The protective effects of Chromofungin in oligomeric amyloid ß42 (Aß42)-induced toxicity in neurons in Alzheimer's disease.

Oligomeric Aß42 is considered to play a harmful role in the pathophysiology of Alzheimer's disease (AD). Prolonged exposure to oligomeric Aß42 could induce neuronal damage including cellular senescence. Amelioration of Aß42-induced cellular senescence has been considered as a promising strategy for the treatment of AD. Chromofungin, a chromogranin A-derived peptide, has displayed various biological functions in different types of cells and tissues. However, the effects of Chromofungin on oligomeric Aß42-induced cellular senescence have not been previously reported. In the current study, we report a novel function of Chromofungin by showing that treatment with Chromofungin could ameliorate Aß42-induced neurotoxicity in M17 neuronal cells. The Cell Counting Kit-8 (CCK-8) assay and the lactate dehydrogenase (LDH) release experiments revealed that 0.5 and 1 mM are the optimal concentrations of Chromofungin for cell culture in M17 cells. Challenging with oligomeric Aß42 (5 µM) for 7 and 14 days led to a significant decrease in telomerase activity, which was rescued by Chromofungin dose-dependently. Additionally, the senescence-associated ß-galactosidase (SA-ß-gal) staining assay demonstrated that Chromofungin mitigated oligomeric Aß42-induced cellular senescence. Correspondingly, treatment with Chromofungin reversed the gene expression of human telomerase reverse transcriptase (hTERT), telomeric repeat-binding factor 2 (TERF2), and p21 against oligomeric Aß42 in M17 neurons. Interestingly, Chromofungin attenuated oligomeric Aß42-induced oxidative stress (OS) in M17 cells by reducing the production of intracellular reactive oxygen species (ROS) but increasing the levels of intracellular superoxide dismutase (SOD). Importantly, the presence of Chromofungin reduced the expression of cyclooxygenase2 (COX-2) as well as the generation of prostaglandin E2 (PGE2). Transduction with Ad-COX-2 impaired the effects of Chromofungin on telomerase activity and the profile of cellular senescence. Our findings suggest that Chromofungin might act as a potential agent for the treatment of AD.

Bioinformatics analysis and experimental verification of the cancer-promoting effect of DHODH in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a malignant tumor of the urinary system. To explore the potential mechanisms of DHODH in ccRCC, we analyzed its molecular characteristics using public databases. TCGA pan-cancer dataset was used to analyze DHODH expression in different cancer types and TCGA ccRCC dataset was used to assess differential expression, prognosis correlation, immune infiltration, single-gene, and functional enrichment due to DHODH. The GSCALite and CellMiner databases were employed to explore drugs and perform molecular docking analysis with DHODH. Protein-protein interaction networks and ceRNA regulatory networks of DHODH were constructed using multiple databases. The effect of DHODH on ccRCC was confirmed in vitro. DHODH was highly expressed in ccRCC. Immune infiltration analysis revealed that DHODH may be involved in regulating the infiltration of immunosuppressive cells such as Tregs. Notably, DHODH influenced ccRCC progression by forming regulatory networks with molecules, such as hsa-miR-26b-5p and UMPS and significantly enhanced the malignant characteristics of ccRCC cells. Several drugs, such as lapatinib, silmitasertib, itraconazole, and dasatinib, were sensitive to DHODH expression and exhibited strong molecular binding with it. Thus, DHODH may promote ccRCC progression and is a candidate effective therapeutic target for ccRCC.

Mid-term Clinical Outcomes of "Light Bulb" Core Decompression with Arthroscopic Assistance in Peri-collapse Osteonecrosis of the Femoral Head: A Retrospective Comparative Study.

