Unsupervised learning reveals interpretable latent representations for translucency perception.

Humans constantly assess the appearance of materials to plan actions, such as stepping on icy roads without slipping. Visual inference of materials is important but challenging because a given material can appear dramatically different in various scenes. This problem especially stands out for translucent materials, whose appearance strongly depends on lighting, geometry, and viewpoint. Despite this, humans can still distinguish between different materials, and it remains unsolved how to systematically discover visual features pertinent to material inference from natural images. Here, we develop an unsupervised style-based image generation model to identify perceptually relevant dimensions for translucent material appearances from photographs. We find our model, with its layer-wise latent representation, can synthesize images of diverse and realistic materials. Importantly, without supervision, human-understandable scene attributes, including the object's shape, material, and body color, spontaneously emerge in the model's layer-wise latent space in a scale-specific manner. By embedding an image into the learned latent space, we can manipulate specific layers' latent code to modify the appearance of the object in the image. Specifically, we find that manipulation on the early-layers (coarse spatial scale) transforms the object's shape, while manipulation on the later-layers (fine spatial scale) modifies its body color. The middle-layers of the latent space selectively encode translucency features and manipulation of such layers coherently modifies the translucency appearance, without changing the object's shape or body color. Moreover, we find the middle-layers of the latent space can successfully predict human translucency ratings, suggesting that translucent impressions are established in mid-to-low spatial scale features. This layer-wise latent representation allows us to systematically discover perceptually relevant image features for human translucency perception. Together, our findings reveal that learning the scale-specific statistical structure of natural images might be crucial for humans to efficiently represent material properties across contexts.

Hypoxia preconditioned DPSC-derived exosomes regulate angiogenesis via transferring LOXL2.

Hypoxia was proved to enhance the angiogenesis of stem cells. However, the mechanism of the angiogenic potential in hypoxia-pretreated dental pulp stem cells (DPSCs) is poorly understood. We previously confirmed that hypoxia enhances the angiogenic potential of DPSC-derived exosomes with upregulation of lysyl oxidase-like 2 (LOXL2). Therefore, our study aimed to illuminate whether these exosomes promote angiogenesis via transfer of LOXL2. Exosomes were generated from hypoxia-pretreated DPSCs (Hypo-Exos) stably silencing LOXL2 after lentiviral transfection and characterized with transmission electron microscopy, nanosight and Western blot. The efficiency of silencing was verified using quantitative real-time PCR (qRT-PCR) and Western blot. CCK-8, scratch and transwell assays were conducted to explore the effects of LOXL2 silencing on DPSCs proliferation and migration. Human umbilical vein endothelial cells (HUVECs) were co-incubated with exosomes to assess the migration and angiogenic capacity through transwell and matrigel tube formation assays. The relative expression of angiogenesis-associated genes was characterized by qRT-PCR and Western blot. LOXL2 was successfully silenced in DPSCs and inhibited DPSC proliferation and migration. LOXL2 silencing in Hypo-Exos partially reduced promotion of HUVEC migration and tube formation and inhibited the expression of angiogenesis-associated genes. Thus, LOXL2 is one of various factors mediating the angiogenic effects of Hypo-Exos.

Crystal or jelly? Effect of color on the perception of translucent materials with photographs of real-world objects.

Translucent materials are ubiquitous in nature (e.g. teeth, food, and wax), but our understanding of translucency perception is limited. Previous work in translucency perception has mainly used monochromatic rendered images as stimuli, which are restricted by their diversity and realism. Here, we measure translucency perception with photographs of real-world objects. Specifically, we use three behavior tasks: binary classification of "translucent" versus "opaque," semantic attribute rating of perceptual qualities (see-throughness, glossiness, softness, glow, and density), and material categorization. Two different groups of observers finish the three tasks with color or grayscale images. We find that observers' agreements depend on the physical material properties of the objects such that translucent materials generate more interobserver disagreements. Further, there are more disagreements among observers in the grayscale condition in comparison to that in the color condition. We also discover that converting images to grayscale substantially affects the distributions of attribute ratings for some images. Furthermore, ratings of see-throughness, glossiness, and glow could predict individual observers' binary classification of images in both grayscale and color conditions. Last, converting images to grayscale alters the perceived material categories for some images such that observers tend to misjudge images of food as non-food and vice versa. Our result demonstrates that color is informative about material property estimation and recognition. Meanwhile, our analysis shows that mid-level semantic estimation of material attributes might be closely related to high-level material recognition. We also discuss individual differences in our results and highlight the importance of such consideration in material perception.

