Identification of susceptibility modules and characteristic genes to osteoarthritis by WGCNA.

The susceptibility modules and characteristic genes of patients with osteoarthritis (OA) were determined by weighted gene co-expression network analysis (WGCNA), and the role of immune cells in OA related microenvironment was analyzed. GSE98918 and GSE117999 data sets are from GEO database. R language was used to conduct difference analysis for the new data set after merging. The formation of gene co-expression network, screening of susceptibility modules and screening of core genes are all through WGCNA. GO and KEGG enrichment analyses were used for Hub genes. The characteristic genes of the disease were obtained by Lasso regression screening. SSGSEA was used to estimate immune cell abundance in sample and a series of correlation analyses were performed. WGCNA was used to form 6 gene co-expression modules. The yellow-green module is identified as the susceptible module of OA. 202 genes were identified as core genes. Finally, RHOT2, FNBP4 and NARF were identified as the characteristic genes of OA. The results showed that the characteristic genes of OA were positively correlated with plasmacytoid dendritic cells, NKT cells and immature dendritic cells, but negatively correlated with active B cells. MDSC were the most abundant immune cells in cartilage. This study identified the Hippo signaling pathway, mTOR signaling pathway, and three characteristic genes (RHOT2, FNBP4, NARF) as being associated with osteoarthritis (OA). These three genes are downregulated in the cartilage of OA patients and may serve as biomarkers for early diagnosis and targeted therapy. Proper regulation of immune cells may aid in the treatment of OA. Future research should focus on developing tools to detect these genes and exploring their therapeutic applications.

Consideration of hormonal changes for orthodontic treatment during pregnancy and lactation - a review.

Hormonal changes in pregnant and lactating women significantly affect bone metabolism and overall stress levels, positioning them as a unique group within the orthodontic population. Fluctuations in estrogen, progesterone, prolactin, and other hormones are closely linked to bone remodeling and the periodontal tissue's response to inflammation caused by dental plaque. Hormones such as thyrotropin, leptin, and melatonin also play crucial roles in pregnancy and bone remodeling, with potential implications for orthodontic tooth movement. Additionally, adverse personal behaviors and changes in dietary habits worsen periodontal conditions and complicate periodontal maintenance during orthodontic treatment. Notably, applying orthodontic force during pregnancy and lactation may trigger stress responses in the endocrine system, altering hormone levels. However, these changes do not appear to adversely affect the mother or fetus. This review comprehensively examines the interaction between hormone levels and orthodontic tooth movement in pregnant and lactating women, offering insights to guide clinical practice.

Electroacupuncture pretreatment inhibits ferroptosis and inflammation after middle cerebral artery occlusion in rats by activating Nrf2.

OBJECTIVE: Electroacupuncture (EA) pretreatment can effectively increase the tolerance of the brain to ischemic stroke. The mechanism of ischemic tolerance induced by EA is related to Nrf2, but its specific mechanism has not been elucidated. This paper was designed to explore the effect of EA pretreatment on brain injury and the related mechanisms. METHODS: Rats were pretreated with EA before middle cerebral artery occlusion (MCAO) modeling. The symptoms of neurological deficit and the volume of cerebral infarction were measured. The levels of inflammatory factors, oxidative stress-related factors, LPO, ROS, and Fe2+ were evaluated by the corresponding kits. Cell apoptosis was determined through TUNEL staining. The mRNA expression of inflammatory factors was examined by RT-qPCR, and the protein expression of ferroptosis-related factors, pyroptosis-related proteins, Keap1, Nrf2, HO-1, and NQO1 by western blotting. RESULTS: EA pretreatment improved the symptoms of neurological deficit and reduced the volume of cerebral infarction. EA pretreatment significantly inhibited oxidative stress, inflammatory response, ferroptosis, pyroptosis, and apoptosis in brain tissues of MCAO rats. Mechanistically, EA pretreatment could activate Nrf2 expression and reduce Keap1 expression. CONCLUSION: EA pretreatment reduced inflammation and oxidative stress and inhibited ferroptosis by activating Nrf2 expression, ultimately delaying the development of ischemic stroke.

Discovery of the Clinical Candidate Sonrotoclax (BGB-11417), a Highly Potent and Selective Inhibitor for Both WT and G101V Mutant Bcl-2.

