Serum klotho levels and mortality patterns in frail individuals: unraveling the u-shaped association.

BACKGROUND: Frailty, a clinical syndrome intricately linked with the aging process, stands as a harbinger of numerous adverse outcomes, most notably mortality. This study aimed to elucidate the association between serum α-klotho concentration and mortality patterns, including all-cause and cause-specific mortality, in patients with frailty. METHODS: The study employed Cox proportional hazard models, smoothed curve fitting, and supplementary analyses, encompassing threshold effect analysis, subgroup and sensitivity analyses, to explore the relationship between α-klotho levels and mortality, including all-cause, CVD, and cancer-related mortality. RESULTS: Among the 2,608 frail individuals (mean age: 60.78 [SD 10.48] years; 59.89% female), the mortality stood at 25.35% during a median follow-up period of 6.95 years. Both unadjusted and adjusted models revealed a significant inverse association between higher serum α-klotho levels and the risk of all-cause and CVD-related mortality ([mean(95% CI) 0.68 (0.55, 0.83)] for all-cause mortality; [mean(95% CI) 0.48 (0.32, 0.74)] for CVD-related mortality, all P for trend < 0.001). Notably, log2-klotho displayed a U-shaped correlation with all-cause mortality and cancer mortality, characterized by thresholds of 9.48 and 9.55, respectively. The robustness of these findings was consistently supported by subgroup and sensitivity analyses. CONCLUSION: This study unveils a U shaped association between serum α-klotho levels and both all-cause and cancer-related mortality among middle-aged and elderly individuals with frailty in the United States. The identified serum α-klotho thresholds, at 714.8 pg/ml for all-cause mortality and 750.6 pg/ml for cancer-related mortality, hold promise as potential targets for interventions aimed at mitigating the risks of premature death and cancer within this vulnerable population.

High temperature and humidity in the environment disrupt bile acid metabolism, the gut microbiome, and GLP-1 secretion in mice.

High temperature and humidity in the environment are known to be associated with discomfort and disease, yet the underlying mechanisms remain unclear. We observed a decrease in plasma glucagon-like peptide-1 levels in response to high-temperature and humidity conditions. Through 16S rRNA gene sequencing, alterations in the gut microbiota composition were identified following exposure to high temperature and humidity conditions. Notably, changes in the gut microbiota have been implicated in bile acid synthesis. Further analysis revealed a decrease in lithocholic acid levels in high-temperature and humidity conditions. Subsequent in vitro experiments demonstrated that lithocholic acid increases glucagon-like peptide-1 secretion in NCI-H716 cells. Proteomic analysis indicated upregulation of farnesoid X receptor expression in the ileum. In vitro experiments revealed that the combination of lithocholic acid with farnesoid X receptor inhibitors resulted in a significant increase in GLP-1 levels compared to lithocholic acid alone. In this study, we elucidate the mechanism by which reduced lithocholic acid suppresses glucagon-like peptide 1 via farnesoid X receptor activation under high-temperature and humidity condition.

The association of urinary heavy metal exposure with frailty susceptibility and mortality in middle-aged and older adults: a population-based study.

Heavy metals' presence as environmental pollutants has a close link to adverse health effects. Frailty, a clinical syndrome hallmarked by elevated vulnerability to stressors, presents a substantial challenge in healthcare. However, the association between exposure to heavy metals and frailty largely remains unexplored. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2003-2018 and correlated with the U.S. National Death Index (NDI) from 2019, we investigated mortality outcomes. Logistic regression, Cox regression, Kaplan-Meier survival curves, weighted quantile-sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were employed to assess the association between heavy metal exposure and frailty incidence and mortality in the frail population. Eight metals were measured in urine using inductively coupled plasma mass spectrometry with values adjusted for urinary creatinine, which was used to reflect heavy metal exposure. The cohort incorporated 5370 female participants aged 45 and above, with 1518 diagnosed with frailty. The findings indicated a substantial correlation between exposure to specific heavy metals, namely tungsten (odds ratio [OR]: 1.94, 95% confidence interval [CI]: 1.31-2.89), cobalt (OR: 1.64, 95% CI: 1.40-1.93), cadmium (OR: 1.93, 95% CI: 1.52-2.43), and uranium (OR: 7.36, 95% CI: 1.53-35.28), and an elevated risk of frailty. WQS and BKMR regression models identified cadmium, cobalt, and tungsten as main contributors to frailty. Cox regression analysis, after adjustment for covariates, suggested that the higher the exposure levels to cadmium and lead, the higher the risk of death in frail patients, with associated hazard ratios (HR) of 95% CI: 1.96 (1.53, 2.52) and 1.30 (1.13, 1.49), respectively. Our study revealed a significant positive correlation between exposure to heavy metal mixtures and frailty onset in middle-aged and older adults, along with increased mortality in frail patients. Cobalt, cadmium, and tungsten emerged as prominent contributors to frailty, with cobalt and cadmium directly impacting the long-term life expectancy of frail patients.

