Ependymal polarity defects coupled with disorganized ciliary beating drive abnormal cerebrospinal fluid flow and spine curvature in zebrafish.

Idiopathic scoliosis (IS) is the most common spinal deformity diagnosed in childhood or early adolescence, while the underlying pathogenesis of this serious condition remains largely unknown. Here, we report zebrafish ccdc57 mutants exhibiting scoliosis during late development, similar to that observed in human adolescent idiopathic scoliosis (AIS). Zebrafish ccdc57 mutants developed hydrocephalus due to cerebrospinal fluid (CSF) flow defects caused by uncoordinated cilia beating in ependymal cells. Mechanistically, Ccdc57 localizes to ciliary basal bodies and controls the planar polarity of ependymal cells through regulating the organization of microtubule networks and proper positioning of basal bodies. Interestingly, ependymal cell polarity defects were first observed in ccdc57 mutants at approximately 17 days postfertilization, the same time when scoliosis became apparent and prior to multiciliated ependymal cell maturation. We further showed that mutant spinal cord exhibited altered expression pattern of the Urotensin neuropeptides, in consistent with the curvature of the spine. Strikingly, human IS patients also displayed abnormal Urotensin signaling in paraspinal muscles. Altogether, our data suggest that ependymal polarity defects are one of the earliest sign of scoliosis in zebrafish and disclose the essential and conserved roles of Urotensin signaling during scoliosis progression.

Associations between trans fatty acids and systemic immune-inflammation index: a cross-sectional study.

BACKGROUND: Previous studies have demonstrated that trans fatty acids (TFAs) intake was linked to an increased risk of chronic diseases. As a novel systemic inflammatory biomarker, the clinical value and efficacy of the systemic immune-inflammation index (SII) have been widely explored. However, the association between TFAs and SII is still unclear. Therefore, the study aims to investigate the connection between TFAs and SII in US adults. METHODS: The study retrieved data from the National Health and Nutrition Examination Survey (NHANES) for the years 1999-2000 and 2009-2010. Following the exclusion of ineligible participants, the study encompassed a total of 3047 individuals. The research employed a multivariate linear regression model to investigate the connection between circulating TFAs and SII. Furthermore, the restricted cubic spline (RCS) model was utilized to evaluate the potential nonlinear association. Subgroup analysis was also conducted to investigate the latent interactive factors. RESULTS: In this investigation, participants exhibited a mean age of 47.40 years, with 53.91% of them being female. Utilizing a multivariate linear regression model, the independent positive associations between the log2-transformed palmitelaidic acid, the log2 transformed-vaccenic acid, the log2-transformed elaidic acid, the log2-transformed linolelaidic acid, and the log2-transformed-total sum of TFAs with the SII (all P < 0.05) were noted. In the RCS analysis, no nonlinear relationship was observed between the log2-transformed palmitelaidic acid, the log2 transformed-vaccenic acid, the log2-transformed elaidic acid, the log2-transformed linolelaidic acid, the log2-transformed-total sum of TFAs and the SII (all P for nonlinear > 0.05). For the stratified analysis, the relationship between the circulating TFAs and the SII differed by the obesity status and the smoking status. CONCLUSIONS: A positive association was investigated between three types of TFA, the sum of TFAs, and the SII in the US population. Additional rigorously designed studies are needed to verify the results and explore the potential mechanism.

Hybrid Domain Consistency Constraints-Based Deep Neural Network for Facial Expression Recognition.

Facial expression recognition (FER) has received increasing attention. However, multiple factors (e.g., uneven illumination, facial deflection, occlusion, and subjectivity of annotations in image datasets) probably reduce the performance of traditional FER methods. Thus, we propose a novel Hybrid Domain Consistency Network (HDCNet) based on a feature constraint method that combines both spatial domain consistency and channel domain consistency. Specifically, first, the proposed HDCNet mines the potential attention consistency feature expression (different from manual features, e.g., HOG and SIFT) as effective supervision information by comparing the original sample image with the augmented facial expression image. Second, HDCNet extracts facial expression-related features in the spatial and channel domains, and then it constrains the consistent expression of features through the mixed domain consistency loss function. In addition, the loss function based on the attention-consistency constraints does not require additional labels. Third, the network weights are learned to optimize the classification network through the loss function of the mixed domain consistency constraints. Finally, experiments conducted on the public RAF-DB and AffectNet benchmark datasets verify that the proposed HDCNet improved classification accuracy by 0.3-3.84% compared to the existing methods.

