Expression pattern analysis of m6A regulators reveals IGF2BP3 as a key modulator in osteoarthritis synovial macrophages.

BACKGROUND: Disruption of N6 methyl adenosine (m6A) modulation hampers gene expression and cellular functions, leading to various illnesses. However, the role of m6A modification in osteoarthritis (OA) synovitis remains unclear. This study aimed to explore the expression patterns of m6A regulators in OA synovial cell clusters and identify key m6A regulators that mediate synovial macrophage phenotypes. METHODS: The expression patterns of m6A regulators in the OA synovium were illustrated by analyzing bulk RNA-seq data. Next, we built an OA LASSO-Cox regression prediction model to identify the core m6A regulators. Potential target genes of these m6A regulators were identified by analyzing data from the RM2target database. A molecular functional network based on core m6A regulators and their target genes was constructed using the STRING database. Single-cell RNA-seq data were collected to verify the effects of m6A regulators on synovial cell clusters. Conjoint analyses of bulk and single-cell RNA-seq data were performed to validate the correlation between m6A regulators, synovial clusters, and disease conditions. After IGF2BP3 was screened as a potential modulator in OA macrophages, the IGF2BP3 expression level was tested in OA synovium and macrophages, and its functions were further tested by overexpression and knockdown in vitro. RESULTS: OA synovium showed aberrant expression patterns of m6A regulators. Based on these regulators, we constructed a well-fitting OA prediction model comprising six factors (FTO, YTHDC1, METTL5, IGF2BP3, ZC3H13, and HNRNPC). The functional network indicated that these factors were closely associated with OA synovial phenotypic alterations. Among these regulators, the m6A reader IGF2BP3 was identified as a potential macrophage mediator. Finally, IGF2BP3 upregulation was verified in the OA synovium, which promoted macrophage M1 polarization and inflammation. CONCLUSIONS: Our findings revealed the functions of m6A regulators in OA synovium and highlighted the association between IGF2BP3 and enhanced M1 polarization and inflammation in OA macrophages, providing novel molecular targets for OA diagnosis and treatment.

A Freestanding 3D Skeleton with Gradationally Distributed Lithiophilic Sites for Realizing Stable Lithium Anodes.

Lithium (Li) metal anodes are drawing considerable attention owing to their ultrahigh theoretical capacities and low electrochemical reduction potentials. However, their commercialization has been hampered by safety hazards induced by continuous dendrite growth. These issues can be alleviated using the ZnO-modified 3D carbon-based host containing carbon nanotubes (CNTs) and carbon felt (CF) fabricated by electroplating in the present study (denoted as ZnO/CNT@CF). The constructed skeleton has lithiophilic ZnO that is gradationally distributed along its thickness. The utilization of an inverted ZnO/CNT@CF-Li anode obtained by flipping over the carbon skeleton after Li electrodeposition is also reported herein. The synergistic effect of the Li metal and lithiophilic sites reduces the nucleation overpotential, thus inducing Li+ to preferentially deposit inside the porous carbon-based scaffold. The composite electrode compels Li to grow away from the separator, thereby significantly improving battery safety. A symmetric cell with the inverted ZnO/CNT@CF-Li electrode operates steadily for 700 cycles at 1 mA cm-2 and 1 mAh cm-2 . Moreover, the ZnO/CNT@CF-Li|S cell exhibits an initial areal capacity of 10.9 mAh cm-2 at a S loading of 10.4 mg cm-2 and maintains a capacity of 3.0 mAh cm-2 after 320 cycles.

Mechanical overloading promotes chondrocyte senescence and osteoarthritis development through downregulating FBXW7.

