Intratumoral and fecal microbiota reveals microbial markers associated with gastric carcinogenesis.

Background: The relationship between dysbiosis of the gastrointestinal microbiota and gastric cancer (GC) has been extensively studied. However, microbiota alterations in GC patients vary widely across studies, and reproducible diagnostic biomarkers for early GC are still lacking in multiple populations. Thus, this study aimed to characterize the gastrointestinal microbial communities involved in gastric carcinogenesis through a meta-analysis of multiple published and open datasets. Methods: We analyzed 16S rRNA sequencing data from 1,642 gastric biopsy samples and 394 stool samples across 11 independent studies. VSEARCH, QIIME and R packages such as vegan, phyloseq, cooccur, and random forest were used for data processing and analysis. PICRUSt software was employed to predict functions. Results: The α-diversity results indicated significant differences in the intratumoral microbiota of cancer patients compared to non-cancer patients, while no significant differences were observed in the fecal microbiota. Network analysis showed that the positive correlation with GC-enriched bacteria increased, and the positive correlation with GC-depleted bacteria decreased compared to healthy individuals. Functional analyses indicated that pathways related to carbohydrate metabolism were significantly enriched in GC, while biosynthesis of unsaturated fatty acids was diminished. Additionally, we investigated non-Helicobacter pylori (HP) commensals, which are crucial in both HP-negative and HP-positive GC. Random forest models, constructed using specific taxa associated with GC identified from the LEfSe analysis, revealed that the combination of Lactobacillus and Streptococcus included alone could effectively discriminate between GC patients and healthy individuals in fecal samples (area under the curve (AUC) = 0.7949). This finding was also validated in an independent cohort (AUC = 0.7712). Conclusions: This study examined the intratumoral and fecal microbiota of GC patients from a dual microecological perspective and identified Lactobacillus, Streptococcus, Roseburia, Faecalibacterium and Phascolarctobacterium as intratumoral and intestinal-specific co-differential bacteria. Furthermore, it confirmed the validity of the combination of Lactobacillus and Streptococcus as GC-specific microbial markers across multiple populations, which may aid in the early non-invasive diagnosis of GC.

Esculin Alleviates Osteoarthritis Progression Through the Sirt1/NF-κB Pathway.

Osteoarthritis (OA), a joint disease associated with inflammatory processes, contributes to joint destruction. Esculin (ESC) extracted from the stem bark of Fraxinus rhynchophylla Hance has been shown to possess anti-inflammatory properties. In this study, we investigated the effect of ESC on chondrocytes treated with IL-1ß and its molecular mechanism. The importance and potential mechanism of ESC in the progression of OA were evaluated. The viability of chondrocytes after exposure to ESC was examined through the CCK-8 assays. The cells were then subjected to quantitative polymerase chain reaction (qPCR), western blot, and enzyme-linked immunosorbent assay (ELISA) techniques to analyze the degradation of the extracellular matrix (ECM) and occurrence of inflammation. The NF-κB mechanism was evaluated by western blot analysis, immunofluorescence (IF), and luciferase reporter assay. Molecular docking was performed to allow for predictions on proteins that interact with ESC. Moreover, the significance of Sirt1 was explored through a knockdown experiment based on siRNA. Micro-computed tomography (CT), H&E, Safranin O-Fast Green (S-O), and immunohistochemical analyses were carried out to assess the treatment efficacy of ESC on OA in destabilization of medial meniscus (DMM) models. ESC treatment effectively inhibited ECM degradation, modulated the levels of pro-inflammatory factors, and regulated the NF-κB signaling in chondrocytes exposed to IL-1ß. Mechanistically, we found that ESCs bound to Sirt1 to inhibit the activity of the NF-κB mechanism. Furthermore, ESC treatment suppressed OA progression in the DMM models. Our findings reveal that ESC ameliorates OA progression via modulating the Sirt1/NF-κB axis. This demonstrates that ESC has the potential to be applied in the treatment of OA.