The Therapeutic Potential of CDK4/6 Inhibitors, Novel Cancer Drugs, in Kidney Diseases.

Inflammation is a crucial pathological feature in cancers and kidney diseases, playing a significant role in disease progression. Cyclin-dependent kinases CDK4 and CDK6 not only contribute to cell cycle progression but also participate in cell metabolism, immunogenicity and anti-tumor immune responses. Recently, CDK4/6 inhibitors have gained approval for investigational treatment of breast cancer and various other tumors. Kidney diseases and cancers commonly exhibit characteristic pathological features, such as the involvement of inflammatory cells and persistent chronic inflammation. Remarkably, CDK4/6 inhibitors have demonstrated impressive efficacy in treating non-cancerous conditions, including certain kidney diseases. Current studies have identified the renoprotective effect of CDK4/6 inhibitors, presenting a novel idea and potential direction for treating kidney diseases in the future. In this review, we briefly reviewed the cell cycle in mammals and the role of CDK4/6 in regulating it. We then provided an introduction to CDK4/6 inhibitors and their use in cancer treatment. Additionally, we emphasized the importance of these inhibitors in the treatment of kidney diseases. Collectively, growing evidence demonstrates that targeting CDK4 and CDK6 through CDK4/6 inhibitors might have therapeutic benefits in various cancers and kidney diseases and should be further explored in the future.

A Cascade Attention Based Facial Expression Recognition Network by Fusing Multi-Scale Spatio-Temporal Features.

The performance of a facial expression recognition network degrades obviously under situations of uneven illumination or partial occluded face as it is quite difficult to pinpoint the attention hotspots on the dynamically changing regions (e.g., eyes, nose, and mouth) as precisely as possible. To address the above issue, by a hybrid of the attention mechanism and pyramid feature, this paper proposes a cascade attention-based facial expression recognition network on the basis of a combination of (i) local spatial feature, (ii) multi-scale-stereoscopic spatial context feature (extracted from the 3-scale pyramid feature), and (iii) temporal feature. Experiments on the CK+, Oulu-CASIA, and RAF-DB datasets obtained recognition accuracy rates of 99.23%, 89.29%, and 86.80%, respectively. It demonstrates that the proposed method outperforms the state-of-the-art methods in both the experimental and natural environment.

An Improved Tiered Head Pose Estimation Network with Self-Adjust Loss Function.

As an important task in computer vision, head pose estimation has been widely applied in both academia and industry. However, there remains two challenges in the field of head pose estimation: (1) even given the same task (e.g., tiredness detection), the existing algorithms usually consider the estimation of the three angles (i.e., roll, yaw, and pitch) as separate facets, which disregard their interplay as well as differences and thus share the same parameters for all layers; and (2) the discontinuity in angle estimation definitely reduces the accuracy. To solve these two problems, a THESL-Net (tiered head pose estimation with self-adjust loss network) model is proposed in this study. Specifically, first, an idea of stepped estimation using distinct network layers is proposed, gaining a greater freedom during angle estimation. Furthermore, the reasons for the discontinuity in angle estimation are revealed, including not only labeling the dataset with quaternions or Euler angles, but also the loss function that simply adds the classification and regression losses. Subsequently, a self-adjustment constraint on the loss function is applied, making the angle estimation more consistent. Finally, to examine the influence of different angle ranges on the proposed model, experiments are conducted on three popular public benchmark datasets, BIWI, AFLW2000, and UPNA, demonstrating that the proposed model outperforms the state-of-the-art approaches.

Benzo/Naphthodifuranone-Based Polymers: Effect of Perpendicular-Extended Main Chain π-Conjugation on Organic Field-Effect Transistor Performances.

