[Ligusticum cycloprolactam inhibits IL-1ß-induced apoptosis and inflammation of rat chondrocytes via HMGB1/TLR4/NF-κB signaling pathway].

Chondrocytes are unique resident cells in the articular cartilage, and the pathological changes of them can lead to the occurrence of osteoarthritis(OA). Ligusticum cycloprolactam(LIGc) are derivatives of Z-ligustilide(LIG), a pharmacodynamic marker of Angelica sinensis, which has various biological functions such as anti-inflammation and inhibition of cell apoptosis. However, its protective effect on chondrocytes in the case of OA and the underlying mechanism remain unclear. This study conducted in vitro experiments to explore the molecular mechanism of LIGc in protecting chondrocytes from OA. The inflammation model of rat OA chondrocyte model was established by using interleukin-1ß(IL-1ß) to induce. LIGc alone and combined with glycyrrhizic acid(GA), a blocker of the high mobility group box-1 protein(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signaling pathway, were used to intervene in the model, and the therapeutic effects were systematically evaluated. The viability of chondrocytes treated with different concentrations of LIGc was measured by the cell counting kit-8(CCK-8), and the optimal LIGc concentration was screened out. Annexin V-FITC/PI apoptosis detection kit was employed to examine the apoptosis of chondrocytes in each group. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the expression of cyclooxygenase-2(COX-2), prostaglandin-2(PGE2), and tumor necrosis factor-alpha(TNF-α) in the supernatant of chondrocytes in each group. Western blot was employed to determine the protein levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), caspase-3, HMGB1, TLR4, and NF-κB p65. The mRNA levels of HMGB1, TLR4, NF-κB p65, and myeloid differentiation factor 88(MyD88) in chondrocytes were determined by real-time fluorescent quantitative PCR(RT-qPCR). The safe concentration range of LIGc on chondrocytes was determined by CCK-8, and then the optimal concentration of LIGc for exerting the effect was clarified. Under the intervention of IL-1ß, the rat chondrocyte model of OA was successfully established. The modeled chondrocytes showed increased apoptosis rate, promoted expression of COX-2, PGE2, and TNF-α, up-regulated protein levels of Bax, caspase-3, HMGB1, TLR4, and NF-κB p65 and mRNA levels of HMGB1, TLR4, NF-κB p65, and MyD88, and down-regulated protein level of Bcl-2. However, LIGc reversed the IL-1ß-induced changes of the above factors. Moreover, LIGc combined with GA showed more significant reversal effect than LIGc alone. These fin-dings indicate that LIGc extracted and derived from the traditional Chinese medicine A. sinensis can inhibit the inflammatory response of chondrocytes and reduce the apoptosis of chondrocytes, and this effect may be related to the HMGB1/TLR4/NF-κB signaling pathway. The pharmacological effect of LIGc on protecting chondrocytes has potential value in delaying the progression of OA and improving the clinical symptoms of patients, and deserves further study.

Hemispheric coupling between structural and functional asymmetries in clinically asymptomatic carotid stenosis with cognitive impairment.

Advanced carotid stenosis is a known risk factor for ischemic stroke and vascular dementia, and it is associated with multidomain cognitive impairment as well as asymmetric alterations in hemispheric structure and function. Here we introduced a novel measure-the asymmetry index of amplitude of low-frequency fluctuations (ALFF_AI)-derived from resting-state functional magnetic resonance imaging. This measure captures the hemispheric asymmetry of intrinsic brain activity using high-dimensional registration. We aimed to investigate functional brain asymmetric alterations in patients with severe asymptomatic carotid stenosis (SACS). Furthermore, we extended the analyses of ALFF_AI to different frequencies to detect frequency-specific alterations. Finally, we examined the coupling between hemispheric asymmetric structure and function and the relationship between these results and cognitive tests, as well as the white matter hyperintensity burden. SACS patients presented significantly decreased ALFF_AI in several clusters, including the visual, auditory, parahippocampal, Rolandic, and superior parietal regions. At low frequencies (0.01-0.25 Hz), the ALFF_AI exhibited prominent group differences as frequency increased. Further structure-function coupling analysis indicated that SACS patients had lower coupling in the lateral prefrontal, superior medial frontal, middle temporal, superior parietal, and striatum regions but higher coupling in the lateral occipital regions. These findings suggest that, under potential hemodynamic burden, SACS patients demonstrate asymmetric hemispheric configurations of intrinsic activity patterns and a decoupling between structural and functional asymmetries.