Diagnostic value of combined detection of AKP, TSGF, and LDH for pediatric osteosarcoma: a case-control study.

OBJECTIVE: To evaluate the diagnostic value of serum alkaline phosphatase (AKP), tumor-supplied growth factor group (TSGF), and lactate dehydrogenase (LDH) for pediatric osteosarcoma. METHODS: A retrospective analysis of clinical data from 81 pediatric osteosarcoma patients (osteosarcoma group) and 63 patients with benign bone tumors (benign bone tumor group) admitted to Yantaishan Hospital from February 2023 to November 2023 was conducted. Basic and clinical data differences between the two groups of children were compared. A multivariate regression model was established to determine predictive factors for pediatric osteosarcoma, and the diagnostic value of identified indicators for pediatric osteosarcoma was evaluated. RESULTS: Osteosarcoma group demonstrated significantly higher serum AKP (375.76±73.47 vs 286.12±76.50 U/L), TSGF (69.01±16.30 vs 53.57±16.37 U/mL), and LDH (269.55±66.96 vs 207.46±59.20 U/L) levels as compared to the benign bone tumor group. Correlation analysis suggested significant positive correlations between AKP (rho=0.505), TSGF (rho=406), LDH (rho=0.449) and pediatric osteosarcoma. Multivariate regression analysis showed serum AKP, TSGF, and LDH were independent predictive factor for pediatric osteosarcoma. The AUC value for AKP was 0.794, with a Youden index of 0.459; the AUC value for TSGF was 0.736, with a Youden index of 0.406; and the AUC value for LDH was 0.761, with a Youden index of 0.462. The combined use of these three biomarkers yielded an AUC of 0.886. CONCLUSION: The combined detection of serum AKP, TSGF, and LDH can enhance the diagnostic accuracy of pediatric osteosarcoma, providing important evidence for clinical treatment.

Biomechanics on Ultra-Sensitivity of Venus Flytrap's Micronewton Trigger Hairs.

Numerous plants evolve ingeniously microcantilever-based hairs to ultra-sensitively detect out-of-plane quasi-static tactile loads, providing a natural blueprint for upgrading the industrial static mode microcantilever sensors, but how do the biological sensory hairs work mechanically? Here, the action potential-producing trigger hairs of carnivorous Venus flytraps (Dionaea muscipula) are investigated in detail from biomechanical perspective. Under tiny mechanical stimulation, the deformable trigger hair, composed of distal stiff lever and proximal flexible podium, will lead to rapid trap closure and prey capture. The multiple features determining the sensitivity such as conical morphology, multi-scale functional structures, kidney-shaped sensory cells, and combined deformation under tiny mechanical stimulation are comprehensively researched. Based on materials mechanics, finite element simulation, and bio-inspired original artificial sensors, it is verified that the omnidirectional ultra-sensitivity of trigger hair is attributed to the stiff-flexible coupling of material, the double stress concentration, the circular distribution of sensory cells, and the positive local buckling. Also, the balance strategy of slender hair between sensitivity and structural stability (i.e., avoiding disastrous collapse) is detailed revealed. The unique basic biomechanical mechanism underlying trigger hairs is essential for significantly enhancing the performance of the traditional industrial static mode microcantilever sensors, and ensure the stability of arbitrary load perception.

Endoscopic submucosal resection (ESD) and endoscopic full-thickness resection (EFTR) via balloon-assisted enteroscopy (BAE) in small bowel subepithelial lesions: experience in treating fifteen cases.

