Cardiovascular health assessed by the new life's essential 8 and the prevalence of urinary incontinence in adults.

OBJECTIVE: To explore the association between cardiovascular health (CVH) measured by Life's Essential 8 (LE8) and the prevalence of urinary incontinence (UI). METHOD: A cross-section study was conducted using data from the National Health and Nutrition Examination Survey 2007-2012. 22,609 people aged ≥ 20 years with complete information on LE8 metrics and UI questionnaires were enrolled. Participants were divided into three groups (low: < 50, moderate: ≥ 50 and < 80, high: ≥ 80) based on the cut-off of LE8. Weighted proportions, multivariable logistic regression analysis and stratified logistic regression were performed to examine the association between LE8 and the prevalence of three types of UI separately (stress UI (SUI), urge UI (UUI), mixed UI (MUI)) by confounding factors adjusted. Spline smooth was conducted to find whether a linear relationship existed. In addition, sensitive analyses were also conducted to observe the stability. RESULT: A total of 22,609 adults were involved in the study, and participants were divided into three groups (low 42.2 ± 6.3, moderate 66.1 ± 8.1, high 86.8 ± 5.1) according to the cut-off points of LE8. The multivariable logistic regression suggested that LE8 is inversely associated with the prevalence of SUI (OR = 0.98, 95%CI 0.98 to 0.99), UUI (OR = 0.98, 95%CI 0.98 to 0.99), and MUI (OR = 0.98, 95%CI 0.97 to 0.98) in the fully-adjusted model. Compared with the low group, people with high scores of LE8 had a lower prevalence of SUI (OR = 0.45, 95%CI 0.37 to 0.55), UUI (OR = 0.49, 95%CI 0.40 to 0.60), and MUI (OR = 0.41, 95%CI 0.30 to 0.55). The result of the sensitive analysis showed the robustness of the main analysis. CONCLUSION: The prevalence of UI (SUI, UUI, or MUI) is inversely associated with the LE8 score, which suggests that maintaining a good CVH with a higher LE8 score is accompanied by lower prevalence rates of UUI, SUI, and MUI.

Exploring the feasibility of multi-elements coupled with chemometrics for discriminating the geographical origins of oysters (Crassostrea ariakensis).

This study explored the efficacy of multi-elements combined with chemometrics to discriminate the geographical origins of oysters (Crassostrea ariakensi). We determined 52 elements in 166 samples from four regions along the southeast coast of China. Significant regional variations of 51 elements were revealed (P < 0.05), while the principal component analysis (PCA) provided no clear regional delineations. The training models (n = 117) established on linear discriminant analysis (LDA), partial least square discriminant analysis (PLS-DA), and random forest (RF) uniformly achieved 100% predictive accuracy. The cross-validation accuracies of the final models (n = 166) derived from LDA, PLS-DA, and RF were 100%, 100%, and 99.4%, respectively. Even with the models simplified to 8 elements (Zn, Al, K, Cd, Cu, Rb, B, and Ag), high predictive and cross-validation accuracies were maintained, underscoring the robustness and algorithm flexibility of elemental profiling for accurately identifying the geographical origins of oysters.

The care cascade of chronic obstructive pulmonary disease in China: a cross-sectional study of individual-level data at enrolment into the national 'Happy Breathing' Programme.