For polymer semiconductors, the backbone structure plays an essential role in determining their physicochemical properties and charge transport behaviors. In this work, two donor-acceptor-type polymers (P-BDF and P-NDF) based on benzodifuranone (BDF) and naphthodifunarone (NDF) as electron-deficient moieties and indaceno-dithiophene as electron-rich groups are designed, synthesized and, for the first time, applied in organic field-effect transistor. P-BDF and P-NDF differ from their backbone structures while P-BDF has a more planar backbone conformation due to its smaller conjugated core size and P-NDF features a perpendicular-extended main chain structure. As a result, P-BDF polymer exhibits bathochromic optical absorption, deeper molecular orbital energy levels, and more importantly, closer π-stacking and stronger aggregation in the solid state and thus affords a more promising hole mobility of up to 0.85 cm2 V-1 s-1 in OFET devices, while that of the P-NDF-based devices is only 0.55 cm2 V-1 s-1 . The results suggest the great potential of BDF/NDF-type chromophores in constructing novel organic semiconductors and also indicate that the main chain coplanarity of polymer semiconductors is more essential than the sole extension of π-conjugations (especially at the perpendicular direction of polymer main chains) for the design of high-performance OFET materials.

Hybrid Attention Cascade Network for Facial Expression Recognition.

As a sub-challenge of EmotiW (the Emotion Recognition in the Wild challenge), how to improve performance on the AFEW (Acted Facial Expressions in the wild) dataset is a popular benchmark for emotion recognition tasks with various constraints, including uneven illumination, head deflection, and facial posture. In this paper, we propose a convenient facial expression recognition cascade network comprising spatial feature extraction, hybrid attention, and temporal feature extraction. First, in a video sequence, faces in each frame are detected, and the corresponding face ROI (range of interest) is extracted to obtain the face images. Then, the face images in each frame are aligned based on the position information of the facial feature points in the images. Second, the aligned face images are input to the residual neural network to extract the spatial features of facial expressions corresponding to the face images. The spatial features are input to the hybrid attention module to obtain the fusion features of facial expressions. Finally, the fusion features are input in the gate control loop unit to extract the temporal features of facial expressions. The temporal features are input to the fully connected layer to classify and recognize facial expressions. Experiments using the CK+ (the extended Cohn Kanade), Oulu-CASIA (Institute of Automation, Chinese Academy of Sciences) and AFEW datasets obtained recognition accuracy rates of 98.46%, 87.31%, and 53.44%, respectively. This demonstrated that the proposed method achieves not only competitive performance comparable to state-of-the-art methods but also greater than 2% performance improvement on the AFEW dataset, proving the significant outperformance of facial expression recognition in the natural environment.

Synthesis and antifungal activity of 1,2,3-triazole phenylhydrazone derivatives.

A series of 1,2,3-triazole phenylhydrazone derivatives were designed and synthesized as antifungal agents. Their structures were determined based on (1)H-NMR spectroscopy, MS, elemental analysis and X-ray single-crystal diffraction. The antifungal activities were evaluated against four phytopathogenic fungi including Rhizoctonia solani, Sclerotinia sclerotiorum, Fusarium graminearum and Phytophthora capsici, by the mycelium growth inhibition method in vitro. Compound 5p exhibited significant anti-phytopathogenic activity, with the EC50 values of 0.18, 2.28, 1.01, and 1.85 µg mL(-1), respectively. In vivo testing demonstrated that 5p was effective in the control of rice sheath blight, rape sclerotinia rot and fusarium head blight. A 3D-QSAR model was built for a systematic SAR profile to explore more potent 1,2,3-triazole phenylhydrazone analogs as novel fungicides.

A highly malignant succinate dehydrogenase A­deficient renal cell carcinoma with bone metastasis misdiagnosed as hereditary leiomyomatosis and renal cell carcinoma: A case report.

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is an autosomal dominant syndrome caused by heterozygous pathogenic germline variants of the SDH gene. SDH mutations are associated with an increased risk of developing RCC, although studies describing SDH-deficient RCC are currently limited. The present study reported a case of SDH-deficient RCC with high malignancy and rare bone metastasis. The patient was diagnosed with a right renal mass through B-mode ultrasound imaging and showed a carcinoma embolus in the right renal vein and inferior vena cava through kidney contrast-enhanced computed tomography. A whole-body bone scan showed radionuclide accumulation in the upper end of the left humerus, which indicated possible pathological bone destruction. As a result, surgical resection was performed. The postoperative pathology indicated a high-grade RCC and although the specific classification remained uncertain, hereditary leiomyomatosis and RCC was suspected. Subsequently, a germline mutation of the succinate dehydrogenase complex flavoprotein subunit A gene was identified through high-throughput sequencing (c.1A>G, p. Met1?) and immunohistochemistry demonstrated the loss of succinate dehydrogenase complex flavoprotein subunit B expression. Postoperatively, the patient underwent radiotherapy and targeted therapy. After 6 months of follow-up treatment, there was no indication of recurrence or metastasis on thoracoabdominal CT and whole-body bone scintigraphy. Based on the present report, germline screening should potentially be encouraged in early-onset patients as family history or pathological results may not provide sufficient information for the early, differential diagnosis of SDH-deficient RCC.