Healthy life expectancy for 202 countries up to 2030: Projections with a Bayesian model ensemble.

Background: Healthy life expectancy (HLE) projections are required for optimising social and health service management in the future. Existing studies on the topic were usually conducted by selecting a single model for analysis. We thus aimed to use an ensembled model to project the future HLE for 202 countries/region. Methods: We obtained data on age-sex-specific HLE and the sociodemographic index (SDI) level of 202 countries from 1990 to 2019 from the Global Burden of Disease (GBD) database and used a probabilistic Bayesian model comprised of 21 forecasting models to predict their HLE in 2030. Results: In general, HLE is projected to increase in all 202 countries, with the least probability of 82.4% for women and 81.0% for men. Most of the countries with the lowest projected HLE would be located in Africa. Women in Singapore have the highest projected HLE in 2030, with a 94.5% probability of higher than 75.2 years, which is the highest HLE in 2019 across countries. Maldives, Kuwait, and China are projected to have a probability of 49.3%, 41.2% and 31.6% to be the new entries of the top ten countries with the highest HLE for females compared with 2019. Men in Singapore are projected to have the highest HLE at birth in 2030, with a 93.4% probability of higher than 75.2 years. Peru and Maldives have a probability of 48.7% and 35.3% being new top ten countries in male's HLE. The female advantage in HLE will shrink by 2030 in 117 countries, especially in most of the high SDI and European countries. Conclusions: HLE will likely continue to increase in most countries and regions worldwide in the future. More attention needs to be paid to combatting obesity, chronic diseases, and specific infectious diseases, especially in African and some Pacific Island countries. Although gender gaps may not be fully bridged, HLE could partially mitigate and even eliminate them through economic development and improvements in health care.

Abdominal pain in an adolescent girl with acute phlegmonous gastritis: a case report.

Acute phlegmonous gastritis (APG), a rare clinical condition, is mainly characterized by bacterial invasion in the gastric lining and is associated with a high mortality rate. The symptoms of APG include abdominal pain, nausea, vomiting, fever, and infection. Notably, the lack of specificity in the clinical presentation presents challenges in the early diagnosis of the disease. APG is often prevalent in adults, with a higher incidence in men than women. However, patients of other ages may also be affected. We herein present a case report of a 12-year-old girl who was admitted to the hospital with gastrointestinal symptoms and fever. The patient's imaging findings were compatible with APG. Despite the requirement for surgical treatment in most cases of phlegmonous gastritis, our patient rapidly improved with imaging and antibiotic therapy. This case demonstrates the success of antibiotic therapy with early diagnosis.

Explainable Machine Learning with Pairwise Interactions for Predicting Conversion from Mild Cognitive Impairment to Alzheimer's Disease Utilizing Multi-Modalities Data.