The approval of venetoclax, a B-cell lymphoma-2 (Bcl-2) selective inhibitor, for the treatment of chronic lymphocytic leukemia demonstrated that the antiapoptotic protein Bcl-2 is a druggable target for B-cell malignancies. However, venetoclax's limited potency cannot produce a strong, durable clinical benefit in other Bcl-2-mediated malignancies (e.g., diffuse large B-cell lymphomas) and multiple recurrent Bcl-2 mutations (e.g., G101V) have been reported to mediate resistance to venetoclax after long-term treatment. Herein, we described novel Bcl-2 inhibitors with increased potency for both wild-type (WT) and mutant Bcl-2. Comprehensive structure optimization led to the clinical candidate BGB-11417 (compound 12e, sonrotoclax), which exhibits strong in vitro and in vivo inhibitory activity against both WT Bcl-2 and the G101V mutant, as well as excellent selectivity over Bcl-xL without obvious cytochrome P450 inhibition. Currently, BGB-11417 is undergoing phase II/III clinical assessments as monotherapy and combination treatment.

Steam Explosion-Assisted Extraction of Polysaccharides from Pleurotus eryngii and Its Influence on Structural Characteristics and Antioxidant Activity.

Pleurotus eryngii (PE) has been sought after for its various health benefits and high content of phenolic compounds. This study explored the feasibility of steam explosion (SE)-assisted extraction of polysaccharides with high antioxidant capacities from PE. An orthogonal experimental design (OED) was used to optimize the SE-assisted extraction of PE. The influence of the optimized SE-assisted extraction on the physicochemical properties of PE polysaccharides was determined by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), monosaccharide compositional analysis and antioxidant capacity assays. Under optimal SE conditions, SE-assisted extraction increased the polysaccharide yield by 138% compared to extraction without SE-assistance. In addition, SEM demonstrated that SE-assisted extraction markedly altered the spatial structure of Pleurotus eryngii polysaccharides (PEP), and monosaccharide compositional analysis revealed that this pretreatment significantly increased the proportions of some monosaccharides, such as glucose, rhamnose and arabinose, in the isolated PEP. FTIR spectra indicated no change in the major chemical functional groups of PEP. PEP extracted by SE-assisted extraction had significantly increased free radical scavenging and antioxidant capacities. In conclusion, SE-assisted extraction appears to be a novel polysaccharide extraction technology, which markedly increases extraction yields and efficiency and can increase the biological activity of polysaccharide extracts.

Spontaneous oscillation of an active filament under viscosity gradients.

We investigate the effects of uniform viscosity gradients on the spontaneous oscillations of an elastic, active filament in viscous fluids. Combining numerical simulations and linear stability analysis, we demonstrate that a viscosity gradient increasing from the filament's base to tip destabilises the system, facilitating its self-oscillation. This effect is elucidated through a reduced-order model, highlighting the delicate balance between destabilising active forces and stabilising viscous forces. Additionally, we reveal that while a perpendicular viscosity gradient to the filament's orientation minimally affects instability, it induces asymmetric ciliary beating, thus generating a net flow along the gradient. Our findings offer new insights into the complex behaviours of biological and artificial filaments in complex fluid environments, contributing to the broader understanding of filament dynamics in heterogeneous viscous media.

Effect of Scanning Strategy on the Manufacturing Quality and Performance of Printed 316L Stainless Steel Using SLM Process.

In this study, the effects of Z-0°, Z-67°, Z-90°, I-67°, and S-67° scanning strategies on the surface morphology, microstructure, and corrosion resistance of the specimens in SLM316L were systematically studied. The results show that the partition scanning path can effectively improve the manufacturing quality of the specimen, reduce the cumulative roughness layer by layer, and increase the density of the specimen. The scan path of the island partition of the fine partition is better than that of the strip partition; moreover, the 67° rotation between each layer reduces the accumulation of the height difference of the melt pool, fills the scanning gap of the previous layer, and improves the molding quality of the sample. Electrochemical tests were performed in an aqueous solution of NaCl (3.5 wt%), including open-circuit potential (OCP), dynamic potential polarization, and electrochemical impedance spectroscopy (EIS). The results show that the specimen with a 67° rotation between each layer achieves stability of the surface potential in a short time, and the I-67° specimen exhibits good corrosion performance, while the Z-0° specimen has the worst corrosion resistance.