MODECP: A Multi-Objective Based Approach for Solving Distributed Controller Placement Problem in Software Defined Network.

Software-Defined Network is an emerging networking paradigm that enables intelligent and flexible network management. Specifically, the design of the control plane is crucial. Therefore, in order to avoid a single point of failure, multiple controllers are deployed constantly in a distributed manner on the control plane. In this paper, we propose a controller placement approach based on multiple objectives (MODECP), including network delay, network security, load-balancing rate, and link occupancy. In the controller placement stage, an improved multi-objective differential evolution algorithm is proposed to search for controllers' positions and assign switches to controllers reasonably. Furthermore, an improved affinity propagation algorithm is proposed to obtain the number of controllers placed in the network partition stage, comprehensively considering the delay, node security, and load. Simulations are performed based on several topologies from Internet Topology Zoo. Extensive results show that the proposed algorithm can realize trade-offs among multiple objectives and improve network performance in delay, security, controller load, and link occupancy compared to the single-objective based approach. Moreover, compared with the genetic algorithm and random placement algorithm, the proposed algorithm performs better with low latency, high security, low load rate, and low link overhead.

Metabolomics reveals a correlation between hydroxyeicosatetraenoic acids and allergic asthma: Evidence from three years' immunotherapy.

BACKGROUND: Subcutaneous immunotherapy (SCIT) is an effective, safe, preventative treatment for allergic asthma; however, potential biomarkers for monitoring SCIT have rarely been reported. OBJECTIVE: Metabolomics was utilized for the discovery of new biomarkers and analyzing disease pathophysiology of allergic asthma, and it was also applied to determine the metabolomic profiles of serum samples from children with asthma undergoing SCIT and identify potential biomarkers for allergic asthma and its therapeutic monitoring. METHODS: Untargeted metabolomics using ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry was performed on 15 asthmatic and 15 healthy pediatric sera to profile carboxylic acids. Statistical analysis combined with pathway enrichment analysis was applied to identify potential biomarkers. Then, targeted metabolomics was performed to study longitudinal changes of eicosanoid profiles on sera from 20 participants with asthma who received SCIT at baseline, 6 months, one, two, and three years (ChiCTR-DDT-13003728). RESULTS: Metabolomic analysis revealed that levels of eicosanoids, particularly 12(S)-hydroxyeicosatetraenoic acid (HETE; AUC = 0.94, p < .0001) and 15(S)-HETE (AUC = 0.89, p = .0028), metabolized from arachidonic acid by lipoxygenase and glutathione peroxidase enzymes, were significantly higher in asthma group than in healthy individuals. Furthermore, levels of these important metabolites increased in the first year of SCIT treatment and then decreased from years one to three, being significantly lower after three years of treatment than baseline levels. CONCLUSION: 12(S)- and 15(S)-HETEs are potential biomarkers to participate in the pathogenesis and treatment of allergic asthma. Moreover, these metabolites may be a new target for biological indicators to monitor the therapeutic effect of SCIT, particularly in the setting of allergic asthma.

Serum levels of specific immunoglobulin E to Dermatophagoides pteronyssinus allergen components in patients with allergic rhinitis or/and asthma.

Background: House-dust mites (HDM) allergen is one of the most important allergens in southern China; however, studies on the Dermatophagoides pteronyssinus components are relatively lacking. Objective: This study analyzed the molecular components of D. pteronyssinus in patients with allergic asthma (AS) and/or allergic rhinitis (AR) sensitized to D. pteronyssinus, and aimed to improve HDM immunotherapy in southern China. Methods: Allergen component-resolved diagnosis detection technology was used to detect the serum levels of specific immunoglobulin E (sIgE) to D. pteronyssinus allergen components (Der p 1, 2, 3, 5, 7, 10, and 23) in patients who were sensitized to D. pteronyssinus and with AR (n = 106), AS (n = 144), or AR combined with AS (n = 134). Results: The highest positive rates of D. pteronyssinus components were Der p 1 (94.8%), followed by Der p 2 (77.6%), Der p 23 (62.5%), Der p 7 (34.6%), Der p 5 (17.7%), Der p 10 (12.2%), and Der p 3 (2.6%). Patients with AR+AS had the highest positive rates to Der p 2 (85.8%), Der p 23 (62.7%), Der p 7 (40.3%), Der p 5 (25.0%), and Der p 10 (16.4%). Der p 1 had the highest positive rate in patients with AR (95.3%). The Der p 3 positive rate in patients with AS (6.0%) was higher than that in patients with AR (0.0%, χ² = 6.872, p < 0.05) and patients with AR+AS (0.7%, χ² = 6.063, p < 0.05) Among the patients with AR+AS, 19.1% were co-sensitized to Der p 1, Der p 2, Der p 23, and Der p 7. Interestingly, only one patient with AR was exclusively sensitized to Der p 23. An optimal scale analysis showed that Der p 5, Der p 23, and Der p 7 had strong connection (Cronbach α = 93.7%). Conclusion: Der p 1 and Der p 2 were the main sensitization components of D. pteronyssinus, and patients with AS+AR had the highest positive rate for five of seven D. pteronyssinus allergen components. This research can provide suggestions for personalized HDM-specific immunotherapy in southern China.