BACKGROUND: Predicting cognition decline in patients with mild cognitive impairment (MCI) is crucial for identifying high-risk individuals and implementing effective management. To improve predicting MCI-to-AD conversion, it is necessary to consider various factors using explainable machine learning (XAI) models which provide interpretability while maintaining predictive accuracy. This study used the Explainable Boosting Machine (EBM) model with multimodal features to predict the conversion of MCI to AD during different follow-up periods while providing interpretability. METHODS: This retrospective case-control study is conducted with data obtained from the ADNI database, with records of 1042 MCI patients from 2006 to 2022 included. The exposures included in this study were MRI biomarkers, cognitive scores, demographics, and clinical features. The main outcome was AD conversion from aMCI during follow-up. The EBM model was utilized to predict aMCI converting to AD based on three feature combinations, obtaining interpretability while ensuring accuracy. Meanwhile, the interaction effect was considered in the model. The three feature combinations were compared in different follow-up periods with accuracy, sensitivity, specificity, and AUC-ROC. The global and local explanations are displayed by importance ranking and feature interpretability plots. RESULTS: The five-years prediction accuracy reached 85% (AUC = 0.92) using both cognitive scores and MRI markers. Apart from accuracies, we obtained features' importance in different follow-up periods. In early stage of AD, the MRI markers play a major role, while for middle-term, the cognitive scores are more important. Feature risk scoring plots demonstrated insightful nonlinear interactive associations between selected factors and outcome. In one-year prediction, lower right inferior temporal volume (<9000) is significantly associated with AD conversion. For two-year prediction, low left inferior temporal thickness (<2) is most critical. For three-year prediction, higher FAQ scores (>4) is the most important. During four-year prediction, APOE4 is the most critical. For five-year prediction, lower right entorhinal volume (<1000) is the most critical feature. CONCLUSIONS: The established glass-box model EBMs with multimodal features demonstrated a superior ability with detailed interpretability in predicting AD conversion from MCI. Multi features with significant importance were identified. Further study may be of significance to determine whether the established prediction tool would improve clinical management for AD patients.

Oxygen enrichment protects against intestinal damage and gut microbiota disturbance in rats exposed to acute high-altitude hypoxia.

Acute high-altitude hypoxia can lead to intestinal damage and changes in gut microbiota. Sustained and reliable oxygen enrichment can resist hypoxic damage at high altitude to a certain extent. However, it remains unclear whether oxygen enrichment can protect against gut damage and changes in intestinal flora caused by acute altitude hypoxia. For this study, eighteen male Sprague-Dawley rats were divided into three groups, control (NN), hypobaric hypoxic (HH), and oxygen-enriched (HO). The NN group was raised under normobaric normoxia, whereas the HH group was placed in a hypobaric hypoxic chamber simulating 7,000 m for 3 days. The HO group was exposed to oxygen-enriched air in the same hypobaric hypoxic chamber as the HH group for 12 h daily. Our findings indicate that an acute HH environment caused a fracture of the crypt structure, loss of epithelial cells, and reduction in goblet cells. Additionally, the structure and diversity of bacteria decreased in richness and evenness. The species composition at Phylum and Genus level was characterized by a higher ratio of Firmicutes and Bacteroides and an increased abundance of Lactobacillus with the abundance of Prevotellaceae_NK3B31_group decreased in the HH group. Interestingly, after oxygen enrichment intervention, the intestinal injury was significantly restrained. This was confirmed by an increase in the crypt depth, intact epithelial cell morphology, increased relative density of goblet cells, and higher evenness and richness of the gut microbiota, Bacteroidetes and Prevotellaceae as the main microbiota in the HO group. Finally, functional analysis showed significant differences between the different groups with respect to different metabolic pathways, including Amino acid metabolism, energy metabolism, and metabolism. In conclusion, this study verifies, for the first time, the positive effects of oxygen enrichment on gut structure and microbiota in animals experiencing acute hypobaric hypoxia.

Publications on ultrasound-guided thermal ablation for thyroid nodules from 2000 to 2022: a bibliometric analysis.

BACKGROUND: Thyroid nodules are increasingly treated with minimally invasive surgery. Thermal ablation could efficiently treat patients with benign thyroid nodules, recurrent thyroid cancer, and low-risk papillary thyroid carcinoma. This research aims to explore the research field of thermal ablation for thyroid nodules using bibliometric analysis. METHODS: The web of science core collection (WoSCC) database was utilized from its inception to 1 October 2022, to collect research articles and reviews on ultrasound-guided thermal ablation for thyroid nodules. We applied the R package 'bibliometrix' to summarize the main findings, calculate the occurrences of the top keywords and visualize the international collaboration networks. The co-authorship and co-occurrence analyses were conducted with VOSviewer software. CiteSpace was used to identify the top references and keywords with the highest citation bursts. RESULTS: A total of 820 publications from 32 countries were retrieved. The annual number of related publications showed an increasing trend. China, Italy, and Korea were the most contributing countries. The University of Ulsan College of Medicine in Korea was the most productive institution, and Jung Hwan Baek published the maximum number of articles. The International Journal of Hyperthermia was the most productive journal. 'Papillary thyroid micro-carcinoma (PTMC)' and 'association guideline' were the most frequently used keywords in the field of thermal ablation for thyroid nodules, which indicated the potential hot research topics and frontiers in the future. CONCLUSION: This bibliometric study conducts a comprehensive analysis of publications on thermal ablation for thyroid nodules, which aids investigators in discovering potential research directions.