AIM: The study objective was to evaluate the primary feasibility of endoscopic submucosal resection (ESD) and endoscopic full-thickness resection (EFTR) via balloon-assisted enteroscopy (BAE) to treat small bowel subepithelial lesions (SELs). METHOD: A retrospective case series study was performed. The first fifteen consecutive patients who underwent ESD (n = 10) and EFTR (n = 5) via BAE to remove small bowel SELs from November 2016 to December 2023 were included. The main outcome measures were the technique success rate, operative time and complication rate. RESULTS: This research focused on 15 cases of jejunoileal SELs, four cases of lipomyoma, three cases of ectopic pancreas, two cases of NETs, three cases of benign fibrous tumours and three cases of angioma. The overall technique success rate was 86.7%, with 100% (10/10) and 60% (3/5) for BAE-ESD and BAE-EFTR, respectively, in removing small bowel SELs. Two cases of EFTR failed, as the BAE operation was unsuitable for tumour resection and suture repair of a perforated wound. No serious bleeding or any postoperative complications occurred. The median time of endoscopic resection via BAE for SELs was 44 min (range 22-68 min). CONCLUSION: ESD and EFTR via BAE might be alternative choices for treating small SELs in the small bowel, with the advantages of clear and accurate positioning and minimal invasiveness. However, its superiority over surgery still needs to be further investigated.

Cardiovascular health and cancer mortality: evidence from US NHANES and UK Biobank cohort studies.

BACKGROUND: The American Heart Association recently introduced a novel cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the relationship between LE8 and cancer mortality risk remains uncertain. METHODS: We investigated 17,076 participants from US National Health and Nutrition Examination Survey (US NHANES) and 272,727 participants from UK Biobank, all free of cancer at baseline. The CVH score, based on LE8 metrics, incorporates four health behaviors (diet, physical activity, smoking, and sleep) and four health factors (body mass index, lipid, blood glucose, and blood pressure). Self-reported questionnaires assessed health behaviors. Primary outcomes were mortality rates for total cancer and its subtypes. The association between CVH score (continuous and categorical variable) and outcomes was examined using Cox model with adjustments. Cancer subtypes-related polygenic risk score (PRS) was constructed to evaluate its interactions with CVH on cancer death risk. RESULTS: Over 141,526 person-years in US NHANES, 424 cancer-related deaths occurred, and in UK Biobank, 8,872 cancer deaths were documented during 3,690,893 person-years. High CVH was associated with reduced overall cancer mortality compared to low CVH (HR 0.58, 95% CI 0.37-0.91 in US NHANES; 0.51, 0.46-0.57 in UK Biobank). Each one-standard deviation increase in CVH score was linked to a 19% decrease in cancer mortality (HR: 0.81; 95% CI: 0.73-0.91) in US NHANES and a 19% decrease (HR: 0.81; 95% CI: 0.79-0.83) in UK Biobank. Adhering to ideal CVH was linearly associated with decreased risks of death from lung, bladder, liver, kidney, esophageal, breast, colorectal, pancreatic, and gastric cancers in UK Biobank. Furthermore, integrating genetic data revealed individuals with low PRS and high CVH exhibited the lowest mortality from eight cancers (HRs ranged from 0.36 to 0.57) compared to those with high PRS and low CVH. No significant modification of the association between CVH and mortality risk for eight cancers by genetic predisposition was observed. Subgroup analyses showed a more pronounced protective association for overall cancer mortality among younger participants and those with lower socio-economic status. CONCLUSIONS: Maintaining optimal CVH is associated with a substantial reduction in the risk of overall cancer mortality. Adherence to ideal CVH correlates linearly with decreased mortality risk across multiple cancer subtypes. Individuals with both ideal CVH and high genetic predisposition demonstrated significant health benefits. These findings support adopting ideal CVH as an intervention strategy to mitigate cancer mortality risk and promote healthy aging.

PU.1 regulates osteoarthritis progression via CSF1R in synovial cells.

