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Background/Aims: Metabolic syndrome is common in patients with acute pancreatitis and its components have been reported to be associated with infectious complications. In this post hoc analysis, we aimed to evaluate whether metabolic abnormalities impact the effect of immune-enhancing thymosin alpha-1 (Tα1) therapy in acute necrotizing pancreatitis (ANP) patients. Methods: All data were obtained from the database for a multicenter randomized clinical trial that evaluated the efficacy of Tα1 in ANP patients. Patients who discontinued the Tα1 treatment prematurely were excluded. The primary outcome was 90-day infected pancreatic necrosis (IPN) after randomization. Three post hoc subgroups were defined based on the presence of hyperglycemia, hypertriglyceridemia, or both at the time of randomization. In each subgroup, the correlation between Tα1 and 90-day IPN was assessed using the Cox proportional-hazards regression model. Multivariable propensity-score methods were used to control potential bias. Results: Overall, 502 participants were included in this post hoc analysis (248 received Tα1 treatment and 254 received matching placebo treatment). Among them, 271 (54.0%) had hyperglycemia, 371 (73.9%) had hypertriglyceridemia and 229 (45.6%) had both. Tα1 therapy was associated with reduced incidence of IPN among patients with hyperglycemia (18.8% vs 29.7%: hazard ratio, 0.80; 95% confidence interval, 0.37 to 0.97; p=0.03), but not in the other subgroups. Additional multivariate regression models using three propensity-score methods yielded similar results. Conclusions: Among ANP patients with hyperglycemia, immune-enhancing Tα1 treatment was associated with a reduced risk of IPN (ClinicalTrials.gov, Registry number: NCT02473406).

Abstract Typical weak signal search experiments rely on resonant effects, where the resonance frequency is scanned over a broad range, resulting in significant time consumption. In this study, we demonstrate an accelerated strategy that surpasses the typical resonance-bandwidth limited scan step without compromising sensitivity. We apply this method to an alkali-noble-gas spin system, achieving an approximately 30-fold increase in scanning step size. Additionally, we obtain an ultrahigh sensitivity of 1.29 fT ⋅ Hz−1/2 at around 5 Hz, corresponding to an energy resolution of approximately 1.8 × 10−23eV ⋅ Hz−1/2, which is among the highest quantum energy resolutions reported. Furthermore, we use this sensor to search for axion-like particles, setting stringent constraints on axion-like particles (ALPs) in the 4.5–15.5 Hz Compton-frequency range coupling to neutrons and protons, improving on previous limits by several-fold. This accelerated strategy has potential applications in other resonant search experiments.

Quantum non-demolition measurement with an off-resonance polarized probe is a widely utilized technique for atomic sensors. We observe previously unexplored spin-alignment polarization induced by the far-detuned off-resonance linear probe in an ultrasensitive optical polarimetry. The evolution of probe-generated multipole moments exacerbates probe noise due to strong magnetic couplings. We demonstrate a method to decouple spin-alignment from magnetic fields by manipulating the multipole moments in zero-fields. The probe noise is suppressed by 10 dB with the proposed method, achieving a noise floor at the standard quantum limit. The realized shot-noise-limited optical polarimetry holds significant promise for atomic sensors aimed at ultra-sensitivity.

Duchenne muscular dystrophy (DMD) is an X-linked recessive progressive degenerative disease of skeletal muscle, characterized by intramuscular inflammation, muscle regeneration disorder and replacement of muscle with fibroadipose tissue. DMD is caused by the absence of normal dystrophy. Impaired self-renew ability and limited differentiation capacity of satellite cells are proved as main reasons for muscle regeneration failure. The deficiency of estrogen impedes the process of muscle regeneration. However, the role of estrogen receptor β (ERβ) in muscle regeneration is still unclear. This study aims to investigate the role and the pharmacological effect of ERβ activation on muscle regeneration in mdx mice. This study showed that mRNA levels of ERβ and myogenic-related genes both witnessed increasing trends in dystrophic context. Our results revealed that treatment with selective ERβ agonist (DPN, diarylpropionitrile) significantly increased myogenic differentiation 1 (MyoD-1) level and promoted muscle regeneration in mdx mice. Similarly, in mdx mice with muscle-specific estrogen receptor α (ERα) ablation, DPN treatment still promoted muscle regeneration. Moreover, we demonstrated that myoblasts differentiation was accompanied by raised nuclear accumulation of ERβ. DPN treatment augmented the nuclear accumulation of ERβ and, thus, contributed to myotubes formation. One important finding was that forkhead box O3A (FOXO3A), as a pivotal transcription factor in Myod-1 transcription, participated in the ERβ-promoted muscle regeneration. Overall, we offered an interesting explanation about the crucial role of ERβ during myogenesis.