Engineered Metallic Ion-Based Hydrogel for Tendon-Bone Reconstruction.

Rotator cuff regeneration is hindered by compromised vascular architecture, inflammation, and instability of the reconstructed tendon-bone interface. Herein, inspired by the phenomenon of magnetic clasps being connected together by a specific structure, an engineered metallic ion-based hydrogel scaffold was constructed through a bioorthogonal click reaction between (DOPA)4-PEG5-N3 and DBCO-BMP-2 peptides and a photopolymerization process in the hydrogel matrix, exhibiting the potential for angiogenesis, bone regeneration, and modulation of the inflammatory milieu, which aimed at facilitating rotator cuff regeneration. In vitro studies showed that the composite hydrogel scaffold stimulated the angiogenic activity of human umbilical vein endothelial cells and osteogenic differentiation of bone marrow mesenchymal stem cells, transforming macrophages from M1 to M2. Moreover, imaging and immunohistochemical analysis of a rat rotator cuff injury models demonstrated that the composite hydrogel could effectively promote regeneration and exhibit remarkable biocompatibility. In summary, this composite hydrogel material established an effective platform for the release of metal ions and clickable peptides, which accelerated the regeneration of rotator cuff injuries and had broad prospects for application in rotator cuff therapy.

Association between niacin intake and knee osteoarthritis pain and function: a longitudinal cohort study.

BACKGROUND: This research investigates the relationship between niacin intake and knee osteoarthritis (OA) severity, focusing on pain and functional ability due to niacin's role as a NAD(P)+ precursor, promoting cellular energy, and offering anti-inflammatory, analgesic, and antioxidant effects. METHODS: The population-based Osteoarthritis Initiative (OAI) cohort with radiographically confirmed knee OA was analyzed through a Food Frequency Questionnaire determining niacin intake and scores from the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), using generalized additive mixed models. RESULTS: A significant correlation was pinpointed in 2375 OA patients (1001 men and 1374 women; 55.96% aged between 45 and 65 and 44.04% aged ≥65) between niacin intake and reduced knee pain and functional degrees after a 48-month follow-up, evident in improved KOOS and WOMAC scores (P < 0.05). The fully adjusted models estimated a decrease of 0.26 points for every additional 1 unit of Ln-niacin intake of daily niacin intake on the WOMAC pain subscale, 0.83 points on the WOMAC function subscale, and an increase of 1.71 and 1.58 on the KOOS pain and quality of life score. Strikingly, subgroups including middle-aged individuals, women, white race, obese individuals, and those with specific dietary habits showed a more substantial improvement with increased niacin. CONCLUSION: The association between increased niacin intake and reduced pain and function scores, as well improved quality of life in knee OA patients, is significant. Certain cohorts, according to a stratified analysis, could see more considerable benefits with increased niacin consumption. HIGHLIGHTS: • Increased niacin intake is linked to reduced knee pain and better function in OA patients. • Specific subgroups, such as middle-aged individuals, women, and those with certain dietary habits, benefit more from increased niacin consumption. • Niacin shows promise for enhancing the quality of life in knee OA patients by reducing pain and improving function.

Dual-Targeted Metal Ion Network Hydrogel Scaffold for Promoting the Integrated Repair of Tendon-Bone Interfaces.