Identifying Potential Co-Sensitization and Cross-Reactivity Patterns Based on Component-Resolved Diagnosis.

BACKGROUND: Component-Resolved diagnosis (CRD) can help to establish immunoglobulin E (IgE) sensitization profiles and potential risks and determines whether specific IgE is the result of primary sensitization or cross-reactivity, especially for those who are polysensitized. METHODS: We recruited 432 patients with mite-sensitized respiratory allergic diseases to study the co-sensitization and cross-reactivity of the 17 allergen components in Guangdong Province, China, using the CRD method and to describe the potential association between allergen components. RESULTS: Among the 432 patients, serum specific immunoglobulin E of the 17 components were tested by EUROIMMUN system. Der p 1 (81.48%), Der f 2 (77.78%), Der f 1 (74.07%), Der p 2 (66.20%) and Der p 23 (54.63%) were the main sensitized components in patients with mite-sensitized respiratory allergy, while the components of cockroach, crab, and shrimp had a lower positive rate. In the crude extract allergen-positive samples, Der f 2 (91.06%) and Der f 1 (86.72%) were the major sensitized components of Der f, while Der p 1 (94.52%), Der p 2 (78.36%), Der p 23 (63.29%) were the major sensitized components of Der p, And other components of Der p such as Der p 7 (34.25%), Der p 5 (17.81%), Der p 10 (12.05%), Der p 3 (1.92%) were all below 50.00%. Blo t 5 (54.55%) was one of the major components of Blo t. The positive rates of all Bla g components were as follows, rBla g 2 (15.56%) >rBla g 5 (8.89%) >rBla g 4 (4.44%) >rBla g 1 (1.11%). The positive rate of the only available pen a 1 component was 9.43%. Using hierarchical cluster and optimal scale analysis, 17 components can be roughly divided into 5 different sensitization clusters. Also, from the results of the Venn diagram, the allergen component in each cluster has a high proportion of co-sensitization and cross-reactivity. Regardless of age, total IgE levels, and disease type factors, similar sensitization profiles were observed for each component in the same category based on hierarchical clustering analysis. CONCLUSIONS: Epidemiological data on allergen components causing allergic symptoms can be further understood using CRD. Der p 1, Der p 2, Der p 23, Der f 1, Der f 2 as the primary sensitizing component of the study cohort. The positive rate for Blo t 5 was 28.01% for all populations and 54.45% for Blo t-positive samples. In addition, CRD allows us to identify more potential allergen associations such as common sensitivities and cross-reactions between component proteins. Based on these results, we suggest that when patients are identified as sensitized to a particular allergen, clinicians can pay more attention to other allergy components that are closely related to it.

Serum SP-A and KL-6 levels can predict the improvement and deterioration of patients with interstitial pneumonia with autoimmune features.

