Environmental controls on the seasonal variations of diatoms and dinoflagellates in the Qingdao coastal region, the Yellow Sea.

Diatoms and dinoflagellates are two typical functional groups of phytoplankton assemblages, which play a crucial role in the structure and functioning of most marine ecosystems. To date, a novel challenge in ecology and biogeochemistry is to address the influences of environmental changes associated with climate change and human activities on the dynamics of diatoms and dinoflagellates. However, the knowledge of the key environmental factors controlling the diatom-dinoflagellate dynamics remains to be improved, particularly in the coastal ecosystems. Therefore, we conducted four cruises along the Qingdao coastline in spring, summer, autumn, and winter 2022 to explore how diatoms and dinoflagellates varied in response to regional environmental changes. The results showed that the phytoplankton communities were dominated by diatoms and dinoflagellates in terms of abundance and species diversity throughout the year in the study region. Yet, there were significant seasonal variability of diatoms and dinoflagellates across the four seasons. For example, diatom species was the most diverse during autumn, and the higher average abundance was observed in the fall and winter. In contrast, the average abundance of dinoflagellates was maximum during the summer and minimum in the autumn season. Moreover, the abundance and species ratios of diatoms/dinoflagellates (dia/dino) also showed significant seasonal variations in the region. The dia/dino abundance ratio was lowest in summer, while the dia/dino species ratio showed an increasing trend from spring to fall and a slight descending trend during winter. Based on the redundancy analysis, we revealed that diatoms and dinoflagellates responded differently to various environmental variables in different seasons, of which temperature and nutrients (especially dissolved inorganic nitrogen, DIN) had highly significant correlations with both the dia/dino abundance and species ratios. Thus, we suggested that temperature and DIN were the key factors controlling the seasonal dynamics of diatoms and dinoflagellates in the Qingdao coastal area.

Interleukin-6 promotes visceral adipose tissue accumulation during aging via inhibiting fat lipolysis.

BACKGROUND: Age-related visceral obesity could contribute to the development of cardiometabolic complications. The pathogenesis of visceral fat mass accumulation during the aging process remains complex and largely unknown. Interleukin-6 (IL-6) has emerged as one of the prominent inflammaging markers which are elevated in circulation during aging. However, the precise role of IL-6 in regulating age-related visceral adipose tissue accumulation remains uncertain. RESULTS: A cross-sectional study including 77 older adults (≥65 years of age) was initially conducted. There was a significant positive association between serum IL-6 levels and visceral fat mass. We subsequently validated a modest but significant elevation in serum IL-6 levels in aged mice. Furthermore, we demonstrated that compared to wildtype control, IL-6 deficiency (IL-6 KO) significantly attenuated the accumulation of visceral adipose tissue during aging. Further metabolic characterization suggested that IL-6 deficiency resulted in improved lipid metabolism parameters and energy expenditure in aged mice. Moreover, histological examinations of adipose depots revealed that the absence of IL-6 ameliorated adipocyte hypertrophy in visceral adipose tissue of aged mice. Mechanically, the ablation of IL-6 could promote the PKA-mediated lipolysis and consequently mitigate lipid accumulation in adipose tissue in aged mice. CONCLUSION: Our findings identify a detrimental role of IL-6 during the aging process by promoting visceral adipose tissue accumulation through inhibition of lipolysis. Therefore, strategies aimed at preventing or reducing IL-6 levels may potentially ameliorate age-related obesity and improve metabolism during aging.

Experimental study of laser spot tracking for underwater optical wireless communication.

In this paper, a novel laser spot tracking algorithm that incorporates the Kalman filter with the continuously adaptive Meanshift algorithm (Cam-Kalm) is proposed and employed in an underwater optical wireless communication (UOWC) system. Since the Kalman filter has the advantage of predicting the state information of the target spot based on its spatial motion features, the proposed algorithm can improve the accuracy and stability of the moving laser spot tracking. A 2 m optical wireless communication experimental system with auto-tracking based on a green laser diode (LD) is built to evaluate the tracking performance of different algorithms. Experimental results verify that the proposed algorithm outperforms conventional tracking algorithms in aspects of tracking accuracy, interference resistance, and response time. With the proposed Cam-Kalm algorithm, the experimental system can establish an effective communication link, while the maximum tracking speed is 20 mm/s given the forward-error-correction (FEC) threshold.