The tendon-bone interface has a complex gradient structure vital for stress transmission and pressure buffering during movement. However, injury to the gradient tissue, especially the tendon and cartilage components, often hinders the complete restoration of the original structure. Here, a metal ion network hydrogel scaffold, with the capability of targeting multitissue, was constructed through the photopolymerization of the LHERHLNNN peptide-modified zeolitic imidazolate framework-8 (LZIF-8) and the WYRGRL peptide-modified magnesium metal-organic framework (WMg-MOF) within the hydrogel scaffold, which could facilitate the directional migration of metal ions to form a dynamic gradient, thereby achieving integrated regeneration of gradient tissues. LZIF-8 selectively migrated to the tendon, releasing zinc ions to enhance collagen secretion and promoting tendon repair. Simultaneously, WMg-MOF migrated to cartilage, releasing magnesium ions to induce cell differentiation and facilitating cartilage regeneration. Infrared spectroscopy confirmed successful peptide modification of nano ZIF-8 and Mg-MOF. Fluorescence imaging validated that LZIF-8/WMg-MOF had a longer retention, indirectly confirming their successful targeting of the tendon-bone interface. In summary, this dual-targeted metal ion network hydrogel scaffold has the potential to facilitate synchronized multitissue regeneration at the compromised tendon-bone interface, offering favorable prospects for its application in the integrated reconstruction characterized by the gradient structure.

Distinct microbiome of tongue coating and gut in type 2 diabetes with yellow tongue coating.

The gut microbiome plays a critical role in the pathogenesis of type 2 diabetes mellitus (T2DM). However, the inconvenience of obtaining fecal samples hinders the clinical application of gut microbiome analysis. In this study, we hypothesized that tongue coating color is associated with the severity of T2DM. Therefore, we aimed to compare tongue coating, gut microbiomes, and various clinical parameters between patients with T2DM with yellow (YC) and non-yellow tongue coatings (NYC). Tongue coating and gut microbiomes of 27 patients with T2DM (13 with YC and 14 with NYC) were analyzed using 16S rDNA gene sequencing technology. Additionally, we measured glycated hemoglobin (HbA1c), random blood glucose (RBG), fasting blood glucose (FBG), postprandial blood glucose (PBG), insulin (INS), glucagon (GC), body mass index (BMI), and homeostasis model assessment of ß-cell function (HOMA-ß) levels for each patient. The correlation between tongue coating and the gut microbiomes was also analyzed. Our findings provide evidence that the levels of Lactobacillus spp. are significantly higher in both the tongue coating and the gut microbiomes of patients with YC. Additionally, we observed that elevated INS and GC levels, along with decreased BMI and HOMA-ß levels, were indicative of a more severe condition in patients with T2DM with YC. Moreover, our results suggest that the composition of the tongue coating may reflect the presence of Lactobacillus spp. in the gut. These results provide insights regarding the potential relationship between tongue coating color, the gut microbiome, and T2DM.

In vitro differentiation of human amniotic epithelial stem cells into keratinocytes regulated by OPN3.

Human amniotic epithelial stem cells (hAESCs) are regarded as potential alternatives to keratinocytes (KCs) used for skin wound healing. Light is an alternative approach for inducing stem cell differentiation. Opsins (OPNs), a family of light-sensitive, G protein-coupled receptors, play a multitude of light-dependent and light-independent functions in extraocular tissues. However, it remains unclear whether the light sensitivity and function of OPNs are involved in light-induced differentiation of hAESCs to KCs. Herein, we determine the role of OPNs in differentiation of hAESCs into KCs through cell and molecular biology approaches in vitro. It is shown that mRNA expression of OPN3 in the amniotic membrane and hAESCs was higher than the other four primary OPNs by RT-qPCR analysis. Changes in OPN3 gene expression had a significant impact on cell proliferation, stemness and differentiation capability of hAESCs. Furthermore, we found a significant upregulation of OPN3, KRT5 and KRT14 with hAESCs treated at 3 × 33 J/cm2 irradiation from blue-light LED. Taken together, these results suggest that OPN3 acts as a positive regulator of differentiation of hAESCs into KCs. This study provides a novel insight into photosensitive OPNs associated with photobiomodulation(PBM)-induced differentiation in stem cells.

Gut microbiota associated with appetite suppression in high-temperature and high-humidity environments.