BACKGROUND: Some patients with interstitial pneumonia with autoimmune features (IPAF) showed a progressive course despite therapy. This study aimed to evaluate whether serial changes in the serum levels of surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) can predict disease progression. METHODS: Sixty-four patients with IPAF and 41 patients with non-fibrotic lung disease (non-FLD) were examined. Based on long-term changes in lung function, 36 IPAF patients who were followed up for more than 3 months were divided into a progressive group (n = 9), an improvement group (n = 13), and a stable group (n = 14). Serum KL-6 and SP-A levels were measured. The sensitivity, specificity, cut-off value, and area under the curve (AUC) value for each of the indices were determined using receiver operating characteristic (ROC) curve analysis. The expression differences in these biomarkers and their correlation with disease severity were analyzed. RESULTS: Compared with non-FLD patients, serum SP-A and KL-6 levels in IPAF patients were increased significantly [SP-A: (p < 0.001); KL-6: (p < 0.001)] and negatively correlated with DLCO (SP-A: rS = - 0.323, p = 0.018; KL-6: rS = - 0.348, p = 0.0011). In patients with progressive disease, the posttreatment serum SP-A and KL-6 levels were increased significantly compared with pretreatment levels [SP-A: (p = 0.021); KL-6: (p = 0.008)]. In patients showing improvement, the levels were decreased significantly [SP-A (p = 0.007) and KL-6 (p = 0.002)]. Changes in serum biomarkers (Delta SP-A and Delta KL-6) were significantly negatively correlated with changes in lung function (Delta FVC, Delta DLCO and Delta FEV1) (rS = 0.482, p < 0.05). A significant positive correlation was found between Delta SP-A and Delta KL-6 (rS = 0.482, p < 0.001). CONCLUSIONS: Serum SP-A and KL-6 offer high sensitivity and specificity for the diagnosis of IPAF. The decrease in serum SP-A and/or KL-6 levels in patients with IPAF is related to the improvement in pulmonary function. SP-A and KL-6 may be important biomarkers for predicting disease progression in patients with IPAF.

Shrimp and cockroach co-sensitization in Southern China: Association with moth sensitization.

Background: Moth is a common allergen in southern China. Shrimp sensitization might be related to the moth allergen. Objective: This study investigated sensitization to moth allergen in patients in southern China sensitized to shrimp and explored the effect of moth sensitization on different allergic diseases. Methods: Serum samples from 212 patients sensitized to shrimp were tested for specific immunoglobulin E (sIgE) to Dermatophagoides pteronyssinus, crab, cockroach, and moth. Results: The patients sensitized to shrimp were co-sensitized to D. pteronyssinus (88.7%), crab (85.4%), cockroach (89.2%), and moth (92.0%). Overall, 75% of the patients sensitized to shrimp tested positive to the above allergens; only four patients were sensitized to shrimp alone. The median (interquartile range [IQR]) concentrations of sIgE to shrimp (2.66 kU/L [1.02-6.11 kU/L] versus 1.61 kU/L [0.70-3.67 kU/L]), crab (2.35 kU/L [0.83-4.18 kU/L] versus 1.30 kU/L [0.59-3.14 kU/L]), cockroach (3.78 kU/L [0.98-6.91 kU/L] versus 1.56 kU/L [0.85-3.17 kU/L]), and moth (4.70 kU/L [2.98-9.62 kU/L] versus 2.85 kU/L [1.16-7.01 kU/L]) in patients with skin allergic diseases was significantly higher than in patients with respiratory allergic diseases (all p < 0.05). The median (IQR) concentration of sIgE to cockroach in the young adults (2.33 kU/L [0.86-5.56 kU/L]) was the highest among all age groups as well as to moth (young adults: 4.14 kU/L [1.93-8.24 kU/L]). With the increasing positive class of shrimp allergen, the sIgE concentration of moth, cockroach, and crab also increased, and the optimal scaling analysis showed that the sIgE of crab, cockroach, and moth had a strong correlation with sIgE to shrimp (Cronbach α = 93.8%). Conclusion: This study found a high rate of co-sensitization between moth, D. pteronyssinus, cockroach, and crab among patients sensitized to shrimp and a strong correlation between shrimp, moth, and cockroach. Shrimp and cockroach co-sensitization might be related to moth allergens.

Co-sensitization and cross-reactivity of Blomia tropicalis with two Dermatophagoides species in Guangzhou, China.

BACKGROUND: Contradictory results have been reported previously in the analyses of cross-reactivity among Blomia tropicalis (Blo t), Dermatophagoides pteronyssinus (Der p), and Dermatophagoides farinae (Der f). This study aims to investigate the characteristics of co-sensitization and the IgE cross-reactivity among them and attempts to identify whether patients are sensitized to Blo t due to cross-reaction or true sensitization. METHODS: Specific IgE (sIgE) in the sera from 1497 allergenic patients was determined by ImmunoCAP. Cross-reactivity was analyzed and determined by sIgE inhibition with 21 sera samples. RESULTS: Around 85.50% of patients were sensitized to Der p, 85.37% of patients were sensitized to Der f, and 71.54% of patients were sensitized to Blo t. Further, 70.14% of patients were co-sensitized to Blo t, Der p, and Der f, and only seven patients were sensitized solely to Blo t. With increasing sIgE levels for Blo t, the positive rates of severe-level (class 5-6) co-sensitization to Der p or Der f significantly increased. Blo t was moderately associated with Der p and Der f, with correlation coefficients of 0.6998 and 0.6782, respectively. Der p and Der f inhibited IgE binding to Blo t more strongly than Blo t inhibited IgE binding to Der p or Der f in the patient groups CBlo t  < CDer p and CBlo t  < CDer f . CONCLUSIONS: This study has established valuable information about the co-sensitization and cross-reactivity of Blo t with two Dermatophagoides species (Der p and Der f) and helps to provide adequate diagnosis and treatment of the mite-allergic patients.