OBJECTIVES: To investigate the role of mechanical stress in cartilage ageing and identify the mechanistic association during osteoarthritis (OA) progression. METHODS: F-box and WD repeat domain containing 7 (FBXW7) ubiquitin ligase expression and chondrocyte senescence were examined in vitro, in experimental OA mice and in human OA cartilage. Mice with Fbxw7 knockout in chondrocytes were generated and adenovirus-expressing Fbxw7 (AAV-Fbxw7) was injected intra-articularly in mice. Destabilised medial meniscus surgery was performed to induce OA. Cartilage damage was measured using the Osteoarthritis Research Society International score and the changes in chondrocyte senescence were determined. mRNA sequencing was performed in articular cartilage from Fbxw7 knockout and control mice. RESULTS: Mechanical overloading accelerated senescence in cultured chondrocytes and in mice articular cartilage. FBXW7 was downregulated by mechanical overloading in primary chondrocytes and mice cartilage, and decreased in the cartilage of patients with OA, aged mice and OA mice. FBXW7 deletion in chondrocytes induced chondrocyte senescence and accelerated cartilage catabolism in mice, as manifested by an upregulation of p16INK4A, p21 and Colx and downregulation of Col2a1 and ACAN, which resulted in the exacerbation of OA. By contrast, intra-articular injection of adenovirus expressing Fbxw7 alleviated OA in mice. Mechanistically, mechanical overloading decreased Fbxw7 mRNA transcription and FBXW7-mediated MKK7 degradation, which consequently stimulated JNK signalling. In particular, inhibition of JNK activity by DTP3, a MKK7 inhibitor, ameliorated chondrocyte senescence and cartilage degeneration CONCLUSIONS: FBXW7 is a key factor in the association between mechanical overloading and chondrocyte senescence and cartilage ageing in the pathology of OA.

Effects of Virtual Reality Intervention on Neural Plasticity in Stroke Rehabilitation: A Systematic Review.

OBJECTIVE: To systematically review and examine the current literature regarding the effects of virtual reality (VR)-based rehabilitation on neural plasticity changes in survivors of stroke. DATA SOURCES: We searched 6 bioscience and engineering databases, including Medline via EBSCO, Embase, PsycINFO, IEEE Explore, Cumulative Index of Nursing and Allied Health, and Scopus. STUDY SELECTION: We selected studies reporting on the pre-post assessment of a VR intervention with neural plasticity measures published between 2000 and 2021. DATA EXTRACTION: Two independent reviewers conducted study selection, data extraction, and quality assessment. They assessed methodological quality of controlled trials using the Physiotherapy Evidence Database scale and evaluated risk of bias of pre-post intervention and case studies using the National Institutes of Health Quality Assessment Tool. DATA SYNTHESIS: We included 27 studies (n=232). We rated 7 randomized-controlled trials as good quality and 2 clinical-controlled trials as moderate. Based on the risk of bias assessment, we graded 1 pre-post study and 1 case study as good quality, 1 pre-post study and 1 case study as poor, and the other 14 studies as fair. After the VR intervention, main neurophysiological findings across studies include: (1) improved interhemispheric balance; (2) enhanced cortical connectivity; (3) increased cortical mapping of the affected limb muscles; (4) the improved neural plasticity measures were correlated to the enhanced behavior outcomes; (5) increased activation of regions in frontal cortex; and (6) the mirror neuron system may be involved. CONCLUSIONS: VR-induced changes in neural plasticity for survivors of stroke. Positive correlations between the neural plasticity changes and functional recovery elucidates the mechanisms of VR-based therapeutic effects in stroke rehabilitation. This review prompts systematic understanding of the neurophysiological mechanisms of VR-based stroke rehabilitation and summarizes the emerging evidence for ongoing innovation of VR systems and application in stroke rehabilitation.

How to use BAPV to alleviate the urban heat island effect: An evolutionary game perspective.

In recent years, the phenomenon of the urban heat island caused by the rapid development of cities is very serious. To solve the problem of the urban heat island, this study proposed a PPP project consisting of the government (GOVT), photovoltaic investment company (PVIC), and residential customers (RS). Based on an evolutionary game model and combined with current policies and industry regulations in China, the evolution process and stable evolution strategies were studied. The result shows that more government subsidies, higher carbon trading prices, and feed-in tariffs will promote the development of the PPP project. For relatively suitable reference value ranges, the installation tilt angle of the BAPV system is 30°, the photovoltaic grid electricity price is 0.1096∼0.1296 $/kWh, the carbon trading is 8.92∼9.42 $/t.