Causal relationship between psychiatric traits and temporomandibular disorders: a bidirectional two-sample Mendelian randomization study.

OBJECTIVES: This study was to investigate the causal relationship between temporomandibular disorders (TMD) and psychiatric disorders by Mendelian randomization (MR) analysis. MATERIALS AND METHODS: A two-sample bidirectional MR analysis was adopted to systematically explore the causal relationship between TMD and eight psychiatric traits, including anxiety disorder (AD), panic disorder (PD), major depressive disorder (MDD), neuroticism, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BIP), and schizophrenia (SCZ). Inverse variance weighted (IVW), weighted median, and MR-Egger regression were used in my study. Furthermore, we also performed three sensitivity analyses to illustrate the reliability of the analysis. RESULTS: Two psychiatric traits have risk effects on TMD: PD (OR = 1.118, 95% CI: 1.047-1.194, P = 8.161 × 10-4, MDD (OR = 1.961, 95% CI: 1.450-2.653, P = 1.230 × 10-5). Despite not surpassing the strict Bonferroni correction applied (P > 0.00625), we could think that there was a suggestive causal effect of neuroticism and SCZ increasing the risk of TMD. On the reverse MR analysis, we found no significant evidence of causal effects of TMD on these psychiatric traits. Except for heterogeneity in the causal analysis for SCZ on TMD, no heterogeneity and horizontal pleiotropy were detected in the other analyses. CONCLUSIONS: Our two-sample MR study has provided further evidence of PD and MDD being related to a higher risk of TMD. CLINICAL RELEVANCE: These findings highlight the importance of closely monitoring mental traits during future TMD treatments to prevent an increased risk of TMD.

Time-Dependent Rheological Properties of Cemented Aeolian Sand-Fly Ash Backfill Vary with Particles Size and Plasticizer.

The use of cemented Aeolian sand-fly ash backfill (CAFB) material to fill the mining area to improve the surface subsidence damage caused by underground coal mining is in the development stage. Their performance with large overflow water and strength loss is not well understood. Few research has been conducted to understand the effects of aeolian sand and coal gangue on the rheological properties of CAFB with plasticizers. Therefore, this study aims to investigate the effects of a plasticizer on the rheological properties, specifically yield stress and viscosity, of CAFB prepared with aeolian sand and coal gangue. CAFB mixes containing 0%, 0.05%, and 0.1% plasticizers were prepared, and yield stress and viscosity were determined at different intervals. Additional tests, such as thermal analysis and zeta potential analysis, were also conducted. It was found that the rheological properties of CAFB are the comprehensive manifestation of the composite characteristics of various models. Reasonable particle size distribution and less plasticizer can ensure the stability of the slurry structure and reduce the slurry settlement and the risk of pipe blocking. The findings of this study will be beneficial in the design and production of CAFB material.

Heel bone mineral density and various oral diseases: a bidirectional Mendelian randomization.

INTRODUCTION: Observational studies demonstrated that the relationship between bone mineral density and oral diseases is mixed. To access the association between heel bone mineral density and various oral diseases, we conducted the Mendelian randomization analysis to explore the association. MATERIALS AND METHODS: Two-sample bidirectional Mendelian analysis was used to explore the relationship between heel bone mineral density and various oral diseases. The inverse-variance weighted (IVW) was used as the primary effect estimate, and various methods were applied to test the reliability and stability of the results, namely MR-Egger, weighted median, simple mode, and weighted mode. RESULTS: This study showed that there was a negative relationship between heel BMD and periodontitis when heel BMD was used as an exposure factor and periodontitis as an outcome factor (IVW OR = 0.85; 95% CI, 0.75-0.95; p = 0.005). Bidirectional Mendelian randomization showed that there was no statistically significant association between periodontitis and heel bone mineral density when chronic periodontitis was the exposure factor (p > 0.05). And there was no significant relationship between heel bone mineral density and other oral diseases (dental caries, diseases of pulp and periapical tissues, impacted teeth, cleft lip, and cleft palate, oral and oropharyngeal cancer) (p > 0.05). CONCLUSION: This study showed that there was a negative relationship between heel bone density and periodontitis, and the decrease in heel bone density could promote the occurrence of periodontitis. In addition, there was no statistically significant relationship between heel bone density and other oral diseases.