Framework Nucleic Acids-Based VEGF Signaling Activating System for Angiogenesis: A Dual Stimulation Strategy.

Angiogenesis is crucial for tissue engineering, wound healing, and regenerative medicine. Nanomaterials constructed based on specific goals can be employed to activate endogenous growth factor-related signaling. In this study, based on the conventional single-stranded DNA self-assembly into tetrahedral framework nucleic acids (tFNAs), the Apt02 nucleic acid aptamer and dimethyloxallyl glycine (DMOG) small molecule are integrated into a complex via a template-based click chemistry reaction and toehold-mediated strand displacement reaction. Thus, being able to simulate the VEGF (vascular endothelial growth factor) function and stabilize HIF (hypoxia-inducible factor), a functional whole is constructed and applied to angiogenesis. Cellular studies demonstrate that the tFNAs-Apt02 complex (TAC) has a conspicuous affinity to human umbilical vein endothelial cells (HUVECs). Further incubation with DMOG yields the tFNAs-Apt02-DMOG complex (TACD), which promotes VEGF secretion, in vitro blood vessel formation, sprouting, and migration of HUVECs. Additionally, TACD enhances angiogenesis by upregulating the VEGF/VEGFR and HIF signaling pathways. Moreover, in a diabetic mouse skin defect repair process, TACD increases blood vessel formation and collagen deposition, therefore accelerating wound healing. The novel strategy simulating VEGF and stabilizing HIF promotes blood-vessel formation in vivo and in vitro and has the potential for broad applications in the vascularization field.

Central nervous system clear cell meningioma: a systematic literature review.

Clear cell meningiomas are a rare histological subtype of World Health Organization (WHO) grade II meningioma. Despite its relatively low frequency, clear cell meningioma has attracted considerable attention because of its unique pathological characteristics, clinical behavior, and challenging management considerations. The purpose of our systematic review is to provide clinicians with a better understanding of this rare disease. PubMed was searched for articles in the English language published from 1988 to 2023 June. The keywords were as follows: "clear cell meningioma," "clear cell" and "meningioma." We analyzed clinical manifestations, radiological manifestations, pathological features, comprehensive treatment strategies, and prognosis to determine the factors influencing recurrence-free survival (RFS). Recurrence-free survival curves of related factors were calculated by the Kaplan‒Meier method. The log-rank test and Cox univariate analysis were adopted to assess the intergroup differences and seek significant factors influencing prognosis and recurrence. Fifty-seven papers met the eligibility criteria, including 207 cases of clear cell meningioma (CCM), which were confirmed by postoperative pathology. The fifty-seven articles involved 84 (40.6%) males and 123 (59.4%) females. The average age at diagnosis was 27.9 years (range, 14 months to 84 years). Among the symptoms observed, headache, neurologic deficit, and hearing loss were the most commonly reported clinical manifestations. Most tumors (47.8%) were located in the skull base region. Most tumors showed significant enhancement, and homogeneous enhancement was more common. A total of 152 (74.1%) patients underwent gross total resection (GTR), and 53 (25.9%) patients underwent subtotal resection (STR). During the follow-up, the tumor recurred in 80 (39.4%) patients. The log-rank test and the Cox univariate analysis revealed that tumor resection range (GTR vs. STR) and adjuvant treatment (YES vs. NO) were significant predictors of recurrence-free survival (RFS). Clear cell meningioma is a rare type of meningioma with challenging diagnosis and therapy. The prognosis of this disease is different from that of regular meningiomas. Recurrence remains a possibility even after total tumor resection. We found that the surgical resection range and adjuvant treatment affected the recurrence period. This finding provides significant guidance for the treatment of clear cell meningioma.

