Response and adaptation mechanisms of Apostichopus japonicus to single and combined anthropogenic stresses of polystyrene microplastics or cadmium.

Microplastics (MPs) have become pervasive in marine ecosystems, exerting detrimental effects on marine life. The concurrent presence and interaction of MPs and heavy metals in aquatic environments could engender more insidious toxicological impacts. This study aimed to elucidate the potential impacts and underlying mechanisms of polystyrene microplastics (PS-MPs), cadmium (Cd), and their combined stress (MPs-Cd) on sea cucumbers (Apostichopus japonicus). It focused on the growth, Cd bioaccumulation, oxidative stress responses, immunoenzymatic activities, and metabolic profiles, specifically considering PS-MPs sizes preferentially ingested by these organisms. The high-dose MPs (MH) treatment group exhibited an increase in cadmium bioavailability within the sea cucumbers. Exposure to PS-MPs or Cd triggered the activation of antioxidant defenses and immune responses. PS-MPs and Cd exhibited a synergistic effect on lysozyme (LZM) activity. A total of 149, 316, 211, 197, 215, 619, 434, and 602 differentially expressed metabolites were identified, distinguishing the low-dose MPs (ML), high-dose MPs (MH), low-dose Cd (LCd), low-dose MPs and low-dose Cd (MLLCd), high-dose MPs and low-dose Cd (MHLCd), high-dose Cd (HCd), low-dose MPs and high-dose Cd (MLHCd), high-dose MPs and high-dose Cd (MHHCd) groups, respectively. Metabolomic analyses revealed disruptions in lipid metabolism, nervous system function, signal transduction, and transport and catabolism pathways following exposure to PS-MPs, Cd, and MPs-Cd. Correlation analyses among key differentially expressed metabolites (DEMs) underscored the interregulation among these metabolic pathways. These results offer new perspectives on the distinct and synergistic toxicological impacts of microplastics and cadmium on aquatic species, highlighting the complex interplay between environmental contaminants and their effects on marine life.

Three different patellar fixation techniques yield similar clinical and radiological outcomes in recurrent patellar dislocation undergoing medial patellofemoral ligament reconstruction.

PURPOSE: The purpose of this study was to evaluate and compare the clinical and radiological outcomes of three different patellar fixation techniques on medial patellofemoral ligament reconstruction (MPFLR) in the treatment of patellar dislocation (PD). METHODS: Between 2015 and 2020, 130 patients with recurrent PD who underwent surgical reconstruction were eligible for this retrospective study: 48 patients were treated with the semi-tunnel bone bridge fixation technique (Group A), 42 patients were treated with the suture anchor fixation technique (Group B) and 40 patients were treated with the transpatellar tunnel fixation technique (Group C). Clinical outcomes included functional outcomes (Kujala, Lysholm and International Knee Documentation Committee scores), activity levels (Tegner activity score and return to sports), physical examinations, patellar re-dislocation rate and complications. Radiological outcomes included patellar congruence angle, patellar tilt angle, lateral patellar translation and lateral patellar angle. RESULTS: All clinical and radiological outcomes improved significantly in all groups, without any significant difference among these three groups. At the final follow-up, no re-dislocation occurred, and all groups achieved a successful return to sports. However, the semi-tunnel bone bridge and suture anchor fixation techniques showed statistically higher Tegner activity scores (p = 0.004) and shorter time from surgery to return to sports (p = 0.007) than the transpatellar tunnel fixation technique. CONCLUSION: The three MPFLR patellar fixation techniques achieved favourable and comparable clinical and radiological outcomes in the treatment of PD. Compared with the transpatellar tunnel fixation technique, the semi-tunnel bone bridge and suture anchor fixation techniques may be more effective with higher activity levels. LEVEL OF EVIDENCE: Level III.

A Novel Hierarchical Cross-Stream Aggregation Neural Network for Semantic Segmentation of 3-D Dental Surface Models.