Temporal and spatial distributions, source identification, and health risk assessment of polycyclic aromatic hydrocarbons in PM2.5 from 2016 to 2021 in Shenzhen, China.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants in the atmosphere that have drawn intense attention due to their carcinogenicity and mutagenicity. In this work, 1424 air samples were collected between January 2016 and December 2021 in three areas of Shenzhen, China to determine the concentrations of PM2.5 and PAHs and their spatiotemporal variation. Human health risks due to the daily intake and uptake of PAHs and the resulting incremental lifetime cancer risk (ILCR) were also evaluated. PAHs were detected frequently in the samples at concentrations between 0.28 and 32.7 ng/m3 (median: 1.04 ng/m3). PM2.5 and PAH concentrations decreased from 2016 to 2021, and the Yantian area had lower median concentrations of PM2.5 (23.0 µg/m3) and PAHs (0.02 ng/m3) than the Longgang and Nanshan areas. The concentrations of PM2.5 and PAHs were significantly higher in winter than in summer. Analysis of diagnostic ratios indicated that petroleum combustion was the dominant source of airborne PAHs in Shenzhen. The estimated daily intake (EDI) and uptake (EDU) of PAHs by local residents decreased gradually with increasing age, indicating that infants are at particular risk of PAH exposure. However, the incremental lifetime cancer risks (ILCRs) were below the threshold value of 10-6, indicating that inhalation exposure to PAHs posed a negligible carcinogenic risk to Shenzhen residents. While promising, these results may underestimate actual PAH exposure levels, so further analysis of health risks due to PAHs in Shenzhen is needed.

Urinary essential and toxic metal mixtures, and type 2 diabetes mellitus: Telomere shortening as an intermediary factor?

The joint effect of metal mixtures on telomere function and type 2 diabetes mellitus (T2DM) is unclear. This large-scale cross-sectional study sought to assess the role of telomere length (TL) in the relationship between urinary essential and toxic metal mixtures, and T2DM in 7410 Chinese adults ≥ 60 years of age. Essential (Cr, Cu, Zn, Se) and non-essential metals (V, Al, Sb, Sn, Cd, Pb) in urine samples were quantified, while leukocyte TL was measured from blood samples. Restricted cubic splines regression showed nonlinear relationships between single metal and T2DM, and between TL and T2DM. Bayesian kernel machine regression and quantile-based g-computation showed that the overall status of urinary metals was positively associated with risk of developing T2DM, which was mainly explained by exposure to Pb, Cd, and Sb, excessive Se intake, and high excretion of Zn. Mediation analyses showed that shortened TL mediated 27.9% of the overall positive effect of metal exposure on T2DM, and this mediation was mainly explained by toxic metal exposure and excessive Se intake. Tobacco smoke exposure, extensive cooking at home, and black tea consumption were found to be important contributors of toxic metal exposures. Further studies are needed to explore the recommended Zn dosage for T2DM patients at different stages, which may ameliorate pancreatic senescence and glycemic progression.

One-Step Synthesis of Fragment-Reduced Graphene Oxide as an Electrode Material for Supercapacitors.

We herein report for the first time a simple environmentally friendly hydrothermal method for one-step synthesis of fragment-reduced graphene oxide (FrGO) under mild conditions without the addition of reducing agents, and we applied it as an electrode material for a supercapacitor. The characterization results show that the introduction of Al2O3 as a spacer and HCl as an etchant results in a macroporous/mesoporous structure, increases the fragmentation of the FrGO microtopography, shortens the electron/ion transport path, and increases the contact between the electrode material and the electrolyte. Compared to the traditional hydrothermal reduced graphene materials, FrGO shows a larger specific capacitance. The results indicate that suitable hydrothermal temperature and time can effectively promote the retention of more oxygen-containing functional groups on the graphene surface. The first-principles density functional theory (DFT) calculation results show that the electrostatic potential in carbonyl group graphene is more negative, favored by the H+ adsorption, and provides the system with a pseudocapacitive effect. Under optimized conditions, FrGO (1:4, 180 °C, 3 h) exhibits 417 F/g at 1 A/g with an outstanding capacitance retention of 78.51% at 50 A/g and exhibits remarkable stability over 20 000 charge/discharge cycles. The proposed FrGO-based synthesis method can be used to guide the development of electrode materials for various supercapacitor devices.