OBJECTIVE: Nontraumatic osteonecrosis of the femoral head (ONFH) is commonly encountered in orthopedics. Without early clinical intervention, most patients with peri-collapse of the ONFH will develop femoral head necrosis and eventually require hip replacement surgery. The aim of this study is to evaluate clinical outcomes in patients with ONFH who underwent "light bulb" core decompression (CD) with arthroscopic assistance and to compare them with the outcomes of those treated with traditional procedures. METHODS: A retrospective review of patients with Stage II and IIIA (Peri-collapse) radiographic findings based on the Association Research Circulation Osseous (ARCO) stage for ONFH who underwent "light bulb" CD with or without arthroscopic assistance by a single-surgeon team between March 2014 and December 2018 was performed. All patients were followed up for a minimum of 2 years. The visual analogue scale (VAS) pain score, Harris hip score (HHS), and radiological imaging were evaluated. The categorical parameters were analyzed by chi-square test and the continuous variables conforming to a normal distribution were analyzed by Student's t-test. RESULTS: The study included a total of 39 patients (18 and 21 patients in the with and without arthroscopic assistance groups, respectively), with a mean age of 40.3 years and a mean follow-up of 22.2 months. Overall, there was a better VAS score in the arthroscopic assistance group than in the control group (p < 0.05), There was a significant difference in HHS (80.1 ± 9.2 vs 75.1 ± 12.7) at the last follow-up (p < 0.05). The rate of good and excellent outcomes was 94%. Similarly, there was no significant difference in the total rate of complications or conversion to THA. CONCLUSION: With arthroscopic assistance, "light bulb" CD could be achieved via hip arthroscopy with less trauma, and it offered the opportunity for more precise evaluation and monitoring for therapy and yielded better VAS scores after surgery and better hip function outcomes at the last follow-up.

Effects of Geo-Stress and Natural Fracture Strength on Hydraulic Fracture Propagation in a Deep Fractured Tight Sandstone Reservoir.

Hydraulic fracturing technology has been widely used in the tight reservoir reconstruction. Unfortunately, with the deepening of mining depth and the increase of geo-stress, the propagation mechanism of medium-pressure fractures in the reservoir is significantly different from that of conventional shallow reservoirs. Based on the combined finite discrete element method, this paper conducts numerical simulation research on deep tight sandstone reservoirs in the west. The discrete fracture network modeling method is used to establish a tight sandstone reservoir model with natural bedding, and the influence of geo-stress difference and natural fracture strength on hydraulic fracture propagation law in a high geo-stress environment is discussed in detail. The results show that the difference between geo-stress and the strength of natural fractures has a significant effect on the shape and expansion of hydraulic fractures under the high geo-stress conditions. The greater the difference in ground stress, the more obvious the tendency of the main fractures of the reservoir, and the shorter the branch fractures. With the increase of natural fracture strength, the changes in propagation pressure, fracture length, area, and width, which can be fitted with a linear function with a goodness of fit as high as 0.99. In addition, the morphological results of hydraulic fractures in the simulation are not only affected by the constitutive parameters of the model but also may be affected by the randomness of the natural fracture network, thus, showing a certain degree of dispersion. Therefore, it is extremely necessary to build a reservoir fracturing model in a specific area based on more detailed geological monitoring data to guide actual construction. The above achievements have certain reference significance for the field operation of deep tight sandstone reservoirs.

Proxy Importance Based Haptic Retargeting With Multiple Props in VR.

In virtual reality applications, in addition to visual feedback, real objects can be used as props for virtual objects to provide passive haptic feedback, which greatly enhances user immersion. Usually, real object props are not one-to-one correspondence with virtual objects. Haptic retargeting technique is proposed to establish the virtual-real correspondence by introducing an offset between the virtual hand and the real hand. Sometimes, the offset is too large to cause user discomfort, and it is necessary to introduce a reset between two haptic retargeting operations to force the virtual hand and the real hand to coincide in order to eliminate the offset. However, too many resets can interfere with this immersion. To address this problem, we propose a haptic retargeting method based on proxy importance calculation using multiple props in virtual reality. The concept of proxy importance for props is introduced first, and then a proxy importance based prop selection and placement method for moving virtual objects are proposed. We also improve the performance of our method by using the props' weighted proxy importance strategy for multi-user collaboration. Compared to the state-of-the-art methods, our method significantly reduces the number of resets, the task completion time, hand movement distances, and task load without the cost of cybersickness in the single-user task. In the multi-user collaborative task, our method also achieves significant improvement using the strategy that weights the proxy importance of the props.