Accurate teeth delineation on 3-D dental models is essential for individualized orthodontic treatment planning. Pioneering works like PointNet suggest a promising direction to conduct efficient and accurate 3-D dental model analyses in end-to-end learnable fashions. Recent studies further imply that multistream architectures to concurrently learn geometric representations from different inputs/views (e.g., coordinates and normals) are beneficial for segmenting teeth with varying conditions. However, such multistream networks typically adopt simple late-fusion strategies to combine features captured from raw inputs that encode complementary but fundamentally different geometric information, potentially hampering their accuracy in end-to-end semantic segmentation. This article presents a hierarchical cross-stream aggregation (HiCA) network to learn more discriminative point/cell-wise representations from multiview inputs for fine-grained 3-D semantic segmentation. Specifically, based upon our multistream backbone with input-tailored feature extractors, we first design a contextual cross-steam aggregation (CA) module conditioned on interstream consistency to boost each view's contextual representation learning jointly. Then, before the late fusion of different streams' outputs for segmentation, we further deploy a discriminative cross-stream aggregation (DA) module to concurrently update all views' discriminative representation learning by leveraging a specific graph attention strategy induced by multiview prototype learning. On both public and in-house datasets of real-patient dental models, our method significantly outperformed state-of-the-art (SOTA) deep learning methods for teeth semantic segmentation. In addition, extended experimental results suggest the applicability of HiCA to other general 3-D shape segmentation tasks. The code is available at https://github.com/ladderlab-xjtu/HiCA.

Intelligent algorithm based on deep learning to predict the dosage for anesthesia: A study on prediction of drug efficacy based on deep learning.

Background and Aims: Anesthetic drugs play a vital role during surgery, however, due to individual differences and complex physiological mechanisms, the prediction of anesthetic drug dosage has always been a challenging problem. In this study, we propose a model for predicting the dosage of anesthetic drugs based on deep learning to help anesthesiologists better control their dosage during surgical procedures. Methods: We design a model based on the artificial neural network to predict the dosage of preoperative anesthetic, and use the SELU activation function and the loss function for weighted regularization to solve the problem of unbalanced sample. Moreover, we design a CNN-based model for the prior extraction of intraoperative features by using a 7 × 1 convolution kernel to enhance the receptive field, and combine maximum pooling and average pooling to extract key features while eliminating noise. A predictive model based on the LSTM network is designed to predict the intraoperative dosage of the anesthetic, and the bidirectional propagation-based LSTM network is used to improve the ability to learn the trend of changes in the physiological states of the patient during surgery. An attention module is added before the connection layer to appropriately attend to areas containing prominent features. Results: The results of experiments showed that the proposed method reduced values of the MAPE to 15.83% and 12.25% compared with the traditional method in predictions of the preoperative and intraoperative doses of the anesthetic, respectively, and increased the values of R2 to 0.887 and 0.915, respectively. Conclusion: The intelligent anesthesia prediction algorithm designed in this study can effectively predict the dosage of anesthetic drugs needed by patients, assist clinical judgment of anesthetic drug dose, and assist the anesthesiologists to ensure the smooth progress of the operation.

Decreased femoral trochlea axial orientation corrected by derotational distal femur osteotomy in patients with patellar dislocation yields satisfactory outcomes.

PURPOSE: The femoral trochlea axial orientation has been shown to be a better predictor of patellar dislocation than the femoral anteversion angle. However, no study has investigated the importance of the femoral trochlea axial orientation in the surgical treatment of patellar dislocation. It is aimed to explore the pathological threshold of the femoral trochlea axial orientation and its guiding implications for surgical interventions in the study. METHODS: Sixty-four patients with patellar dislocation and 64 controls were included for measurement of the femoral trochlea axial orientation. The ability to predict the patellar dislocation and the pathologic threshold of the femoral trochlea axial orientation were evaluated using the receiver operating characteristic curve. One hundred patients with medial patellofemoral ligament reconstruction and 25 patients with derotational distal femur osteotomy were divided into two groups based on the femoral trochlea axial orientation cut-off value and their postoperative knee functions, and patellar tilt angles were compared. RESULTS: There were significant differences in the femoral trochlea axial orientation (60.8 ± 7.9 vs. 67.8 ± 4.6, p < 0.05) between patients with patellar dislocation and the normal population. The sensitivity and specificity of the femoral trochlea axial orientation were 0.641 and 0.813, respectively, at the femoral trochlea axial orientation smaller than 63.8°. Amongst patients having had isolated medial patellofemoral ligament reconstruction with decreased femoral trochlea axial orientation, knee function was poorer after surgery. The prognosis of patients with the femoral trochlea axial orientation correction in derotational distal femur osteotomy was better than that for patients without correction. CONCLUSIONS: The femoral trochlea axial orientation had good predictive efficiency for patellar dislocation. Isolated medial patellofemoral ligament reconstruction is not sufficiently effective for patients with patellar dislocation and decreased femoral trochlea axial orientation. Patients with a decreased femoral trochlea axial orientation can have better surgical outcomes after correction by derotational distal femur osteotomy. LEVEL OF EVIDENCE: Level III.