This study elucidates the molecular mechanisms driving osteoarthritis (OA) by focusing on the transcription factor PU.1's role in synovial cells, specifically macrophages and fibroblast-like synoviocytes (FLS). Analyzing OA-related synovial gene expression from the GEO database highlighted immune regulation pathways in OA. Using protein-protein interaction and the JASPAR database, we pinpointed essential genes in OA development. Synovial tissues from OA patients and controls revealed pronounced PU.1 and its target CSF1R presence. In a surgically induced OA mouse model with PU.1 and CSF1R knockdown, ChIP assays confirmed PU.1's binding to the CSF1R promoter. Dual luciferase reporter assays and immunohistochemistry validated PU.1's regulatory impact on CSF1R transcription. Combined analysis of microarrays GSE55235 and GSE206848 showed heightened PU.1 expression in OA, associated with immune regulation in macrophages. In vitro findings aligned with in vivo results, emphasizing PU.1's influence on macrophage polarization and FLS-induced inflammation. PU.1's direct activation of CSF1R transcription underpins its key role in OA progression. This research offers insights into OA's molecular basis, suggesting potential therapeutic targets.

The functional subclasses of AT1 receptor autoantibody in patients with coronary heart disease.

Recently, the identification of autoantibodies (AT1-AA) targeting the second extracellular loop of angiotensin II type 1 receptor (AT1R-ECII) in patients with coronary heart disease (CHD) offers a novel perspective on the interplay between immunity and cardiovascular disease. However, much remains unknown regarding the functional diversity of AT1-AA. In this study, we measured the levels of AT1-AA in the sera of 306 CHD patients and purified AT1-AA from patient's sera (n = 127). The subclasses of AT1-AA were categorized based on their impact on intracellular calcium ([Ca2+]i) levels in mouse arterial smooth muscle cells (MASMCs). Our findings revealed 4 distinct [Ca2+]i response patterns indicating the existence of 4 functional subclasses named H1-, H2-, H3-, and H4-AT1-AA. The correlation analysis demonstrated a positive association between H1-AT1-AA and endogenous coagulation, as well as between H2-AT1-AA and exogenous coagulation; no significant correlation was observed between H3-AT1-AA and the indicators we analyzed. Conversely, H4-AT1-AA exhibited a negative correlation with both leukocyte number and bile acid levels. Logistic regression analysis showed that H2-AT1-AA possessed predictive value for severe CHD. Furthermore, in vitro experiments indicated that both H1- and H2-AT1-AA exerted cytotoxic effects on MASMCs, while H4-AT1-AA increased cell viability. Additionally, an AT1-AA-positive rat model was established by subcutaneously injecting with AT1R-ECII peptide, which produced four similar functional subclasses of rat AT1-AA upon active immunization. This study suggested that classifying different functional subclasses of AT1-AAs can facilitate more accurate evaluation of the condition and prognosis in patients with CHD, thereby providing a novel basis for clinical diagnosis and treatment.

Diurnal variation of postoperative delirium in elderly patients undergoing esketamine anesthesia for elective noncardiac surgery: a randomized clinical trial.

BACKGROUND: Postoperative delirium (POD) is a serious and common complication. The aim of present study is to investigate the diurnal variation of POD and the effects of esketamine in elderly patients. METHODS: A randomized, double-blind, placebo-controlled clinical trial with factorial design was conducted. Patients (aged 65 to 85 years) with normal Mini-Mental State Examination (MMSE) score were stratified by age (≤70 vs. >70) and American Society of Anesthesiologists physical status classification (Ⅱ vs. Ⅲ), then randomly assigned to either morning (08:00-12:00) or afternoon (14:00-18:00) noncardiac operation under general anesthesia with or without esketamine administration (0.2 mg/kg). The primary outcome was the incidence of POD (3-Minute Diagnostic Interview for Confusion Assessment Method-defined Delirium, 3D-CAM) on postoperative days 1, 3, and 7. The secondary outcomes were the scores of MMSE and Hospital Anxiety and Depression Scale. The intention-to-treat analysis of the outcomes were performed by generalized estimating equation. RESULTS: Six patients who did not receive an intervention because of canceled operation were excluded after randomization. The datasets containing 426 cases were analyzed following the intention-to-treat principle after handling missing data via multiple imputation method. The incidence of POD declined from about 55% on postoperative day 1 to 31 and 18% on postoperative days 3 and 7, respectively. Afternoon operation [B=-0.583, OR (95% CI) 0.558 (0.319-0.976); P=0.041], but not esketamine, significantly decreased the incidence of POD. Both esketamine and operation time failed to significantly affect MMSE, HAD, and NRS score. There was no interaction among operation time, esketamine, and follow up time. CONCLUSION: Elderly patients undergoing elective noncardiac surgery in the afternoon displayed lower POD incidence than those operated in the morning. A single low-dose of esketamine before general anesthesia induction failed to significantly decrease the risk of POD but decrease the risk of intraoperative hypotension and emergence agitation.

