N-doped Cu2O with the tunable Cu0 and Cu+ sites for selective CO2 electrochemical reduction to ethylene.

The electrochemical carbon dioxide reduction reaction (CO2RR) to high value-added fuels or chemicals driven by the renewable energy is promising to alleviate global warming. However, the selective CO2 reduction to C2 products remains challenge. Cu-based catalyst with the specific Cu0 and Cu+ sites is important to generate C2 products. This work used nitrogen (N) to tune amounts of Cu0 and Cu+ sites in Cu2O catalysts and improve C2-product conversion. The controllable Cu0/Cu+ ratio of Cu2O catalyst from 0.16 to 15.19 was achieved by adjusting the N doping amount using NH3/Ar plasma treatment. The major theme of this work was clarifying a volcano curve of the ethylene Faraday efficiency as a function of the Cu0/Cu+ ratio. The optimal Cu0/Cu+ ratio was determined as 0.43 for selective electroreduction CO2 to ethylene. X-ray spectroscopy and density functional theory (DFT) calculations were employed to elucidate that the strong interaction between N and Cu increased the binding energy of NCu bond and stabilize Cu+, resulting in a 92.3% reduction in the potential energy change for *CO-*CO dimerization. This study is inspiring in designing high performance electrocatalysts for CO2 conversion.

3-(2-Trifluoromethyl-3-aryl-4H-chromen-4-yl)-1H-indoles: Mastering anti-inflammation and analgesia while mitigating gastrointestinal side effects.

A series of 3-(2-trifluoromethyl-3-aryl-4H-chromen-4-yl)-1H-indoles (5-1 to 5-29) were developed and characterized. Most of compounds were found to be potent for inhibiting the production of NO in LPS-induced RAW264.7 cells, of which 3-(3-(4-chlorophenyl)-6-methoxy-2-(trifluoromethyl)-4H-chromen-4-yl)-1H-indole (5-25) was the most optimal (IC50 = 4.82 ± 0.34 µΜ) and was capable of significantly suppressing the release of PGE2. The inhibitory effect of 5-25 on human recombinant COX-2 (IC50 = 51.7 ± 1.3 nM) was measured and molecular docking was performed, determining 5-25 as a COX-2 inhibitor. Additionally, the interaction between 5-25 and COX-2 was determined by the CETSA technique. Then, 5-25 inhibited the degradation of IκB, the phosphorylation and nuclear translocation of NF-κB p65, and the expression of COX-2 and iNOS. Moreover, it was verified that 5-25 exhibited efficacy in rodent models of inflammation and pain, encompassing the paw edema, cotton pellet-induced granuloma, acid-induced writhing, and adjuvant-induced arthritis models. Therefore, the mechanism of 5-25 may be to bind to COX-2 and exert anti-inflammatory and analgesic effects in vitro and in vivo by suppressing the NF-κB pathway. Encouragingly, in comparison with indomethacin, 5-25 exhibited a lower ulcerative potential in rats, as manifested by generating smaller areas and fewer ulcers, less inflammatory infiltration, a lower expression of MMP-9, and less apoptosis. In conclusion, 5-25 is a candidate drug with high activity and low ulcerogenic potential, and it deserves further research for the treatment of inflammation, pain, and other symptoms in which COX-2 plays a role in their pathogenesis.

Regional differences in the Association of Healthy Aging with the incidence of falls: an analysis based on the China Health and Retirement Longitudinal Study from 2011 to 2020.

Background: Falls frequently occur among the older adult population. In this study, we examined the variations in fall incidence across different regions over time, focusing on the disparities between urban and rural areas among older adult Chinese individuals, Healthy aging is comprised of five dimensions: (1) absence of chronic diseases, (2) good physical functioning, (3) normal cognitive function, (4) active social participation, and (5) absence of depression. Additionally, we explored the relationship between healthy aging and the occurrence of falls in middle-aged and older adults. Falls are defined as events that occurred within the past two years. Results: Among 9,918 participants, 33.8% lived in urban areas and 23.0% achieved healthy aging. In contrast, 66.2% resided in rural areas with 16.5% achieving healthy aging. In 2011, rural residents had a higher fall incidence rate (17% in rural vs. 13.5% in urban); by 2020, the fall rate remained higher in rural areas (19.5% in rural vs. 17.3% in urban). Unhealthy aging (HR = 1.08, 95%CI: 1.00-1.16) were risk factors for falls. Subgroup analysis revealed that in rural areas, unhealthy aging increased the risk of falls. In urban areas, the increased risk of falls associated with unhealthy aging was not significant (Rural HR = 1.11, 95%CI:1.01-1.22; Urban HR = 1.05, 95%CI: 0.93-1.18). Conclusion: Healthy aging may be more strongly associated with a lower risk of falls in rural areas, while this association might be less pronounced in urban areas due to different environmental and social factors. This highlights the need for environment-specific fall prevention strategies and targeted measures for the older adult.