Biomimetic Gradient Bouligand Structure Enhances Impact Resistance of Ceramic-Polymer Composites.

Biological materials relied on multiple synergistic structural design elements typically exhibit excellent comprehensive mechanical properties. Hierarchical incorporation of different biostructural elements into a single artificial material is a promising approach to enhance mechanical properties, but remains challenging. Herein, a biomimetic structural design strategy is proposed by coupling gradient structure with twisted plywood Bouligand structure, attempting to improve the impact resistance of ceramic-polymer composites. Via robocasting and sintering, kaolin ceramic filaments reinforced by coaxially aligned alumina nanoplatelets are arranged into Bouligand structure with a gradual transition in filament spacing along the thickness direction. After the following polymer infiltration, biomimetic ceramic-polymer composites with a gradient Bouligand (GB) structure are eventually fabricated. Experimental investigations reveal that the incorporation of gradient structure into Bouligand structure improves both the peak force and total energy absorption of the obtained ceramic-polymer composites. Computational modeling further suggests the substantial improvement in impact resistance by adopting GB structure, and clarifies the underlying deformation behavior of the biomimetic GB structured composites under impact. This biomimetic design strategy may provide valuable insights for developing lightweight and impact-resistant structural materials in the future.

Deep learning-based automatic sella turcica segmentation and morphology measurement in X-ray images.

BACKGROUND: Although the morphological changes of sella turcica have been drawing increasing attention, the acquirement of linear parameters of sella turcica relies on manual measurement. Manual measurement is laborious, time-consuming, and may introduce subjective bias. This paper aims to develop and evaluate a deep learning-based model for automatic segmentation and measurement of sella turcica in cephalometric radiographs. METHODS: 1129 images were used to develop a deep learning-based segmentation network for automatic sella turcica segmentation. Besides, 50 images were used to test the generalization ability of the model. The performance of the segmented network was evaluated by the dice coefficient. Images in the test datasets were segmented by the trained segmentation network, and the segmentation results were saved in binary images. Then the extremum points and corner points were detected by calling the function in the OpenCV library to obtain the coordinates of the four landmarks of the sella turcica. Finally, the length, diameter, and depth of the sella turcica can be obtained by calculating the distance between the two points and the distance from the point to the straight line. Meanwhile, images were measured manually using Digimizer. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to analyze the consistency between automatic and manual measurements to evaluate the reliability of the proposed methodology. RESULTS: The dice coefficient of the segmentation network is 92.84%. For the measurement of sella turcica, there is excellent agreement between the automatic measurement and the manual measurement. In Test1, the ICCs of length, diameter and depth are 0.954, 0.953, and 0.912, respectively. In Test2, ICCs of length, diameter and depth are 0.906, 0.921, and 0.915, respectively. In addition, Bland-Altman plots showed the excellent reliability of the automated measurement method, with the majority measurements differences falling within ± 1.96 SDs intervals around the mean difference and no bias was apparent. CONCLUSIONS: Our experimental results indicated that the proposed methodology could complete the automatic segmentation of the sella turcica efficiently, and reliably predict the length, diameter, and depth of the sella turcica. Moreover, the proposed method has generalization ability according to its excellent performance on Test2.

A ratiometric fluorescent probe based on spiropyran in situ switching for tracking dynamic changes of lysosomal autophagy and anticounterfeiting.

Autophagy is the controlled breakdown of cellular components that dysfunctional or nonessential, and the decomposition products are further recycled and synthesized for the normal physiological activities of cells. Lysosomal autophagy has been implicated in cancer, neurological disorders, Parkinson's disease, etc. Therefore, it is necessary to develop a fluorescent probe that can clearly describe the process of lysosomal autophagy. However, there are currently limited fluorescent probes for ratiometric monitoring of the autophagic process in dual channels. To solve this problem, a fluorescent probe based on spiropyran with lysosomal targeting and pH response for ratiometric monitoring the autophagy process of lysosomes were designed. The sensitive response of the probe to pH in vitro was verified by UV and fluorescence spectrum tests. Meanwhile, the probe demonstrated the ability to monitor the intracellular pH fluctuations. In addition, the application of Lyso-SD in the field of anti-counterfeiting has been proposed based on the obvious photoluminescence ability of Lyso-SD under UV irradiation.