Abstract Background Ischemic stroke presents a significant threat to human health due to its high disability rate and mortality. Currently, the clinical treatment drug, rt-PA, has a narrow therapeutic window and carries a high risk of bleeding. There is an urgent need to find new effective therapeutic drugs for ischemic stroke. Icariin (ICA), a key ingredient in the traditional Chinese medicine Epimedium, undergoes metabolism in vivo to produce Icaritin (ICT). While ICA has been reported to inhibit neuronal apoptosis after cerebral ischemia-reperfusion (I/R), yet its underlying mechanism remains unclear. Methods PC-12 cells were treated with 200 µM H2O2 for 8 h to establish a vitro model of oxidative damage. After administration of ICT, cell viability was detected by Thiazolyl blue tetrazolium Bromide (MTT) assay, reactive oxygen species (ROS) and apoptosis level, mPTP status and mitochondrial membrane potential (MMP) were detected by flow cytometry and immunofluorescence. Apoptosis and mitochondrial permeability transition pore (mPTP) related proteins were assessed by Western blotting. Middle cerebral artery occlusion (MCAO) model was used to establish I/R injury in vivo. After the treatment of ICA, the neurological function was scored by ZeaLonga socres; the infarct volume was observed by 2,3,5-Triphenyltetrazolium chloride (TTC) staining; HE and Nissl staining were used to detect the pathological state of the ischemic cortex; the expression changes of mPTP and apoptosis related proteins were detected by Western blotting. Results In vitro: ICT effectively improved H2O2-induced oxidative injury through decreasing the ROS level, inhibiting mPTP opening and apoptosis. In addition, the protective effects of ICT were not enhanced when it was co-treated with mPTP inhibitor Cyclosporin A (CsA), but reversed when combined with mPTP activator Lonidamine (LND). In vivo: Rats after MCAO shown cortical infarct volume of 32–40%, severe neurological impairment, while mPTP opening and apoptosis were obviously increased. Those damage caused was improved by the administration of ICA and CsA. Conclusions ICA improves cerebral ischemia-reperfusion injury by inhibiting mPTP opening, making it a potential candidate drug for the treatment of ischemic stroke. Graphical Abstract

Affect-biased attention is the phenomenon of prioritizing attention to emotionally salient stimuli and away from goal-directed stimuli. It is thought that affect-biased attention to emotional stimuli is a driving factor in the development of depression. This effect has been well-studied in adults, but research shows that this is also true during adolescence, when the severity of depressive symptoms are correlated with the magnitude of affect-biased attention to negative emotional stimuli. Prior studies have shown that trainings to modify affect-biased attention may ameliorate depression in adults, but this research has also been stymied by concerns about reliability and replicability. This study describes a clinical application of augmented reality-guided EEG-based attention modification (“AttentionCARE”) for adolescents who are at highest risk for future depressive disorders (i.e., daughters of depressed mothers). Our results (n = 10) indicated that the AttentionCARE protocol can reliably and accurately provide neurofeedback about adolescent attention to negative emotional distractors that detract from attention to a primary task. Through several within and cross-study replications, our work addresses concerns about the lack of reliability and reproducibility in brain-computer interface applications, offering insights for future interventions to modify affect-biased attention in high-risk adolescents.

Abstract The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment. However, the sensitivity of existing detection techniques is not sufficient, and the criteria for evaluating optimal force have not been yet established. Here, by employing 3D finite element analysis methodology, we found that the apical distal region (A-D region) of mesial roots is particularly sensitive to orthodontic force in rats. Tartrate-resistant acidic phosphatase (TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams (g), leading to alveolar bone resorption and tooth movement. When the force reached 80 g, TRAP-positive osteoclasts started appearing on the root surface in the A-D region. Additionally, micro-computed tomography revealed a significant root resorption at 80 g. Notably, the A-D region was identified as a major contributor to whole root resorption. It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement, inclination, and hyalinization. These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model. Collectively, our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients’ orthodontic treatment.

In recent years, owing to the rapid advancements in deep learning, advanced object detection methods, such as You Only Look Once (YOLO) and Efficient Detector (EfficientDet), have been frequently used to detect underwater organisms. However, due to the complexity of underwater scenarios and deployment limitations, these models often encounter various challenges, such as blurred targets, occlusions, and high model computing costs. On this basis, we propose a YOLO network (CGC-YOLO) based on Cross-Stage Partial Convolutional Block Attention Module (CSPCBAM), Ghost module, and cluster non-maximum suppression (Cluster-NMS). Firstly, CSPCBAM enhances the model’s ability to extract intricate features by amplifying pertinent feature information across both channel and spatial dimensions. This augmentation contributes to an improved detection performance of the model, especially when dealing with fuzzy targets. Secondly, the Ghost module is employed to optimize the model’s efficiency by decreasing its parameters and reducing the computational load in terms of floating-point operations per second (FLOPs). Finally, by introducing Cluster-NMS and Score Penalty Mechanism (SPM) to reweight the confidence of bounding boxes, the model can retain the real object with occlusion. The experimental results show that on the Underwater Robot Picking Competition 2020 (URPC 2020) and brackish water dataset, the mAP@0.5 of our proposed CGC-YOLO reaches 87.2% and 98.6% respectively, which is at least 1 percentage point higher than all other models. The CGC-YOLO has 14.8 FLOPs and speeds of 7.1ms and 6.3ms, respectively, which is also better than all other models. Ablation experiments and qualitative analysis show that CGC-YOLO can deal with fuzzy and obscured objects well, with lower computational cost and faster inference speed.

Background: Early detection of Parkinson's disease (PD) patients at high risk for mild cognitive impairment (MCI) can help with timely intervention. White matter structural connectivity is considered an early and sensitive indicator of neurodegenerative disease. Objectives: To investigate whether baseline white matter structural connectivity features from diffusion tensor imaging (DTI) of de novo PD patients can help predict PD-MCI conversion at an individual level using machine learning methods. Methods: We included 90 de novo PD patients who underwent DTI and 3D T1-weighted imaging. Elastic net-based feature consensus ranking (ENFCR) was used with 1000 random training sets to select clinical and structural connectivity features. Linear discrimination analysis (LDA), support vector machine (SVM), K-nearest neighbor (KNN) and naïve Bayes (NB) classifiers were trained based on features selected more than 500 times. The area under the ROC curve (AUC), accuracy (ACC), sensitivity (SEN) and specificity (SPE) were used to evaluate model performance. Results: A total of 57 PD patients were classified as PD-MCI nonconverters, and 33 PD patients were classified as PD-MCI converters. The models trained with clinical data showed moderate performance (AUC range: 0.62–0.68; ACC range: 0.63–0.77; SEN range: 0.45–0.66; SPE range: 0.64–0.84). Models trained with structural connectivity (AUC range, 0.81–0.84; ACC range, 0.75–0.86; SEN range, 0.77–0.91; SPE range, 0.71–0.88) performed similar to models that were trained with both clinical and structural connectivity data (AUC range, 0.81–0.85; ACC range, 0.74–0.85; SEN range, 0.79–0.91; SPE range, 0.70–0.89). Conclusions: Baseline white matter structural connectivity from DTI is helpful in predicting future MCI conversion in de novo PD patients.