IRF9 and STAT1 as biomarkers involved in T-cell immunity in atherosclerosis.

Atherosclerosis is a common cardiovascular disease in which the arteries are thickened due to buildup of plaque. This study aims to identify programmed cell death (PCD)-related biomarkers and explore the crucial regulatory mechanisms of atherosclerosis. Gene expression profiles of atherosclerosis and control groups from GSE20129 and GSE23746 were obtained. Necroptosis was elevated in atherosclerosis. Weighted gene coexpression network analysis (WGCNA) was conducted in GSE23746 and GSE56045 to identify PCD-related modules and to perform enrichment analysis. Two necroptosis-related genes (IRF9 and STAT1) were identified and considered as biomarkers. Enrichment analysis showed that these gene modules were mainly related to immune response regulation. In addition, single-cell RNA sequencing data from GSE159677 were obtained and the characteristic cell types of atherosclerosis were identified. A total of 11 immune cell types were identified through UMAP dimension reduction. Most immune cells were mainly enriched in plaque samples, and STAT1 and IRF9 were primarily expressed in T-cells and macrophages. Moreover, the roles of IRF9 and STAT1 were assessed and found to be significantly upregulated in atherosclerosis, which was associated with increased risk of atherosclerosis. This study provides a molecular feature of atherosclerosis, offering an important basis for further research on its pathological mechanisms and the search for new therapeutic targets.

Effect of different concentrations of sufentanil combined with ropivacaine on epidural fever during labor: A single-center retrospective study.

Labor epidural analgesia (LEA) is associated with increased maternal body temperature; however, the responsible mechanism is unknown. Recent studies suggest that changes in EA affect the incidence of fever and that epidural sufentanil supplementation enhances analgesia and reduces the amount of local anesthetic. The aim of this study was to evaluate the effect of different concentrations of sufentanil combined with ropivacaine on intrapartum fever during delivery. We performed a retrospective study comparing maternal fever rates in patients receiving labor analgesia between December 2018 and January 2019. Each patient receiving different concentrations of sufentanil in their EA received either proposal H (0.08% ropivacaine + 0.4 µg/mL sufentanil) or proposal L (0.08% ropivacaine + 0.2 µg/mL sufentanil), with the same nulliparous status. The primary outcome of this study was the incidence of intrapartum maternal fever, which was defined as any temperature ≥ 38°C during labor using Fisher exact test. Secondary outcome measures included visual analog scale (VAS) pain scores, birth events, and neonatal outcomes. We observed a perinatal fever incidence rate of 11.7% in the group receiving proposal L, while the incidence rate was 19.8% in the group receiving proposal H (P = .001). Five hours after administration, the average body temperature of the puerpera decreased significantly in the proposal L group compared with proposal H group. In addition, treatment with 0.2 µg/mL sufentanil provided satisfactory pain relief during labor, shortened the first stage of labor and total labor time, reduced oxytocin use, and had no significant adverse effects on neonatal outcomes. EA may increase the risk of intrapartum epidural-associated fever. Compared with the 0.4 µg/mL sufentanil group, the 0.2 µg/mL sufentanil group can provide better analgesia and improve maternal fever. These retrospective results highlighted the importance of prospective and mechanistic studies of maternal fever associated with intraspinal analgesia.

Prospective Study of Lung Function with Prodromal, Clinical Parkinson's Disease, and Mortality.