Reliability of Tibial Tubercle-Trochlear Groove Distance for Assessing Tibial Tubercle Lateralization: A Study Comparing Different Anatomic References.

Background: The tibial tubercle-trochlear groove (TT-TG) distance is a measurement used to quantitatively assess tibial tubercle lateralization (TTL), and it has important reference value for the treatment of patellar dislocation (PD). However, TT-TG distance accuracy has been questioned, so many new parameters have been proposed. Purpose: To compare which of the TT-TG, tibial tubercle-midepicondyle (TT-ME), tibial tubercle-Roman arch (TT-RA), tibial tubercle-tibial intercondylar midpoint (TT-TIM), and tibial tubercle-mid inter-epicondyle trochlea intersection (TT-MIELTI) distances better reflect TTL in patients with PD. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: A total of 96 patients who had undergone surgery for PD and 96 patients without PD (controls) were included in the study. The patients had all undergone computed tomography examination. The TT-TG, TT-ME, TT-RA, TT-TIM, TT-MIELTI distances and the TTL distance were measured independently by 2 surgeons in a blinded and randomized fashion. The t test was used to detect whether the parameters were significantly different between the 2 groups. The TTL distance was used as a reference value for lateralization of tibial tubercle. Pearson correlation coefficients were calculated to determine correlations between the defined measurements. Results: The intra- and interobserver reliability of the defined measurements was excellent. All parameters except for TT-TIM distance were significantly larger in the PD group than the control group (P < .01 for all). There was a moderate correlation (r = 0.601) between the TT-TG distance and TTL, and other parameters were less correlated with TTL. Conclusion: Among 5 the parameters tested, the TT-TG distance still had the highest correlation with TTL and was able to reflect TTL better in patients with PD. The role of TT-TIM distance in the assessment of PD needs further study.

TP508 Promotes Bone Regeneration on Distraction Osteogenesis via the Activation of Wnt/ß-catenin Signaling Pathway.

INTRODUCTION: TP508 is a thrombin peptide that participates in the inflammatory response and wound healing. Its role in the molecular mechanism of distraction osteogenesis remains unclear. This study established a tibia distraction osteogenesis (DO) model in rats and investigated the role and mechanism of TP508 in bone regeneration during DO. METHOD: Micro-computed tomography (Micro-CT) and hematoxylin-eosin (HE) staining were used to track osteogenesis. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to measure the expression of osteoblast-related factors, Wnt/ß- catenin signaling-related proteins and genes. Immunohistochemistry was used to measure the expression of ß-catenin in the cytoplasm and nucleus. TP508 accelerated bone regeneration increased the expression of the osteoblast-related factors Alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN). RESULTS: After the Wnt signaling was inhibited by LGK974, the expression of osteoblast-related factors was downregulated, leading to a decrease in bone regeneration ability. More importantly, TP508 upregulated ß-catenin and its target CYCLIN-D1 and could reverse the decreased osteogenic ability caused by LGK974. CONCLUSION: In conclusion, TP508 promotes bone regeneration in DO by activating the Wnt/ß- catenin signaling pathway.

Hippo/YAP1 promotes osteoporotic mice bone defect repair via the activating of Wnt signaling pathway.

BACKGROUND: This study is to investigate the role and mechanism of Hippo/YAP1 in the repair of osteoporotic bone defects in aged mice, both in vivo and in vitro. METHODS: We investigated the expression differences of the Hippo signaling in young and aged individuals both in vivo and in vitro. By manipulating the expression of Lats1/2 and Yap1, we investigated the role of Hippo/YAP1 in regulating osteogenic differentiation in aged BMSCs. In vivo, by intervening in the local and systemic expression of Lats1/2 and Yap1 respectively, we sought to demonstrate whether Hippo/YAP1 promotes the repair of bone defects in aged osteoporotic conditions. Finally, we delved into the underlying mechanisms of Hippo/YAP1 in regulating osteogenic differentiation. RESULTS: We observed differences in the expression of the Hippo signaling between young and aged individuals. After knocking out Lats1/2 in aged BMSCs, we observed that the upregulation of endogenous YAP1 promotes cellular osteogenic differentiation and proliferation capacity. Through interference with Yap1 expression, we provided strong evidence for the role of Hippo/YAP1 in promoting osteogenic differentiation in aged BMSCs. In vivo, we confirmed that Hippo/YAP1 promotes the repair of bone defects in aging osteoporosis. Moreover, we discovered an interaction relationship among YAP1, ß-catenin, and TEAD1. CONCLUSION: This study elucidates the role of Hippo/YAP1 in promoting the repair of osteoporotic bone defects in aged mice. Mechanistically, YAP1 functions by activating the Wnt/ß-catenin pathway, and this process is not independent of TEAD1.