Background: Understanding the chronic obstructive pulmonary disease (COPD) care cascade is crucial for identifying where and when to intervene to improve COPD outcomes. We aimed to determine the proportion of patients with COPD seeking care in China's health system who are lost at each stage of the COPD care cascade and how the patterns of loss vary across geographical regions and population groups. Methods: From November 3, 2018, to April 22, 2021, we used individual-level patient data from the national Chinese 'Happy Breathing' Programme, which aims to identify patients with COPD and provide appropriate care. COPD was defined as a post-bronchodilator ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) <0.70. We calculated the proportions of individuals who, at enrolment into the 'Happy Breathing' Programme, (i) had ever undergone a pulmonary function test, (ii) had been diagnosed with COPD in the past, (iii) were currently on treatment for COPD, and (iv) had achieved control of their COPD. We examined the association between reaching each stage of the care cascade and individual patient characteristics as well as regional-level economic development and available resources in the health system using multilevel regression. Findings: Among the 29,201 patients with COPD in the 'Happy Breathing' Programme, 41.0% (95% confidence interval [CI]: 40.4-41.6%) had ever been tested for COPD, 17.6% (95% CI: 17.1-18.0%) had previously been diagnosed with COPD, 8.5% (95% CI: 8.2-8.8%) were currently on treatment for COPD, 4.6% (95% CI: 4.3-4.8%) of patients had mild or no exacerbations in the prior year, and 3.9% (95% CI: 3.7-4.2%) of patients had suffered no exacerbations in the prior year. On average, patients living in the cities of Beijing, Wuhan, and Yinchuan had progressed further along the COPD care cascade than patients living in Daqing and Luoyang. Using multilevel regression, we found that young age, rural residence, and low regional per-capita GDP were significantly associated with larger losses at each stage of the COPD care cascade. Interpretation: Substantial proportions of patients with COPD are lost at each stage of the COPD care cascade in the Chinese health system. The largest losses occur during the initial stages of the cascade, when diagnosis first occurs. New policies and interventions are required to boost COPD care, especially screening and diagnosis, in the Chinese health system to reduce this large disease burden. Funding: This work was supported by Major Programme of National Natural Science Foundation of China (82090011), CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-049), and Horizon Europe (HORIZON-MSCA-2021-SE-01; project number 101086139-PoPMeD-SuSDeV). TB was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt professorship award.

Analysis of the Therapeutic Efficacy of Hysteroscopic Electric Resection in the Treatment of Atypical Endometrial Hyperplasia and Factors Influencing Prognosis.

Objective: The objective of this study was to evaluate the efficacy of hysteroscopic electroresection in the treatment of atypical endometrial hyperplasia and to determine the prognostic factors. Methods: 226 patients with endometrial dysplasia treated in hospital from January 2021 to August 2022 were selected and divided into control group (113 cases) and study group (113 cases) according to different treatment methods selected by the patients themselves. The control group received curettage plus conventional progesterone treatment, while the study group received hysteroscopic electroresection plus conventional progesterone treatment. After 6 months of treatment, the clinical efficacy (complete response, partial response and progress) of the two groups were evaluated, complications and adverse drug reactions of the two groups were analyzed, and estrogen levels before and after treatment were compared between the two groups. After 1 year follow-up, patients were divided into relapse group and non-recurrence group according to whether they had relapse or not. Clinical data of the two groups were compared to analyze the related factors affecting the prognosis of patients. Results: (1) Chi-square test results showed that the total effective rate of the study group was higher (96.46% VS 77.88%) than that of the control group (P < .05). The complication rate and recurrence rate of the study group were lower than those of the control group (1.77% VS 7.96%, 4.42% VS 21.24%) (P < .05). (2) t test results of independent samples showed that after 6 months of treatment, the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the study group were lower than those in the control group (P < .05); (3) The t test results of independent samples indicated that the age and body mass index of the relapsed group were higher than those of the non-relapsed group (P < .05); Chi-square test results showed that the proportion of diabetes was higher than that of the group without recurrence, and the proportion of hysteroscopic electroresection was lower than that of the group without recurrence (P < .05). (4) Logistic regression model was established, and the results showed that age (OR=1.159), body mass index (OR=1.529) and diabetes (OR=3.861) were the risk factors for prognosis of patients with endometrial dysplasia (P < .05), and hysteroscopic electroresection was the protective factor (OR < 1, P < .05). Conclusion: Hysteroscopic electroresection shows significant potential in the treatment of atypical hyperplasia of endometrial, and can improve clinical efficacy and reduce complications by effectively regulating estrogen secretion. In addition, studies have shown that the prognosis of endometrial dysplasia may be related to the age of patients, body mass index and diabetes mellitus. Therefore, for patients with the above risk factors, early consideration of hysteroscopic electrotomy therapy is recommended to reduce recurrence rates and provide important informational support for treatment protocols and clinical guidelines.