Background: The association of lung function with the risk of developing prodromal and clinical-diagnosed Parkinson's disease (PD) and with the risk of mortality among individuals with PD remains unknown. Objective: To prospectively examine the associations of lung function with the risk of prodromal, clinical-diagnosed PD, and PD-related mortality in participants of the UK Biobank. Methods: Included were 452,518 participants free of PD at baseline. Baseline lung function, including forced expiratory volume in 1-s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), and FEV1/FVC ratio, was assessed. Eight prodromal features were measured using self-reported diagnoses, hospital admission, and primary care data. Incident PD cases were identified using linkages with hospital admission, death register, and self-report. Vital status and date of death were provided by the UK National Health Service (NHS) and the NHS Central Register. We used Cox proportional hazard models to evaluate these associations. Results: Poor lung function was associated with higher risk of PD in a dose-response relationship: the adjusted hazard ratio comparing the lowest vs. the highest lung function quintile was 1.18 (95% CI, 1.02- 1.37) for FEV1, 1.14 (95% CI, 0.99- 1.29) for FVC, and 1.23 (95% CI, 1.08- 1.41) for PEF (p-trend <0.05 for all). Similar results were obtained for risk of prodromal PD and mortality among individuals with PD. Conclusions: The current study showed that individuals with poor lung function had a high future risk of prodromal and clinical PD and a higher rate of PD-related mortality.

Long-term outcomes in rapamycin on renal allograft function: a 30-year follow-up from a single-center experience.

OBJECTIVES: To evaluate long-term renal graft prognosis and the role of rapamycin from a single-center in China over a 30-year follow-up. METHODS: This study enrolled a total of 654 patients who underwent kidney transplantation between 1989 and 2020. The basic characteristics of the included patients were collected. Graft survival was described and compared using Kaplan-Meier curves (K-M curves). Both continuous and categorical variables were included in a multivariate Cox proportional-hazards model. Patients were divided into rapamycin-based quadruple immunosuppression regimen group (rapa group, n = 41) and conventional tacrolimus-based triple immunosuppression regimen group (control group, n = 218). The indication biopsy results of the two groups were further reviewed to compare the incidence of rejection, acute rejection, and banff score. RESULTS: The overall 5, 10, 15, 20-year graft survival rate of our center is 87.5%, 62.4%, 46.4% and 20.9%, respectively. The median survival time after surgery is 14 years. Multiple Cox regression analysis identified BMI (p = 0.035), dialysis type (p < 0.001), immunosuppressants (p < 0.01), urine albumen (p < 0.001), globulin (p = 0.041), and blood glucose (p = 0.002) as risk factors. The 20-year, 10-year and 5-year AUC is 0.78, 0.75 and 0.75. The combination of FK506 and rapamycin was further suggested by the model to effectively improve the graft prognosis (p < 0.01, HR = 0.763). The K-M curve showed that the long-term survival rate of renal grafts in the rapa group was significantly better than that in the conventional group (p < 0.001). In addition, indication biopsy records revealed a lower possibility of immune rejection in the rapa group than that in the conventional group (p < 0.001). Banff score indicated that rapa group had less vascular inflammation in the transplanted kidney. CONCLUSIONS: In this study, a 30-year follow-up was performed in a single center, and a total graft 20-year survival rate of 20.9% was reported. The prognostic model and subgroup analysis suggested that FK506 combined with rapamycin could effectively improve the prognosis of renal transplantation, which could be explained by reduced acute rejection and less vascular inflammation.

Lung-Targeted Lipid Nanoparticle-Delivered siUSP33 Attenuates SARS-CoV-2 Replication and Virulence by Promoting Envelope Degradation.

As a structural protein of SARS-CoV-2, the envelope (E) protein not only plays a key role in the formation of viral particles, but also forms ion channels and has pathogenic functions, including triggering cell death and inflammatory responses. The stability of E proteins is controlled by the host ubiquitin-proteasome system. By screening human deubiquitinases, it is found that ubiquitin-specific protease 33 (USP33) can enhance the stability of E proteins depending on its deubiquitinase activity, thereby promoting viral replication. In the absence of USP33, E proteins are rapidly degraded, leading to a reduced viral load and inflammation. Using lipid nanoparticle (LNP) encapsulation of siUSP33 by adjusting the lipid components (ionizable cationic lipids), siUSP33 is successfully delivered to mouse lung tissues, rapidly reducing USP33 expression in the lungs and maintaining knockdown for at least 14 days, effectively suppressing viral replication and virulence. This method of delivery allows efficient targeting of the lungs and a response to acute infections without long-term USP33 deficiency. This research, based on the deubiquitination mechanism of USP33 on the E protein, demonstrates that LNP-mediated siRNA delivery targeting USP33 plays a role in antiviral and anti-inflammatory responses, offering a novel strategy for the prevention and treatment of SARS-CoV-2.