The margin of stability is affected differently when walking under quasi-random treadmill perturbations with or without full visual support.

Background: Sensory-motor perturbations have been widely used to assess astronauts' balance in standing during pre-/post- spaceflight. However, balance control during walking, where most falls occur, was less studied in these astronauts. A study found that applying either visual or platform oscillations reduced the margin of stability (MOS) in the anterior-posterior direction (MOSap) but increased MOS in the medial-lateral direction (MOSml) as a tradeoff. This tradeoff induced an asymmetric gait. This study extended the current knowledge to investigate overall stability under unpredictable environments. This study aimed to determine (1) whether quasi-random treadmill perturbations with or without full vision support would result in a significant reduction in MOSap but an increase in MOSml and (2) regardless of whether vision support was provided, quasi-random treadmill perturbations might result in asymmetric gait patterns. Methods: Twenty healthy young adults participated in this study. Three experimental conditions were semi-randomly assigned to these participants as follows: (1) the control condition (Norm), walking normally with their preferred walking speed on the treadmill; (2) the treadmill perturbations with full vision condition (Slip), walking on the quasi-random varying-treadmill-belt-speeds with full vision support; and (3) the treadmill perturbations without full vision condition (Slip_VisionBlocked, blackout vision through customized vision-blocked goggles), walking on the quasi-random varying-treadmill-belt-speeds without full vision support. The dependent variables were MOSap, MOSml, and respective symmetric indices. A one-way repeated ANOVA measure or Friedman Test was applied to investigate the differences among the conditions mentioned above. Results: There was an increase in MOSap in Slip (p = 0.001) but a decrease in MOSap in Slip_VisionBlocked (p = 0.001) compared to Norm condition. The MOSml was significantly greater in both Slip and Slip_VisionBlocked conditions compared to the Norm condition (p = 0.011; p < 0.001). An analysis of Wilcoxon signed-rank tests revealed that the symmetric index of MOSml in Slip_VisionBlocked (p = 0.002) was greater than in the Norm condition. Conclusion: The novelty of this study was to investigate the effect of vision on the overall stability of walking under quasi-random treadmill perturbations. The results revealed that overall stability and symmetry were controlled differently with/without full visual support. In light of these findings, it is imperative to take visual support into consideration while developing a sensory-motor training protocol. Asymmetric gait also required extra attention while walking on the quasi-random treadmill perturbations without full vision support to maintain overall stability.

Therapeutic Effect and Side Effects of Pharmacotherapy in Patients With Parkinson Disease and Myasthenia Gravis: A Systematic Review of Case Reports and Case Series Studies.

PURPOSE: The co-existence of Parkinson disease (PD) and myasthenia gravis (MG) in an individual should be exceptionally rare. The purpose of this study was to systematically review the current literature regarding the therapeutic effect and side effects of pharmacotherapy on patients with PD and MG. METHODS: Five bioscience and engineering databases (MEDLINE via PubMed, Cochrane Library, Scopus, EMBASE, and China National Knowledge Infrastructure) were searched from inception through February 21, 2022. Case reports and case series studies investigating pharmacotherapy in patients with PD and MG were included. Procedures were followed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The methodologic quality of included studies was evaluated by using the National Institutes of Health Quality Assessment Tool for Case Series Studies. FINDINGS: Sixteen case reports and 5 case series studies with 32 participants met the inclusion criteria. Eight studies were rated as good quality, 10 were fair quality, and 3 were poor quality. The side effects of pharmacotherapy for PD or MG led to another disease, indicating an imbalance between dopamine and acetylcholine within human bodies. IMPLICATIONS: When treating a patient who has PD or MG, health providers should be cautious about the occurrence of another disease. Timely treatment must rely on monitoring new symptoms as soon as the pharmacotherapy for PD or MG is initiated. Physical therapy may be helpful in decreasing the side effects of pharmacotherapy in patients with PD and MG. A new treatment pattern of pharmacotherapy + physical therapy for patients with PD and MG warrants further research. International Prospective Register of Systematic Reviews identifier: CRD42022308066.