Visualize and quantify the structural alteration of the rat spinal cord injury based on multiphoton microscopy.

The development of imaging technique to visualize and quantify the structural alteration of the spinal cord injury (SCI) may lead to better understanding and treatments of the injuries. In this work, multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) was tentatively applied to quantitatively visualize the cellular microstructures of SCI to demonstrate the feasibility and superiority of MPM in SCI imaging. High-contrast MPM images of normal and injured spinal cord tissue were obtained for comparison. Moreover, the changes of injured spinal cord were characterized by the quantitative analysis of the MPM images. These results showed that MPM combined with quantitative method has the ability to identify the characteristics of spinal cord injury including the changes in the contents of nerve fibers and extracellular matrix. With the advancement of MPM, we believe that this technique has great potential to provide the histological diagnosis for the monitoring and evaluation of SCI.

Longitudinal Brain Functional Connectivity Changes of the Cortical Motor-Related Network in Subcortical Stroke Patients with Acupuncture Treatment.

In clinical practice, the effectiveness of the rehabilitation therapy such as acupuncture combining conventional Western medicine (AG) on stroke people's motor-related brain network and their behaviors has not been systematically studied. In the present study, seventeen adult ischemic patients were collected and divided into two groups: the conventional Western medicine treatment group (CG) and the AG. The neurological deficit scores (NDS) and resting-state functional MRI data were collected before and after treatment. Compared with the CG patients, AG patients exhibited a significant enhancement of the percent changes of NDS from pre- to posttreatment intervention. All patients showed significant changes of functional connectivity (FC) between the pair of cortical motor-related regions. After treatment, both patient groups showed a recovery of brain connectivity to the nearly normal level compared with the controls in these pairs. Moreover, a significant correlation between the percent changes of NDS and the pretreatment FC values of bilateral primary motor cortex (M1) in all patients was found. In conclusion, our results showed that AG therapy can be an effective means for ischemic stroke patients to recover their motor function ability. The FC strengths between bilateral M1 of stroke patients can predict stroke patients' treatment outcome after rehabilitation therapy.

Probing the Link Between Vision and Language in Material Perception Using Psychophysics and Unsupervised Learning.

We can visually discriminate and recognize a wide range of materials. Meanwhile, we use language to express our subjective understanding of visual input and communicate relevant information about the materials. Here, we investigate the relationship between visual judgment and language expression in material perception to understand how visual features relate to semantic representations. We use deep generative networks to construct an expandable image space to systematically create materials of well-defined and ambiguous categories. From such a space, we sampled diverse stimuli and compared the representations of materials from two behavioral tasks: visual material similarity judgments and free-form verbal descriptions. Our findings reveal a moderate but significant correlation between vision and language on a categorical level. However, analyzing the representations with an unsupervised alignment method, we discover structural differences that arise at the image-to-image level, especially among materials morphed between known categories. Moreover, visual judgments exhibit more individual differences compared to verbal descriptions. Our results show that while verbal descriptions capture material qualities on the coarse level, they may not fully convey the visual features that characterize the material's optical properties. Analyzing the image representation of materials obtained from various pre-trained data-rich deep neural networks, we find that human visual judgments' similarity structures align more closely with those of the text-guided visual-semantic model than purely vision-based models. Our findings suggest that while semantic representations facilitate material categorization, non-semantic visual features also play a significant role in discriminating materials at a finer level. This work illustrates the need to consider the vision-language relationship in building a comprehensive model for material perception. Moreover, we propose a novel framework for quantitatively evaluating the alignment and misalignment between representations from different modalities, leveraging information from human behaviors and computational models.