Differential effects of oxytetracycline on detoxification and antioxidant defense in the hepatopancreas and intestine of Chinese mitten crab under cadmium stress.

This study aims to evaluate the effects of oxytetracycline (OTC) on detoxification and oxidative defense in the hepatopancreas and intestine of Chinese mitten crab (Eriocheir sinensis) under cadmium (Cd) stress. The crab was exposed to 0.6 µM Cd, 0.6 µM OTC, and 0.6 µM Cd plus 0.6 µM OTC for 42 days. Our results showed that in the intestine, OTC alone enhanced protein carboxylation (PC) and malondialdehyde (MDA) contents, which was associated with the increased OTC accumulation. Compared to Cd alone, Cd plus OTC increased Cd and OTC contents, and reduced detoxification (i.e., glutathione (GSH) content, gene expressions of cytochrome P450 (CYP) isoforms, 7-ethoxyresorufin O-deethylase (EROD) activity, mRNA levels and activities of glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)), and antioxidant defense (i.e., gene expressions and activities of catalase (CAT) and superoxide dismutase (SOD)) in the intestine, leading to the increased in PC and MDA contents, suggesting that OTC had a synergistic effect on Cd-induced oxidative damage. In the hepatopancreas, although OTC alone increased OTC accumulation, it did not affect PC and MDA contents. Compared to Cd alone, Cd plus OTC reduced MDA content, which was closely related to the improvement of detoxification (i.e., GSH content, mRNA levels of CYP isoforms, EROD activity, gene expressions and activities of GPx, GR and GST), and antioxidant defense (gene expressions and activities of CAT and SOD, metallothionein content). Aryl hydrocarbon receptor (AhR) and nuclear factor E2-related factor 2 (Nrf2) transcriptional expressions were positively correlated with most detoxification- and antioxidant-related gene expressions, respectively, indicating that AhR and Nrf2 were involved in the regulation of these gene expressions. Our results unambiguously demonstrated that OTC had tissue-specific effects on Cd-induced toxicological effect in E. sinensis, which contributed to accurately evaluating Cd toxicity modulated by TCs in crab.

Experimental analysis and safety assessment of thermal runaway behavior in lithium iron phosphate batteries under mechanical abuse.

Mechanical abuse can lead to internal short circuits and thermal runaway in lithium-ion batteries, causing severe harm. Therefore, this paper systematically investigates the thermal runaway behavior and safety assessment of lithium iron phosphate (LFP) batteries under mechanical abuse through experimental research. Mechanical abuse experiments are conducted under different conditions and battery state of charge (SOC), capturing force, voltage, and temperature responses during failure. Subsequently, characteristic parameters of thermal runaway behavior are extracted. Further, mechanical abuse conditions are quantified, and the relationship between experimental conditions and battery characteristic parameters is analyzed. Finally, regression models for battery safety boundaries and the degree of thermal runaway risk are established. The research results indicate that the extracted characteristic parameters effectively reflect internal short circuit (ISC) and thermal runaway behaviors, and the regression models provide a robust description of the battery's safety boundaries and thermal runaway risk degree. This work sheds light on understanding thermal runaway behavior and safety assessment methods for lithium-ion cells under mechanical abuse.

Methods to increase the diagnostic efficiency of endoscopic ultrasound-guided fine-needle aspiration for solid pancreatic lesions: An updated review.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a means to procure adequate specimens for histological and cytologic analysis. The ideal EUS-FNA should be safe, accurate, and have a high sample adequacy rate and low adverse events rate. In recent years, many guidelines and trials on EUS-FNA have been published. The purpose of this article is to provide an update on the influence of some of the main factors on the diagnostic efficiency of EUS-FNA as well as a rare but serious complication known as needle tract seeding.

Using firefly algorithm to optimally size a hybrid renewable energy system constrained by battery degradation and considering uncertainties of power sources and loads.