SIPA1 promotes epithelial-mesenchymal transition in colorectal cancer through STAT3 activation.

Colorectal cancer (CRC) is the third leading cancer type worldwide and accounts for the second highest rate of cancer-related mortality. Liver metastasis significantly contributes to the mortality associated with CRC, but the fundamental mechanisms behind it remain unclear. Signal-induced proliferation-associated protein 1 (SIPA1), a GTPase activating protein, has been shown to promote metastasis in breast cancer. In this study, our objective was to explore the role of SIPA1 in regulating epithelial-mesenchymal transition (EMT) in CRC. The analysis of The Cancer Genome Atlas (TCGA) database revealed that the expression level of SIPA1 mRNA was notably upregulated and exhibited a positively correlated with EMT and STAT3 signaling pathways in CRC. Knockdown of SIPA1 impairs CRC cell proliferation and migration. Further studies on the reliance of SIPA1 on STAT3 signaling for EMT regulation have shown that SIPA1 stimulates the activation of STAT3, resulting in its nuclear translocation. The co-treatment of overexpressed SIPA1 with the STAT3 inhibitor STTITA has shown that SIPA1 regulates the expression of EMT-related markers through STAT3. Our study indicate that SIPA1 promotes CRC metastasis by activating the STAT3 signaling pathway, underscoring the potential of SIPA1 as a therapeutic target for metastatic CRC patients.

NCAPD2 augments the tumorigenesis and progression of human liver cancer via the PI3K­Akt­mTOR signaling pathway.

Non­SMC condensin I complex subunit D2 (NCAPD2) is a newly identified oncogene; however, the specific biological function and molecular mechanism of NCAPD2 in liver cancer progression remain unknown. In the present study, the aberrant expression of NCAPD2 in liver cancer was investigated using public tumor databases, including TNMplot, The Cancer Genome Atlas and the International Cancer Genome Consortium based on bioinformatics analyses, and it was validated using a clinical cohort. It was revealed that NCAPD2 was significantly upregulated in liver cancer tissues compared with in control liver tissues, and NCAPD2 served as an independent prognostic factor and predicted poor prognosis in liver cancer. In addition, the expression of NCAPD2 was positively correlated with the percentage of Ki67+ cells. Finally, single­cell sequencing data, gene­set enrichment analyses and in vitro investigations, including cell proliferation assay, Transwell assay, wound healing assay, cell cycle experiments, cell apoptosis assay and western blotting, were carried out in human liver cancer cell lines to assess the biological mechanisms of NCAPD2 in patients with liver cancer. The results revealed that the upregulation of NCAPD2 enhanced tumor cell proliferation, invasion and cell cycle progression at the G2/M­phase transition, and inhibited apoptosis in liver cancer cells. Furthermore, NCAPD2 overexpression was closely associated with the phosphatidylinositol 3­kinase (PI3K)­Akt­mammalian target of rapamycin (mTOR)/c­Myc signaling pathway and epithelial­mesenchymal transition (EMT) progression in HepG2 and Huh7 cells. In addition, upregulated NCAPD2 was shown to have adverse effects on overall survival and disease­specific survival in liver cancer. In conclusion, the overexpression of NCAPD2 was shown to lead to cell cycle progression at the G2/M­phase transition, activation of the PI3K­Akt­mTOR/c­Myc signaling pathway and EMT progression in human liver cancer cells.

Photoswitchable dynamics and RNAi synergist with tailored interface and controlled release reprogramming tumor immunosuppressive niche.