Combinatorial accumulation, stress response, detoxification and synaptic transmission effects of cadmium and selenium in clams Ruditapes philippinarum.

This study investigated the toxicological effects and mechanisms of cadmium (Cd) (5 and 50 µg/L) and selenium (Se) (3 and 30 µg/L) at environmentally relevant concentrations on the gills and digestive glands of clams Ruditapes philippinarum. Results indicated that Cd and Se could tissue-specifically impact osmoregulation, energy metabolism, and synaptic transmission in the gills and digestive glands of clams. After exposure to 50 µg/L Cd, the digestive glands of clams up-regulated the expression of methionine-gamma-lyase and metallothionein for detoxification. Clam digestive glands exposed to 3 µg/L Se up-regulated the expression of catalase and glutathione peroxidase to alleviate oxidative stress, and down-regulated the expression of selenide-water dikinase to reduce the conversion of inorganic Se. Additionally, the interaction mode between Cd and Se largely depended on their molar ratio, with a ratio of 11.71 (50 µg/L Cd + 3 µg/L Se) demonstrated to be particularly harmful, as manifested by significantly more lesions, oxidative stress, and detoxification demand in clams than those exposed to Cd or Se alone. Collectively, this study revealed the complex interaction patterns and mechanisms of Cd and Se on clams, providing a reference for exploring their single and combined toxicity.

A randomized, multicenter phase III Study of once-per-cycle administration of efbemalenograstim alfa (F-627), a novel long-acting rhG-CSF, for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer.

BACKGROUND: F-627 (efbemalenograstim alfa) is a novel long acting granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This studyevaluated the efficacy and safety of F-627, also known as efbemalenograstim alfa (Ryzneuta®) in reducing neutropenia compared with filgrastim (GRAN®). METHODS: This was a multicenter, randomized, open-label, active-controlled non-inferiority study. Two hundred thirty nine (239) patients were enrolled in thirteen centers and received the chemotherapy with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive either a single 20 mg subcutaneous (s.c.) injection of F-627 on day 3 of each cycle or daily s.c. injection of filgrastim 5 µg/kg/d starting from day 3 of each cycle. The primary endpoint was the duration of grade 3 or 4 neutropenia in cycle 1. The safety profile was also evaluated. RESULTS: The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.68 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimate of the between-group median difference (F-627 vs filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of the one-sided 97.5% CI was 0 day, which was within the prespecified non-inferiority margin of 1-day. Results for all efficacy endpoints in cycles 2 - 4 were consistent with the results in cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed in the F-627 group compared with the filgrastim group. The ANC nadir in the F-627 group was significantly higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as standard daily filgrastim. CONCLUSIONS: A single fixed dose of 20 mg of F-627 in each cycle was as safe and effective as a daily dose of filgrastim 5 µg/kg/d in reducing neutropenia and its complications in patients who received four cycles of EC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04174599, on 22/11/2019.

Potential and metabolic impacts of double enrichments of docosahexaenoic acid and 25-hydroxy vitamin D3in tissues of broiler chickens.