In this paper, the planning of a hybrid system of wind turbine units, photovoltaic panels, and battery storage is presented by taking into account the limitation of the storage degradation. The scheme minimizes the construction and maintenance cost of power sources and storage equipment. The constraints of the problem include the operating model of the mentioned elements, the limitation of the number of the mentioned elements, the limitation of the storage degradation, and the power balance in the hybrid system. This scheme is subject to uncertainties of the demand and output power generation of wind turbines and photovoltaics, which are modeled using a scenario-based stochastic optimization. The problem has a mixed-integer non-linear structure, and the paper adopts the firefly algorithm to solve the problem. The contributions of the paper include considering the degradation model of the battery, presenting a stochastic modelling for planning the islanded system, and taking into account the uncertainties of load and renewable power. Finally, based on the numerical results, a low planning cost is obtained for the hybrid system in the case of using renewable resources. Batteries are capable of providing flexibility for the hybrid system so that they can cover oscillations of renewable power with respect to the load. The firefly algorithm can find a reliable optimal solution. Stochastic modeling raises the planning cost of the islanded system in comparison to the deterministic model, but it yields a more reliable solution. The battery degradation model incurs no additional costs in system planning, although it offers a far more precise representation of the battery's behavior.

Interpretable conservation laws as sparse invariants.

Discovering conservation laws for a given dynamical system is important but challenging. In a theorist setup (differential equations and basis functions are both known), we propose the sparse invariant detector (SID), an algorithm that autodiscovers conservation laws from differential equations. Its algorithmic simplicity allows robustness and interpretability of the discovered conserved quantities. We show that SID is able to rediscover known and even discover new conservation laws in a variety of systems. For two examples in fluid mechanics and atmospheric chemistry, SID discovers 14 and 3 conserved quantities, respectively, where only 12 and 2 were previously known to domain experts.

Mohawk protects against tendon damage via suppressing Wnt/ß-catenin pathway.

Degenerative tendon injuries are common clinical problems associated with overuse or aging, and understanding the mechanisms of tendon injury and regeneration can contribute to the study of tendon healing and repair. As a transcription factor, Mohawk (Mkx) is responsible for tendons development, yet, the roles of which in tendon damage remain mostly elusive. In this study, using Mkx overexpressed mice on long treadmill as an in vivo model and MkxOE Achilles tenocytes stimulated by equiaxial stretch as an in vitro model, we anaylsed the effects of Mkx overexpression on the tendon. Mkx and tendon tension strength were decreased after the expose to excessive mechanical forces, and Mkx overexpression protected the tendon from damage. Moreover, we revealed that the Wnt/ß-catenin activation, inflammation, and Runx2 expression were increased at the injured Achilles tendon, upregulated Mkx significantly reversed the increased Wnt/ß-catenin pathway, Tnf-α, Il-1ß, and Il-6 levels, and reduced tendon cell damage. However, Wnt3a, IWR and BIO had not significantly affected the Mkx expression in achilles tenocytes. In conclusion, Mkx is involved in tendon healing and protects the tendon from damage through suppressing Wnt/ß-catenin pathway, suggesting Mkx/Wnt/ß-catenin pathway may be potential therapeutic targets for tendon damage.

Dopamine regulates colonic glial cell-derived neurotrophic factor secretion through cholinergic dependent and independent pathways.