Different levels of physical activity and risk of developing type 2 diabetes among adults with prediabetes: a population-based cohort study.

OBJECTIVES: This study aimed to evaluate the association between different levels of physical activity and risk of developing type 2 diabetes (T2D) mellitus among adults with prediabetes in Chinese population. METHODS: This prospective population-based cohort study included 12,424 participants (mean [SD] age, 52.8 [16.8] years; 82.2% men) with prediabetes at 2014 survey of the Kailuan study. Physical activity information was collected through the International Physical Activity Questionnaire-Short Form and categorized by metabolic equivalent (MET) of task as low, moderate, and high. Cox regression models were built to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between physical activity levels and incident T2D. RESULTS: During a median follow-up of 3.6 years, 2,207 (17.8%) participants developed T2D. The incident rate of T2D were 55.83/1000, 35.14/1000, and 39.61/1000 person-years in the low, moderate, and high physical activity level group, respectively. Both moderate (HR 0.57, 95% CI 0.49 to 0.67) and high (HR 0.76, 95% CI 0.66 to 0.89) physical activity levels were associated with lower risks of developing T2D compared to low physical activity level (P for trend < 0.001). The association between high physical activity level and T2D was primarily observed in participants without metabolic syndrome (P for interaction < 0.001). Moreover, participants with moderate or high levels of physical activity had significantly decreased fasting blood glucose levels during follow-up when compared to those with low level (P group*time < 0.001). CONCLUSION: This study suggested that individuals with prediabetes might benefit from moderate and high levels of physical activity.

Protective effect of carvacrol hydrogel on the alveolar bone in rats with periodontitis.

OBJECTIVES: This study aimed to investigate the protective effect and mechanism of carvacrol hydrogel on the alveolar bone in rats with periodontitis. METHODS: A thermosensitive hydrogel supported by carvacrol was prepared using poloxamer and hydroxypropyl methyl cellulose as matrix. SD rats were randomly divided into blank group, periodontitis group, blank hydrogel group, and low-, medium-, and high-dose hydrogel groups. The periodontitis symptoms and the CT structure of the alveolar bone were observed. The changes in liver, spleen, kidney, and periodontal tissues were observed. The related indexes of bone metabolism in serum were detected. The expression of osteoprotegerin (OPG) and nuclear transcription factor-κB (NF-κB) pathway proteins was determined by Western blot. The levels of inflammatory factors were assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: Carvacrol hydrogel had good slow release, biocompatibility, and cell adhesion. The periodontitis of rats in the carvacrol hydrogel group was significantly alleviated, the expression of OPG protein in gingival tissue was significantly increased (P<0.01), and the levels of receptor activator of NF-κB ligand (RANKL), receptor activator of NF-κB (RANK), NF-κB protein, and inflammatory factors were significantly decreased (P<0.01). CONCLUSIONS: Carvacrol hydrogel can regulate the OPG and NF-κB pathways, reduce alveolar bone absorption, and improve periodontal inflammation.

Lutein protects senescent ciliary muscle against oxidative stress through the Keap1/Nrf2/ARE pathway.