BACKGROUND: Food is crucial for maintaining vital human and animal activities. Disorders in appetite control can lead to various metabolic disturbances. Alterations in the gut microbial composition can affect appetite and energy metabolism. While alterations in the gut microbiota have been observed in high-temperature and high-humidity (HTH) environments, the relationship between the gut microbiota during HTH and appetite remains unclear. METHODS: We utilised an artificial climate box to mimic HTH environments, and established a faecal bacteria transplantation (FMT) mouse model. Mendelian randomisation (MR) analysis was used to further confirm the causal relationship between gut microbiota and appetite or appetite-related hormones. FINDINGS: We found that, in the eighth week of exposure to HTH environments, mice showed a decrease in food intake and body weight, and there were significant changes in the intestinal microbiota compared to the control group. After FMT, we observed similar changes in food intake, body weight, and gut bacteria. Appetite-related hormones, including ghrelin, glucagon-like peptide-1, and insulin, were reduced in DH (mice exposed to HTH conditions) and DHF (FMT from mice exposed to HTH environments for 8 weeks), while the level of peptide YY initially increased and then decreased in DH and increased after FMT. Moreover, MR analysis further confirmed that these changes in the intestinal microbiota could affect appetite or appetite-related hormones. INTERPRETATION: Together, our data suggest that the gut microbiota is closely associated with appetite suppression in HTH. These findings provide novel insights into the effects of HTH on appetite. FUNDING: This work was supported by the National Natural Science Foundation of China and Guangzhou University of Chinese Medicine.

The influence of zinc and iron intake on osteoarthritis patients' subchondral sclerosis progression: A prospective observational study using data from the osteoarthritis Initiative.

Objective: The purpose of this investigation was to elucidate the relationship between the zinc and iron intake and the advancement of subchondral sclerosis among patients with osteoarthritis (OA). The goal was to establish personalized, nutritionally-informed strategies designed to retard the progression of subchondral sclerosis and conserve joint structure. Methods: For the purposes of this research, we derived data from the Bone Ancillary Study (BAS), a constituent study of the Osteoarthritis Initiative (OAI). The intake of zinc and iron was evaluated via a food frequency questionnaire. Magnetic Resonance Imaging trabecular morphometry was employed to ascertain the microarchitecture of the subchondral bone. For the analysis of collected data, we employed logistic regression along with generalized additive models (GAMs). Results: The participant cohort was comprised of 474 OA patients (216 females, 258 males, mean [SD] age 64.1[9.2]). Notably, an increment in zinc consumption was linked with a significantly reduced likelihood of deterioration in Tb.N (OR = 0.967, 95 % CI, 0.939-0.996, P-value = 0.026), Tb.Th (OR = 0.958, 95 % CI, 0.929-0.989, P-value = 0.008), and Tb.Sp (OR = 0.967, 95 % CI, 0.939-0.996, P-value = 0.013). An elevation in iron intake seemed to enhance the risk of subchondral sclerosis, as indicated by the GAM. Subgroup analysis revealed an interaction between the effectiveness of zinc intake and factors such as gender, age, radiographic severity, and macronutrient consumption. An increased intake of calcium amplified the beneficial impact of zinc on subchondral sclerosis. Conclusions: Our findings indicate a positive association between elevated zinc intake and a slowdown in the progression of subchondral sclerosis in OA patients, notably among females, middle-aged individuals, and those with higher calcium and magnesium intake. Conversely, a higher iron intake might intensify subchondral sclerosis. These results suggest that personalized, diet-based interventions focusing on zinc consumption, in tandem with adequate calcium intake, could potentially decelerate the progression of subchondral sclerosis in individuals afflicted with OA.

Opsin 3 expression in human Langerhans cell histiocytosis and its mediation of ELD-1 cellular function.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a type of -histiocytic disorder characterized by aberrant function, differentiation or proliferation of mononuclear phagocyte system cells, however, the pathogenesis is not fully understood. Opsin 3 (OPN3) plays an important role in regulating cell function. OBJECTIVES: We aimed to investigate OPN3 expression in LCH and Langerhans cells and evaluate its possible regulation of cellular function in a Langerhans cell-like cell line (ELD-1). MATERIALS & METHODS: Expression of OPN3 in LCH and paired adjacent healthy skin tissue was determined using microscopic tools (immunohistochemical and immunofluorescence staining) and RNA scope. OPN3 protein and mRNA levels in primary dendritic cells and ELD-1 were measured by real-time quantitative PCR and western blotting, respectively. The effects of reduced or over-expressed OPN3 mRNA level, via a lentiviral vector, were examined on ELD-1 proliferation, migration, cell cycle and apoptosis using the Cell Counting Kit 8, EdU-594 kit, Transwell assays and Cell Cycle Analysis Kit and Annexin V-PE apoptosis kit, respectively. Lastly, the signalling pathway mediating these functions was investigated via RNA sequencing and western blotting. RESULTS: OPN3 was highly expressed in human LCH tissue compared to healthy tissue, and was expressed in primary dendritic cells and ELD-1. Knockdown of OPN3 in ELD-1 inhibited cell proliferation, the cell cycle, and cell migration, while over-expression reversed these processes. These functions correlated with induction of the MAPK (p38/JNK/ERK) signalling pathway. CONCLUSION: Our results provide insight into the role of OPN3 in LCH which may become a molecular target for the clinical treatment of LCH.