Adverse events associated with eteplirsen: A disproportionality analysis using the 2016-2023 FAERS data.

Background: Eteplirsen (Exondys 51) is an orphan drug approved for the treatment of Duchenne muscular dystrophy (DMD), having received accelerated approval from the U.S. Food and Drug Administration (FDA) in 2016. The primary aim of this study is to closely monitor adverse events (AEs) associated with eteplirsen and to identify emerging signals to better characterize their safety profile. Methods: AEs due to eteplirsen usage reported from the third quarter (Q3) of 2016 to the fourth quarter (Q4) of 2023 were collected from the FDA Adverse Event Reporting System (FAERS). The role_code of AEs mainly includes primary suspect (PS), secondary suspect (SS), concomitant (C), and interaction (I). This study targeted reports with a role_cod of 'PS.' According to the FDA deduplication rule, the latest FDA_DT is selected when the CASEID is the same, and the higher PRIMARYID is selected when the CASEID and FDA_DT are the same. Disproportionality analyses, encompassing four algorithms for reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian configuration promotion neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were utilized to quantify the signals of AEs associated with eteplirsen. Results: From the FAERS database, a total of 13,205,369 reports were amassed throughout the study duration. Following the eradication of duplicates, the number of reports with eteplirsen designated as the PS amounted to 1480 encompassed 25 organ systems. Among these, "general disorders and administration site conditions," "injury, poisoning, and procedural complications," "respiratory, thoracic, and mediastinal disorders," "infections and infestations," "vascular disorders," and "product issues" met at least one of the four computational criteria. Additionally, 55 Preferred Terms (PTs) aligned with the prescribed algorithms. The median time to AEs in these patients was 903 days with an interquartile range (IQR) of 269-1575 days. Moreover, 70.04 % of AEs manifested one year or more after the initiation of treatment. Conclusion: As an orphan drug granted accelerated approval, our study has confirmed well-known adverse drug reactions and identified potential safety issues associated with eteplirsen treatment. This has contributed to a deeper understanding of the complex interrelations between adverse reactions and the use of eteplirsen. The findings underscore the critical importance of ongoing monitoring and sustained observation to promptly detect and effectively manage AEs, thereby enhancing the overall safety and well-being of patients treated with eteplirsen for DMD.

Predictive Value of Quantitative Electroencephalogram Combined with Transcranial Doppler Ultrasound in Delayed Cerebral Ischemia after Subarachnoid Hemorrhage.

OBJECTIVE: To explore the predictive value of transcranial Doppler ultrasound (TCD) combined with quantitative electroencephalogram (QEEG) in delayed cerebral ischemia (DCI) caused by aneurysmal subarachnoid hemorrhage (aSAH). METHODS: The participants were 105 patients with aSAH treated from June 2020 to December 2022. Patients were divided into DCI group (n = 34) and non-DCI group (n = 71) according to the presence of DCI 14 days after onset. Further comparison was conducted on the baseline data as well as the parameters of QEEG and TCD within 24 hours after admission. Multivariate logistic analysis was performed to investigate risk factors related to DCI within 14 days of admission in aSAH patients. RESULTS: There were significant differences in the comparison of the proportion of Hunt-Hess grading, relative δ power (RDP), relative α power (RAP), relative α/ß power ratio (ADR), as well as peak systolic velocity (Vs), mean blood flow velocity (MBFV) and pulsatility index (PI) of middle cerebral artery between the two groups (P < 0.05). Furthermore, Logistic regression analysis revealed that ADR (odds ratio 1.668, 95% CI 1.369-4.345) and MBFV of middle cerebral artery (odds ratio 3.279, 95% CI 2.332-6.720) were risk factors for the occurrence of DCI in aSAH patients (P < 0.05). In addition, evaluation of the predictive value revealed that combined use of the 2 indicators showed the highest predictive value (area under the curve 0.959, 95% CI 0.896-0.993). CONCLUSIONS: Patients with aSAH complicated by DCI have relatively higher MBFV of middle cerebral artery and ADR. Combined use of the 2 indicators can provide reference for early prediction of DCI in aSAH patients.