Immunosuppressive tumor microenvironment (ITM) severely limited the efficacy of immunotherapy against triple-negative breast cancer (TNBC). Herein, Apt-LPR, a light-activatable photodynamic therapy (PDT)/RNAi immune synergy-enhancer was constructed by co-loading miR-34a and photosensitizers in cationic liposomes (in phase III clinical trial). Interestingly, the introduction of tumor-specific aptamers creates a special "Liposome-Aptamer-Target" interface, where the aptamers are initially in a "lying down" state but transform to "standing up" after target binding. The interfacing mechanism was elaborately revealed by computational and practical experiments. This unique interface endowed Apt-LPR with neutralized surface potential of cationic liposomes to reduce non-specific cytotoxicity, enhanced DNase resistance to protect aptamers, and preserved target-binding ability for selective drug delivery. Upon near-infrared irradiation, the generated reactive oxygen species would oxidize unsaturated phospholipids to destabilize both liposomes and lysosomes, realizing stepwise lysosomal escape of miR-34a for tumor cell apoptosis and downregulation of PD-L1 to suppress immune escape. Together, tumor-associated antigens released from PDT-damaged mitochondria and endoplasmic reticulum could activate the suppressive immune cells to establish an "immune hot" milieu. The collaborative immune-enhancing strategy effectively aroused systemic antitumor immunity and inhibited primary and distal tumor progression as well as lung metastasis in 4T1 xenografted mouse models. The photo-controlled drug release and specific tumor-targeting capabilities of Apt-LPR were also visualized in MDA-MB-231 xenografted zebrafish models. Therefore, this photoswitchable PDT/RNAi immune stimulator offered a powerful approach to reprogramming ITM and reinforcing cancer immunotherapy efficacy.

Immune response of Rhinogobio ventralis to Ichthyophthirius multifiliis infection: Insights from histopathological and real-time gene expression analyses.

Ichthyophthirius multifiliis is a parasite that poses a considerable threat to aquaculture and the ornamental fish industry, but with limited effective treatment options available. This study employed RT-qPCR to detect and analyze the expression changes of partial toll-like receptor (TLR) genes (TLR1 and TLR21), adapter protein and signal transduction molecule genes (MyD88, TRIF, NF-κB, IRAK4, and IRF3), and cytokines (IL-6, IL-8, IL-13, CXC-α and CXCR1), as well as complement C3, in the skin, gill, fin, liver, head kidney and spleen of Rhinogobio ventralis under different infection conditions. Additionally, tissue sections and scanning electron microscopy were utilized to observe the pathological changes in the gills and fins of R. ventralis after infection with I. multifiliis. The expression patterns of TLR-related DEGs (differentially expressed genes) in diseased wild fish were analyzed, revealing upregulation of TLR1, TLR21, MyD88, NF-κB, IRAK4, TRIF, IRF3, IL-6, IL-8, IL-13, CXC-α, CXCR1, and C3 genes in various tissues, indicating that these genes may be involved in the immune response of R. ventralis to I. multifiliis infection. To further analyze the gene expression of sampled from the field, an artificial infection model of R. ventralis was established under laboratory conditions, with additional sampling from the skin and fins. These genes continued to show varying degrees of upregulation, but the results were not entirely consistent with those from Wudongde samples, which may be due to the more complex environment in the wild or differences in the degree of I. multifiliis infection in wild fish. The infection of I. multifiliis caused severe damage to the gills and fins of R. ventralis, characterized by extensive secretions on the gill and fin surfaces, with the presence of attached I. multifiliis trophonts, including damage and loss of gill filaments, swollen gill lamellae, and deformed gill plates, as well as cell proliferation and necrosis of gill epithelial cells. This study sheds light on the role of the TLR signaling pathway in resisting I. multifiliis infection and its associated histopathological changes in R. ventralis, providing valuable insights for the prevention and treatment of I. multifiliis infection in R. ventralis.

An infusible biologically active adhesive for chemotherapy-related heart failure in elderly rats.