Mechanisms of Peitu Yimu acupuncture in repairing intestinal mucosal barrier by regulating CRF/CRFR1 pathway in diarrhea-predominant irritable bowel syndrome rats. / 培土抑木针法调节CRF/CRFR1é€šè·¯ä¿®å¤è ¹æ³»åž‹è‚ æ˜“æ¿€ç»¼åˆå¾å¤§é¼ è‚ é»è†œå±éšœçš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To investigate the effect of Peitu Yimu(strengthening spleen and soothing liver) acupuncture on intestinal mucosal barrier function and corticotropin-releasing factor (CRF)/CRF receptor 1 (CRFR1) pathway in rats with diarrhea-predominant irritable bowel syndrome (IBS-D), so as to explore its underlying mechanism in alleviating IBS-D. METHODS: Forty female SD rats were randomly divided into blank, model, electroacupuncture (EA), and agonist groups, with 10 rats in each group. Except for the blank group, rats in the other groups were given folium sennae infusion by gavage combined with chronic unpredictable mild stress to establish IBS-D model. Rats in the EA group received acupuncture at "Tianshu"(ST25) and EA at "Zusanli"(ST36) and "Taichong"(LR3) (2 Hz/15 Hz) on one side for 20 min, with the side chosen alternately every other day, for 14 days after modeling. Rats in the agonist group received acupuncture 30 min after intravenous injection of CRFR1 agonist urocortin, with the same manipulation method and time as the EA group. Before and after intervention, visceral pain threshold and stool Bristol scores were measured. Elevated plus maze test and open field test were used to detect anxiety and depression like behavior of rats. ELISA was used to detect the contents of CRF and CRFR1 in rats serum. Immunohistochemistry was used to detect the positive expressions of CRF, CRFR1, zonula occludens protein 1(ZO-1), occlusal protein(Occludin), and closure protein 1 (Claudin-1) in colon tissue. RESULTS: Compared with the blank group, the visceral pain threshold, open arm time percentage (OT%), total distance of movement in the open field test, and positive expression of ZO-1, Occludin, and Claudin-1 in colon were decreased (P<0.01, P<0.05), while Bristol stool scores, serum CRF and CRFR1 contents, and positive expressions of CRF and CRFR1 in colon were increased (P<0.01) in the model group. After intervention and compared with the model group, the visceral pain threshold, OT%, total distance of movement in the open field test, and positive expressions of ZO-1, Occludin, and Claudin-1 in colon were increased (P<0.05, P<0.01), while Bristol stool scores, serum CRF and CRFR1 contents, and positive expressions of CRF and CRFR1 in colon were decreased (P<0.01) in the EA group；the Bristol stool scores, serum CRF content, and CRF positive expression in colon were significantly decreased in the agonist group (P<0.01). CONCLUSIONS: Peitu Yimu acupuncture can significantly improve visceral hypersensitivity and anxiety-depression state in IBS-D rats. Its mechanism may be related to the inhibition of CRF/CRFR1 pathway and restoration of intestinal tight junction protein expressions.

Unraveling ferroptosis in osteogenic lineages: implications for dysregulated bone remodeling during periodontitis progression.

Periodontitis is a highly prevalent disease characterized by inflammation and destruction of tooth-supporting tissues that leads to tooth loss in extreme situations. Elucidating the underlying mechanisms of periodontitis pathogenesis and progression will establish the groundwork for developing effective treatment strategies. Recently, evidence concerning the role of ferroptosis in periodontitis progression has emerged. Osteogenic lineage cells are key regulators of bone remodeling. Osteogenic cell death, as observed in experimental periodontitis models, disrupts the balance between bone resorption and bone formation. However, whether the osteogenic lineage undergoes ferroptosis during periodontitis and the corresponding effect on periodontitis progression remain elusive. Here, we investigated cell-specific ferroptosis within the alveolar bone in a murine periodontitis model. Through immunofluorescence double staining and immunohistochemistry, we identified ferroptotic osteocytes and osteoblasts in inflammatory alveolar bone. Next, in vivo administration of erastin or liproxstatin-1 was conducted to either induce or inhibit ferroptosis, respectively. Severe bone resorption and inflammation, accompanied by increased osteoclast formation and impaired osteogenic potential were detected following ferroptosis activation. Subsequently, we carried out in vitro experiments on osteocytes and further verified that ferroptosis enhanced the osteocytic expression of RANKL and IL-6. These findings suggest that ferroptosis occurring within the osteogenic lineage acts as a catalyst in the progression of periodontitis by stimulating osteoclastogenesis through the secretion of inflammatory cytokines and inhibiting osteoblastic function, providing insights into ferroptosis-induced alterations in microenvironment-based intercellular communication. Ferroptosis is a promising target for controlling inflammation and preventing bone resorption in periodontitis.