Comparison Between Effects of Galvanic and Vibration-Based Vestibular Stimulation on Postural Control and Gait Performance in Healthy Participants: A Systematic Review of Cross-Sectional Studies.

Electricity and vibration were two commonly used physical agents to provide vestibular stimulation in previous studies. This study aimed to systematically review the effects of galvanic (GVS) and vibration-based vestibular stimulation (VVS) on gait performance and postural control in healthy participants. Five bioscience and engineering databases, including MEDLINE via PubMed, CINAHL via EBSCO, Cochrane Library, Scopus, and Embase, were searched until March 19th, 2023. Studies published between 2000 and 2023 in English involving GVS and VVS related to gait performance and postural control were included. The procedure was followed via the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The methodological quality of included studies was assessed using the NIH study quality assessment tool for observational cohort and cross-sectional studies. A total of 55 cross-sectional studies met the inclusion criteria and were included in this study. Five studies were good-quality while 49 were moderate-quality and 1 was poor-quality. There were 50 included studies involving GVS and 5 included studies involving VVS. GVS and VVS utilized different physical agents to provide vestibular stimulation and demonstrated similar effects on vestibular perception. Supra-threshold GVS and VVS produced vestibular perturbation that impaired gait performance and postural control, while sub-threshold GVS and VVS induced stochastic resonance phenomenon that led to an improvement. Bilateral vestibular stimulation demonstrated a greater effect on gait and posture than unilateral vestibular stimulation. Compared to GVS, VVS had the characteristics of better tolerance and fewer side effects, which may substitute GVS to provide more acceptable vestibular stimulation.

Near-gapless genome and transcriptome analyses provide insights into fruiting body development in Lentinula edodes.

Fruiting body development in macrofungi is an intensive research subject. In this study, high-quality genomes were assembled for two sexually compatible monokaryons from a heterokaryotic Lentinula edodes strain WX1, and variations in L. edodes genomes were analyzed. Specifically, differential gene expression and allele-specific expression (ASE) were analyzed using the two monokaryotic genomes and transcriptome data from four different stages of fruiting body development in WX1. Results revealed that after aeration, mycelia sensed cell wall stress, pheromones, and a decrease in CO2 concentration, leading to up-regulated expression in genes related to cell adhesion, cell wall remodeling, proteolysis, and lipid metabolism, which may promote primordium differentiation. Aquaporin genes and those related to proteolysis, mitosis, lipid, and carbohydrate metabolism may play important roles in primordium development, while genes related to tissue differentiation and sexual reproduction were active in fruiting body. Several essential genes for fruiting body development were allele-specifically expressed and the two nuclear types could synergistically regulate fruiting body development by dominantly expressing genes with different functions. ASE was probably induced by long terminal repeat-retrotransposons. Findings here contribute to the further understanding of the mechanism of fruiting body development in macrofungi.

RPL35 downregulated by mechanical overloading promotes chondrocyte senescence and osteoarthritis development via Hedgehog-Gli1 signaling.