Chemotherapy-induced cardiotoxicity with subsequent heart failure (HF) is a major cause of morbidity and mortality in cancer survivors worldwide. Chemotherapy-induced HF is exceptionally challenging as it generally manifests in patients who are typically not eligible for left ventricular device implantation or heart transplantation. To explore alternative treatment strategies for cancer survivors suffering from chemotherapy-induced HF, we developed a minimally invasive infusible cardiac stromal cell secretomes adhesive (MISA) that could be delivered locally through an endoscope-guided intrapericardial injection. To mimic the typical clinical presentation of chemotherapy-induced HF in elder patients, we established an aged rat model in which restrictive cardiomyopathy with sequential HF was induced via consecutive doxorubicin injections. In vitro, we prove that MISA not only enhanced cardiomyocytes proliferation potency and viability, but also inhibited their apoptosis. In vivo, we prove that MISA improved the ventricular contractility indexes and led to beneficial effects on histological and structural features of restrictive cardiomyopathy via promoting cardiomyocyte proliferation, angiogenesis, and mitochondrial respiration. Additionally, we also evaluated the safety and feasibility of MISA intrapericardial delivery in a healthy porcine model with an intact immune system. In general, our data indicates that MISA has a strong potential for translation into large animal models and ultimately clinical applications for chemotherapy-induced HF prior to the final option of heart transplantation.

Rhodium(III) Complex Noncanonically Potentiates Antitumor Immune Responses by Inhibiting Wnt/ß-Catenin Signaling.

Metal-based chemoimmunotherapy has recently garnered significant attention for its capacity to stimulate tumor-specific immunity beyond direct cytotoxic effects. Such effects are usually caused by ICD via the activation of DAMP signals. However, metal complexes that can elicit antitumor immune responses other than ICD have not yet been described. Herein, we report that a rhodium complex (Rh-1) triggers potent antitumor immune responses by downregulating Wnt/ß-catenin signaling with subsequent activation of T lymphocyte infiltration to the tumor site. The results of mechanistic experiments suggest that ROS accumulation following Rh-1 treatment is a critical trigger of a decrease in ß-catenin and enhanced secretion of CCL4, a key mediator of T cell infiltration. Through these properties, Rh-1 exerts a synergistic effect in combination with PD-1 inhibitors against tumor growth in vivo. Taken together, our work describes a promising metal-based antitumor agent with a noncanonical mode of action to sensitize tumor tissues to ICB therapy.

Mineralized aggregates based on native protein phase transition for non-destructive diagnosis of seborrheic skin by surface-enhanced Raman spectroscopy.

The non-homeostasis of sebum secretion by the sebaceous glands in a complicated microenvironment dramatically impacts the skin health of many people in the world. However, the complexity and hydrophobicity of sebum mean a lack of diagnostic tools, which makes it challenging to determine the reason behind cortical imbalances. Herein, a biomimetic mineralized aggregates (PTL@Au and PTB@Au) strategy has been proposed, which could obtain molecular information about sebum by surface-enhanced Raman spectroscopy (SERS). The breaking of disulfide bonds leads to changes in hydrogen bonding, which transform the natural protein into amyloid-like phase transition protein with ß-sheets. It provides sites for the nucleation and crystallization of gold nanocrystals to build mineralized aggregates. The mineralized aggregates show robust adhesion stability at the interfaces of different materials through hydrogen bonding and electrostatic interactions. The stabilization, hydrophobicity (contact angle: 134°), and optical transmission (75%) of the structure could result in superior SERS performance for sebum analysis. It should be noted that this enables the sebum detection of clinical samples while ensuring safety. Such generalized bionic mineralization construction and diagnosis methods also serve as an advanced paradigm for a range of biomedical applications.

High-temperature quantum valley Hall effect with quantized resistance and a topological switch.

Edge states of a topological insulator can be used to explore fundamental science emerging at the interface of low dimensionality and topology. Achieving a robust conductance quantization, however, has proven challenging for helical edge states. In this work, we show wide resistance plateaus in kink states-a manifestation of the quantum valley Hall effect in Bernal bilayer graphene-quantized to the predicted value at zero magnetic field. The plateau resistance has a very weak temperature dependence up to 50 kelvin and is flat within a dc bias window of tens of millivolts. We demonstrate the electrical operation of a topology-controlled switch with an on/off ratio of 200. These results demonstrate the robustness and tunability of the kink states and its promise in constructing electron quantum optics devices.

CRISPR/Cas12a-triggered ordered concatemeric DNA probes signal-on/off multifunctional analytical sensing system for ultrasensitive detection of thalassemia.