Association between dietary folate intake and bone mineral density in a diverse population: a cross-sectional study.

BACKGROUND: Osteoporosis is a major public health problem, yet the association between dietary folate intake and bone health has been rarely studied. This study aimed to investigate the relationship between dietary folate intake and bone mineral density (BMD) in the general population of the USA. METHODS: Utilizing data from the National Health and Nutrition Examination Survey, dietary folate intake was gauged through 24-h dietary recall and BMD was determined via dual-energy X-ray absorptiometry. Multivariate linear regression models and generalized additive models were employed for correlation analysis. RESULTS: The study incorporated 9839 participants (48.88% males, aged 20-85 years, mean age: 47.62 ± 16.22). The average dietary folate intake stood at 401.1 ± 207.9 µg/day. And the average total femur, femoral neck, trochanter, intertrochanter, and lumbar BMD were 0.98 ± 0.16 g/cm2, 0.84 ± 0.15 g/cm2, 0.73 ± 0.13 g/cm2, 1.16 ± 0.19 g/cm2, and 1.03 ± 0.15 g/cm2, respectively. The higher quartiles of dietary folate intake directly correlated with increased total femoral, femoral neck, intertrochanteric, and lumbar BMD (P for trend = 0.003, 0.016, < 0.001, and 0.033, respectively). A consistent positive association between folate intake and BMD across age groups was observed, with significant findings for individuals over 80 years and non-Hispanic whites. Physical activity level and serum 25-hydroxyvitamin D levels influenced the association, with an optimal daily folate intake of 528-569 µg recommended for postmenopausal women. CONCLUSION: In summary, our study reveals a significant positive association between dietary folate intake and BMD, across different age groups and particularly among individuals over 80 years old. Non-Hispanic whites benefit the most from increased folate intake. Physical activity level and serum 25-hydroxyvitamin D levels interact with this association. Screening and early intervention for osteoporosis may be essential for individuals with low dietary folate intake.

BMP-2 releasing mineral-coated microparticle-integrated hydrogel system for enhanced bone regeneration.

Introduction: Large bone defects (LBD) caused by trauma, infection, and tumor resection remain a significant clinical challenge. Although therapeutic agents such as bone morphogenetic protein-2 (BMP-2), have shown substantial potency in various clinical scenarios, their uncontrollable release kinetics has raised considerable concern from the clinical viewpoint. Mineral-coated microparticle (MCM) has shown its excellent biologics loading and delivery potential due to its superior protein-binding capacity and controllable degradation behaviors; thus, it is conceivable that MCM can be combined with hydrogel systems to enable optimized BMP-2 delivery for LBD healing. Methods: Herein, BMP-2 was immobilized on MCMs via electrostatic interaction between its side chains with the coating surface. Subsequently, MCM@BMP-2 is anchored into a hydrogel by the crosslinking of chitosan (CS) and polyethylene glycol (PEG). Results and Discussion: This microparticle-hydrogel system exhibits good biocompatibility, excellent vascularization, and the sustained release of BMP-2 in the bone defect. Furthermore, it is observed that this microsphere-hydrogel system accelerates bone formation by promoting the expression of osteogenesis-related proteins such as RUNX2, osteopontin, and osteocalcin in bone marrow mesenchymal stem cells (BMSCs). Thus, this newly developed multifunctional microparticle-hydrogel system with vascularization, osteogenesis, and sustained release of growth factor demonstrates an effective therapeutic strategy toward LBD.

Intracellular Delivery of Itaconate by Metal-Organic Framework-Anchored Hydrogel Microspheres for Osteoarthritis Therapy.