Perforated gastric ulcer causing mediastinal emphysema: A case report.

BACKGROUND: Mediastinal emphysema is a condition in which air enters the mediastinum between the connective tissue spaces within the pleura for a variety of reasons. It can be spontaneous or secondary to chest trauma, esophageal perforation, medically induced factors, etc. Its common symptoms are chest pain, tightness in the chest, and respiratory distress. Most mediastinal emphysema patients have mild symptoms, but severe mediastinal emphysema can cause respiratory and circulatory failure, resulting in serious consequences. CASE SUMMARY: A 75-year-old man, living alone, presented with sudden onset of severe epigastric pain with chest tightness after drinking alcohol. Due to the remoteness of his residence and lack of neighbors, the patient was found by his nephew and brought to the hospital the next morning after the disease onset. Computed tomography (CT) showed free gas in the abdominal cavity, mediastinal emphysema, and subcutaneous pneumothorax. Upper gastrointestinal angiography showed that the esophageal mucosa was intact and the gastric antrum was perforated. Therefore, we chose to perform open gastric perforation repair on the patient under thoracic epidural anesthesia combined with intravenous anesthesia. An operative incision of the muscle layer of the patient's abdominal wall was made, and a large amount of subperitoneal gas was revealed. And a continued incision of the peritoneum revealed the presence of a perforation of approximately 0.5 cm in the gastric antrum, which we repaired after pathological examination. Postoperatively, the patient received high-flow oxygen and cough exercises. Chest CT was performed on the first and sixth postoperative days, and the mediastinal and subcutaneous gas was gradually reduced. CONCLUSION: After gastric perforation, a large amount of free gas in the abdominal cavity can reach the mediastinum through the loose connective tissue at the esophageal hiatus of the diaphragm, and upper gastrointestinal angiography can clarify the site of perforation. In patients with mediastinal emphysema, open surgery avoids the elevation of the diaphragm caused by pneumoperitoneum compared to laparoscopic surgery and avoids increasing the mediastinal pressure. In addition, thoracic epidural anesthesia combined with intravenous anesthesia also avoids pressure on the mediastinum from mechanical ventilation.

Combined Transcranial Doppler and Melatonin Levels to Predict Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.

OBJECTIVE: To investigate the early prediction value of transcranial Doppler ultrasound (TCD) combined with serum melatonin level for delayed cerebral ischemia (DCI) caused by subarachnoid hemorrhage (SAH). METHODS: This paper is a prospective study. A total of 120 patients with SAH treated were included. The patients were divided into the DCI group (40 cases) and non-DCI group (80 cases) according to whether DCI occurred 14 days after SAH (DCI usually occurs 4 to 14 d after bleeding). Baseline data, serum melatonin level, and TCD test results within 24 hours after admission were compared between the 2 groups. Multivariate logistic analysis was used to analyze the factors affecting the occurrence of DCI after SAH. The value of serum melatonin level, middle cerebral artery mean blood flow velocity (MBFV) and their combination in predicting DCI in SAH patients was evaluated. RESULTS: Univariate analysis showed that there were statistically significant differences in the proportion of Fisher grade, Hunt-Hess grade, serum melatonin level, middle cerebral artery systolic blood flow velocity (Vs), MBFV and pulse index (PI) between the 2 groups (P<0.05). Serum melatonin levels, middle cerebral artery Vs, MBFV, and PI in the DCI group were higher than those in non-DCI group. Logistic regression (LR) analysis showed that serum melatonin level (OR=1.796, 95% CI: 1.575-4.123) and middle cerebral artery MBFV (OR=3.279, 95% CI: 2.112-4.720] were the influencing factors for DCI in SAH patients (P<0.05). CONCLUSION: Middle cerebral artery MBFV and serum melatonin levels were higher in patients with SAH complicated with DCI, and the combination of the 2 could provide a reference for early clinical prediction of DCI in patients with aneurysmal subarachnoid hemorrhage (aSAH).