Based on CRISPR/Cas12a triggered ordered concatemeric DNA probes, a "on/off" self-powered biosensor is developed to achieve highly sensitive detection of thalassemia gene CD142 through open-circuit potential-assisted visual signal output. The ingeniously constructed glucose oxidase (GOD)-functionalized ordered concatemeric DNA probe structure can significantly amplify signal output, while the coupled CRISPR/Cas12a system is served as a "signal switch" with excellent signal-transducing capabilities. When the ordered concatemeric DNA probe structure is anchored on electrode, the response signal of the sensing system is in the "signal on" mode. While, the presence of the target activates the non-specific cleavage activity of the CRISPR/Cas12a system, causing the sensing system to switch to the "signal off" mode. In the detection system, GOD catalyzes the oxidation of glucose to produce hydrogen peroxide, which further catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to form a color product, enabling visual signal of the target through naked-eye color contrast. By employing a multifunctional analytical mode combining electrochemical and visual signal outputs, accurate determination of the target is achieved, with linear ranges of 0.0001-100 pM, and detection limits of 48.1 aM (S/N = 3). This work provides a reference method for sensitive detection of thalassemia genes and holds great diagnostic potential in biomedical applications.

Mapping every adult baobab (Adansonia digitata L.) across the Sahel and relationships to rural livelihoods.

The baobab tree (Adansonia digitata L.) is an integral part of rural livelihoods throughout the African continent. However, the combined effects of climate change and increasing global demand for baobab products are currently exerting pressure on the sustainable utilization of these resources. Here we use sub-metre-resolution satellite imagery to identify the presence of nearly 2.8 million (underestimation bias 27.1%) baobab trees in the Sahel, a dryland region of 2.4 million km2. This achievement is considered an essential step towards an improved management and monitoring system of valuable woody species. Using Senegal as a case country, we find that 94% of rural buildings have at least one baobab tree in their immediate surroundings and that the abundance of baobabs is associated with a higher likelihood of people consuming a highly nutritious food group: dark green leafy vegetables. The generated database showcases the feasibility of mapping the location of single tree species at a sub-continental scale, providing vital information in times when deforestation and climate change cause the extinction of numerous tree species.

Biomolecule-regulation of fluorescent probe signaling: Homogeneous rapid portable protease sensing in serum.

BACKGROUND: As is well documented, prostate cancer (PCa) being the second most prevalent cancer in men worldwide, emphasizing the importance of early diagnosis for prognosis. However, conventional prostate-specific antigen (PSA) testing lacks sufficient diagnostic efficiency due to its relatively low sensitivity and limited detection range. Mounting evidence suggests that matrix metalloproteinase 9 (MMP-9) expression increases with the aggressive behavior of PCa, highlighting the significance of detecting the serum level of MMP-9 in patients. Developing a non-immune rapid, portable MMP-9 detection strategy and investigating its representativeness of PCa serum markers hold considerable implications. RESULTS: Herein, our study developed a simple, homogeneous dual fluorescence and smartphone-assisted red-green-blue (RGB) visualization peptide sensor of MMP-9, utilizing cadmium telluride quantum dots (CdTe QDs) and calcein as signal reporters. The essence of our approach revolves around the proteolytic ability of MMP-9, exploiting the selective recognition of molecule-Cu2+ complexes with different molecular weights by CdTe QDs and calcein. Under optimized conditions, the limits of detection (LODs) for MMP-9 were 0.5 pg/mL and 6 pg/mL using fluorescence and RGB values readouts, respectively. Indeed, this strategy exhibited robust specificity and anti-interference ability. MMP-9 was quantified in 42 clinical serum samples via dual-fluorescence analysis, with 12 samples being visually identified with a smartphone. According to receiver operating characteristic curve (ROC) analysis, its sensitivity and specificity were 90 % and 100 %, respectively, with an area under curve (AUC) value of 0.903. SIGNIFICANCE AND NOVELTY: Of note, the results of the aforementioned analysis were highly consistent with the serum level of PSA, clinical color Doppler flow imaging (CDFI), and histopathological results. Therefore, this simple, rapid, homogeneous fluorescence and visualization strategy can reliably measure MMP-9 levels and exhibit promising potential in point-of-care testing (POCT) applications for PCa patients.