Table-based fact verification requests parsing table and statement structure and performing numerical and logical reasoning. Previous methods may select erroneous programs and ignore the interpretability of table-based fact verification. Thus, we propose a double graph attention network reasoning method based on filtering and program-like evidence (DGMFP). In detail, we initially obtain the filtering evidence based on tables and the program-like evidence based on logical forms to incorporate the semantic and symbolic information of evidence. Then, we construct an evidence graph with statement-evidence pairs as nodes and use the kernel in graph neural network to conduct more fine-grained joint reasoning and improve the interpretability of table-based fact verification. We also construct a connected graph with all entities and functions in the program-like evidence as nodes and use the graph attention network (GAT) to capture more fine-grained relationships within the program-like evidence. Finally, we connect the outputs of two GAT models and BERT model to predict labels. Experimental results on TABFACT show that DGMFP outperforms all baselines with 76.1% accuracy. Ablation studies further indicate that constructed two graphs, filtering evidence, and program-like evidence play an important role in better understanding the semi-structured table.

Abstract Freezing of gait (FOG) greatly impacts the daily life of patients with Parkinson’s disease (PD). However, predictors of FOG in early PD are limited. Moreover, recent neuroimaging evidence of cerebral morphological alterations in PD is heterogeneous. We aimed to develop a model that could predict the occurrence of FOG using machine learning, collaborating with clinical, laboratory, and cerebral structural imaging information of early drug-naïve PD and investigate alterations in cerebral morphology in early PD. Data from 73 healthy controls (HCs) and 158 early drug-naïve PD patients at baseline were obtained from the Parkinson’s Progression Markers Initiative cohort. The CIVET pipeline was used to generate structural morphological features with T1-weighted imaging (T1WI). Five machine learning algorithms were calculated to assess the predictive performance of future FOG in early PD during a 5-year follow-up period. We found that models trained with structural morphological features showed fair to good performance (accuracy range, 0.67–0.73). Performance improved when clinical and laboratory data was added (accuracy range, 0.71–0.78). For machine learning algorithms, elastic net-support vector machine models (accuracy range, 0.69–0.78) performed the best. The main features used to predict FOG based on elastic net-support vector machine models were the structural morphological features that were mainly distributed in the left cerebrum. Moreover, the bilateral olfactory cortex (OLF) showed a significantly higher surface area in PD patients than in HCs. Overall, we found that T1WI morphometric markers helped predict future FOG occurrence in patients with early drug-naïve PD at the individual level. The OLF exhibits predominantly cortical expansion in early PD.

Abstract Bone regeneration remains a great clinical challenge. Low intensity near-infrared (NIR) light showed strong potential to promote tissue regeneration, offering a promising strategy for bone defect regeneration. However, the effect and underlying mechanism of NIR on bone regeneration remain unclear. We demonstrated that bone regeneration in the rat skull defect model was significantly accelerated with low-intensity NIR stimulation. In vitro studies showed that NIR stimulation could promote the osteoblast differentiation in bone mesenchymal stem cells (BMSCs) and MC3T3-E1 cells, which was associated with increased ubiquitination of the core circadian clock protein Cryptochrome 1 (CRY1) in the nucleus. We found that the reduction of CRY1 induced by NIR light activated the bone morphogenetic protein (BMP) signaling pathways, promoting SMAD1/5/9 phosphorylation and increasing the expression levels of Runx2 and Osterix. NIR light treatment may act through sodium voltage-gated channel Scn4a, which may be a potential responder of NIR light to accelerate bone regeneration. Together, these findings suggest that low-intensity NIR light may promote in situ bone regeneration in a CRY1-dependent manner, providing a novel, efficient and non-invasive strategy to promote bone regeneration for clinical bone defects.

Introduction: With the global prevalence of coronavirus disease 2019 (COVID-19), an increasing number of people are experiencing respiratory discomfort. Respiratory biomechanics can monitor breathing patterns and respiratory movements and it is easier to prevent, diagnose, treat or rehabilitate. However, there is still a lack of global knowledge structure in the field of respiratory biomechanics. With the help of CiteSpace software, we aim to help researchers identify potential collaborators and collaborating institutions, hotspots and research frontiers in respiratory biomechanics.Methods: Articles on respiratory biomechanics from 2003 to 2022 were retrieved from the Web of Science Core Collection by using a specific strategy, resulting a total of 2,850 publications. We used CiteSpace 6.1.R6 to analyze the year of publication, journal/journals cited, country, institution, author/authors cited, references, keywords and research trends. Co-citation maps were created to visually observe research hot spots and knowledge structures.Results and discussion: The number of annual publications gradually increased over the past 20 years. Medical Physics published the most articles and had the most citations in this study. The United States was the most influential country, with the highest number and centrality of publications. The most productive and influential institution was Harvard University in the United States. Keall PJ was the most productive author and MCCLELLAND JR was the most cited authors The article by Keall PJ (2006) article (cocitation counts: 55) and the article by McClelland JR (2013) were the most representative and symbolic references, with the highest cocitation number and centrality, respectively. The top keywords were “radiotherapy”, “volume”, and “ventilation”. The top Frontier keywords were “organ motion,” “deep inspiration,” and “deep learning”. The keywords were clustered to form seven labels. Currently, the main area of research in respiratory biomechanics is respiratory motion related to imaging techniques. Future research may focus on respiratory assistance techniques and respiratory detection techniques. At the same time, in the future, we will pay attention to personalized medicine and precision medicine, so that people can monitor their health status anytime and anywhere.