Treatment of osteoarthritis (OA) remains a significant clinical challenge. Itaconate (IA), an emerging regulator of intracellular inflammation and oxidative stress, may potentially be harnessed to treat OA. However, the short joint residence time, inefficient drug delivery, and cell-impermeable property of IA can seriously hamper the clinical translation. Herein, IA-encapsulated zeolitic imidazolate framework-8 (IA-ZIF-8) nanoparticles were self-assembled by zinc ions, 2-methylimidazole, and IA to render them pH-responsive. Subsequently, IA-ZIF-8 nanoparticles were firmly immobilized in hydrogel microspheres via one-step microfluidic technology. It was demonstrated in vitro experiments that IA-ZIF-8-loaded hydrogel microspheres (IA-ZIF-8@HMs) exhibited good anti-inflammatory and anti-oxidative stress effects by releasing pH-responsive nanoparticles into chondrocytes. Importantly, compared with IA-ZIF-8, IA-ZIF-8@HMs showed better performance in the treatment of OA due to their superior performance in sustained release. Thus, such hydrogel microspheres not only hold enormous potential for OA therapy, but also provide a novel avenue for cell-impermeable drugs by constructing appropriate drug delivery systems.

Co-expression prognostic-related genes signature base on propofol and sevoflurane anesthesia predict prognosis and immunotherapy response in glioblastoma.

OBJECTIVES: Anesthetic drugs had been reported may impact the bio-behavior of the tumor. Propofol and sevoflurane are common anesthetics in the operation for glioblastoma (GBM). This study aims to establish a co-expression prognostic-related genes signature base on propofol and sevoflurane anesthesia to predict prognosis and immunotherapy response in GBM. METHOD: GPM tissues with different anesthetics gene expression profiles (GSE179004) were obtained from the Gene Expression Omnibus (GEO) database. Core modules and central genes associated with propofol and sevoflurane anesthesia were identified by weighted gene coexpression network analysis (WGCNA) and establish a risk score prognostic model. Immune cell signature analysis in TCGA datasets was predicted via CIBERSORT. At last, serum methylation level of O6-methylguanine-DNA methyltransferase (MGMT) promoter was detected in GPM patient in different time during perioperative period. RESULTS: The burlywood1 group screened was significantly associated with sevoflurane-treated GBM tissue. 22 independent prognostic differential genes were construct a prognostic-related genes risk score in GBM, and showed good predictive ability. The risk score was strongly correlated with the age of the patients, but not with the sex of the patients. In addition, the differential responses to immunotherapy in high and low risk groups were analyzed, indicating that sevoflurane signature genes were consistent in the classification of gliomas. High-risk patients have high T-cell damage score and are less sensitive to immunotherapy. At last, serum methylation level of MGMT promoter was decreased in GBM patients during propofol and sevoflurane anesthesia. CONCLUSIONS: Propofol and sevoflurane anesthesia associated impact on the gene expression of GBM, included the methylation level of MGMT promoter. Propofol and sevoflurane anesthesia-based risk score prognostic model, which has good prognostic power and is an independent prognostic factor in GBM patients. Therefore, this model can be used as a new biomarker for judging the prognosis of GBM patients.KEY MESSAGESPropofol and sevoflurane anesthesia-based risk score prognostic model has good prognostic power and is an independent prognostic factor in GBM patients.High Propofol and sevoflurane anesthesia-based risk score GBM patients have high T-cell damage scores and are less sensitive to immunotherapy.Serum methylation level of MGMT promoter decrease during propofol and sevoflurane anesthesia in GBM patients.

Adsorption Behaviors of Different Components of Shale Oil in Quartz Slits Studied by Molecular Simulation.

Understanding the adsorption state and molecular behavior of the diverse components of shale oil in shale slits is of critical importance for exploring novel enhanced shale oil recovery techniques, but it is hard to be achieved by experimental measurements. In this paper, molecular dynamics (MD) simulations are performed to quantitatively describe the microbehavior of shale oil mixtures containing different kinds of hydrocarbon components, including asphaltene, in quartz slits. The spatial distributions of all the presenting components are given, the interaction energy between the components and quartz is analyzed, and the diffusion coefficients of all the components are calculated. It was found that asphaltene molecules play a vitally important role in restricting the detachment and diffusion movement of all hydrocarbon components, which is actually a key problem limiting the recovery efficiency of shale oil. The effects of temperature, slit aperture, and the appearance of CO2 on the adsorption behavior of the different shale oil components are examined; the results suggest that the light and medium components are the fractions with the most potential in thermal exploitation, while injection of CO2 is beneficial for the extraction of all the components, especially the medium components. This work gives insights into the effect of asphaltene on shale oil recovery in quartz slits and might provide guidance on the utilization of thermal and CO2-enhanced enhanced oil recovery (EOR) techniques in shale oil production.