A Dynamical Systems Investigation of the Co-regulation between Perceived Daily Parental Warmth and Adolescent Attention-deficit/hyperactivity Disorder Symptoms.

Longitudinal research demonstrates that child ADHD symptoms and behaviors exhibit reciprocal associations with parenting behaviors over time. However, minimal research has investigated these associations and their dynamic links at the daily level. Intensive longitudinal data can disentangle stable between-person differences from within-person fluctuations and reveal nuanced short-term family dynamics on a micro timescale. Using 30-day daily diary data from a community sample of 86 adolescents (Mage = 14.5, 55% female, 56% White, 22% Asian) and latent differential equation modeling, this study examined the links between perceived daily parental warmth and ADHD symptoms as coupled dynamical systems. The results show that the magnitude of fluctuations in perceived daily parental warmth generally remains stable, while elevated ADHD symptoms return to their normal level over time. Perceived parental warmth is sensitive to change in ADHD symptoms such that adolescents feel that their parents will fine-tune their warmth with gradual changes when adolescents demonstrate heightened symptoms. There are substantial between-family differences in these regulating system dynamics. Among families with more baseline parental non-harsh discipline, both perceived parental warmth and ADHD symptoms tend to be more stable and fluctuate less often. Intensive longitudinal data and dynamical systems approaches offer a new lens to uncover short-term family dynamics and adolescent adjustment at a refined micro level. Future research should explore antecedents and consequences of between-family differences in these short-term family dynamics on multiple timescales.

LATS1/YAP1 Axis Controls Bone Regeneration on Distraction Osteogenesis by Activating Wnt/ß-Catenin.

The Hippo signaling pathway inhibits cell growth, and its components and functions are highly conserved in mammals. LATS1 is a core component of the Hippo signaling pathway associated with lymphatic invasion, astrogliosis, apoptosis, and autophagy. Nevertheless, the role of Hippo/LATS1 in osteogenesis remains unclear. In this study, we used ribonucleic acid (RNA) lentiviruses to inhibit the expression of Lats1 in bone marrow-derived stem cells (BMSCs) and distraction osteogenic regions in rats. Increased osteogenic, proliferative, and migratory abilities of BMSCs were observed in Lats1-inhibited BMSCs, while these phenotypes were partially reversed by YAP1 inhibition. In vivo, we found that the LATS1/YAP1 axis promoted osteogenesis during distraction osteogenesis (DO). ß-catenin was positively correlated with YAP1 expression in vivo and in vitro. When YAP1 was strongly positive in the nucleus, ß-catenin expression was upregulated; when YAP1 expression was inhibited by verteporfin, ß-catenin was not expressed in the nucleus. These findings suggest that the LATS1/YAP1 signaling axis promotes DO by activating the Wnt/ß-catenin signaling pathway. This study provides insights into the molecular mechanism of osteogenesis and a potential therapeutic strategy for bone regeneration in DO by associating with LATS1/YAP1-ß-catenin.

The larger patellar tilt angle and lower intercondylar notch angle might increase posterior cruciate ligament injury risk: a retrospective comparative study.