Studies investigating the diversity and structure of soil microbial systems in response to ionizing radiation are scarce. In particular, effects of long-term low-dose radiation is rarely studied because of its unique conditions. In this study, an area in Chengdu, China, which has been irradiated by the radionuclide thorium-232 for more than 10 years was investigated. Four groups of samples with absorbed dose rates ranging from 192.906 ± 5.05 to 910.964 ± 41.09 nGy/h were collected to analyze the compositional and functional changes of the soil microbial systems in the region. The diversity and structure of the soil microbial systems were determined using high-throughput sequencing. Our results showed that long-term low-dose ionizing radiation had no significant effect on soil bacterial diversity, but had a great impact on fungal diversity. Long-term ionizing radiation strongly affected soil microbial community structure. Long-term low-dose ionizing radiation was shown to have a promoting effect on iron-oxidizing bacteria and ectomycorrhizal fungi and have an inhibiting effect on predatory or parasitic fungi, further affecting the soil C/N ratio. This study is of great reference significance for future research on the impact of long-term low-dose ionizing radiation on soil ecosystems.

Summary: Background: Immune-enhancing thymosin alpha 1 (Tα1) therapy may reduce infected pancreatic necrosis (IPN) in acute necrotising pancreatitis (ANP). However, the efficacy might be impacted by lymphocyte count due to the pharmacological action of Tα1. In this post-hoc analysis, we tested the hypothesis that pre-treatment absolute lymphocyte count (ALC) determines whether patients with ANP benefit from Tα1 therapy. Methods: A post-hoc analysis of data from a multicentre, double-blind, randomised, placebo-controlled trial testing the efficacy of Tα1 therapy in patients with predicted severe ANP was performed. Patients from 16 hospitals of China were randomised to receive a subcutaneous injection of Tα1 1.6 mg every 12 h for the frst 7 days and 1.6 mg once a day for the following 7 days or a matching placebo during the same period. Patients who discontinued the Tα1 regimen prematurely were excluded. Three subgroup analyses were conducted using the baseline ALC (at randomisation), and the group allocation was maintained as intention-to-treat. The primary outcome was the incidence of IPN 90 days after randomisation. The fitted logistic regression model was applied to identify the range of baseline ALC where Tα1 therapy could exert a maximum effect. The original trial is registered with ClinicalTrials.gov, NCT02473406. Findings: Between March 18, 2017, and December 10, 2020, a total of 508 patients were randomised in the original trial, and 502 were involved in this analysis, with 248 in the Tα1 group and 254 in the placebo group. Across the three subgroups, there was a uniform trend toward more significant treatment effects in patients with higher baseline ALC. Within the subgroup of patients with baseline ALC≥0.8 × 10ˆ9/L (n = 290), the Tα1 therapy significantly reduced the risk of IPN (covariate adjusted risk difference, −0.12; 95% CI, −0.21,-0.02; p = 0.015). Patients with baseline ALC between 0.79 and 2.00 × 10ˆ9/L benefited most from the Tα1 therapy in reducing IPN (n = 263). Interpretation: This post-hoc analysis found that the efficacy of immune-enhancing Tα1 therapy on the incidence of IPN may be associated with pretreatment lymphocyte count in patients with acute necrotising pancreatitis. Funding: National Natural Science Foundation of China.

Abstract Background Neuroinflammation-induced injury is intimately associated with poor prognosis in patients with cerebral venous sinus thrombosis (CVST). The cyclic GMP-AMP synthase–stimulator of interferon gene (cGAS–STING) axis is a cytoplasmic double-stranded DNA (dsDNA) sensing pathway has recently emerged as a crucial mediator of neuroinflammation in ischemic stroke. However, the role of the cGAS–STING pathway in modulating post-CVST inflammation and the underlying mechanisms involved remain unclear. Methods A CVST model was induced by ferric chloride in male C57BL/6J mice. The selective cGAS inhibitor RU.521, STING agonist 2′3′-cGAMP, and STING siRNA were delivered by intranasal administration or intraventricular injection. Post-CVST assessments included rotarod test, TUNEL staining, Fluoro-Jade C staining, dihydroethidium staining, western blotting, qPCR, immunofluorescence, immunohistochemistry, ELISA and flow cytometry. Results cGAS, STING, NLRP3 and GSDMD were significantly upregulated after CVST and mostly in the microglia of the mouse brain. CVST triggered the release of dsDNA into the cytoplasm and elicited an inflammatory response via activating the cGAS–STING axis. RU.521 decreased the levels of 2′3′-cGAMP, STING and downstream inflammatory cytokines, and suppressed the expressions of NLRP3 inflammasome and pyroptosis-pertinent components containing cleaved caspase-1, GSDMD, GSDMD-C, pro- and cleaved IL-1β, and cleaved IL-1β/pro-IL-1β. Besides, RU.521 treatment also reduced oxidative stress, lessened the numbers of microglia and neutrophils, and ameliorated neuronal apoptosis, degeneration along with neurological deficits post-CVST. 2′3'-cGAMP delivery enhanced the expressions of STING and related inflammatory mediators, NLRP3 inflammasome and pyroptosis-relevant proteins, whereas these alterations were significantly abrogated by the silencing of STING by siRNA. Conclusions Our data demonstrate that repression of the cGAS–STING pathway diminishes the neuroinflammatory burden of CVST and highlight this approach as a potential therapeutic tactic in CVST-mediated pathologies.