BACKGROUND: Aging-induced decline in ciliary muscle function is an important factor in visual accommodative deficits in elderly adults. With this study, we provide an innovative investigation of the interaction between ciliary muscle aging and oxidative stress. METHODS: Tricolor guinea pigs were used for the experiments in vivo and primary guinea pig ciliary smooth muscle cells were used for the experiments in vitro. RESULTS: We enriched for genes associated with muscle-aging-lutein relationship using bioinformatics, including Nuclear factor-erythroid 2-related factor-2 (Nrf2), Glutathione Peroxidase (GPx) gene family, Superoxide Dismutase (SOD) gene family, NAD(P)H: Quinone Oxidoreductase 1 (NQO1) and Heme Oxygenase-1 (HO-1). After gavage to aged guinea pigs, lutein reduced Reactive Oxygen Species (ROS) and P21 levels in senescent ciliary muscle; lutein decreased refractive error and restored accommodation of the eye. In addition, lutein increased GPx, SOD, and Catalase (CAT) levels in serum; lutein increased GPx and CAT levels in ciliary bodies. Lutein regulated the expression of proteins such as Nrf2, Kelch-like ECH-associated protein 1 (Keap1), and downstream proteins in senescent ciliary bodies. Similarly, guinea pig ciliary muscle cell senescence was associated with oxidative stress. In vitro, 100 µM lutein reversed the damage caused by 800 µM H2O2; it reduced Senescence-Associated ß-galactosidase (SA-ß-Gal) and ROS activites, cell apoptosis and cell migration. Also, lutein increased the expression of smooth muscle contractile proteins. Lutein also increased the expression of Nrf2, GPx2, NQO1 and HO-1, decreased the expression of Keap1. A reduction in Nrf2 activity led to a reduction in the ability of lutein to activate antioxidant enzymes in the cells, thus reducing its inhibitory effect on cell senescence. CONCLUSION: lutein improved resistance to oxidative stress in senescent ciliary muscle in vivo and in vitro by regulating the Keap1/Nrf2/Antioxidant Response Element pathway. We have innovatively demonstrated the molecular pharmacological mechanism by which lutein reverse age-related ciliary muscle systolic and diastolic deficits.

Association between different stages of cardiovascular-kidney-metabolic syndrome and the risk of all-cause mortality.

BACKGROUND AND AIMS: Poor cardiovascular-kidney-metabolic (CKM) health is a major determinant of all-cause mortality, which poses a significant burden on global public health systems and socio-economics. However, the association between different stages of CKM syndrome and the risk of all-cause mortality remains unclear. This study aimed to evaluate the association between different stages of CKM syndrome and risk of all-cause mortality. METHODS: A total of 97,777 adults from the Kailuan Study were included. Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) of all-cause mortality according to different stages of CKM syndrome. RESULTS: Over a median follow-up of 15.0 (14.7-15.2) years, we identified 14,805 all-cause mortality cases. The stage of CKM syndrome was positively associated with the risk of all-cause mortality (p-trend <0.001). Compared with Stage 0, the multivariable-adjusted HRs (95 % CIs) of all-cause mortality were 1.24 (1.06-1.45) for Stage 1, 1.72 (1.48-2.00) for Stage 2, 2.58 (2.22-3.01) for Stage 3 and 3.73 (3.19-4.37) for Stage 4. Moreover, the observed associations were more pronounced in younger adults (aged <60 years) compared with older adults (p for interaction <0.001). CONCLUSIONS: Our data showed that a higher stage of CKM syndrome was associated with a higher risk of all-cause mortality, with a particularly pronounced association observed in younger adults. The study emphasized the need for targeted public health strategies and clinical management tailored to the stages of CKM syndrome, aiming to alleviate its burden on individuals and healthcare systems.

GPX4 restricts ferroptosis of NKp46+ILC3s to control intestinal inflammation.

Group 3 innate lymphoid cells (ILC3s) are essential for both pathogen defense and tissue homeostasis in the intestine. Dysfunction of ILC3s could lead to increased susceptibility to intestinal inflammation. However, the precise mechanisms governing the maintenance of intestinal ILC3s are yet to be fully elucidated. Here, we demonstrated that ferroptosis is vital for regulating the survival of intestinal ILC3. Ferroptosis-related genes, including GPX4, a key regulator of ferroptosis, were found to be upregulated in intestinal mucosal ILC3s from ulcerative colitis patients. Deletion of GPX4 resulted in a decrease in NKp46+ILC3 cell numbers, impaired production of IL-22 and IL-17A, and exacerbated intestinal inflammation in a T cell-independent manner. Our mechanistic studies revealed that GPX4-mediated ferroptosis in NKp46+ILC3 cells was regulated by the LCN2-p38-ATF4-xCT signaling pathway. Mice lacking LCN2 in ILC3s or administration of a p38 pathway inhibitor exhibited similar phenotypes of ILC3 and colitis to those observed in GPX4 conditional knock-out mice. These observations provide novel insights into therapeutic strategies for intestinal inflammation by modulating ILC3 ferroptosis.

