, we present an accurate classification model based on metric learning, designed to overcome the challenges posed by inter-class similarity and batch effects. Our framework exhibits state-of-the-art performance with exceptional robustness in both chromosome segmentation and classification. The proposed KaryoXpert framework showcases its capacity for instance-level chromosome segmentation even in the absence of annotated data, offering novel insights into the research for automated chromosome segmentation. The proposed method has been successfully deployed to support clinical karyotype diagnosis.

Nucleic Acid Sensing by STING Induces an IFN-like Antiviral Response in a Marine Invertebrate.

The cytosolic detection of pathogen-derived nucleic acids has evolved as an essential strategy for host innate immune defense in mammals. One crucial component in this process is the stimulator of IFN genes (STING), which acts as a vital signaling adaptor, connecting the cytosolic detection of DNA by cyclic GMP-AMP (cGAMP) synthase (cGAS) to the downstream type I IFN signaling pathway. However, this process remains elusive in invertebrates. In this study, we present evidence demonstrating that STING, an ortholog found in a marine invertebrate (shrimp) called Litopenaeus vannamei, can directly detect DNA and initiate an IFN-like antiviral response. Unlike its homologs in other eukaryotic organisms, which exclusively function as sensors for cyclic dinucleotides, shrimp STING has the ability to bind to both double-stranded DNA and cyclic dinucleotides, including 2'3'-cGAMP. In vivo, shrimp STING can directly sense DNA nucleic acids from an infected virus, accelerate IFN regulatory factor dimerization and nuclear translocation, induce the expression of an IFN functional analog protein (Vago4), and finally establish an antiviral state. Taken together, our findings unveil a novel double-stranded DNA-STING-IKKε-IRF-Vago antiviral axis in an arthropod, providing valuable insights into the functional origins of DNA-sensing pathways in evolution.

Increased miR-6132 promotes deep vein thrombosis formation by downregulating FOXP3 expression.

Background: Deep vein thrombosis (DVT) is associated with aberrant gene expression that is a common peripheral vascular disease. Here, we aimed to elucidate that the epigenetic modification of forkhead box protein 3 (FOXP3) at the post-transcriptional level, which might be the key trigger leading to the down-regulation of FOXP3 expression in DVT. Methods: In order to explore the relationship between microRNAs (miRNAs) and FOXP3, mRNA and microRNA microarray analysis were performed. Dual luciferase reporter assay was used to verify the upstream miRNAs of FOXP3. Quantitative real-time polymerase chain reaction, flow cytometry and Western blot were used to detect the relative expression of miR-6132 and FOXP3. Additionally, DVT models were established to investigate the role of miR-6132 by Murine Doppler Ultrasound and Hematoxylin-Eosin staining. Results: Microarray and flow cytometry results showed that the FOXP3 expression was decreased while miR-6132 level was increased substantially in DVT, and there was significant negative correlation between miR-6132 and FOXP3. Moreover, we discovered that overexpressed miR-6132 reduced FOXP3 expression and aggravated DVT formation, while miR-6132 knockdown increased FOXP3 expression and alleviated DVT formation. Dual luciferase reporter assay validated the direct binding of miR-6132 to FOXP3. Conclusion: Collectively, our data elucidate a new avenue through which up-regulated miR-6132 contributes to the formation and progression of DVT by inhibiting FOXP3 expression.