BACKGROUND AND PURPOSE: Glial cell-derived neurotrophic factor (GDNF) maintains gut homeostasis. Dopamine promotes GDNF release in astrocytes. We investigated the regulation by dopamine of colonic GDNF secretion. EXPERIMENTAL APPROACH: D1 receptor knockout (D1 R-/- ) mice, adeno-associated viral 9-short hairpin RNA carrying D2 receptor (AAV9-shD2 R)-treated mice, 6-hydroxydopamine treated (6-OHDA) rats and primary enteric glial cells (EGCs) culture were used. Incubation fluid from colonic submucosal plexus and longitudinal muscle myenteric plexus were collected for GDNF and ACh measurements. KEY RESULTS: D2 receptor-immunoreactivity (IR), but not D1 receptor-IR, was observed on EGCs. Both D1 receptor-IR and D2 receptor-IR were co-localized on cholinergic neurons. Low concentrations of dopamine induced colonic GDNF secretion in a concentration-dependent manner, which was mimicked by the D1 receptor agonist SKF38393, inhibited by TTX and atropine and eliminated in D1 R-/- mice. SKF38393-induced colonic ACh release was absent in D1 R-/- mice. High concentrations of dopamine suppressed colonic GDNF secretion, which was mimicked by the D2 receptor agonist quinpirole, and absent in AAV-shD2 R-treated mice. Quinpirole decreased GDNF secretion by reducing intracellular Ca2+ levels in primary cultured EGCs. Carbachol ( ACh analogue) promoted the release of GDNF. Quinpirole inhibited colonic ACh release, which was eliminated in the AAV9-shD2 R-treated mice. 6-OHDA treated rats with low ACh and high dopamine content showed decreased GDNF content and increased mucosal permeability in the colon. CONCLUSION AND IMPLICATIONS: Low concentrations of dopamine promote colonic GDNF secretion via D1 receptors on cholinergic neurons, whereas high concentrations of dopamine inhibit GDNF secretion via D2 receptors on EGCs and/or cholinergic neurons.

UTDNet: A unified triplet decoder network for multimodal salient object detection.

Image Salient Object Detection (SOD) is a fundamental research topic in the area of computer vision. Recently, the multimodal information in RGB, Depth (D), and Thermal (T) modalities has been proven to be beneficial to the SOD. However, existing methods are only designed for RGB-D or RGB-T SOD, which may limit the utilization in various modalities, or just finetuned on specific datasets, which may bring about extra computation overhead. These defects can hinder the practical deployment of SOD in real-world applications. In this paper, we propose an end-to-end Unified Triplet Decoder Network, dubbed UTDNet, for both RGB-T and RGB-D SOD tasks. The intractable challenges for the unified multimodal SOD are mainly two-fold, i.e., (1) accurately detecting and segmenting salient objects, and (2) preferably via a single network that fits both RGB-T and RGB-D SOD. First, to deal with the former challenge, we propose the multi-scale feature extraction unit to enrich the discriminative contextual information, and the efficient fusion module to explore cross-modality complementary information. Then, the multimodal features are fed to the triplet decoder, where the hierarchical deep supervision loss further enable the network to capture distinctive saliency cues. Second, as to the latter challenge, we propose a simple yet effective continual learning method to unify multimodal SOD. Concretely, we sequentially train multimodal SOD tasks by applying Elastic Weight Consolidation (EWC) regularization with the hierarchical loss function to avoid catastrophic forgetting without inducing more parameters. Critically, the triplet decoder separates task-specific and task-invariant information, making the network easily adaptable to multimodal SOD tasks. Extensive comparisons with 26 recently proposed RGB-T and RGB-D SOD methods demonstrate the superiority of the proposed UTDNet.

The Distal Fascicle of the Anterior Inferior Tibiofibular Ligament: A Potential Landmark for Lateral Ankle Ligament Reconstruction.