Objectives: To investigate the potential role of Ribosomal protein L35 (RPL35) in regulating chondrocyte catabolic metabolism and to examine whether osteoarthritis (OA) progression can be delayed by overexpressing RPL35 in a mouse compression loading model. Methods: RNA sequencing analysis was performed on chondrocytes treated with or without 20 % elongation strain loading for 24 h. Experimental OA in mice was induced by destabilization of the medial meniscus and compression loading. Mice were randomly assigned to a sham group, an intra-articular adenovirus-mediated overexpression of the negative group, and an intra-articular adenovirus-mediated overexpression of the RPL35 operated group. The Osteoarthritis Research Society International score was used to evaluate cartilage degeneration. Immunostaining and western blot analyses were conducted to detect relative protein levels. Primary mouse chondrocytes were treated with 20 % elongation strain loading for 24 h to investigate the role of RPL35 in modulating chondrocyte catabolic metabolism and regulating cellular senescence in chondrocytes. Results: The protein expression of RPL35 in mouse chondrocytes was significantly reduced when excessive mechanical loading was applied, while elevated protein levels of RPL35 protected articular chondrocytes from degeneration. In addition, the RPL35 knockdown alone induced chondrocyte senescence, decreased the expression of anabolic markers, and increased the expression of catabolic markers in vitro in part through the hedgehog (Hh) pathway. Conclusions: These findings demonstrated a functional pathway important for OA development and identified intra-articular injection of RPL35 as a potential therapy for OA prevention and treatment. The translational potential of this article: It is necessary to develop new targeted drugs for OA due to the limitations of conventional pharmacotherapy. Our study explores and demonstrates the protective effect of RPL35 against excessive mechanical stress in OA models in vivo and in vitro in animals. These findings might provide novel insights into OA pathogenesis and show its translational potential for OA therapy.

Different types of plantar vibration affect gait characteristics differently while walking on different inclines.

Background: Plantar vibration has been widely used to strengthen the sensation of the somatosensory system, further enhancing balance during walking on a level surface in patients with stroke. However, previous studies with plantar vibration only involved the level surface, which neglected the importance of inclined/declined walking in daily life. Thus, combining the plantar vibration and inclined/declined walking might answer a critical research question: whether different types of plantar vibration had different effects on gait characteristics during walking on different inclines. Methods: Eighteen healthy young adults were recruited. Fifteen walking conditions were assigned randomly to these healthy adults (no, sub-, and supra-threshold plantar vibration × five different inclines: +15%, +8%, 0%, -8%, -15% grade). A motion capture system with eight cameras captured 12 retro-reflective markers and measured the stride time, stride length, step width, and respective variabilities. Results: A significant interaction between vibration and inclination was observed in the stride time (p < 0.0001) and step width (p = 0.015). Post hoc comparisons found that supra-threshold vibration significantly decreased the stride time (-8%: p < 0.001; -15%: p < 0.001) while the sub-threshold vibration significantly increased the step width (-8%: p = 0.036) in comparison with no plantar vibration. Conclusions: When walking downhill, any perceivable (supra-threshold) vibration on the plantar area decreased the stride time. Also, the increase in step width was observed by non-perceivable (sub-threshold) plantar vibration while walking uphill. These observations were crucial as follows: (1) applying sub-threshold plantar vibrations during uphill walking could increase the base of support, and (2) for those who may need challenges in locomotor training, applying supra-threshold vibration during downhill walking could reach this specific training goal.

The effect of mechanical vibration-based stimulation on dynamic balance control and gait characteristics in healthy young and older adults: A systematic review of cross-sectional study.

BACKGROUND: A good dynamic balance control and stable gait played an important role in the daily ambulation, especially for older adults with sensorimotor degeneration. This study aimed to systematically review the effects and potential mechanisms of mechanical vibration-based stimulation (MVBS) on dynamic balance control and gait characteristics in healthy young and older adults. METHOD: Five bioscience and engineering databases, including MEDLINE via PubMed, CINAHL via EBSCO, Cochrane Library, Scopus, and Embase, were searched until September 4th, 2022. Studies published between 2000 and 2022 in English and Chinese involving mechanical vibration related to gait and dynamic balance were included. The procedure was followed via the preferred reporting items for systematic reviews and meta-analysis method. The methodological quality of included studies was assessed using the NIH study quality assessment tool for observational cohort and cross-sectional studies. RESULTS: A total of 41 cross-sectional studies met the inclusion criteria and were included in this study. Eight studies were good-quality while 26 were moderate-quality and 7 were poor-quality. There were six categories of MVBS at various frequencies and amplitudes utilized in included studies, including plantar vibration, focal muscle vibration, Achilles tendon vibration, vestibular vibration, cervical vibration, and vibration on nail of hallux. SIGNIFICANCE: Different types of MVBS targeting different sensory systems affected the dynamic balance control and gait characteristics differently. MVBS could be used to provide improvement or perturbation to specific sensory systems, to induce different sensory reweight strategies during gait.