Effect of acupuncture on Hashimoto thyroiditis: A systematic review and meta-analysis.

BACKGROUND: Hashimoto thyroiditis (HT) is a common autoimmune thyroid disease for which there is no specific treatment. Oral levothyroxine sodium tablets significantly improved thyroid function but did not promote a reduction in thyroid-related antibody concentrations. Acupuncture can improve clinical symptoms and thyroid function in HT patients, reduce serum TPOAb and TGAb levels in HT patients, and improve patients' quality of life. METHODS: We conducted a systematic review and meta-analysis to evaluate the effect of acupuncture versus levothyroxine sodium tablets on Hashimoto thyroiditis. We searched Web of Science, Embase, China National Knowledge Infrastructure, WanFang, VIP, SinoMed and the Cochrane Central Registry of Controlled Trials to identify candidate randomized controlled trials (RCTs). RESULTS: A total of 1020 patients participated in 14 randomized controlled trials. The results of meta-analysis showed that acupuncture regulated TPOAb content (mean difference [MD] = -63.18, 95%CI = -91.73 to -34.62, P < .00001), TGAb content (MD = -68.56, 95%CI = -101.55 to -35.57, P < .00001), serum free triiodothyronine (FT3) content (MD = 0.74, 95%CI = 0.20 to 1.27, P < .00001), serum free thyroxine (FT4) content (MD = 1.10, 95%CI = 0.29 to 1.92, P < .00001), TSH content (MD = -2.16, 95%CI = -3.14 to -1.19, P < .00001) had a significant effect. CONCLUSION: Compared with levothyroxine sodium tablets alone, acupuncture can significantly regulate the contents of TPOAb, TGAb, FT3, FT4 and TSH.

Interleukin-19 in Bone Marrow Contributes to Bone Loss Via Suppressing Osteogenic Differentiation Potential of BMSCs in Old Mice.

BACKGROUND: Cellular senescence is an important process related to the pathogenic mechanism of different disorders, especially bone loss. During senescence, bone marrow stromal cells (BMSCs) lose their self-renewal and functional differentiation abilities. Therefore, finding signals opposing the osteogenic differentiation of BMSCs within bone marrow microenvironment is the important for elucidating these above-mentioned mechanisms. Inflammatory cytokines affect bone physiology and remodeling. However, the function of interleukin-19 (IL-19) in skeletal system remains unclear. METHODS: The mouse model of IL-19 knockout was established through embryonic stem cell injection for analyzing how IL-19 affected bone formation. Micro-CT examinations were performed to evaluate bone microstructures. We performed a three-point bending test to measure bone stiffness and the ultimate force. Antibody arrays were performed to detect interleukin family members in bone marrow aspirates. BMSCs were cultured and induced for osteogenic differentiation. RESULTS: According to our findings, there was increased IL-19 accumulation within bone marrow in old mice relative to that in their young counterparts, resulting in bone loss via the inhibition of BMSCs osteogenic differentiation. Among Wnt/ß-catenin pathway members, IL-19 strongly upregulated sFRP1 via STAT3 phosphorylation. The inhibition of STAT3 and sFRP1 abolished IL-19's inhibition against the BMSCs osteogenic differentiation. CONCLUSION: To sum up, IL-19 inhibited BMSCs osteogenic differentiation in old mice. Our findings shed novel lights on pathogenic mechanism underlying age-related bone loss and laid a foundation for further research on identifying novel targets to treat senile osteoporosis.

DNA Demethylation of Promoter Region Facilitates Atoh-1-Induced Interleukin-19 Expression Activation in Bone Marrow Monocytes of Old Mice.

With increasing age, there is a notable increase in the differentiation of bone marrow-derived mononuclear cells (BMMs) into osteoclasts, accompanied by a concurrent rise in both osteoclast quantity and activity. This escalation in osteoclastic activity accelerates bone resorption, which in turn contributes to age-related bone loss and metabolic bone disorders, notably osteoporosis. Our study confirms that elevated IL-19 expression promotes aging-induced bone loss in aged mice and sheds light on the regulatory mechanisms upstream of IL-19 expression and secretion. Primarily, it is the methylation status of the IL-19 gene's promoter region that impacts Atonal BHLH Transcription Factor 1 (Atoh1)'s ability to bind to the promoter. We found that this specific mechanism involves reduced expression and binding affinity of Dnmt1 to the IL-19 promoter region. The findings of our study suggest that targeting IL-19 could be a potential strategy for managing bone loss-related conditions and enhance the current understanding of how DNA methylation levels contribute to age-related bone loss.