[Nomogram-Based Prediction of Risk of Cervical Lymph Node Metastasis in Differentiated Thyroid Carcinoma].

Objective To establish a nomogram for predicting the risk of cervical lymph node metastasis in differentiated thyroid carcinoma (DTC). Methods The patients with complete clinical data of DTC and cervical lymph node ultrasound and diagnosed based on pathological evidence from January 2019 to December 2021 were assigned into a training group (n=444) and a validation group (n=125).Lasso regression was performed to screen the data with differences between groups,and multivariate Logistic regression to establish a prediction model with the factors screened out by Lasso regression.C-index and calibration chart were employed to evaluate the prediction performance of the established model. Results The predictive factors for establishing the model were lymph node short diameter≥0.5 cm,long-to-short-axis ratio<2,disappearance of lymph node hilum,cystic transformation,hyperechogenicity,calcification,and abnormal blood flow (all P<0.001).The established model demonstrated a good discriminative ability,with the C index of 0.938 (95%CI=0.926-0.961) in the training group. Conclusion The nomogram established based on the ultrasound image features of cervical lymph nodes in DTC can accurately predict the risk of cervical lymph node metastasis in DTC.

[Influencing Factors and Prediction Model of Performance of Needle Visualization in Fine Needle Aspiration of Thyroid Nodules].

Objective To investigate the influencing factors and establish a model predicting the performance of needle visualization in fine-needle aspiration (FNA) of thyroid nodules. Methods This study prospectively included 175 patients who underwent FNA of thyroid nodules in the Department of Ultrasound in China-Japan Friendship Hospital and compared the display of the needle tips in the examination of 199 thyroid nodules before and after the application of needle visualization.We recorded the location,the positional relationship with thyroid capsule,ultrasonic characteristics,and the distribution of the soft tissue strip structure at the puncture site of the nodules with unclear needle tips display before using needle visualization.Furthermore,according to the thyroid imaging reporting and data system proposed by the American College of Radiology,we graded the risk of the nodules.Lasso-Logistic regression was employed to screen out the factors influencing the performance of needle visualization and establish a nomogram for prediction. Results The needle tips were not clearly displayed in the examination of 135 (67.8%) and 53 (26.6%) nodules before and after the application of needle visualization,respectively,which showed a significant difference (P<0.001).Based on the positional relationship between the nodule and capsule,anteroposterior/transverse diameter (A/T) ratio,blood supply,and the distribution of subcutaneous strip structure at the puncture site,a nomogram was established to predict the probability of unclear display of the needle tips after application of needle visualization.The C-index of the prediction model was 0.75 (95%CI=0.67-0.84) and the area under the receiver operating characteristic curve was 0.72.The calibration curve confirmed the appreciable reliability of the prediction model,with the C-index of 0.70 in internal validation. Conclusions Needle visualization can improve the display of the needle tip in ultrasound-guided FNA of thyroid nodules.The nomogram established based on ultrasound features such as the positional relationship between the nodule and capsule,A/T ratio,blood supply,and the distribution of subcutaneous strip structure at the puncture site can predict whether needle visualization is suitable for the examination of nodules.

A nationwide investigation of trace elements in rice and wheat flour in China: Levels, spatial distributions and implications for human exposure.