BACKGROUND: Posterior cruciate ligament (PCL) injuries are common ligament injuries of the knee, and previous studies often focused on the associations between the morphology of the knee and PCL injuries. Studies on the correlation between PCL injuries and patellofemoral alignment are limited. METHODS: This retrospective study included 92 patients with PCL injured and 92 patients with PCL intact. Measurement parameters were compared between the two groups, including patellar tilt angle, congruence angle, patellar height, hip-knee-ankle angle, lateral trochlear inclination, femoral condyle ratio, bicondylar width, intercondylar notch width and index, notch angle, trochlear facet asymmetry, and trochlear sulcus depth and angle. Independent risk factors associated with PCL injuries were identified by logistic regression analyses. RESULTS: In the PCL injured group, the patellar tilt angle was significantly larger (13.19 ± 5.90° vs. 10.02 ± 4.95°, P = 0.04); the intercondylar notch angle was significantly lower (60.97 ± 7.83° vs. 67.01 ± 6.00°, P = 0.004); the medial and lateral femoral condyle ratio were significantly larger (0.63 ± 0.64 vs. 0.60 ± 0.56, P = 0.031; 0.65 ± 0.60 vs. 0.58 ± 0.53, P = 0.005) than in the PCL intact group. There were 11 patients with patellar dislocation in the PCL injured group, accounting for 12%. In these patients, the patellar height was higher (1.39 ± 0.17 vs. 1.09 ± 0.25, P = 0.009); the trochlear sulcus angle was larger (157.70 ± 8.7° vs. 141.80 ± 8.78°, P < 0.001); and the trochlear sulcus depth was shallower (3.10 ± 1.20mm vs. 5.11 ± 1.48mm, P = 0.003) than those in the patients without patellar dislocation. Multivariate analyses showed that patellar tilt angle (each increase 1 degree, OR = 1.14) and intercondylar notch angle (each increase 1 degree, OR = 0.90) were independent risk factors for PCL injuries. CONCLUSION: The patients with PCL injuries had larger patellar tilt angles, lower intercondylar notch angles, and longer posterior femoral condyles than patients with PCL intact. The larger patellar tilt angle and lower intercondylar notch angle might be risk factors for PCL injuries.

Methane hydrate phase equilibrium considering dissolved methane concentrations and interfacial geometries from molecular simulations.

Natural gas hydrates, mainly existing in permafrost and on the seabed, are expected to be a new energy source with great potential. The exploitation technology of natural gas hydrates is one of the main focuses of hydrate-related studies. In this study, a large-size liquid aqueous solution wrapping a methane hydrate system was established and molecular dynamics simulations were used to investigate the phase equilibrium conditions of methane hydrate at different methane concentrations and interfacial geometries. It is found that the methane concentration of a solution significantly affects the phase equilibrium of methane hydrates. Different methane concentrations at the same temperature and pressure can lead to hydrate formation or decomposition. At the same temperature and pressure, in a system reaching equilibrium, the size of spherical hydrate clusters is coupled to the solution concentration, which is proportional to the Laplace pressure at the solid-liquid interface. Lower solution concentrations reduce the phase equilibrium temperature of methane hydrates at the same pressure; as the concentration increases, the phase equilibrium temperature gradually approaches the actual phase equilibrium temperature. In addition, the interfacial geometry of hydrates affects the thermodynamic stability of hydrates. The spherical hydrate particles have the highest stability for the same volume. Through this study, we provide a stronger foundation to understand the principles driving hydrate formation/dissociation relevant to the exploitation of methane hydrates.

Predicting the Probability of Recurrence Based on Individualized Risk Factors After Primary Lateral Patellar Dislocation Treated Nonoperatively.

PURPOSE: To develop a comprehensive and effective personalized scoring system on the basis of demographic and clinical characteristics for predicting recurrence probability in patients with primary lateral patellar dislocation (LPD). METHODS: Participants included 261 primary patients with LPD with 2-year minimum follow-up from our hospital across 2013 to 2020. Demographic and clinical characteristics were collected retrospectively. The backward stepwise method was performed to identify independent predictors and construct a nomogram to predict the probability of recurrence. The predictive performance was assessed by receiver operating characteristic curves, calibration plots, and decision curve analysis. RESULTS: After variables selection, 6 independent predictors of recurrence (skeletal maturity, trochlear dysplasia, tibial tuberosity-trochlear groove distance, mechanical axis deviation, Insall-Salvati index, and patellar tilt) were enrolled in our model. Validation of this nomogram in both training and validation cohort revealed powerful predictive ability, with an area under the curve of 0.962 and 0.977, respectively. The nomogram also showed great calibration and good clinical practicability. CONCLUSIONS: Our study presented a nomogram that incorporates 6 independent risk factors (skeletal maturity, trochlear dysplasia, tibial tuberosity-trochlear groove distance, mechanical axis deviation, Insall-Salvati index, and patellar tilt), which can be conveniently used to accurately predicts the risk of recurrence after primary LPD in individual cases. LEVEL OF EVIDENCE: Level III, retrospective comparative prognostic study.

Facilitation of Hydrate Dissociation and Structural Evolution by Major Marine Anions under Static Electric Fields.