SIRT1 activated by AROS sensitizes glioma cells to ferroptosis via induction of NAD+ depletion-dependent activation of ATF3.

Ferroptosis is a type of programmed cell death resulting from iron overload-dependent lipid peroxidation, and could be promoted by activating transcription factor 3 (ATF3). SIRT1 is an enzyme accounting for removing acetylated lysine residues from target proteins by consuming NAD+, but its role remains elusive in ferroptosis and activating ATF3. In this study, we found SIRT1 was activated during the process of RSL3-induced glioma cell ferroptosis. Moreover, the glioma cell death was aggravated by SIRT1 activator SRT2183, but suppressed by SIRT inhibitor EX527 or when SIRT1 was silenced with siRNA. These indicated SIRT1 sensitized glioma cells to ferroptosis. Furthermore, we found SIRT1 promoted RSL3-induced expressional upregulation and nuclear translocation of ATF3. Silence of ATF3 with siRNA attenuated RSL3-induced increases of ferrous iron and lipid peroxidation, downregulation of SLC7A11 and GPX4 and depletion of cysteine and GSH. Thus, SIRT1 promoted glioma cell ferroptosis by inducting ATF3 activation. Mechanistically, ATF3 activation was reinforced when RSL3-induced decline of NAD+ was aggravated by FK866 that could inhibit NAD + synthesis via salvage pathway, but suppressed when intracellular NAD+ was maintained at higher level by supplement of exogenous NAD+. Notably, the NAD + decline caused by RSL3 was enhanced when SIRT1 was further activated by SRT2183, but attenuated when SIRT1 activation was inhibited by EX527. These indicated SIRT1 promoted ATF3 activation via consumption of NAD+. Finally, we found RSL3 activated SIRT1 by inducing reactive oxygen species-dependent upregulation of AROS. Together, our study revealed SIRT1 activated by AROS sensitizes glioma cells to ferroptosis via activation of ATF3-dependent inhibition of SLC7A11 and GPX4.

Clinical efficacy and risk factors for suction curettage and hysteroscopy in patients with type I and II cesarean scar pregnancy.

OBJECTIVE: To investigate the clinical efficacy and evaluate risk factors for suction curettage (SC) and hysteroscopy in the treatment of type I and II cesarean scar pregnancy (CSP). METHODS: This was a retrospective study including 100 women diagnosed with type I/II CSP. Patients were treated with either ultrasound-guided SC (SC group) or hysteroscopy resection (surgery group). The success rates, mean operation time, hospitalization duration, hospitalization cost, risk factors, adverse events, and complications were analyzed. RESULTS: The success rate of the SC and surgery groups were 85% and 100%, respectively, and the difference was statistically significant (P = 0.032). There was one case of type I CSP and eight cases of type II CSP that failed SC treatment. No failed cases were found in the surgery group. Analysis of the causes of treatment failure revealed that diameter of the gestational sac was a risk factor for SC failure (odds ratio, 19.66 [95% confidence interval {CI}, 1.70-227.72], P = 0.017). Comparing the clinical outcomes between the SC and surgery groups, although the mean operation time of the SC group was significantly shorter than the surgery group (15 [CI, 15-20] vs. 30 [CI, 27-40], P = 0.001), the cost and duration of hospitalization were significantly lower in the surgery group than that in the SC group. No significant differences were observed for adverse events and complications between the two groups (P > 0.05). CONCLUSION: Hysteroscopy is an effective and economical method for treating type I/II CSP. Moreover, SC is not recommended for patients with type I/II CSP with a gestation age ≥8 weeks.

Optimal design of integrated visible light communication and positioning system with energy harvesting.