BACKGROUND: A reliable landmark and precise distances from the ligament attachments are needed for lateral ankle stabilization surgery. The distal fascicle of the anterior inferior tibiofibular ligament (AITFL) has been used to locate the anterior talofibular ligament (ATFL) or calcaneofibular ligament (CFL) centers on the fibula. However, there is no anatomic study to validate the distal fascicle of the AITFL as a landmark of lateral ankle ligament stabilization, and more importantly, the exact distances from the ATFL or CFL attachments to the distal fascicle of the AITFL are unknown. METHODS: Sixteen frozen cadaveric specimens (8 paired specimens) with no previous history of ankle injury were used in this study. Whether the distal fascicle of AITFL was present in each specimen was confirmed. Then, the distances from the most distal insertion of the AITFL's distal fascicle to the footprint centers of the ATFL and CFL on the fibula were measured. All measurements were performed by 2 observers, and the intraobserver and interobserver reliabilities were analyzed by intraclass correlation coefficients (ICCs). RESULTS: The distal fascicle of the AITFL was found in all specimens (100%). The mean distance from the most distal insertion of the AITFL's distal fascicle to the footprint centers of the ATFL, CFL, and the intersection center of the 2 ligaments on the fibula was 6.0 to 7.1 mm, 11.5 to 13.2 mm, and 9.0 to 10.0 mm, respectively. Excellent interobserver and intraobserver agreement (all ICCs > 0.9, P < .01) was shown in the anatomic measurements of these distances. CONCLUSION: In this cadaveric study, we found that the distal fascicle was a constant structure of the AITFL in the lateral ankle. The distances from the most distal insertion of the AITFL's distal fascicle to the ligamentous footprint centers were reliable and may be used to identify the origins of the ATFL and CFL for lateral ankle ligament reconstruction. CLINICAL RELEVANCE: This anatomic study validates the AITFL's distal fascicle as a potential landmark and, more importantly, determines the range of distances from AITFL's distal fascicle to the attachment centers of lateral ankle ligaments by anatomic measurements. The data may be used to identify the ATFL and CFL for lateral ankle stabilization surgery and become particularly valuable for endoscopic or arthroscopic techniques.

Standardized construction of a porcine model for acute obstructive jaundice and training of endoscopic ultrasound-guided choledochoduodenostomy.

Background: Endoscopic ultrasound-guided biliary drainage (EUS-BD) is an alternative to endoscopic retrograde cholangiopancreatography (ERCP) for patients with obstructive jaundice. However, it is still a challenge for many endoscopists because of its novelty and complexity. This study aimed to establish an ideal bile duct dilatation model for the training and practice of endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS). Methods: The 34 healthy Bama miniature pigs were divided into the part of developing the standardized EUS-CDS (n=9) and the part of trainees training (n=25). Part one, two different methods were used to clip Vater's ampulla using metal clips to establish an extrahepatic bile duct dilatation model. Part two, five trainees were trained on EUS-CDS with 25 pigs. Following a 2-week observation period, the feasibility and effectiveness of the technique were evaluated. Results: In the group with three metal clips perpendicular to the duodenal wall clipping Vater's ampulla, the success rate of extrahepatic bile duct dilation greater than 1 cm in 24 h was 5/6, whereas the remaining one pig was 48 h. All five trainees can finally complete the EUS-CDS independently. No death occurred during the 2-week observation period. Conclusion: Clipping Vater's ampulla with three metal clips perpendicular to the duodenal wall is an effective and stable method to create a porcine bile duct dilatation model.

Phillyrin ameliorates influenza a virus-induced pulmonary inflammation by antagonizing CXCR2 and inhibiting NLRP3 inflammasome activation.

Influenza is an acute viral respiratory illness with high morbidity rates worldwide. Excessive pulmonary inflammation is the main characteristic of lethal influenza A virus (IAV) infections. Therapeutic options for managing influenza are limited to vaccines and some antiviral medications. Phillyrin is one of the major bioactive components of the Chinese herbal medicine Forsythia suspensa, which has the functions of sterilization, heat clearing and detoxification. In this work, the effect and mechanism of phillyrin on H1N1 influenza (PR8)-induced pneumonia were investigated. We reported that phillyrin (15 mg/kg) treatment after viral challenge significantly improved the weight loss, ameliorated pulmonary inflammation and inhibited the accumulation of multiple cytokines and chemokines in bronchoalveolar lavage fluid on 7 days post infection (dpi). In vitro, phillyrin suppressed influenza viral replication (Matrixprotein and nucleoprotein messenger RNA level) and reduced influenza virus-induced cytopathic effect (CPE). Furthermore,chemokine receptor CXCR2 was confirmed to be markedly inhibited by phillyrin. Surface plasmon resonance results reveal that phillyrin exhibits binding affinity to CXCR2, having a binding affinity constant (KD) value of 1.858e-5 M, suggesting that CXCR2 is a potential therapeutic target for phillyrin. Moreover, phillyrin inhibited the mRNA and protein expression levels of Caspase1, ASC and NLRP3 in the lungs of mice with H1N1-induced pneumonia.This study reveals that phillyrin ameliorates IAV-induced pulmonary inflammation by antagonizing CXCR2 and inhibiting NLRP3 inflammasome activation partly.