Rises in trace element contents in rice and wheat flour, which are staple foods for almost all the Chinese population, associated with rapid economic development have raised major concerns. This study aimed to assess trace element concentrations in these foods nationwide in China and associated human exposure risks. For these purposes, nine trace elements were measured in 260 rice samples and 181 wheat flour samples with 17 and 12 widely scattered geographical origins in China, respectively. Mean concentrations (mg kg-1) of the trace elements declined in the following orders: Zn > Cu > Ni > Pb > As > Cr > Cd > Se > Co in rice, and Zn > Cu > Ni > Se > Pb > Cr > Cd > As > Co in wheat flour. Significant regional differences in levels of trace elements in both rice and wheat flour were detected (p < 0.05), which may be related to local economic indicators. The hazard index (HI) of trace elements in rice samples from all origins exceeded 1, mainly due to the contribution of As, suggesting a potential non-carcinogenic risk. The total carcinogenic risk (TCR) for rice and wheat flour of all origins exceeded the safe level.

[Characteristics of Soil Microbial Community in Different Habitats in the Process of Ecological Restoration of Haifeng Wetland in Guangdong].

Soil microorganisms can respond to changes in wetland ecosystem quality and functional evolution sensitively. To explore the changes and response mechanisms of soil microorganisms under ecological restoration measures, the characteristics of the soil microbial community and their influencing factors were analyzed using high-throughput sequencing technology in four different habitats (revegetation area, native vegetation area, tidal creek, and tidal flat) during the ecological restoration process in Haifeng wetland in Guangdong. The results showed that:soil physicochemical properties of the four different habitats were significantly different; the contents of TC, TN, TOC, and TK in the tidal creek were significantly higher than those in the other habitats; and the contents of TC, TN, and TP in the revegetation restoration area were significantly higher than those in the tidal flat. The EC values in the tidal creeks and tidal flat were significantly higher than those in the revegetation area and the native vegetation area. The diversity index and abundance of soil bacteria in the tidal creek were the highest, and those in the vegetation restoration area were significantly higher than those in the bare flat. The archaea in the tidal creek were significantly more complex than those in the other three habitats, and the fungal community diversity index and abundance in the native vegetation area were significantly higher than those in the other areas, which had the most complex community structure. TN and TC were the main factors affecting the bacterial community, whereas TN and EC were the main factors affecting the archaea community, and pH, TN, and TP were the key factors affecting the fungal community. In conclusion, the planting of vegetation on the tidal flat increased the diversity and richness of the soil microbial community during the process of ecological restoration, indicating that it has resulted in positive feedback on ecological restoration so far. The results of this study can provide a theoretical basis for the selection of ecological restoration strategies for the tidal flat.

Trace elements in aquatic products from Shenzhen, China and their implications for human exposure.

Aquatic organisms in industrially polluted areas can accumulate large quantities of heavy metals. To assess the resulting health risks, 11 trace elements in 184 aquatic products representing 14 species of fish, crustaceans, and bivalves collected from Shenzhen, China were determined. Aluminum (Al), chromium (Cr), nickel (Ni), selenium (Se), antimony (Sb), manganese (Mn), copper (Cu), arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) were determined by inductively coupled plasma mass spectrometry. The pollution levels of each product and the human health risk resulting from their consumption were then assessed. The concentrations of As in 57 % of samples and Cd in 11 % of samples exceeded the upper limits stipulated by the Chinese National Food Safety Standards (GB 2762-2017), which was mainly due to high concentrations of trace elements in crustaceans and bivalves. The Nemerow integrated pollution index indicated that the aquatic products accumulated high levels of As and Cd. Health risk assessments using the target hazard quotient (THQ) and hazard index (HI) suggested that As and Cd exposure due to consumption of aquatic products presents a potential health risk for residents of Shenzhen.

Contrast-enhanced ultrasound combined targeted microbubbles for diagnosis of highly aggressive papillary thyroid carcinoma.