The highlighted energy consumption of Internet data center (IDC) in China has become a pressing issue with the implementation of the Chinese dual carbon strategic goal. This paper provides a comprehensive review of cooling technologies for IDC, including air cooling, free cooling, liquid cooling, thermal energy storage cooling and building envelope. Firstly, the environmental requirements for the computer room and the main energy consumption items for IDC are analyzed. The evaluation indicators and government policies for promoting green IDC are also summarized. Next, the traditional cooling technology is compared to four new cooling technologies to find effective methods to maximize energy efficiency in IDC. The results show that traditional cooling consumes a significant amount of energy and has low energy efficiency. The application of free cooling can greatly improve the energy efficiency of IDC, but its actual implementation is highly dependent on geographical and climatic conditions. Liquid cooling, on the other hand, has higher energy efficiency and lower PUE compared to other cooling technologies, especially for high heat density servers. However, it is not yet mature and its engineering application is not widespread. In addition, thermal energy storage (TES) based cooling offers higher energy efficiency but must be coupled with other cooling technologies. Energy savings can also be achieved through building envelope improvements. Considering the investment and recovery period for IDC, it is essential to seek efficient cooling solutions that are suitable for IDC and take into account factors such as IDC scale, climate conditions, maintenance requirements, etc. This paper serves as a reference for the construction and development of green IDC in China.

We aim to build a system incorporating electroencephalography (EEG) and augmented reality (AR) that is capable of identifying the presence of visual spatial neglect (SN) and mapping the estimated neglected visual field. An EEG-based brain-computer interface (BCI) was used to identify those spatiospectral features that best detect participants with SN among stroke survivors using their EEG responses to ipsilesional and contralesional visual stimuli. Frontal-central delta and alpha, frontal-parietal theta, Fp1 beta, and left frontal gamma were found to be important features for neglect detection. Additionally, temporal analysis of the responses shows that the proposed model is accurate in detecting potentially neglected targets. These targets were predicted using common spatial patterns as the feature extraction algorithm and regularized discriminant analysis combined with kernel density estimation for classification. With our preliminary results, our system shows promise for reliably detecting the presence of SN and predicting visual target responses in stroke patients with SN.

This article investigates an inverse problem for variable physical and mechanical comprehensive parameters. A back analysis method based on an improved BFGS (Broyden-Fletcher-Goldfarb Shanno-Newtonian iteration) and AC (adjustment coefficient) is proposed to estimate the physical and mechanical comprehensive parameters of complex concrete arch dam structures. These quasi-viscoelastic variable physical and mechanical comprehensive parameters of concrete arch dam structures are established based on in situ monitoring data and test results. By studying the constitutive model of concrete arch dam structures and the corresponding characterization method of the gradual changes of those parameters, a method utilizing adjustment coefficient is established to determine the initial values of the physical and mechanical comprehensive parameters and an adjoin method combined with BFGS Newtonian iteration method is proposed to inverse the variable physical and mechanical comprehensive parameters of concrete arch dam structures and analyze the variation regulation of these parameters. The proposed inversion analysis method was successfully implemented for the second-highest concrete double curvature arch dam. The results indicate that the proposed method has high precision and strong generalizability.

Summary: Background: Tumor-resident microbiota has been documented for various cancer types. Oral squamous cell carcinoma (OSCC) is also enriched with microbiota, while the significance of microbiota in shaping the OSCC microenvironment remains elusive. Methods: We used bioinformatics and clinical sample analysis to explore relationship between F. nucleatum and OSCC progression. Xenograft tumor model, metabolic screening and RNA sequencing were performed to elucidate mechanisms of pro-tumor role of F. nucleatum. Findings: We show that a major protumorigenic bacterium, F. nucleatum, accumulates in invasive margins of OSCC tissues and drives tumor-associated macrophages (TAMs) formation. The mechanistic dissection shows that OSCC-resident F. nucleatum triggers the GalNAc-Autophagy-TBC1D5 signaling, leading to GLUT1 aggregation in the plasma membrane and the deposition of extracellular lactate. Simultaneous functional inhibition of GalNAc and GLUT1 efficiently reduces TAMs formation and restrains OSCC progression. Interpretation: These findings suggest that tumor-resident microbiota affects the immunomodulatory and protumorigenic microenvironment via modulating glycolysis and extracellular lactate deposition. The targeted intervention of this process could provide a distinct clinical strategy for patients with advanced OSCC. Funding: This work was supported by the National Natural Science Foundation of China for Key Program Projects (82030070, to LC) and Distinguished Young Scholars (31725011, to LC), as well as Innovation Team Project of Hubei Province (2020CFA014, to LC).