Smart classroom learning environment preferences of higher education teachers and students in China: An ecological perspective.

By evaluating learners' perceived preferences for the learning environment, we can understand the important characteristics and better improve the learning environment, ultimately to provide great potential for the optimization of teaching practice. Seeing that the current research pays less attention to teachers' and students' preferences for the space environment simultaneously, based on the survey of 1937 undergraduates and 107 teachers from a university in central China, this study aims to explore their preferences for smart learning environment. Based on the ecological theory and research results of the existing learning environment, this paper constructed an ecological model and a conceptual model of learning space preferences. An empirical study was conducted to explore the impact of sociodemographic variables on personal spatial preference. The results showed that teachers and students had a positive attitude towards the smart learning environment, and gender, age, grade, subject category and other variables had limited impact on spatial preference.

Interleukin-19 promotes bone resorption by suppressing osteoprotegerin expression in BMSCs in a lipopolysaccharide-induced bone loss mouse model.

Aims: Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Interleukin-19 (IL-19), a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. The aim of our study was to investigate the effect of IL-19 on osteoporosis. Methods: Blood and femoral bone marrow suspension IL-19 levels were first measured in the lipopolysaccharide (LPS)-induced bone loss model. Small interfering RNA (siRNA) was applied to knock down IL-19 for further validation. Thereafter, osteoclast production was stimulated with IL-19 in combination with mouse macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). The effect of IL-19 was subsequently evaluated using tartrate-resistant acid phosphatase (TRAP) staining and quantitative real-time polymerase chain reaction (RT-qPCR). The effect of IL-19 on osteoprotegerin (OPG) was then assessed using in vitro recombinant IL-19 treatment of primary osteoblasts and MLO-Y4 osteoblast cell line. Finally, transient transfection experiments and chromatin immunoprecipitation (ChIP) experiments were used to examine the exact mechanism of action. Results: In the LPS-induced bone loss mouse model, the levels of IL-19 in peripheral blood serum and femoral bone marrow suspension were significantly increased. The in vivo results indicated that global IL-19 deletion had no significant effect on RANKL content in the serum and bone marrow, but could increase the content of OPG in serum and femoral bone marrow, suggesting that IL-19 inhibits OPG expression in bone marrow mesenchymal stem cells (BMSCs) and thus increases bone resorption. Conclusion: IL-19 promotes bone resorption by suppressing OPG expression in BMSCs in a LPS-induced bone loss mouse model, which highlights the potential benefits and side effects of IL-19 for future clinical applications.

The Effect of Cutting Fluid on Machined Surface Integrity of Ultra-High-Strength Steel 45CrNiMoVA.

The surface integrity of ultra-high-strength steel has a significant influence on service performance, and cutting fluid plays an important role in maintaining surface integrity in production. In this paper, the surface integrity of ultra-high-strength steel 45CrNiMoVA was investigated under three cutting fluids: HY-103 (micro-emulsion), TRIM E709 (emulsion), and Vasco 7000 (micro-emulsion) from the aspects of cutting force, surface morphology, residual stress, micro hardness, microstructure, etc. The results showed that the changing trend of the cutting forces in three directions is HY-103 > Vasco 7000 > TRIM E709. The TRIM E709 contains the maximum lubricants, which reduce cutting force and Sa roughness, while the Vasco 7000 contains the minimum corrosive elements, which results in the least pitting. Both tangential and axial stresses under cutting fluid are tensile stresses. TRIM E709 and Vasco 7000 are reduced axially by 4.45% and 7.60% relative to HY-103, respectively. The grain refinement layer depths of HY-103, TRIM E709, and Vasco 7000 are 9 µm, 4 µm, and 8 µm, respectively, and TRIM E709 can induce recrystallized grains to grow along {001} of the sample cross section, which results from the lowest cooling rate. This work may provide an innovative control strategy for cutting fluid to improve surface integrity and service performance.