Anti-colorectal cancer activity of mannatide from spent brewer's yeast by regulating immune cells and immune function in the tumor microenvironment.

Chemotherapy and radiotherapy are generally accompanied by adverse effects, which reduce tolerance to cancer therapies. Immunonutrition improves the clinical outcomes of cancer patients. Hence, natural immunomodulator is therefore considered as a favorable alternative. This study aimed to elucidate the anti-colorectal cancer (CRC) effect of mannatide (MTE) from the immunostimulatory perspective. MTE (concentrations≥1200 µg/mL) significantly inhibited HT-29 cells viabilities compared with the 5-fluorouracil (5-FU) group and all predetermined concentrations of MTE promoted the proliferation of RAW264.7 (p < 0.01). Moreover, MTE treatment suppressed tumor growth, decreased leukocyte and platelet count, and regulated immune organ indexes compared with the model group. In comparison of Model and 5-FU groups, MTE treatment reshaped tumor-associated macrophages (TAMs) from alternatively activated macrophages (M2)-like into classical activated macrophages (M1)-like phenotype. Also, it increased the proportion of CD8+ and CD4+ T cells accompanied by secreting pro-inflammatory cytokines (interferon (IFN)-γ and tumor necrosis factor (TNF)-α) and decreasing pro-inflammatory cytokines (interleukin (IL)-4, interleukin (IL)-6, arginine (Arg)-1, and cyclooxygenase (COX)-2) to reduce immunosuppression. Moreover, MTE-administrated alleviated intestinal mucositis and improved the prognostic indexes compared with the 5-FU group. Notably, the ability of low-dose MTE to regulate immune cells and the function of the tumor microenvironment was higher than that of high-dose. Generally, MTE as an immunomodulator presents great potential to strengthen anti-CRC activity.

Prediction of Lymph Node Metastasis in Endometrial Cancer Based on Color Doppler Ultrasound Radiomics.

RATIONALE AND OBJECTIVES: To construct a model using radiomics features based on ultrasound images and evaluate the feasibility of noninvasive assessment of lymph node status in endometrial cancer (EC) patients. METHODS: In this multicenter retrospective study, a total of 186 EC patients who underwent hysterectomy and lymph node dissection were included, Pathology confirmed the presence or absence of lymph node metastasis (LNM). The study encompassed patients from seven centers, spanning from September 2018 to November 2023, with 93 patients in each group (with or without LNM). Extracted ultrasound radiomics features from transvaginal ultrasound images, used five machine learning (ML) algorithms to establish US radiomics models, screened clinical features through univariate and multivariate logistic regression to establish a clinical model, and combined clinical and radiomics features to establish a nomogram model. The diagnostic ability of the three models for LNM with EC was compared, and the diagnostic performance and accuracy of the three models were evaluated using receiver operating characteristic curve analysis. RESULTS: Among the five ML models, the XGBoost model performed the best, with AUC values of 0.900 (95% CI, 0.847-0.950) and 0.865 (95% CI, 0.763-0.950) for the training and testing sets, respectively. In the final model, the nomogram based on clinical features and the ultrasound radiomics showed good resolution, with AUC values of 0.919 (95% CI, 0.874-0.964) and 0.884 (0.801-0.967) in the training and testing sets, respectively. The decision curve analysis verified the clinical practicality of the nomogram. CONCLUSION: The ML model based on ultrasound radiomics has potential value in the noninvasive differential diagnosis of LNM in patients with EC. The nomogram constructed by combining ultrasound radiomics and clinical features can provide clinical doctors with more comprehensive and personalized image information, which is highly important for selecting treatment strategies.

Pan-cancer analysis of the role of α2C-adrenergic receptor (ADRA2C) in human tumors and validation in glioblastoma multiforme models.