ObjectiveTo explore alterations in white matter network topology in de novo Parkinson's disease (PD) patients with rapid eye movement sleep behavior disorder (RBD).Materials and MethodsThis study included 171 de novo PD patients and 73 healthy controls (HC) recruited from the Parkinson's Progression Markers Initiative (PPMI) database. The patients were divided into two groups, PD with probable RBD (PD-pRBD, n = 74) and PD without probable RBD (PD-npRBD, N = 97), according to the RBD screening questionnaire (RBDSQ). Individual structural network of brain was constructed based on deterministic fiber tracking and analyses were performed using graph theory. Differences in global and nodal topological properties were analyzed among the three groups. After that, post hoc analyses were performed to explore further differences. Finally, correlations between significant different properties and RBDSQ scores were analyzed in PD-pRBD group.ResultsAll three groups presented small-world organization. PD-pRBD patients exhibited diminished global efficiency and increased shortest path length compared with PD-npRBD patients and HCs. In nodal property analyses, compared with HCs, the brain regions of the PD-pRBD group with changed nodal efficiency (Ne) were widely distributed mainly in neocortical and paralimbic regions. While compared with PD-npRBD group, only increased Ne in right insula, left middle frontal gyrus, and decreased Ne in left temporal pole were discovered. In addition, significant correlations between Ne in related brain regions and RDBSQ scores were detected in PD-pRBD patients.ConclusionsPD-pRBD patients showed disrupted topological organization of white matter in the whole brain. The altered Ne of right insula, left temporal pole and left middle frontal gyrus may play a key role in the pathogenesis of PD-RBD.

Both catalase and peroxiredoxin show high activities of H2O2 decomposition and coexist in the same organism; however, their division of labor in defense against H2O2 is unclear. We focused on the major peroxiredoxin (PrxA) and catalase (CatB) in Aspergillus nidulans at different growth stages to discriminate their antioxidant roles. The dormant conidia lacking PrxA showed sensitivity to high concentrations of H2O2 (>100 mM), revealing that PrxA is one of the important antioxidants in dormant conidia. Once the conidia began to swell and germinate, or further develop to young hyphae (9 h to old age), PrxA-deficient cells (ΔprxA) did not survive on plates containing H2O2 concentrations higher than 1 mM, indicating that PrxA is an indispensable antioxidant in the early growth stage. During these early growth stages, absence of CatB did not affect fungal resistance to either high (>1 mM) or low (2O2. In the mature hyphae stage (24 h to old age), however, CatB fulfills the major antioxidant function, especially against high doses of H2O2. PrxA is constitutively expressed throughout the lifespan, whereas CatB levels are low in the early growth stage of the cells developing from swelling conidia to early growth hyphae, providing a molecular basis for their different contributions to H2O2 resistance in different growth stages. Further enzyme activity and cellular localization analysis indicated that CatB needs to be secreted to be functionalized, and this process is confined to the growth stage of mature hyphae. Our results revealed differences in effectiveness and timelines of two primary anti-H2O2 enzymes in fungus.

Abstract Background Transforming growth factor‐β‐activated kinase 1 (TAK1) plays a key role in regulating fibroblast and myoblast proliferation and differentiation. However, the TAK1 changes associated with Duchenne muscular dystrophy (DMD) are poorly understood, and it remains unclear how TAK1 regulation could be exploited to aid the treatment of this disease. Methods Muscle biopsies were obtained from control donors or DMD patients for diagnosis (n = 6 per group, male, 2–3 years, respectively). Protein expression of phosphorylated TAK1 was measured by western blot and immunofluorescence analysis. In vivo overexpression of TAK1 was performed in skeletal muscle to assess whether TAK1 is sufficient to induce or aggravate atrophy and fibrosis. To explore whether TAK1 inhibition protects against muscle damage, mdx (loss of dystrophin) mice were treated with adeno‐associated virus (AAV)‐short hairpin TAK1 (shTAK1) or NG25 (a TAK1 inhibitor). Serum analysis, skeletal muscle performance and histology, muscle contractile function, and gene and protein expression were performed. Results We found that TAK1 was activated in the dystrophic muscles of DMD patients (n = 6, +72.2%, P

Abstract Periodontitis, a bacterium-induced inflammatory disease that is characterized by alveolar bone loss, is highly prevalent worldwide. Elucidating the underlying mechanisms of alveolar bone loss in periodontitis is crucial for understanding its pathogenesis. Classically, bone cells, such as osteoclasts, osteoblasts and bone marrow stromal cells, are thought to dominate the development of bone destruction in periodontitis. Recently, osteocytes, the cells embedded in the mineral matrix, have gained attention. This review demonstrates the key contributing role of osteocytes in periodontitis, especially in alveolar bone loss. Osteocytes not only initiate physiological bone remodeling but also assist in inflammation-related changes in bone remodeling. The latest evidence suggests that osteocytes are involved in regulating bone anabolism and catabolism in the progression of periodontitis. The altered secretion of receptor activator of NF-κB ligand (RANKL), sclerostin and Dickkopf-related protein 1 (DKK1) by osteocytes affects the balance of bone resorption and formation and promotes bone loss. In addition, the accumulation of prematurely senescent and apoptotic osteocytes observed in alveolar bone may exacerbate local destruction. Based on their communication with the bloodstream, it is noteworthy that osteocytes may participate in the interaction between local periodontitis lesions and systemic diseases. Overall, further investigations of osteocytes may provide vital insights that improve our understanding of the pathophysiology of periodontitis.