Adversarial co-training for semantic segmentation over medical images.

BACKGROUND AND OBJECTIVE: Abundant labeled data drives the model training for better performance, but collecting sufficient labels is still challenging. To alleviate the pressure of label collection, semi-supervised learning merges unlabeled data into training process. However, the joining of unlabeled data (e.g., data from different hospitals with different acquisition parameters) will change the original distribution. Such a distribution shift leads to a perturbation in the training process, potentially leading to a confirmation bias. In this paper, we investigate distribution shift and develop methods to increase the robustness of our models, with the goal of improving performance in semi-supervised semantic segmentation of medical images. We study distribution shift and increase model robustness to it, for improving practical performance in semi-supervised segmentation over medical images. METHODS: To alleviate the issue of distribution shift, we introduce adversarial training into the co-training process. We simulate perturbations caused by the distribution shift via adversarial perturbations and introduce the adversarial perturbation to attack the supervised training to improve the robustness against the distribution shift. Benefiting from label guidance, supervised training does not collapse under adversarial attacks. For co-training, two sub-models are trained from two views (over two disjoint subsets of the dataset) to extract different kinds of knowledge independently. Co-training outperforms single-model by integrating both views of knowledge to avoid confirmation bias. RESULTS: For practicality, we conduct extensive experiments on challenging medical datasets. Experimental results show desirable improvements to state-of-the-art counterparts (Yu and Wang, 2019; Peng et al., 2020; Perone et al., 2019). We achieve a DSC score of 87.37% with only 20% of labels on the ACDC dataset, almost same to using 100% of labels. On the SCGM dataset with more distribution shift, we achieve a DSC score of 78.65% with 6.5% of labels, surpassing 10.30% over Peng et al. (2020). Our evaluative results show superior robustness against distribution shifts in medical scenarios. CONCLUSION: Empirical results show the effectiveness of our work for handling distribution shift in medical scenarios.

Different Types of Mastoid Process Vibrations Affect Dynamic Margin of Stability Differently.

The vestibular system is critical for human locomotion. Any deteriorated vestibular system leads to gait instability. In the past decades, these alternations in gait patterns have been majorly measured by the spatial-temporal gait parameters and respective variabilities. However, measuring gait characteristics cannot capture the full aspect of motor controls. Thus, to further understand the effects of deteriorated vestibular system on gait performance, additional measurement needs to be taken into consideration. This study proposed using the margin of stability (MOS) to identify the patterns of dynamic control under different types of mastoid vibrations in walking. This study hypothesized that (1) using the MOS method could facilitate the understanding of another aspect of motor control induced by different types of mastoid vibrations, and (2) applying the mastoid vibrations could induce the asymmetric MOS. Twenty healthy young adults were recruited. Two electromechanical vibrotactile transducers were placed on the bilateral mastoid process to apply different types of vestibular vibrations (bilateral, unilateral, and no vibration). A motion capture system with eight cameras was used to measure the MOSap (margin of stability in the anterior-posterior direction), MOSml (margin of stability in the medial-lateral direction), and respective variabilities. The results were in line with the hypotheses that both bilateral and unilateral mastoid vibrations significantly increased MOSap (p = 0.036, p < 0.001), MOSml (p = 0.012, p < 0.001), and respective variabilities p = 0.001, p < 0.001; p = 0.001, p < 0.01 when compared to the no vibration condition. Also, significantly larger MOSml (p = 0.001), MOSml variability (p < 0.023), MOSap (p < 0.001), and MOSap variability (p = 0.002) were observed under the unilateral vibration condition than that observed under the bilateral vibration condition. The above-mentioned result found that different types of mastoid vibrations affected the MOS differently, suggesting different patterns of control mechanisms under different sensory-conflicted situations. Besides, a significant difference between the dominant and non-dominant legs was observed in MOSml. Moreover, applying the unilateral mastoid vibrations induced a greater symmetric index of MOSml, suggesting that more active control in balance was needed in the medial-lateral than in the anterior-posterior direction.