Single-cell RNA sequencing combined with proteomics of infected macrophages reveals prothymosin-α as a target for treatment of apical periodontitis.

INTRODUCTION: Chronic apical periodontitis (CAP) is a common infectious disease of the oral cavity. Immune responses and osteoclastogenesis of monocytes/macrophages play a crucial role in CAP progression, and this study want to clarify role of monocytes/macrophages in CAP, which will contribute to treatment of CAP. OBJECTIVES: We aim to explore the heterogeneity of monocyte populations in periapical lesion of CAP tissues and healthy control (HC) periodontal tissues by single-cell RNA sequencing (scRNA-seq), search novel targets for alleviating CAP, and further validate it by proteomics and in vitro and in vivo evaluations. METHODS: ScRNA-seq was used to analyze the heterogeneity of monocyte populations in CAP, and proteomics of THP-1-derived macrophages with porphyromonas gingivalis infection were intersected with the differentially expressed genes (DEGs) of macrophages between CAP and HC tissues. The upregulated PTMA (prothymosin-α) were validated by immunofluorescence staining and quantitative real time polymerase chain reaction. We evaluated the effect of thymosin α1 (an amino-terminal proteolytic cleavage product of PTMA protein) on inflammatory factors and osteoclast differentiation of macrophages infected by P. gingivalis. Furthermore, we constructed mouse and rat mandibular bone lesions caused by apical periodontitis, and estimated treatment of systemic and topical administration of PTMA for CAP. Statistical analyses were performed using GraphPad Prism software (v9.2) RESULTS: Monocytes were divided into seven sub-clusters comprising monocyte-macrophage-osteoclast (MMO) differentiation in CAP. 14 up-regulated and 21 down-regulated genes and proteins were intersected between the DEGs of scRNA-seq data and proteomics, including the high expression of PTMA. Thymosin α1 may decrease several inflammatory cytokine expressions and osteoclastogenesis of THP-1-derived macrophages. Both systemic administration in mice and topical administration in the pulp chamber of rats alleviated periapical lesions. CONCLUSIONS: PTMA upregulation in CAP moderates the inflammatory response and prevents the osteoclastogenesis of macrophages, which provides a basis for targeted therapeutic strategies for CAP.

RAB27B-regulated exosomes mediate LSC maintenance via resistance to senescence and crosstalk with the microenvironment.

The fate of leukaemia stem cells (LSCs) is determined by both their inherent mechanisms and crosstalk with their niches. Although LSCs were confirmed to be eradicated by restarting senescence, the specific key regulators of LSC resistance to senescence and remodelling of the niche to obtain a microenvironment suitable for stemness remain unknown. Here, we found that RAB27B, a gene regulating exosome secretion, was overexpressed in LSCs and associated with the poor prognosis of acute myeloid leukaemia (AML) patients. The increased RAB27B in LSCs prevented their senescence and maintained their stemness in vitro and in vivo. Mechanically, the increased RAB27B expression in LSCs selectively promoted the loading and release of exosomes rich in senescence-inducing proteins by direct combination. Furthermore, RAB27B-regulated LSC-derived exosomes remodelled the niche and induced senescence of mesenchymal stem cells (MSCs) with increased RAB27B expression ex vivo and in vivo. The increased RAB27B in the senescent MSCs conversely promoted LSC maintenance ex vivo and in vivo via selective excretion of exosomes rich in stemness-promoting proteins. Therefore, we identified the specifically increased RAB27B in LSCs and their educated senescent MSCs as a hub molecule for LSC resistance to senescence and maintenance through crosstalk with its niche via selective exosome excretion.

The Effects and Potential Mechanisms of Moxibustion for Rheumatoid Arthritis-Related Pain: A Randomized, Controlled Trial.