Background Duchenne muscular dystrophy (DMD) is a progressive muscle disease caused by the loss of dystrophin, which results in inflammation, fibrosis, and the inhibition of myoblast differentiation in skeletal muscle. Catalpol, an iridoid glycoside, improves skeletal muscle function by enhancing myogenesis; it has potential to treat DMD. We demonstrate the positive effects of catalpol in dystrophic skeletal muscle. Methods mdx (loss of dystrophin) mice (n = 18 per group) were treated with catalpol (200 mg/kg) for six consecutive weeks. Serum analysis, skeletal muscle performance and histology, muscle contractile function, and gene and protein expression were performed. Molecular docking and ligand–target interactions, RNA interference, immunofluorescence, and plasmids transfection were utilized to explore the protective mechanism in DMD by which catalpol binding with transforming growth factor‐β–activated kinase 1 (TAK1) in skeletal muscle. Results Six weeks of catalpol treatment improved whole‐body muscle health in mdx mice, which was characterized by reduced plasma creatine kinase (n = 18, −35.1%, P

Objective: Ischemic cardiomyopathy (ICM) is a major cardiovascular state associated with prominently increased morbidity and mortality. Our purpose was to detect reliable gene signatures for ICM through integrated feature selection strategies.Methods: Transcriptome profiles of ICM were curated from the GEO project. Classification models, including least absolute shrinkage and selection operator (LASSO), support vector machine (SVM), and random forest, were adopted for identifying candidate ICM-specific genes for ICM. Immune cell infiltrates were estimated using the CIBERSORT method. Expressions of candidate genes were verified in ICM and healthy myocardial tissues via Western blotting. JC-1 staining, flow cytometry, and TUNEL staining were presented in hypoxia/reoxygenation (H/R)-stimulated H9C2 cells with TRMT5 deficiency.Results: Following the integration of three feature selection methods, we identified seven candidate ICM-specific genes including ASPN, TRMT5, LUM, FCN3, CNN1, PCNT, and HOPX. ROC curves confirmed the excellent diagnostic efficacy of this combination of previous candidate genes in ICM. Most of them presented prominent interactions with immune cell infiltrates. Their deregulations were confirmed in ICM than healthy myocardial tissues. TRMT5 expressions were remarkedly upregulated in H/R-stimulated H9C2 cells. TRMT5 deficiency enhanced mitochondrial membrane potential and reduced apoptosis in H/R-exposed H9C2 cells.Conclusion: Collectively, our findings identified reliable gene signatures through combination strategies of diverse feature selection methods, which facilitated the early detection of ICM and revealed the underlying mechanisms.

The coronavirus disease 2019 (COVID-19) pandemic is wreaking havoc on public-health and economic systems worldwide. Among the several neurological symptoms of patients with COVID-19 reported in clinical practice, olfactory dysfunction (OD) is the most common. OD occurs as the earliest or the only clinical manifestation in some patients. Increasing research attention has focused on OD, which is listed as one of the main diagnostic symptoms of severe acute respiratory syndrome-coronavirus-2 infection. Multiple clinical and basic-science studies on COVID-19-induced OD are underway to clarify the underlying mechanism of action. In this review, we summarize the clinical characteristics, mechanisms, evaluation methods, prognosis, and treatment options of COVID-19-induced OD. In this way, we hope to improve the understanding of COVID-19-induced OD to aid early identification and precise intervention.

Atherosclerosis (AS), one of the most common types of cardiovascular disease, has initially been attributed to the accumulation of fats and fibrous materials. However, more and more researchers regarded it as a chronic inflammatory disease nowadays. Infective disease, such as periodontitis, is related to the risk of atherosclerosis. Porphyromonas gingivalis (P. gingivalis), one of the most common bacteria in stomatology, is usually discovered in atherosclerotic plaque in patients. Furthermore, it was reported that P. gingivalis can promote the progression of atherosclerosis. Elucidating the underlying mechanisms of P. gingivalis in atherosclerosis attracted attention, which is thought to be crucial to the therapy of atherosclerosis. Nevertheless, the pathogenesis of atherosclerosis is much complicated, and many kinds of cells participate in it. By summarizing existing studies, we find that P. gingivalis can influence the function of many cells in atherosclerosis. It can induce the dysfunction of endothelium, promote the formation of foam cells as well as the proliferation and calcification of vascular smooth muscle cells, and lead to the imbalance of regulatory T cells (Tregs) and T helper (Th) cells, ultimately promoting the occurrence and development of atherosclerosis. This article summarizes the specific mechanism of atherosclerosis caused by P. gingivalis. It sorts out the interaction between P. gingivalis and AS-related cells, which provides a new perspective for us to prevent or slow down the occurrence and development of AS by inhibiting periodontal pathogens.

Plant leaf functional traits can reflect the adaptive strategies of plants to environmental changes. Exploring the patterns and causes of geographic variation in leaf functional traits is pivotal for improving ecological theory at the macroscopic scale. In order to explore the geographical variation and the dominant factors of leaf functional traits in the forest ecosystems of China, we measured 15 environmental factors on 16 leaf functional traits in 33 forest reserves in China. The results showed leaf area (LA), carbon-to-nitrogen ratio (C/N), carbon-to-phosphorus ratio (C/P), nitrogen-to-phosphorus ratio (N/P), phosphorus mass per area (Pa) and nitrogen isotope abundance (δ15N)) were correlated with latitude significantly. LA, Pa and δ15N were also correlated with longitude significantly. The leaf functional traits in southern China were predominantly affected by climatic factors, whereas those in northern China were mainly influenced by soil factors. Mean annual temperature (MAT), mean annual precipitation (MAP) and mean annual humidity (MAH) were shown to be the important climate factors, whereas available calcium (ACa), available potassium (AK), and available magnesium (AMg) were shown to be the important climate factors that affect the leaf functional traits of the forests in China. Our study fills the gap in the study of drivers and large-scale geographical variability of leaf functional traits, and our results elucidate the operational mechanisms of forest–soil–climate systems. We provide reliable support for modeling global forest dynamics.