Electric fields have been proven to be capable of significantly affecting the equilibrium state of hydrates. In this study, the thermodynamic properties and structural changes of methane hydrate (MH) in various anion solutions in an electric field at 0.7 V/nm were investigated by molecular dynamics simulations. The presence of anions significantly enhances the instability of methane hydrates under electric fields, leading to a staged dissociation process. First, the anions coexist with MH to form a temporary metastable structure under the action of an electric field. Then, the migration of anions causes the dissociation of nearby hydrates and the formation of flow channels in the hydrate layer, which leads to the complete dissociation of MH after a period. The promotive effects of F-, Br-, I-, and Cl- ions were close, while SO42- was relatively weak. The anions are still in hydration shells in the MH phase, but the structure of the hydration shells differs slightly from that in solution (the coordination numbers of I- and SO42- ions increased). The migration resistances of multiple anions to cross the surface of the hydrate layer are similar. However, inside the hydrate phase, the anions with a larger radius have a higher migration resistance. It is difficult for SO42- ions to migrate inside the hydrate phase, and they tend to form a metastable structure on the hydrate surface. Combining our previous studies, SrCl2 solution has the best hydrate promotion under an electric field environment.

Age at menarche and metabolic dysfunction-associated fatty liver disease: Evidence from a large population-based epidemiological study in Southwest China.

BACKGROUND: The relationship between age at menarche and metabolic dysfunction-associated fatty liver disease remains largely not clear. The objective of this study was to examine the association between age at menarche (AAM) and metabolic dysfunction-associated fatty liver disease (MAFLD) in Chinese women and whether any observed associations were mediated by early adulthood adiposity. METHODS: The cross-sectional study included 46,873 Chinese women, aged 30-79 from baseline data of the China Multi-Ethnic Cohort study. Logistic regression models were used to evaluate the association between AAM and MAFLD. Mediation analysis was adopted to examine whether early adulthood adiposity (around 25 years) mediated the association between AAM and MAFLD. RESULTS: AAM was linearly and inversely associated with the risk of MAFLD (P for nonlinearity =0.743). In a multivariable-adjusted model, the odds ratios and 95% confidence interval (ORs (95% CI)) for MAFLD comparing menarche at <12, 12, 13, 15, 16, 17, ≥18 years to menarche at 14 years were 1.290 (1.082-1.537), 1.172 (1.068-1.285), 1.042 (0.960-1.131), 0.937 (0.861-1.020), 0.911(0.835-0.994), 0.868 (0.786-0.959), and 0.738 (0.670-0.814), respectively (P for trend <0.001). The 6.4% increased MAFLD risk was associated with each preceding year in AAM. The association between AAM and MAFLD was modified by age, ethnicity, and menopause. Early adulthood adiposity partially mediated this association. CONCLUSION: The findings of this study suggest that obesity prevention strategies are needed from young adulthood in women who undergo early menarche to reduce the risk of MAFLD.

Investigating the potential mechanism of quercetin against cervical cancer.

BACKGROUND: Cervical cancer is emerging as a potential target of increased susceptibility to coronavirus disease-2019 (COVID-19), leading to compromised survival rates. Despite this critical link, efficacious anti-cervical cancer/COVID-19 interventions remain limited. Quercetin, known for its efficacy against both cancer and viral infections, holds promise as a therapeutic agent. This study aims to elucidate quercetin's anti-cervical cancer/COVID-19 mechanisms and potential targets. METHODS: We initiated our investigation with differential gene expression analysis using cervical cancer transcriptome data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx), focusing on intersections with COVID-19-related genes. Network pharmacology was employed to identify the shared targets between cervical cancer/COVID-19 DEGs and quercetin's targets. Subsequently, Cox proportional hazards analyses were employed to establish a risk score based on these genes. Molecular docking techniques were applied to predict quercetin's therapeutic targets and mechanisms for mitigating cervical cancer and COVID-19. RESULTS: Our findings unveiled 45 potential quercetin targets with anti-cervical cancer/COVID-19 actions. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses highlighted significant enrichment in immune pathways and COVID-19-related pathways. A refined risk score model, comprising PLA2G7, TNF, TYK2, F2, and NRP1, effectively stratified cervical cancer patients into distinct risk groups. Importantly, molecular docking analyses illuminated quercetin's remarkable binding affinity to the primary protease of the coronavirus. CONCLUSIONS: In summation, our study suggests that quercetin holds promise as a potential therapeutic agent for mitigating coronavirus function, specifically through its interaction with the primary protease. This research offers novel insights into exploring COVID-19 susceptibility and enhancing survival in cervical cancer patients.