A preliminary study for the clinical effect of one combinational physiotherapy and its potential influence on gut microbial composition in children with Tourette syndrome.

Introduction: Tourette syndrome (TS) is a chronic neuropsychiatric disorder with unknown causes and inadequate therapies. Inspired by the important roles of gut microbiota in some mental illnesses, the interactions between gut microbiota and TS via the gut-brain axis have gained more and more attention. This study aimed to characterize the gut microbial profiles in children with TS, and explore the clinical effects of one combinational physiotherapy and its potential influence on gut microbial composition. Methods: The gut microbial profiles were depicted based on the sequence data of 32 patients and 29 matched health children by 16S rDNA amplicon pyrosequencing. Thirty of thirty-two patients underwent uninterrupted two 10-day courses of combinational physiotherapy, which included a 60-minute cranial electrotherapy stimulation (CES) training followed by a 30-minute biofeedback training per session, 2 sessions a day. Results: Our results indicated that the gut microbial composition in children with TS was different from that in healthy controls. Multiple GBM neurotransmitter modules obtained through Picrust2 functional predictive analysis were significantly increased in patients, including Histamine degradation, Dopamine degradation, and DOPAC synthesis. Moreover, this combinational physiotherapy could significantly diminish tic activity, whose positive effects were first reported in children with TS. Lastly, different gut microbial compositions and predictive metabolic pathways were also observed between patients before and after this treatment, with lower abundances of the genera (e.g., Dorea) and significant decreases of GBM neurotransmitter modules (e.g. dopamine degradation) in patients after this treatment, indicating that improved clinical symptoms might be accompanied by an improvement of intestinal microenvironment. Discussion: Children with TS showed a cognizable gut microbial profile, and certain enriched bacteria with pro-inflammatory potential might induce neuroinflammatory responses. This combinational physiotherapy could significantly diminish tic activity, and the gut microbial compositions in patients after this treatment were different from those without any treatment, indicating the existence of bidirectional communication of the gut-brain axis in TS. But studies on the gut microbial characteristics in TS patients, the influences of gut microbiota on tic severity, the efficacy and safety of this treatment, and the bidirectional regulatory mechanism between brain signals and gut microbiota in TS still need to be explored.

Interlocking Evaluation of Mesoscopic Skeleton with the Compaction Degree of Hot-Mix Asphalt.

Asphalt mixtures are multi-phase composites composed of aggregates, bitumen, mineral powders, and voids, and various structures are intertwined during the compaction process. Most of the traditional research focuses on the macro-scale domain, and it is difficult to obtain the internal structure of asphalt mixture in different compaction processes. With the continuous development of digital image technology, the influence of the meso-structure of the asphalt mixture on the compaction quality of the asphalt mixture has become a new means to evaluate the performance of the asphalt mixture. In this paper, different numbers of compactions are selected to represent different stages in the compaction process, the digital images of specimens in different compaction stages are obtained by industrial CT scanning technology. Then, the images are processed and reconstructed in three dimensions using improved image segmentation methods, and the position characteristics and geometric information of coarse aggregate are obtained by combining the Oriented Bounding Box (OBB). The meso-response characteristics of the skeleton structure of the asphalt mixture during compaction were studied. The influence of the internal structure of the mixture on the compaction quality of the mixture was obtained, which is of great significance for the study of improving the durability of the pavement. The results show that the "effective coordination number" (the number of aggregate particles that can transmit force in the skeleton structure) is greatly related to the aggregate size. With the compaction process, the centroid of coarse aggregate in the upper layer of the specimen reflects the overall downward movement trend. The inclination angle of the aggregate spindle tends to be in the range of 80°~100°; the anisotropic amplitude of the xy plane increases, and the direction of the aggregate spindle becomes more and more consistent. With the increase in the number of rotational compactions, these four parameters showed obvious rules, indicating that this meso-characteristic index could well characterize the compaction quality of the asphalt mixture in the compaction process.