The inclusion of micro bubbles often exists in polyimide films (PI) during the liquid molding process, which can largely affect the mechanical performance. However, there lacks an effective method to quantify the bubble content. Herein, an obvious tension variation of a pre-stressed polyimide film is observed firstly in a vacuum test. This phenomenon is assumed that, when the vacuum level of the testing environment increases, the inner bubbles would expand mainly out of plane, resulting in an in-plane contraction, and the tension varies accordingly. This tension variation ability is found quite stable despite of the stochastic micro-bubble distribution, which could be utilized to quantify the bubble content. Moreover, a film with meso-size bubbles is tested to have the similar tension variation ability. According to the experimental results, the tension variation ability can be basically stable when the bubbles in the length and width directions reach a certain number (e.g. 10).

Although neural stem cells (NSCs) could migrate towards lesions after central nervous system (CNS) injury, the migration ability always is restricted due to the disturbed composition and density of the adhesion ligands and extracellular matrix (ECM) gradient after CNS injury. To date, various methods have been developed to enhance NSC migration and a number of factors, which are affecting NSC migration potential, have been identified. Here, primary NSCs were cultured and the expression of actin alpha 2 (ACTA2) in NSCs was determined using reverse transcription polymerase chain reaction (RT-PCR) and immunostaining. Next, the role of ACTA2 in regulating NSC migration and the potential mechanism was explored. Our results demonstrated that ACTA2 expressed in NSCs. Meanwhile, downregulated ACTA2 using siRNA inhibited NSC migration through hindering actin filament polymerization via increasing RhoA expression and decreasing Rac1 expression. The present study might enrich the basic knowledge of ACTA2 in NSC migration and open an avenue for enhancing NSC migration potential, subsequently providing an intervention target for functional recovery after CNS injury.

Four new anthraquinone derivatives, namely saliniquinones G−I (1–3) and heraclemycin E (4), were obtained from the Antarctic marine-derived actinomycete Nocardiopsis aegyptia HDN19-252, guided by the Global Natural Products Social (GNPS) molecular networking platform. Their structures, including absolute configurations, were elucidated by extensive NMR, MS, and ECD analyses. Compounds 1 and 2 showed promising inhibitory activity against six tested bacterial strains, including methicillin-resistant coagulase-negative staphylococci (MRCNS), with MIC values ranging from 3.1 to 12.5 μM.

Abstract In this study, silver nanoparticles (Ag NPs) coated with catechol-conjugated chitosan (CSS) were prepared using green methods. Interestingly, we uncovered that CSS-coated Ag NPs (CSS-Ag NPs) exhibited a higher toxicity against gram-negative Escherichia coli (E. coli) bacteria than against gram-positive Staphylococcus aureus (S. aureus) bacteria. The differences revealed that the CSS-Ag NPs killed gram bacteria with distinct, species-specific mechanisms. The aim of this study is to further investigate these underlying mechanisms through a series of analyses. The ultrastructure and morphology of the bacteria before and after treatment with CSS-Ag NPs were observed. The results demonstrated the CSS-Ag NPs killed gram-positive bacteria through a disorganization of the cell wall and leakage of cytoplasmic content. In contrast, the primary mechanism of action on gram-negative bacteria was a change in membrane permeability, induced by adsorption of CSS-Ag NPs. The species-specific mechanisms are caused by structural differences in the cell walls of gram bacteria. Gram-positive bacteria are protected from CSS-Ag NPs by a thicker cell wall, while gram-negatives are more easily killed due to an interaction between a special outer membrane and the nanoparticles. Our study offers an in-depth understanding of the antibacterial behaviors of CSS-Ag NPs and provides insights into ultimately optimizing the design of Ag NPs for treatment of bacterial infections.

The relationship between periodontitis and systemic diseases, notably including atherosclerosis and diabetes, has been studied for several years. Porphyromonas gingivalis, a prominent component of oral microorganism communities, is the main pathogen that causes periodontitis. As a result of the extensive analysis of this organism, the evidence of its connection to systemic diseases has become more apparent over the last decade. A significant amount of research has explored the role of Porphyromonas gingivalis in atherosclerosis, Alzheimer’s disease, rheumatoid arthritis, diabetes, and adverse pregnancy outcomes, while relatively few studies have examined its contribution to respiratory diseases, nonalcoholic fatty liver disease, and depression. Here, we provide an overview of the current state of knowledge about Porphyromonas gingivalis and its systemic impact in an aim to inform readers of the existing epidemiological evidence and the most recent preclinical studies. Additionally, the possible mechanisms by which Porphyromonas gingivalis is involved in the onset or exacerbation of diseases, together with its effects on systemic health, are covered. Although a few results remain controversial, it is now evident that Porphyromonas gingivalis should be regarded as a modifiable factor for several diseases.

Objective. As a complicated symbiotic system, intestinal flora is reported closely related to the development of type 2 diabetes recently. Sleeve gastrectomy is one of the approaches of bariatric surgery and could improve blood glucose control in type 2 diabetes patients. This study was to explore the relationship between remodeled intestinal flora and glucose metabolism in diabetic rats. Methods. 20 male diabetic rats were operated; 10 of them underwent sleeve gastrectomy, and 10 of them underwent sham operation. Meanwhile 10 male normal rats underwent sleeve gastrectomy as control. The animals’ weight and FBG had been measured. The composition changes of intestinal flora were detected by 16S rDNA sequence analysis. Results. In diabetic rats, weight and fasting blood glucose decreased significantly after sleeve gastrectomy. However, there was no significant change for weight and blood glucose in normal rats after operation. The intestinal flora of diabetic rats reduced in the proportion of Firmicutes and increased in the proportion of Bacteroidetes after sleeve gastrectomy. Conclusion. The change of dominant microorganisms in intestinal flora might play an important role in the glucose metabolism.