BACKGROUND: Chicken may be enriched with 25-hydroxy D3 [25(OH)D3] and docosahexaenoic acid (DHA) to enhance dietary intakes of the public. OBJECTIVES: Two experiments were conducted to determine potential and metabolic impacts of enriching both DHA and 25(OH)D3 in tissues of broiler chickens. METHODS: In Expt. 1, 144 chicks (6 cages/treatment, 6 birds/cage) were fed a corn-soybean meal basal-diet (BD), BD+10,000 IU 25(OH)D3/kg [BD+25(OH)D3], BD+1% DHA-rich Aurantiochytrium (1.2 g DHA/kg; BD+DHA), or BD+25(OH)D3+DHA for 6 wk. In Expt. 2, 180 chicks were fed the BD, BD+DHA-rich microalgal oil (1.5 to 3.0 g DHA/kg, BD+DHA), BD+DHA + eicosapentaenoic acid (EPA)-rich microalgae (0.3 to 0.6 g EPA/kg, BD+DHA+EPA), BD+DHA+25(OH)D3 [6,000 to 12,000 IU/kg diet; BD+DHA+25(OH)D3], and BD+DHA+EPA+25(OH)D3 for 6 wk. RESULTS: Supranutrition of these two nutrients resulted in 57 to 62 mg of DHA and 1.9 to 3.3 µg of 25(OH)D3 per 100 g of breast or thigh muscles. The DHA enrichment was independent of dietary EPA or 25(OH)D3, but that of 25(OH)D3 in the liver was decreased (68%, P < 0.05) by dietary DHA in Expt. 1. Compared with BD, BD+25(OH)D3 enhanced (P < 0.05) gene expression related to D3 absorption (SRB1, NPC1L1) in the liver and D3 degradation (CYP24A1) in the breast and decreased mRNA or protein levels of vitamin D binding protein in the adipose tissue or thigh muscle. Supranutrition of DHA decreased mRNA levels of lipid metabolism-related genes (FADS1,2, ELOVL5, FADS2, FASN, and SREBP1). CONCLUSIONS: Both DHA and 25(OH)D3 were enriched in the muscles up to meeting 50% to 100% of the suggested intakes of these nutrients by consuming two servings of 100 g of fortified chicken. The enrichments altered gene expression related to lipid biosynthesis and vitamin D transport or storage.

Monitoring Soybean Soil Moisture Content Based on UAV Multispectral and Thermal-Infrared Remote-Sensing Information Fusion.

By integrating the thermal characteristics from thermal-infrared remote sensing with the physiological and structural information of vegetation revealed by multispectral remote sensing, a more comprehensive assessment of the crop soil-moisture-status response can be achieved. In this study, multispectral and thermal-infrared remote-sensing data, along with soil-moisture-content (SMC) samples (0~20 cm, 20~40 cm, and 40~60 cm soil layers), were collected during the flowering stage of soybean. Data sources included vegetation indices, texture features, texture indices, and thermal-infrared vegetation indices. Spectral parameters with a significant correlation level (p < 0.01) were selected and input into the model as single- and fuse-input variables. Three machine learning methods, eXtreme Gradient Boosting (XGBoost), Random Forest (RF), and Genetic Algorithm-optimized Backpropagation Neural Network (GA-BP), were utilized to construct prediction models for soybean SMC based on the fusion of UAV multispectral and thermal-infrared remote-sensing information. The results indicated that among the single-input variables, the vegetation indices (VIs) derived from multispectral sensors had the optimal accuracy for monitoring SMC in different soil layers under soybean cultivation. The prediction accuracy was the lowest when using single-texture information, while the combination of texture feature values into new texture indices significantly improved the performance of estimating SMC. The fusion of vegetation indices (VIs), texture indices (TIs), and thermal-infrared vegetation indices (TVIs) provided a better prediction of soybean SMC. The optimal prediction model for SMC in different soil layers under soybean cultivation was constructed based on the input combination of VIs + TIs + TVIs, and XGBoost was identified as the preferred method for soybean SMC monitoring and modeling, with its R2 = 0.780, RMSE = 0.437%, and MRE = 1.667% in predicting 0~20 cm SMC. In summary, the fusion of UAV multispectral and thermal-infrared remote-sensing information has good application value in predicting SMC in different soil layers under soybean cultivation. This study can provide technical support for precise management of soybean soil moisture status using the UAV platform.