Background: Several studies have reported the relationship between α2C-adrenergic receptor (ADRA2C) and both neoplastic and non-neoplastic diseases. However, a comprehensive pan-cancer analysis is currently lacking. Methods: Utilizing the RNA sequencing (RNA-seq) datasets from The Cancer Genome Atlas (TCGA) database, the roles of ADRA2C in human pan-cancer were analyzed through a variety of bioinformatics approaches, including R programming language and single-cell sequencing data analysis, et al. Besides, cell migration assay and immunochemistry were employed to further validate the role of ADRA2C in glioblastoma multiforme (GBM) cell lines and GBM mouse model. Results: A total of 33 cancer types were involved in this study. It was revealed that the expression level of ADRA2C varied across different clinical stages in patients with breast invasive carcinoma (BRCA), esophageal adenocarcinoma (ESCA), kidney renal papillary cell carcinoma (KIRP) and lung squamous cell carcinoma (LUSC). Meanwhile, it was found that ADRA2C may play roles in prognosis of adrenocortical carcinoma (ACC), glioblastoma multiforme and lower grade glioma (GBM-LGG), and uveal melanoma (UVM). Functional enrichment analysis suggested that ADRA2C expression level was highly correlated with neuronal system-related pathways. Moreover, ADRA2C may be a promising diagnostic marker for cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), cholangiocarcinoma (CHOL), GBM, GBMLGG, kidney chromophobe (KICH), and KIRP. Additionally, ADRA2C expression level was correlated with the levels of several infiltrating cells and immune checkpoint genes. Besides, the single-cell sequencing data analysis indicated that ADRA2C played a role in multiple tumor development processes in GBM, retinoblastoma (RB), and UVM. Finally, in vitro and in vivo experiments confirmed that the expression level of ADRA2C may be associated with glioma cell migration, apoptosis, and invasion. Conclusion: ADRA2C exhibited to play a notable role in several cancer types, suggesting that ADRA2C could serve as a promising biomarker or target for cancer diagnosis, prognosis, and treatment, particularly for GBM.

Erythropoietin regulates osteoclast formation via up-regulating PPARγ expression.

Erythropoietin (EPO), expressed in red blood progenitor cells, primarily regulates erythropoiesis by binding to its receptor. Besides anemia, recent studies have identified new therapeutic indications for EPO that are not connected to red blood cell formation. Elevated EPO levels harm bone homeostasis in adult organisms and are associated with increased osteoclast; however, the underlying molecular mechanisms remain unclear. This study demonstrated that EPO enhanced osteoclast differentiation and bone resorption in vitro. We showed that EPO promoted osteoclast formation by up-regulating PPARγ expression through activating the Jak2/ERK signaling pathway. Consistently, PPARγ antagonists rescued the hyperactivation of osteoclasts due to EPO, while PPARγ agonists reversed the EMP9-mediated decrease in osteoclast differentiation. Further, exposing female mice to EPO for two months led to a decrease in bone mass and increased osteoclast numbers. The present results suggested that EPO promotes osteoclastogenesis by regulating the Jak2/ERK/ PPARγ signaling pathway. From a clinical perspective, the risk of compromised bone health should be considered when using EPO to treat anemia in post-operative patients with intertrochanteric fractures of the femur, as it could significantly impact the patient's recovery and quality of life.

Correction: Spontaneous mutations and mutational responses to penicillin treatment in the bacterial pathogen Streptococcus pneumoniae D39.

[This corrects the article DOI: 10.1007/s42995-024-00220-6.].

Polydopamine-Based Biomaterials in Orthopedic Therapeutics: Properties, Applications, and Future Perspectives.

Polydopamine is a versatile and modifiable polymer, known for its excellent biocompatibility and adhesiveness. It can also be engineered into a variety of nanoparticles and biomaterials for drug delivery, functional modification, making it an excellent choice to enhance the prevention and treatment of orthopedic diseases. Currently, the application of polydopamine biomaterials in orthopedic disease prevention and treatment is in its early stages, despite some initial achievements. This article aims to review these applications to encourage further development of polydopamine for orthopedic therapeutic needs. We detail the properties of polydopamine and its biomaterial types, highlighting its superior performance in functional modification on nanoparticles and materials. Additionally, we also explore the challenges and future prospects in developing optimal polydopamine biomaterials for clinical use in orthopedic disease prevention and treatment.