Uncertainty teacher with dense focal loss for semi-supervised medical image segmentation.

In medical scenarios, obtaining pixel-level annotations for medical images is expensive and time-consuming, even if considering its importance for automating segmentation tasks. Due to the scarcity of labels in the training phase, semi-supervised methods are widely applied for various medical tasks. To better utilize the unlabeled data, several works have explored the method of uncertainty estimation and exhibited huge success. Despite their impressive performance, we believe that the underlying information of the unlabeled data has been largely unexplored. Meanwhile, there is an extreme foreground-background class imbalance during the training phase of semantic segmentation, which may cause a vast number of easily classified samples to overwhelm the loss during training and lead to a model collapse. In this paper, we proposed uncertainty teacher with dense focal loss, a method that can take good advantage of unlabeled data simultaneously and address the class imbalance problem, based on Deep Co-Training. On one hand, the uncertainty teacher framework is presented to better utilize the unlabeled data by introducing a novel method to regularize uncertainty in the right direction, and the uncertainty is estimated by Monte Carlo Sampling. On the other hand, the dense focal loss is proposed to help solve the class imbalance problem between different classes of samples in medical image segmentation and effectively convert the multi-variate entropy into a multiple binary entropy. We implemented our method on three challenging public medical datasets and experimental results have shown desirable improvements to state-of-the-art.

Uncertainty-aware deep co-training for semi-supervised medical image segmentation.

Semi-supervised learning has made significant strides in the medical domain since it alleviates the heavy burden of collecting abundant pixel-wise annotated data for semantic segmentation tasks. Existing semi-supervised approaches enhance the ability to extract features from unlabeled data with prior knowledge obtained from limited labeled data. However, due to the scarcity of labeled data, the features extracted by the models are limited in supervised learning, and the quality of predictions for unlabeled data also cannot be guaranteed. Both will impede consistency training. To this end, we proposed a novel uncertainty-aware scheme to make models learn regions purposefully. Specifically, we employ Monte Carlo Sampling as an estimation method to attain an uncertainty map, which can serve as a weight for losses to force the models to focus on the valuable region according to the characteristics of supervised learning and unsupervised learning. Simultaneously, in the backward process, we joint unsupervised and supervised losses to accelerate the convergence of the network via enhancing the gradient flow between different tasks. Quantitatively, we conduct extensive experiments on three challenging medical datasets. Experimental results show desirable improvements to state-of-the-art counterparts.

Pentraxin 3 regulated by miR-224-5p modulates macrophage reprogramming and exacerbates osteoarthritis associated synovitis by targeting CD32.

Emerging evidence has shown an imbalance in M1/M2 macrophage polarization to play an essential role in osteoarthritis (OA) progression. However, the underlying mechanistic basis for this polarization is unknown. RNA sequencing of OA M1-polarized macrophages found highly expressed levels of pentraxin 3 (PTX3), suggesting a role for PTX3 in OA occurrence and development. Herein, PTX3 was found to be increased in the synovium and articular cartilage of OA patients and OA mice. Intra-articular injection of PTX3 aggravated, while PTX3 neutralization reversed synovitis and cartilage degeneration. No metabolic disorder or proteoglycan loss were observed in cartilage explants when treated with PTX3 alone. However, cartilage explants exhibited an OA phenotype when treated with culture supernatants of macrophages stimulated with PTX3, suggesting that PTX3 did not have a direct effect on chondrocytes. Therefore, the OA anti-chondrogenic effects of PTX3 are primarily mediated through macrophages. Mechanistically, PTX3 was upregulated by miR-224-5p deficiency, which activated the p65/NF-κB pathway to promote M1 macrophage polarization by targeting CD32. CD32 was expressed by macrophages, that when stimulated with PTX3, secreted abundant pro-inflammation cytokines that induced severe articular cartilage damage. The paracrine interaction between macrophages and chondrocytes produced a feedback loop that enhanced synovitis and cartilage damage. The findings of this study identified a functional pathway important to OA development. Blockade of this pathway and PTX3 may prevent and treat OA.