Characterization of Wing Kinematics by Decoupling Joint Movement in the Pigeon.

Birds have remarkable flight capabilities due to their adaptive wing morphology. However, studying live birds is time-consuming and laborious, and obtaining information about the complete wingbeat cycle is difficult. To address this issue and provide a complete dataset, we recorded comprehensive motion capture wing trajectory data from five free-flying pigeons (Columba livia). Five key motion parameters are used to quantitatively characterize wing kinematics: flapping, sweeping, twisting, folding and bending. In addition, the forelimb skeleton is mapped using an open-chain three-bar mechanism model. By systematically evaluating the relationship of joint degrees of freedom (DOFs), we configured the model as a 3-DOF shoulder, 1-DOF elbow and 2-DOF wrist. Based on the correlation analysis between wingbeat kinematics and joint movement, we found that the strongly correlated shoulder and wrist roll within the stroke plane cause wing flap and bending. There is also a strong correlation between shoulder, elbow and wrist yaw out of the stroke plane, which causes wing sweep and fold. By simplifying the wing morphing, we developed three flapping wing robots, each with different DOFs inside and outside the stroke plane. This study provides insight into the design of flapping wing robots capable of mimicking the 3D wing motion of pigeons.

A Peptide-Drug Conjugate-Based Nanoplatform for Immunometabolic Activation and In Situ Nerve Regeneration in Advanced-Stage Alzheimer's Disease.

The formidable protection of physiological barriers and unclear pathogenic mechanisms impede drug development for Alzheimer's disease (AD). As defenders of the central nervous system, immune-metabolism function, and stemness of glial cells remain dormant during degeneration, representing a significant challenge for simultaneously targeting and modulating. Here, a modular nanoplatform is presented composed of peptide-drug conjugates and an inflammation-responsive core. The nanoplatform is transported through the blood-brain barrier via transcytosis and disassembles in the oxidative stress microenvironment upon intravenous administration. The released drug-conjugated modules can specifically target and deliver hydroxychloroquine (HCQ) and all-trans retinoic acid (ATRA) to microglia and astrocytes, respectively. The immune function of chronic tolerant microglia is activated by metabolic modulation, and reactive astrocytes trans-differentiate into functional neurons. In a transgenic mouse model, nanoplatform reduces levels of toxic proteins and inflammation while increasing neuronal density. This results in the amelioration of learning and memory decline. The modular nanoplatform provides design principles for multi-cellular targeting and combination nano-therapy for inflammation-related diseases.

A Micromanipulation-Actuated Large-Scale Screening to Identify Optimized Microphysiological Model Parameters in Skeletal Muscle Regeneration.

Hydrogel-based 3D cell cultures are extensively utilized to create biomimetic cellular microstructures. However, there is still lack of effective method for both evaluation of the complex interaction of cells with hydrogel and the functionality of the resulting micro-structures. This limitation impedes the further application of these microstructures as microphysiological models (microPMs) for the screening of potential culture condition combinations to enhance the skeletal muscle regeneration. This paper introduces a two-probe micromanipulation method for the large-scale assessment of viscoelasticity and contractile force (CF) of skeletal muscle microPMs, which are produced in high-throughput via microfluidic spinning and 96-well culture. The collected data demonstrate that viscoelasticity parameters (E* and tanδ) and CF both measured in a solution environment are indicative of the formation of cellular structures without hydrogel residue and the subsequent generation of myotubes, respectively. This study have developed screening criterias that integrate E*, tanδ, and CF to examine the effects of multifactorial interactions on muscle fiber repair under hypoxic conditions and within bioprinted bipennate muscle structures. This approach has improved the quality of hypoxic threshold evaluation and aligned cell growth in 3D. The proposed method is useful in exploring the role of different factors in muscle tissue regeneration with limited resources.