Application Analysis of Multidisciplinary Diagnosis and Treatment Nursing Mode Based on Doctor-Nurse-Integration for Stroke Patients Undergoing Emergency Intervention Surgery.

Purpose: To analyze the application value of multidisciplinary diagnosis and treatment (MDT) nursing mode based on doctor-nurse-integration for stroke patients undergoing emergency intervention surgery. Methods: In this study, a historical comparative study method was adopted. 118 stroke patients and medical staff (9 doctors and 11 nurses) who met the diagnosis and inclusion criteria of emergency intervention surgery admitted from July 2021 to February 2022 were treated clinically according to the traditional medical care mode (TMC group), 87 stroke patients and medical staff (9 doctors and 11 nurses) who met the diagnosis and inclusion criteria of emergency intervention surgery admitted from February 2022 to June 2022 were treated and cared according to the MDT nursing mode based on medical integration (MDT group). Comparison of perioperative time indicators, postoperative outcome indicators, treatment compliance, secondary complications and visit satisfaction between the two groups of patients, and comparison of cooperation satisfaction between the two groups of medical staff. Results: The MDT group had shorter onset-emergency physician's reception time, arrival at CT room-completion time of CT/MR, notify intervention chamber-arrival time at catheter chamber, admission-femoral artery puncture time, admission-first vessel recanalization time, mean postural restraint time than the TMC group (P < 0.05). The postoperative mortality rate in the MDT group (5.75%) was comparable to that in the TMC group (8.47%) (P > 0.05); the postoperative disability rate in the MDT group (28.74%) was less than that in the TMC group (45.76%) (P < 0.05); the NIHSS score in the MDT group was lower than that in the TMC group, and the FMA score and BI score were both higher than those in the TMC group (P < 0.05). The MDT group had higher treatment compliance than the TMC group, fewer secondary complications than the TMC group, and higher patient visit satisfaction and medical staff cooperation satisfaction than the TMC group (P < 0.05). Conclusion: The implementation of the MDT nursing mode based on the doctor-nurse-integration for stroke patients undergoing emergency intervention surgery can improve the work efficiency of rescuing patients, improve the clinical treatment outcome of patients, and improve the satisfaction of doctors, nurses, and patients.

Nanoarchitectonics of Cartilage-Targeting Hydrogel Microspheres with Reactive Oxygen Species Responsiveness for the Repair of Osteoarthritis.

Clinically, intra-articular administration can hardly achieve the truly targeted therapy, and the drugs are usually insufficient to show local and long-term therapeutic effects because of their rapid clearance. Herein, inspired by the phenomenon that bees track the scent of flowers to collect nectar, we developed cartilage-targeting hydrogel microspheres with reactive oxygen species (ROS)-responsive ability via combining the microfluidic method and photopolymerization processes to integrate cartilage-targeting peptides and ROS-responsive nanoparticles in the hydrogel matrix. The hydrogel microspheres with cartilage-targeting properties promoted better retention in the joint cavity and enhanced cellular uptake of the nanoparticles. Moreover, the ROS-responsive nanoparticles could react with osteoarthritis (OA)-induced intracellular ROS, resulting in the depolymerization of nanoparticles, which could not only eliminate excess ROS and reduce inflammation but also promote the release of dexamethasone (Dex) and kartogenin (KGN) in situ, realizing effective OA therapy. It was demonstrated that this hydrogel microsphere showed favorable ROS-responsive ability and enhanced chondrogenic differentiation as well as the downregulation of pro-inflammatory factors in vitro. Additionally, the hydrogel microspheres, similar to bees, could target and effectively repair cartilage in the OA model. Thus, the injectable hydrogel microspheres exerted an excellent potential to repair OA and may also provide an effective avenue for inflammatory bowel disease therapy.