In this paper, an optimization scheme that can simultaneously transmit communication information, positioning the information and energy in a visible light communication and positioning (VLCP) system with energy harvesting is proposed. The time switching-power splitting (TS-PS) method is applied, where the power and time allocation factors are defined as optimization variables, so that the system can maximize the harvested energy under the constraints of the information rate and positioning error. The multi-verse optimization (MVO) algorithm is introduced to obtain the optimal power and time allocation. In addition, the performance of the integrated system using the TS-PS method is investigated and compared with that using other conventional methods. The results show that a maximized harvested energy solution using the TS-PS method can harvest the most energy. Moreover, the effects of main external environment conditions, namely, the room height and field of view (FoV) of a photo diode (PD) on the system performance are also analyzed. The increase of the room height and FoV of the PD reduces the harvested energy, but does not change the information rate and positioning accuracy in the optimized system adopted in this paper.

Enhanced YOLOv5 Object Detection Algorithm for Accurate Detection of Adult Rhynchophorus ferrugineus.

The red palm weevil (RPW, Rhynchophorus ferrugineus) is an invasive and highly destructive pest that poses a serious threat to palm plants. To improve the efficiency of adult RPWs' management, an enhanced YOLOv5 object detection algorithm based on an attention mechanism is proposed in this paper. Firstly, the detection capabilities for small targets are enhanced by adding a convolutional layer to the backbone network of YOLOv5 and forming a quadruple down-sampling layer by splicing and down-sampling the convolutional layers. Secondly, the Squeeze-and-Excitation (SE) attention mechanism and Convolutional Block Attention Module (CBAM) attention mechanism are inserted directly before the SPPF structure to improve the feature extraction capability of the model for targets. Then, 2600 images of RPWs in different scenes and forms are collected and organized for data support. These images are divided into a training set, validation set and test set following a ratio of 7:2:1. Finally, an experiment is conducted, demonstrating that the enhanced YOLOv5 algorithm achieves an average precision of 90.1% (mAP@0.5) and a precision of 93.8% (P), which is a significant improvement compared with related models. In conclusion, the enhanced model brings a higher detection accuracy and real-time performance to the RPW-controlled pest pre-detection system, which helps us to take timely preventive and control measures to avoid serious pest infestation. It also provides scalability for other pest pre-detection systems; with the corresponding dataset and training, the algorithm can be adapted to the detection tasks of other pests, which in turn brings a wider range of applications in the field of monitoring and control of agricultural pests.

Identifying a distinct fibrosis subset of NAFLD via molecular profiling and the involvement of profibrotic macrophages.

BACKGROUND: There are emerging studies suggesting that non-alcoholic fatty liver disease (NAFLD) is a heterogeneous disease with multiple etiologies and molecular phenotypes. Fibrosis is the key process in NAFLD progression. In this study, we aimed to explore molecular phenotypes of NAFLD with a particular focus on the fibrosis phenotype and also aimed to explore the changes of macrophage subsets in the fibrosis subset of NAFLD. METHODS: To assess the transcriptomic alterations of key factors in NAFLD and fibrosis progression, we included 14 different transcriptomic datasets of liver tissues. In addition, two single-cell RNA sequencing (scRNA-seq) datasets were included to construct transcriptomic signatures that could represent specific cells. To explore the molecular subsets of fibrosis in NAFLD based on the transcriptomic features, we used a high-quality RNA-sequencing (RNA-seq) dataset of liver tissues from patients with NAFLD. Non-negative matrix factorization (NMF) was used to analyze the molecular subsets of NAFLD based on the gene set variation analysis (GSVA) enrichment scores of key molecule features in liver tissues. RESULTS: The key transcriptomic signatures on NAFLD including non-alcoholic steatohepatitis (NASH) signature, fibrosis signature, non-alcoholic fatty liver (NAFL) signature, liver aging signature and TGF-ß signature were constructed by liver transcriptome datasets. We analyzed two liver scRNA-seq datasets and constructed cell type-specific transcriptomic signatures based on the genes that were highly expressed in each cell subset. We analyzed the molecular subsets of NAFLD by NMF and categorized four main subsets of NAFLD. Cluster 4 subset is mainly characterized by liver fibrosis. Patients with Cluster 4 subset have more advanced liver fibrosis than patients with other subsets, or may have a high risk of liver fibrosis progression. Furthermore, we identified two key monocyte-macrophage subsets which were both significantly correlated with the progression of liver fibrosis in NAFLD patients. CONCLUSION: Our study revealed the molecular subtypes of NAFLD by integrating key information from transcriptomic expression profiling and liver microenvironment, and identified a novel and distinct fibrosis subset of NAFLD. The fibrosis subset is significantly correlated with the profibrotic macrophages and M2 macrophage subset. These two liver macrophage subsets may be important players in the progression of liver fibrosis of NAFLD patients.