Effects of multilingualism on Australian infants' language environments in early childhood education centers.

This study investigates differences in the language environments experienced by multilingual and monolingual infants in early childhood education and care (ECEC) settings. The Language Environment Analysis (LENA) technology was used to collect day-long audio-recordings from 181 one-year-old infants (age range from 12 to 21 months). We examined whether infants' multilingual status predicts the amount of educators' language input (adult word count, AWC), child vocalizations (CVC) and conversational turns (CTC), as well as interaction effects on AWC, CVC and CTC of infants' multilingual status and other infant, home and ECEC characteristics. Multilevel mixed effects models revealed no main effect of infants' multilingual status on the language environment outcome variables. Instead, infant gender significantly predicted adult word count, with female infants hearing more words from educators than male infants. There was a significant interaction effect between the infants' multilingual status and both their age and length of time in an ECEC setting on child vocalizations. While monolingual infants produced more vocalizations as their age increased, multilingual infants did not show this increase in vocalizations with age. Further, the difference between monolingual and multilingual children's vocalizations decreased as the length of time in ECEC increased. There were no significant predictors of conversational turns. Findings from this study suggest that early childhood educators do not adjust their talk according to the multilingual status of the infants. However, multilingual infants do not increase their vocalizations as their age increases to the same extent as do their monolingual peers. The interaction effect between multilingualism and the length of ECEC attendance also implies that ECEC environments may be particularly beneficial for supporting multilingual infants' vocalizations. This study highlights the need to provide pedagogical support to educators to help them to encourage multilingual infants' vocalizations in ECEC settings.

A novel promising diagnosis model for colorectal advanced adenoma and carcinoma based on the progressive gut microbiota gene biomarkers.

BACKGROUND: Colorectal cancer (CRC), a commonly diagnosed cancer often develops slowly from benign polyps called adenoma to carcinoma. Altered gut microbiota is implicated in colorectal carcinogenesis. It is warranted to find non-invasive progressive microbiota biomarkers that can reflect the dynamic changes of the disease. This study aimed to identify and evaluate potential progressive fecal microbiota gene markers for diagnosing advanced adenoma (AA) and CRC. RESULTS: Metagenome-wide association was performed on fecal samples from different cohorts of 871 subjects (247 CRC, 234 AA, and 390 controls). We characterized the gut microbiome, identified microbiota markers, and further constructed a colorectal neoplasms classifier in 99 CRC, 94 AA, and 62 controls, and validated the results in 185 CRC, 140 AA, and 291 controls from 3 independent cohorts. 21 species and 277 gene markers were identified whose abundance was significantly increased or decreased from normal to AA and CRC. The progressive gene markers were distributed in metabolic pathways including amino acid and sulfur metabolism. A diagnosis model consisting of four effect indexes was constructed based on the markers, the sensitivities of the Adenoma Effect Index 1 for AA, Adenoma Effect Index 2 for high-grade dysplasia (HGD) adenoma were 71.3% and 76.5%, the specificities were 90.5% and 90.3%, respectively. CRC Effect Index 1 for all stages of CRC and CRC Effect Index 2 for stage III-IV CRC to predict CRC yielded an area under the curve (AUC) of 0.839 (95% CI 0.804-0.873) and 0.857 (95% CI 0.793-0.921), respectively. Combining with fecal immunochemical test (FIT) significantly improved the sensitivity of CRC Effect Index 1 and CRC Effect Index 2 to 96.7% and 100%. CONCLUSIONS: This study reports the successful diagnosis model establishment and cross-region validation for colorectal advanced adenoma and carcinoma based on the progressive gut microbiota gene markers. The results suggested that the novel diagnosis model can significantly improve the diagnostic performance for advanced adenoma.

A Prestressing Strategy Enabled Synergistic Energy-Dissipation in Impact-Resistant Nacre-Like Structures.