Intelligent Fault Diagnosis Method Based on Cross-Device Secondary Transfer Learning of Efficient Gated Recurrent Unit Network.

In response to the issues of low model recognition accuracy and weak generalization in mechanical equipment fault diagnosis due to scarce data, this paper proposes an innovative solution, a cross-device secondary transfer-learning method based on EGRUN (efficient gated recurrent unit network). This method utilizes continuous wavelet transform (CWT) to transform source domain data into images. The EGRUN model is initially trained, and shallow layer weights are frozen. Subsequently, random overlapping sampling is applied to the target domain data to enhance data and perform secondary transfer learning. The experimental results demonstrate that this method not only significantly improves the model's ability to learn fault features but also enhances its classification accuracy and generalization performance. Compared to current state-of-the-art algorithms, the model proposed in this study shows faster convergence speed, higher diagnostic accuracy, and superior robustness and generalization, providing an effective approach to address the challenges arising from scarce data and varying operating conditions in practical engineering scenarios.

Development and validation of a COVID-19 vaccination prediction model based on self-reporting results in Chinese older adults from September 2022 to November 2022: A nationwide cross-sectional study.

It was common to see that older adults were reluctant to be vaccinated for coronavirus disease 2019 (COVID-19) in China. There is a lack of practical prediction models to guide COVID-19 vaccination program. A nationwide, self-reported, cross-sectional survey was conducted from September 2022 to November 2022, including people aged 60 years or older. Stratified random sampling was used to divide the dataset into derivation, validation, and test datasets at a ratio of 6:2:2. Least absolute shrinkage and selection operator and multivariable logistic regression were used for variable screening and model construction. Discrimination and calibration were assessed primarily by area under the receiver operating characteristic curve (AUC) and calibration curve. A total of 35057 samples (53.65% males and mean age of 69.64 ± 7.24 years) were finally selected, which constitutes 93.73% of the valid samples. From 33 potential predictors, 19 variables were screened and included in the multivariable logistic regression model. The mean AUC in the validation dataset was 0.802, with sensitivity, specificity, and accuracy of 0.732, 0.718 and 0.729 respectively, which were similar to the parameters in the test dataset of 0.755, 0.715 and 0.720, respectively, and the mean AUC in the test dataset was 0.815. There were no significant differences between the model predicted values and the actual observed values for calibration in these groups. The prediction model based on self-reported characteristics of older adults was developed that could be useful for predicting the willingness for COVID-19 vaccines, as well as providing recommendations in improving vaccine acceptance.

TRIM16 mitigates impaired osteogenic differentiation and antioxidant response in D-galactose-induced senescent osteoblasts.

Senile osteoporosis (SOP), characterized by significant bone loss, poses a substantial threat to elderly skeletal health, with oxidative stress playing a crucial role in its pathogenesis. Although Tripartite Motif 16 (TRIM16) has been identified as a promoter of antioxidant response and osteogenic differentiation, its regulatory role in SOP remains incompletely understood. This study aims to elucidate the underlying mechanism of TRIM16 in mitigating D-galactose (D-gal)-induced senescent osteoblasts. Initially, we observed diminished bone mineral density (BMD) and impaired bone microstructure in naturally aging (24 months) and D-gal-induced (18 months) aged mice through Dual-energy X-ray absorptiometry (DEXA), micro-CT, hematoxylin and eosin staining, and Masson staining. Immunohistochemistry analysis revealed downregulation of TRIM16 and osteogenic differentiation markers (Collagen-1, Runx-2, osteopontin) in femur samples of aged mice. Furthermore, in D-gal-induced senescent MC3T3-E1 osteoblasts, we observed the suppression of osteogenic differentiation and maturity, along with cytoskeleton impairment via Alkaline phosphatase (ALP), Alizarin Red S, and Rhodamine-phalloidin staining. The protein expression of TRIM16, osteogenic differentiation markers, and antioxidant indicators (Nrf-2, HO-1, SOD1) decreased, while the production of reactive oxygen species (ROS) significantly increased. Knockdown and overexpression of TRIM16 using lentivirus in osteoblasts revealed that the downregulation of TRIM16 inhibited osteogenic differentiation and induced oxidative stress. Notably, TRIM16 overexpression partially attenuated D-gal-induced inhibition of osteogenic differentiation and increased oxidative stress. These findings suggest TRIM16 may mitigate impaired osteogenic differentiation and antioxidant response in D-gal-induced senescent osteoblasts, suggesting its potential as a therapeutic target for SOP.