Effectiveness of clear aligners in achieving proclination and intrusion of incisors among Class II division 2 patients: a multivariate analysis.

BACKGROUND: The predictability of incisor movement achieved by clear aligners among Class II division 2 patients is poorly understood. The aim of this retrospective study was to determine the effectiveness of clear aligners in proclining and intruding upper incisors and its influencing factors. METHODS: Eligible patients with Class II division 2 malocclusion were included. For clear aligner therapy, three types of incisor movements were designed: proclination, intrusion and labial movement. Pre-treatment and post-treatment dental models were superimposed. The differences between predicted and actual (DPA) tooth movement of incisors were analyzed. Univariate and multivariate linear regression were used to analyze the potential influencing factors. RESULTS: A total of 51 patients and their 173 upper incisors were included. Actual incisor proclination and intrusion were less than predicted ones (both P < 0.001), while actual labial movement was greater than predicted one (P < 0.001). Predictability of incisor proclination and intrusion was 69.8% and 53.3%, respectively. Multivariate linear regression revealed that DPA of proclination was significantly positively associated with predicted proclination (B = 0.174, P < 0.001), ipsilateral premolar extraction (B = 2.773, P < 0.001) and ipsilateral canine proclination (B = 1.811, P < 0.05), while negatively associated with molar distalization (B = - 2.085, P < 0.05). The DPA of intrusion was significantly positively correlated with predicted intrusion (B = 0.556, P < 0.001) while negatively associated with labial mini-implants (B = - 1.466, P < 0.001). The DPA of labial movement was significantly positively associated with predicted labial movement (B = 0.481, P < 0.001), while negatively correlated with molar distalization (B = - 1.004, P < 0.001), labial mini-implants (B = - 0.738, P < 0.001) and age (B = - 0.486, P < 0.05). CONCLUSIONS: For Class II division 2 patients, predicted incisor proclination (69.8%) and intrusion (53.3%) are partially achieved with clear aligner therapy. Excessive labial movement (0.7 mm) of incisors may be achieved. Incisor movement is influenced by predicted movement amount, premolar extraction, canine proclination, molar distalization, mini-implants and age.

Corrigendum: Role of aerobic exercise in ameliorating NASH: Insights into the hepatic thyroid hormone signaling and circulating thyroid hormones.

[This corrects the article DOI: 10.3389/fendo.2022.1075986.].

Influence of group B streptococcus and vaginal cleanliness on the vaginal microbiome of pregnant women.

BACKGROUND: The vaginal microbiome plays a critical role in the health of pregnant women and their newborns. Group B Streptococcus (GBS) and vaginal cleanliness significantly affect the vaginal microecosystem and are closely associated with vaginal diseases. AIM: To explore the effects of GBS status and vaginal cleanliness on vaginal microecosystems. METHODS: We collected 160 vaginal swabs from pregnant women and divided them into the following four groups based on GBS status and vaginal cleanliness: GBS-positive + vaginal cleanliness I-II degree, GBS-negative + vaginal cleanliness I-II degree, GBS-positive + vaginal cleanliness III-IV degree, and GBS-negative + vaginal cleanliness III-IV degree. Samples were subjected to 16S rRNA gene amplicon sequencing. RESULTS: Alpha diversity analysis showed that the Shannon index did not significantly differ between the four groups. We identified significant variation in taxa abundance between the GBS-positive and GBS-negative groups and between the vaginal cleanliness I-II degree and III-IV degree groups. Principal coordinate analysis and non-metric multidimensional scaling analysis further confirmed the microbial diversity of the four groups. Moreover, the linear discriminant analysis demonstrated that Lactobacillus jensenii and Actinobacteria were strongly associated with GBS-positive status, and Lactobacillus iners, Lactobacillaceae, Lactobacillus, Lactobacillales, Bacilli and Firmicutes were closely correlated with GBS-negative status. CONCLUSION: GBS status and vaginal cleanliness significantly affect vaginal microbiome differences in pregnant women. Our findings provide instructional information for clinical antibiotic treatment in pregnant women with different GBS statuses and vaginal cleanliness degrees.