Epidemiology of autism spectrum disorders: Global burden of disease 2019 and bibliometric analysis of risk factors.

Background: To explore the geographical pattern and temporal trend of autism spectrum disorders (ASD) epidemiology from 1990 to 2019, and perform a bibliometric analysis of risk factors for ASD. Methods: In this study, ASD epidemiology was estimated with prevalence, incidence, and disability-adjusted life-years (DALYs) of 204 countries and territories by sex, location, and sociodemographic index (SDI). Age-standardized rate (ASR) and estimated annual percentage change (EAPC) were used to quantify ASD temporal trends. Besides, the study performed a bibliometric analysis of ASD risk factors since 1990. Publications published were downloaded from the Web of Science Core Collection database, and were analyzed using CiteSpace. Results: Globally, there were estimated 28.3 million ASD prevalent cases (ASR, 369.4 per 100,000 populations), 603,790 incident cases (ASR, 9.3 per 100,000 populations) and 4.3 million DALYs (ASR, 56.3 per 100,000 populations) in 2019. Increases of autism spectrum disorders were noted in prevalent cases (39.3%), incidence (0.1%), and DALYs (38.7%) from 1990 to 2019. Age-standardized rates and EAPC showed stable trend worldwide over time. A total of 3,991 articles were retrieved from Web of Science, of which 3,590 were obtained for analysis after removing duplicate literatures. "Rehabilitation", "Genetics & Heredity", "Nanoscience & Nanotechnology", "Biochemistry & Molecular biology", "Psychology", "Neurosciences", and "Environmental Sciences" were the hotspots and frontier disciplines of ASD risk factors. Conclusions: Disease burden and risk factors of autism spectrum disorders remain global public health challenge since 1990 according to the GBD epidemiological estimates and bibliometric analysis. The findings help policy makers formulate public health policies concerning prevention targeted for risk factors, early diagnosis and life-long healthcare service of ASD. Increasing knowledge concerning the public awareness of risk factors is also warranted to address global ASD problem.

Effect of Minor Er Additions on the Microstructures and Mechanical Properties of Cast Al-Cu-Mg-Ag Alloys.

The microstructures and mechanical properties of novel cast Al-Cu-Mg-Ag alloys with and without minor additions of Er (0.09 and 0.2 wt %) are investigated by Vickers hardness tests, tensile tests, optical metallographic examination, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD). The results reveal that the Er addition decreases the hardness value of peak-aged Al-Cu-Mg-Ag alloy but has little influence on the time required for achieving the peak aging condition. Meanwhile, the Ω phase is suppressed in Er-added alloys, leading to a lower tensile strength at room temperature, which causes the (Mg, Ag, Er, V, Ti)-rich phase in the matrix in Er-added alloys. This blocky phase consumes available Mg and Ag atoms for Ω nucleation, leading to the low number density of Ω plates. The strength properties of Er-added alloys at 300 °C are found to be enhanced, which benefits from the pinning effect of the Al8Cu4Er phase on grain boundaries. Meanwhile, the brittle fracture of Er-added alloys at room temperature is directly associated with the Al8Cu4Er phase and the blocky (Mg, Ag, Er, V, Ti)-rich phase, which acts as the source of microcracks during deformation. In addition, no obvious grain refinement effect can be observed in Er-added alloys.