Portable spirometer-based pulmonary function test willingness in China: A nationwide cross-sectional study from the "Happy Breathing Program".

BACKGROUND: Understanding willingness to undergo pulmonary function tests (PFTs) and the factors associated with poor uptake of PFTs is crucial for improving early detection and treatment of chronic obstructive pulmonary disease (COPD). This study aimed to understand willingness to undergo PFTs among high-risk populations and identify any barriers that may contribute to low uptake of PFTs. METHODS: We collected data from participants in the "Happy Breathing Program" in China. Participants who did not follow physicians' recommendations to undergo PFTs were invited to complete a survey regarding their willingness to undergo PFTs and their reasons for not undergoing PFTs. We estimated the proportion of participants who were willing to undergo PFTs and examined the various reasons for participants to not undergo PFTs. We conducted univariable and multivariable logistic regressions to analyze the impact of individual-level factors on willingness to undergo PFTs. RESULTS: A total of 8475 participants who had completed the survey on willingness to undergo PFTs were included in this study. Out of these participants, 7660 (90.4%) were willing to undergo PFTs. Among those who were willing to undergo PFTs but actually did not, the main reasons for not doing so were geographical inaccessibility ( n  = 3304, 43.1%) and a lack of trust in primary healthcare institutions ( n  = 2809, 36.7%). Among the 815 participants who were unwilling to undergo PFTs, over half ( n  = 447, 54.8%) believed that they did not have health problems and would only consider PFTs when they felt unwell. In the multivariable regression, individuals who were ≤54 years old, residing in rural townships, with a secondary educational level, with medical reimbursement, still working, with occupational exposure to dust, and aware of the abbreviation "COPD" were more willing to undergo PFTs. CONCLUSIONS: Willingness to undergo PFTs was high among high-risk populations. Policymakers may consider implementing strategies such as providing financial incentives, promoting education, and establishing community-based programs to enhance the utilization of PFTs.

FGF18 encoding circular mRNA-LNP based on glycerolipid engineering of mesenchymal stem cells for efficient amelioration of osteoarthritis.

Mesenchymal stem cells (MSCs) exhibit substantial potential for osteoarthritis (OA) therapy through cartilage regeneration, yet the realization of optimal therapeutic outcomes is hampered by their limited intrinsic reparative capacities. Herein, MSCs are engineered with circular mRNA (cmRNA) encoding fibroblast growth factor 18 (FGF18) encapsulated within lipid nanoparticles (LNP) derived from a glycerolipid to facilitate OA healing. A proprietary biodegradable and ionizable glycerolipid, TG6A, with branched tails and five ester bonds, forms LNP exhibiting above 9-fold and 41-fold higher EGFP protein expression in MSCs than commercial LNP from DLin-MC3-DMA and ALC-0315, respectively. The introduction of FGF18 not only augmented the proliferative capacity of MSCs but also upregulated the expression of chondrogenic genes and glycosaminoglycan (GAG) content. Additionally, FGF18 enhanced the production of proteoglycans and type II collagen in chondrocyte pellet cultures in a three-dimensional culture. In an OA rat model, transplantation with FGF18-engineered MSCs remarkably preserved cartilage integrity and facilitated functional repair of cartilage lesions, as evidenced by thicker cartilage layers, reduced histopathological scores, maintenance of zone structure, and incremental type II collagen and extracellular matrix (ECM) deposition. Taken together, our findings suggest that TG6A-based LNP loading with cmRNA for engineering MSCs present an innovative strategy to overcome the current limitations in OA treatment.