A Novel and Effective Model to Predict Skip Metastasis in Papillary Thyroid Carcinoma Based on a Support Vector Machine.

Introduction: Skip metastasis, referred to as lymph node metastases to the lateral neck compartment without involvement of the central compartment, is generally unpredictable in papillary thyroid carcinoma (PTC). This study aims to establish an effective predictive model for skip metastasis in PTC. Meterials and Methods: Retrospective analysis was performed of clinical samples from 18192 patients diagnosed with thyroid cancer between 2016 to 2020. The First Affiliated Hospital of Wenzhou Medical University. The lateral lymph node metastasis was occureed in the training set (630 PTC patients) and validation set (189 PTC patients). The univariate and multivariate analyses were performed to detect the predictors of skip metastasis and the support vector machine (SVM) was used to establish a model to predict skip metastasis. Results: The rate of skip metastasis was 13.3% (84/631). Tumor size (≤10 mm), upper location, Hashimoto's thyroiditis, extrathyroidal extension, absence of BRAFV600E mutation, and less number of central lymph node dissection were considered as independent predictors of skip metastasis in PTC. For the training set, these predictors performed with 91.7% accuracy, 86.4% sensitivity, 92.2% specificity, 45.2% positive predictive value (PPV), and 98.9% negative predictive value (NPV) in the model. Meanwhile, these predictors showed 91.5% accuracy,71.4% sensitivity, 93.1% specificity, 45.5% PPV, and 97.6% NPV in validation set. Conclusion: This study screened the predictors of the skip lateral lymph node metastasis and to establish an effective and economic predictive model for skip metastasis in PTC. The model can accurately distinguish the skip metastasis in PTC using a simple and affordable method, which may have potential for daily clinical application in the future.

Tetrahedral Framework Nucleic Acids Connected with MicroRNA-126 Mimics for Applications in Vascular Inflammation, Remodeling, and Homeostasis.

The repair of damaged endothelium is crucial for vascular homeostasis maintenance, which comprises the recovery of early stage impaired endothelial cells and migration of surrounding unimpaired endothelial cells. MicroRNAs (miRNAs) play an indispensable role in balancing gene expression in organisms. For vascular tissues, miR-126 is one of the most important regulators and might have substantial application potential in maintaining vascular homeostasis. In this study, a type of sticky-end-modified tetrahedral framework nucleic acids (tFNAs-SE) was employed to successfully link the miR-126 5p mimic duplex, which was termed tFNAs-miR-126 5p mimics (tFNAs-MMs). Existing vascular endothelial growth factors (VEGF), tFNAs-MMs can improve cell viability, resist apoptosis, and recover the state and functions of LPS-induced impaired human umbilical vein endothelial cells (HUVECs). The angiogenesis ability of impaired HUVECs was recovered by tFNAs-MMs in vitro and in vivo. The mechanisms underlying these phenomena were demonstrated to be related to the downregulation of caspase3 and negative regulators of VEGF (SPRED1 and PIK3R2). Moreover, tFNAs-MMs promoted the migration and proliferation of HUVECs. Briefly, the strategy of sticky-end-modified tFNAs connecting miRNA mimics is available for miRNA gain of function, while tFNAs-MMs might be a promising agent for repairing early stage vascular damage and maintaining vascular homeostasis.