Background: Accurate diagnosis of highly aggressive papillary thyroid cancer (PTC) may greatly help avoid overdiagnosis and overtreatment of PTC. However, there is still a lack of a convenient and accurate method. Targeted microbubbles, an emerging ultrasound contrast agent, have the potential to accurately diagnose highly aggressive PTC. Purpose: To design and prepare a targeted microbubble for specific contrast-enhanced ultrasound (CEUS) imaging of highly invasive PTC. Methods: Using ß-galactoside-binding protein galectin-3 (Gal-3) overexpressed on the surface of highly invasive PTC cells as a target, C12 polypeptide (ANTPCGPYTHDCPVKR) with high affinity and specificity for Gal-3 was coupled to the surface of lipid microbubbles to prepare targeted microbubbles (Gal-3-C12@lipo MBs). The targeted microbubbles were prepared by thin-film hydration method and mechanical shaking method. The morphology, diameter, concentration and stability of microbubbles were investigated by fluorescence microscopy and an AccuSizer. The biosafety of microbubbles was studied using BCPAP cells through CCK8 assay. Confocal laser scanning microscope and flow cytometry were applied to research the cellular uptake of microbubbles to investigate the targeting ability to highly aggressive PTC. Finally, the specific contrast-enhanced ultrasound imaging of microbubbles in highly invasive PTC was validated on the mice bearing subcutaneous BCPAP tumor model via a clinically ultrasound imaging system. Results: Gal-3-C12@lipo MBs were successfully prepared which showed a well-defined spherical morphology with an average diameter of 1.598 ± 0.848 µm. Gal-3-C12@lipo MBs showed good stability without rupture within 4 hours after preparation. At the cellular level, Gal-3-C12@lipo MBs exhibited favorable biosafety and superior targeting ability to BCPAP cells, with 2.8-fold higher cellular uptake than non-targeted lipid microbubbles (Lipo MBs). At the animal level, Gal-3-C12@lipo MBs significantly improved the quality of contrast-enhanced ultrasound imaging in highly invasive PTC, with an echo intensity of tumor significantly higher than that of Lipo MBs. Conclusion: We designed and fabricated a novel targeted microbubble for the specific ultrasound imaging diagnosis of highly aggressive PTC. The targeted microbubbles have good stability, superior biosafety and high targeting specificity, which can significantly improve the tumor signal-to-noise ratio of highly invasive PTC, and have the potential to facilitate and accurately diagnose highly invasive PTC.

A "Motivation" model of couple support for digital technology use among rural older adults.

Although recent research has demonstrated spouse support for technology use among older adults, by treating them as a homogeneous group, it has overlooked differences caused by socio-demographic dimensions in their digital engagement. Following the approach of the grounded theory and interviewing 15 couples in a developing aging region (Wuzhi County, Henan, China), this study paints a fuller picture of couple support for technology adoption among older adults in terms of their psychological motivations by dividing older adults into two categories: technology supports and technology recipients. The resulting concepts of motivation (e.g., social norms, benefit driven, perceptual elements, and value satisfaction), particularly limiting motivational factors (e.g.,individual status) reveal the psychological mechanisms behind this process and are conceptualized as a "motivation" model of couple support for digital technology use among rural older adults. Our study has strong implications for active and healthy aging, as policymakers can stimulate external motivation for technology adoption among older adults by fostering a sense of family responsibility and social ethos that encourages couples to help each other. In addition, local communities as stakeholders can educate older adults about the usefulness, ease of use, and risk-averse means of digital technology, and satisfy their altruistic and egoistic psychological needs to increase the inner value satisfaction they gain from the couple support process. By doing this, motivation and engagement are thereby increased, and ultimately, technology adoption in disadvantaged socioeconomic groups may be improved.

Ion and Molecule Sieving through Highly Stable Graphene-Based Laminar Membranes.

Biological ion channels use both their sizes and residual groups to reject large ions and molecules and allow highly selective permeation of small species with similar sizes. To realize these properties in artificial membranes, the main challenge is the precise control of both the channel size and the interior at the nanoscale. Here we report the permeation of ions and molecules through interlayer channels in graphene-based laminar membranes. The amino groups decorated on channel walls are found to form hydrogen bond networks with intercalated water molecules, thus providing a highly stable laminate structure and a controlled channel size. Solutes with hydration diameters of >10 Å are precisely sieved out. Small species permeate through with selectivities of up to a few thousand, governed by their distinct electrical interactions with channels depending on the atomistic distance from the charged species to the channel walls. Our work offers important insights into manipulating channel structures for enhanced separation performance at the nanoscale.