Recent advances in 2D van der Waals magnets: Detection, modulation, and applications.

The emergence of two-dimensional (2D) van der Waals magnets provides an exciting platform for exploring magnetism in the monolayer limit. Exotic quantum phenomena and significant potential for spintronic applications are demonstrated in 2D magnetic crystals and heterostructures, which offer unprecedented possibilities in advanced formation technology with low power and high efficiency. In this review, we summarize recent advances in 2D van der Waals magnetic crystals. We focus mainly on van der Waals materials of truly 2D nature with intrinsic magnetism. The detection methods of 2D magnetic materials are first introduced in detail. Subsequently, the effective strategies to modulate the magnetic behavior of 2D magnets (e.g., Curie temperature, magnetic anisotropy, magnetic exchange interaction) are presented. Then, we list the applications of 2D magnets in the spintronic devices. We also highlight current challenges and broad space for the development of 2D magnets in further studies.

Global hotspots and trends in interactions of microplastics and heavy metals: a bibliometric analysis and literature review.

Microplastics (MPs) are identified as emerging contaminants; however, their interactions with heavy metals in the environment have not been well elucidated. Here, the research progress, hotspots, and trends in the interactions of MPs and heavy metals were analyzed at a global scale using a bibliometric analysis combined with a literature review. We comprehensively searched the Web of Science Core Collection database from 2008 to July 5, 2022. A total of 552 articles published in 124 journals were selected, which came from 70 countries and 841 institutions. The most contributing journals, countries, institutions, and authors were identified. Visualization methods were used to identify high co-citation references and hot keywords in the 552 articles. Evolutionary and cluster analyses of hot keywords suggested several research hotspots in the co-contamination of MPs and heavy metals, including their toxicity and bioaccumulation, the adsorption and desorption behaviors, the environmental pollution and risk assessment, and their detection and characterization. Based on the current research status, several directions of priority are recommended to understand the interactions between MPs and heavy metals and their potential risks. This article can help recognize the current research status and future directions in this field.

Platelet-Derived Exosomes Alleviate Knee Osteoarthritis by Attenuating Cartilage Degeneration and Subchondral Bone Loss.

BACKGROUND: Osteoarthritis (OA) is the most prevalent chronic degenerative joint disease among the aged population. However, current treatments for OA are limited to alleviating symptoms, with no therapies that prevent and regenerate cartilage deterioration. PURPOSE: To assess the effects of platelet-derived exosomes (Plt-exos) on OA and then to explore the potential molecular mechanism. STUDY DESIGN: Controlled laboratory study. METHODS: Exosomes derived from human apheresis platelets were isolated and identified. The effects of Plt-exos in protecting chondrocytes under interleukin 1ß stimulation were evaluated by analyzing the proliferation and migration in human primary chondrocytes. RNA sequencing was later performed in vitro for primary chondrocytes to reveal the underlying mechanisms of Plt-exo treatment. Anterior cruciate ligament transection was used to construct an OA mice model, and intra-articular injection of Plt-exos was given once a week for 6 weeks. Mice were sacrificed 4 weeks after the last injection. Histologic and immunohistochemistry staining and micro-computed tomography analysis were performed to assess alterations of articular cartilage and subchondral bone. RESULTS: Plt-exos significantly promoted proliferation and migration of chondrocytes within a dose-dependent manner, as well as dramatically promoted cartilage regeneration and attenuated abnormal tibial subchondral bone remodeling, thus slowing the progression of OA. After being treated with Plt-exos, 1797 genes were differentially expressed in chondrocytes (923 upregulated and 874 downregulated genes). Functional enrichment results and hub genes were mainly involved in anti-inflammatory effects, mediating cell adhesion, stimulating cartilage repair, promoting anabolism, and inhibiting catabolism. CONCLUSION: Our results demonstrated that Plt-exos promoted chondrocyte proliferation and migration in vitro, as well as attenuated cartilage degeneration, improved the microarchitecture of subchondral bone, and retarded OA progression in vivo. CLINICAL RELEVANCE: Our study illustrated that the administered Plt-exos could alleviate knee OA by attenuating cartilage degeneration and subchondral bone loss, possibly serving as a novel promising treatment for OA in the future.