Role of aerobic exercise in ameliorating NASH: Insights into the hepatic thyroid hormone signaling and circulating thyroid hormones.

Aim: Triiodothyronine (T3) administration significantly eliminates hepatic steatosis and also has a therapeutic effect on non-alcoholic steatohepatitis (NASH). However, the potential mechanism by which T3-mediated exercise improves NASH is unknow. This study aimed to explore the effect of aerobic exercise on liver injury in NASH. Methods: Aerobic exercise was conducted to explore the effects of exercise on liver injury in NASH model induced by Atherosclerotic (Ath) diet. Biochemical evaluations, histological staining and real-time PCR were first applied to confirm the amelioration effects of exercise on NASH. RNA-sequencing (RNA-seq) analysis for livers of each group were further used to identify the underlying mechanisms of aerobic exercise. Bioinformatics methods were used to explore the key functional pathways involved in the improvement of liver tissue in NASH mice by aerobic exercise. Results: Aerobic exercise improved hepatic steatosis, lobular inflammation and fibrosis in NASH mice. multiple inflammation-related pathways were significantly enriched in the liver of NASH group and improved by aerobic exercise. The results of gene set variation analysis (GSVA) showed a higher enrichment score of T3 response signature in NASH mice with exercise. Increased Dio1 expression in the liver of NASH with exercise mice and increased circulating FT3 and FT4 levels upon aerobic exercise were confirmed. Conclusions: We found that aerobic exercise could significantly reduce hepatic lipid accumulation, inflammatory infiltration and fibrosis progression in the liver of NASH mice. Hepatic thyroid hormone signaling activation and circulating thyroid hormones is potentially involved in the amelioration effect of aerobatic exercise on NASH progression.

Molecular mechanism in trigeminal nerve and treatment methods related to orthodontic pain.

BACKGROUND: Orthodontic treatment is the main treatment approach for malocclusion. Orthodontic pain is an inevitable undesirable adverse reaction during orthodontic treatment. It is reported orthodontic pain has become one of the most common reason that patients withdraw from orthodontic treatment. Therefore, understanding the underlying mechanism and finding treatment of orthodontic pain are in urgent need. AIMS: This article aims to sort out the mechanisms and treatments of orthodontic pain, hoping to provide some ideas for future orthodontic pain relief. MATERIALS: Tooth movement will cause local inflammation. Certain inflammatory factors and cytokines stimulating the trigeminal nerve and further generating pain perception, as well as drugs and molecular targeted therapy blocking nerve conduction pathways, will be reviewed in this article. METHOD: We review and summaries current studies related to molecular mechanisms and treatment approaches in orthodontic pain control. RESULTS: Orthodontics pain related influencing factors and molecular mechanisms has been introduced. Commonly used clinical methods in orthodontic pain control has been evaluated. DISCUSSION: With the clarification of more molecular mechanisms, the direction of orthodontic pain treatment will shift to targeted drugs.

Substrate stiffness regulates the differentiation profile and functions of osteoclasts via cytoskeletal arrangement.