Purpose: To investigate the effects of moxibustion in relieving pain, and other clinical symptoms for patients with rheumatoid arthritis (RA), and explore the potential mechanism of moxibustion treatment for RA. Patients and Methods: Seventy qualified RA patients were randomly assigned in a 1:1 ratio to the moxibustion group or the routine group. The routine group only took oral methotrexate tablets and folic acid tablets. The moxibustion group was treated with moxibustion based on oral pharmaceutical. Moxibustion was performed two times weekly for 8 weeks, a total of 16 sessions. Patients scored their pain on a visual analog scale (VAS). The American College of Rheumatology improvement criteria of 20%, 50% and 70% (ACR20, ACR50 and ACR70) after treatment were investigated. Clinical symptoms, a disease activity score using 28 joint counts (DAS28), simplified disease activity index (SDAI), clinical disease activity index (CDAI), health assessment questionnaire (HAQ), interleukin 1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) of RA patients were analyzed before and after treatment. Results: After treatment, the VAS scores, tender and swollen joint counts, morning stiffness scores, disease activity scores (DAS28, SDAI, CDAI), HAQ scores in the two groups were both improved, and the effects of moxibustion group were more obvious (P < 0.05). The ACR20 and ACR50 of the moxibustion group were greater than that of the routine group (P < 0.05), no significant difference of the ACR70 existed between the two groups (P > 0.05). In addition, the decreases of IL-1ß, TNF-α, VEGF of the moxibustion group were better than that of the routine group (P < 0.05). Conclusion: Moxibustion could effectively relieve pain, ameliorate the clinical symptoms, and decrease the disease activity of RA. The potential mechanism may be the decrease in the level of serum inflammatory factors.

A study of allergen detection panel in Guangzhou, southern China based on real-world data from the past 7 years.

This study aims to reduce the cost of allergen testing for Guangzhou, China by limiting the number of allergens for which patients are tested, and provide a testing panel to improve diagnostic and therapeutic efficiency. This retrospective study of real-world data from 2012 to 2019 included 39,570 patients with suspected allergies in Guangzhou, southern China. All the patients were tested for one or more of the following allergens serum specific immunoglobulin E (sIgE): Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat dander, dog dander, Artemisia vulgaris, Aspergillus fumigatus, Alternaria alternata, Blattella germanica, egg whites, milk, wheat, peanuts, soybeans, Cancer pagurus, and Penaeus monodon by PhadiaCAP 1000. Totally, only the positive rates of allergens sIgE in D. farinae, D. pteronyssinus, milk, egg whites, B. germanica, C. pagurus, A. alternata, and P. monodon were > 10%, the other allergens were between 4-7%. Moreover, among the allergic diseases, dust mites exhibited the overall highest positive rate, followed by milk and B. germanica. In children, milk was the main allergen, whereas in adults, mites, cockroaches, shrimp, and crab allergens had higher positive rates. The optimal scale analysis shows that the multiple sensitization classification of patients can be divided into three categories: I D. farinae and D. pteronyssinus; II. C. pagurus, P. monodon, and B. germanica; III. Milk and egg whites. Generally, a panel including 4 allergens can detect > 90% of the potential allergy in this local population. In Guangzhou, southern China, D. farinae, milk, B. germanica, and A. alternata as a panel screening allergy for suspected allergic patients was suggested base on this study.

The Impact and Correlation of Anxiety and Depression on Pressure Pain Threshold of Acupoints in Patients with Chronic Pelvic Inflammatory Disease.

Background: Chronic pelvic inflammatory disease (CPID) is a clinically common gynecological disease. Patients experience chronic pelvic pain and often accompany with emotional dysfunction. However, the impact and correlation of anxiety and depression on pain sensitization is not completely known. Objective: To explore the differences and correlations among anxiety, depression, and pressure pain threshold (PPT) of acupoints in patients with CPID. Methods: One hundred and forty-seven patients with CPID were recruited. The Visual Analog Scale (VAS) and short-form McGill Pain Questionnaire (SF-MPQ) were used to assess pain. Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were used to evaluate the emotional state of patients. The PPT of acupoints was collected using an electronic Von Frey by two licensed acupuncturists. Results: The CPID patients were divided into anxiety-depression group (group A) or nonanxiety-depression group (group B), according to the SAS and SDS scores. Finally, there were 73 patients in group A and 74 patients in group B. Group A had significantly higher SAS, SDS, VAS, and SF-MPQ scores than group B (P < 0.05). In addition, significant differences were observed in the PPTs of ST28 (R), ST29 (R), SP10 (R), SP9 (R), SP9 (L), ST36 (R), and LR3 (L) between the two groups (P < 0.05). No considerable differences in PPTs at the other acupoints were observed between the two groups. SAS scores showed a positive correlation with PPTs of ST29 (R), SP10 (R), SP9 (L), ST36 (R), and LR3 (L). No remarkable correlation was observed between the SDS scores and PPTs. Conclusion: Anxiety and depression can affect the PPT of some acupoints in CPID patients, which may provide a reference for acupoint selection for acupuncture treatment of CPID with emotional disorders. This trial is registered with ChiCTR2100052632.