The application of prestresses is a valuable strategy for enhancing the overall mechanical performances of structural materials. Residual stresses, acting as prestresses, exist naturally in biological structural materials, such as the nacre with the 3D "brick-and-mortar" arrangement. Although regulation of the tablets sliding has recently been demonstrated to be vital to improve toughness in synthetic nacre-like structures, the effects of prestresses on the tablets-sliding mechanism in these nacre-like structures remain unclear. Here, by a combination of simulation, additive manufacturing, and drop tower testing the authors reveal that, at a critical prestress, synergistic effects between the prestress-enhanced tablets sliding and prestress-weakened structural integrality result in optimized impact resistance of nacre-like structures. Furthermore, the prestressing strategy is easily implemented to a designed nacre-inspired separator to enhance the impact resistance of lithium batteries. The findings demonstrate that the prestressing strategy combined with bioinspired architectures can be exploited for enhancing the impact resistance of engineering structural materials and energy storage devices.

Gut Metagenome as a Potential Diagnostic and Predictive Biomarker in Slow Transit Constipation.

Slow transit constipation (STC) is one of the most frequent gastrointestinal diagnoses. In this study, we conducted a quantitative metagenomics study in 118 Chinese individuals. These participants were divided into the discovery cohort of 50 patients with STC and 40 healthy controls as well as a validation cohort of 16 patients and 12 healthy controls. We found that the intestinal microbiome of patients with STC was significantly different from that of healthy individuals at the phylum, genus, and species level. Patients with STC had markedly higher levels of Alistipes and Eubacterium and lower abundance of multiple species belonging to the Roseburia genus. Patients with STC gene expression levels and the Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology pathway (such as fatty acid biosynthesis, butanoate metabolism, and methane metabolism pathways) enrichment were also substantially different from those of healthy controls. These microbiome and metabolite differences may be valuable biomarkers for STC. Our findings suggest that alteration of the microbiome may lead to constipation by changing the levels of microbial-derived metabolites in the gut. Above findings may help us in the development of microbial drugs.

Blast Alleviation of Sacrificial Cladding with Graded and Uniform Cellular Materials.

Graded cellular material is a superb sandwich candidate for blast alleviation, but it has a disadvantage for the anti-blast design of sacrificial cladding, i.e., the supporting stress for the graded cellular material cannot maintain a constant level. Thus, a density graded-uniform cellular sacrificial cladding was developed, and its anti-blast response was investigated theoretically and numerically. One-dimensional nonlinear plastic shock models were proposed to analyze wave propagation in density graded-uniform cellular claddings under blast loading. There are two shock fronts in a positively graded-uniform cladding; while there are three shock fronts in a negatively graded-uniform cladding. Response features of density graded-uniform claddings were analyzed, and then a comparison with the cladding based on the uniform cellular material was carried out. Results showed that the cladding with uniform cellular materials is a good choice for the optimal mass design, while the density graded-uniform cladding is more advantageous from the perspective of the critical length design indicator. A partition diagram for the optimal length of sacrificial claddings under a defined blast loading was proposed for engineering design. Finally, cell-based finite element models were applied to verify the anti-blast response results of density graded-uniform claddings.

Effect of multi-pollutant state of ozone and sulfur dioxide on atmospheric corrosivity map of Guangdong Province.

Guangdong Province, which is located in southern China, has a tropical climate with high temperatures and humidity, making it extremely unfavourable for the corrosion resistance of various materials. Meanwhile, as a quickly developing region in China, Guangdong Province is also facing multi-pollutant conditions, which seriously affect the atmospheric degradation of the materials in this region. It is therefore necessary to identify the key air pollutants that affect the atmospheric corrosivity of Guangdong Province and to propose targets of air pollutant control. An analysis of the environmental data and corrosion rates in Guangdong Province showed that the atmospheric corrosivity of the entire region is closely related to the presence of sulfur dioxide (SO2) and ozone (O3). In addition, a superposition model was utilised to reflect the synergistic effect of SO2 and O3, and a superimposed map of both pollutants was drawn to demonstrate their amount. To control the corrosion rate of carbon steel and avoid exceeding the C2 classification in ISO 9223, the following targets of air pollutant control are proposed: an SO2 concentration of lower than 10 µg m-3 and an O3 level of lower than 85 µg m-3.