OBJECTIVES: Aging and common diseases alter the stiffness of bone tissue, causing changes to the microenvironment of the mechanosensitive bone cells. Osteoclasts, the sole bone-resorbing cells, play a vital role in bone remodeling. This study was performed to elucidate the mechanism through which osteoclasts sense and react to substrate stiffness signals. MATERIALS AND METHODS: We fabricated polydimethylsiloxane (PDMS) substrates of different stiffness degrees for osteoclast formation progressed from osteoclast precursors including bone marrow-derived macrophages (BMMs) and RAW264.7 monocytes. Osteoclast differentiation in response to the stiffness signals was determined by examining the cell morphology, fusion/fission activities, transcriptional profile, and resorption function. Cytoskeletal changes and mechanosensitive adhesion molecules were also assessed. RESULTS: Stiffer PDMS substrates accelerated osteoclast differentiation, firstly observed by variations in their morphology and fusion/fission activities. Upregulation of canonical osteoclast markers (Nfatc1, Acp5, Ctsk, Camk2a, Mmp9, Rela, and Traf6) and the fusion master regulator DC-stamp were detected on stiffer substrates, with similar increases in their bone resorption functions. Additionally, the activation of cytoskeleton-associated adhesion molecules, including fibronectin and integrin αvß3, followed by biochemical signaling cascades of paxillin, FAK, PKC, and RhoA, was detected on the stiffer substrates. CONCLUSIONS: This is the first study to provide evidence proving that extracellular substrate stiffness is a strong determinant of osteoclast differentiation and functions. Higher stiffness upregulated the differentiation profile and activity of osteoclasts, revealing the mechanical regulation of osteoclast activity in bone homeostasis and diseases.

Pan-cancer analysis of the prognostic and immunological role of PSMB8.

Recently some evidence has demonstrated the significance of PSMB8 in various malignancies. Nevertheless, PSMB8 (proteasome subunit beta 8), more familiar in the field of immunology contributing to the process of antigen presentation, is indeterminate in the role as a survival predictor of human pan-cancer. Besides, how PSMB8 interacts with immune cell infiltration in the tumor microenvironment requires further research. We then penetrated into the analysis of the PSMB8 expression profile among 33 types of cancer in the TCGA database. The results show that overexpression of PSMB8 was associated with poor clinical outcomes in overall survival (Sartorius et al. in Oncogene 35(22):2881-2892, 2016), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) in most cancer varieties. In addition, there existed distinctly positive correlations between PSMB8 and immunity, reflected straightforwardly in the form of immune scores, tumor-infiltrating immune cells (TIICs) abundance, microsatellite instability, tumor mutation burden, and neoantigen level. Notably, specific markers of dendrite cells exhibited the tightest association with PSMB8 expression in terms of tumor-related immune infiltration patterns. Moreover, gene enrichment analysis showed that elevated PSMB8 expression was related to multiple immune-related pathways. We finally validated the PSMB8 expression in our local breast samples via quantitative PCR assays and concluded that PSMB8 appeared to perform well in predicting the survival outcome of BRCA patients. These findings elucidate the pivotal role of the antigen presentation-related gene PSMB8, which could potentially serve as a robust biomarker for prognosis determination in multiple cancers.

Are Osteoclasts Mechanosensitive Cells?

Skeleton metabolism is a process in which osteoclasts constantly remove old bone and osteoblasts form new osteoid and induce mineralization; disruption of this balance may cause diseases. Osteoclasts play a key role in bone metabolism, as osteoclastogenesis marks the beginning of each bone remodeling cycle. As the only cell capable of bone resorption, osteoclasts are derived from the monocyte/macrophage hematopoietic precursors that terminally adhere to mineralized extracellular matrix, and they subsequently break down the extracellular compartment. Bone is generally considered the load-burdening tissue, bone homeostasis is critically affected by mechanical conductions, and the bone cells are mechanosensitive. The functions of various bone cells under mechanical forces such as chondrocytes and osteoblasts have been reported; however, the unique bone-resorbing osteoclasts are less studied. The oversuppression of osteoclasts in mechanical studies may be because of its complicated differentiation progress and flexible structure, which increases difficulty in targeting mechanical structures. This paper will focus on recent findings regarding osteoclasts and attempt to uncover proposed candidate mechanosensing structures in osteoclasts including podosome-associated complexes, gap junctions and transient receptor potential family (ion channels). We will additionally describe possible mechanotransduction signaling pathways including GTPase ras homologue family member A (RhoA), Yes-associated protein/transcriptional co-activator with PDZ-binding motif (TAZ), Ca2+ signaling and non-canonical Wnt signaling. According to numerous studies, evaluating the possible influence of various physical environments on osteoclastogenesis is conducive to the study of bone homeostasis.