Effect of Mono- and Polysaccharide on the Structure and Property of Soy Protein Isolate during Maillard Reaction.

As a protein extracted from soybeans, soy protein isolate (SPI) may undergo the Maillard reaction (MR) with co-existing saccharides during the processing of soy-containing foods, potentially altering its structural and functional properties. This work aimed to investigate the effect of mono- and polysaccharides on the structure and functional properties of SPI during MR. The study found that compared to oat ß-glucan, the reaction rate between SPI and D-galactose was faster, leading to a higher degree of glycosylation in the SPI-galactose conjugate. D-galactose and oat ß-glucan showed different influences on the secondary structure of SPI and the microenvironment of its hydrophobic amino acids. These structural variations subsequently impact a variety of the properties of the SPI conjugates. The SPI-galactose conjugate exhibited superior solubility, surface hydrophobicity, and viscosity. Meanwhile, the SPI-galactose conjugate possessed better emulsifying stability, capability to produce foam, and stability of foam than the SPI-ß-glucan conjugate. Interestingly, the SPI-ß-glucan conjugate, despite its lower viscosity, showed stronger hypoglycemic activity, potentially due to the inherent activity of oat ß-glucan. The SPI-galactose conjugate exhibited superior antioxidant properties due to its higher content of hydroxyl groups on its molecules. These results showed that the type of saccharides had significant influences on the SPI during MR.

Cyano-determined mercury (II) ion selective fluorescence assay over polymeric carbon nitride.

Selective response is the key index to evaluate the performance of polymeric carbon nitride (PCN)-based heavy metal ion fluorescence sensors. Herein, to explore the role of cyano groups on selectivity, four kinds of PCN, including PCN-Cl, PCN-Ac, PCN-B and PCN-K were prepared by the molten salt method of sodium chloride and sodium acetate, the reduction method of sodium borohydride and the etching method of potassium hydroxide, respectively. These PCNs exhibited different surface cyano characteristics, but all of them had significant blue emission under ultraviolet excitation. It is proved that the assistant of sodium chloride or potassium hydroxide is an effective method to prepare PCNs with abundant surface cyano group. A series of fluorescence quenching experiments of metal ions showed that the cyano-rich degree of PCN is closely related to its selective response to mercury (II) ions. PCN-Cl and PCN-K emerged good selective quenching of mercury (II) ions, which may be related to the soft acid-soft base strong interaction between mercury (II) ions and cyano groups. Both PCN-Cl and PCN-K fluorescent probes for mercury (II) ions had a linear range of 5 âˆ¼ 50 µmol L-1, and PCN-Cl exhibited a lower detection limit of 0.38 µmol L-1. This work confirmed the selective fluorescence response of cyano-rich PCN to mercury (II) ions, proposed the mechanism of selective fluorescence quenching response of mercury (II) ions, and provided a new idea for the design of efficient and accurate PCN-based fluorescence probes.

Participation in Multidisciplinary Teams Among Healthcare Professionals: A Discrete Choice Experiment in Tertiary Public Hospitals in China.

Purpose: Healthcare professionals' participation is crucial for the efficient implementation of multidisciplinary team (MDT) collaboration models. We identified the key factors influencing healthcare professionals' preference to participate in MDTs in tertiary hospitals. Methods: To clarify the attributes and levels of the discrete choice experiment (DCE), we conducted a targeted literature review and conducted in-depth interviews with MDT service providers. Following this, a DCE was designed to evaluate healthcare professionals' preferences for MDT participation, and the influence of factors such as salary subsidies, leadership attention, patient participation, quality assessment, working intensity, and case complexity. A conditional logit model estimated the utility of each attribute. Willingness-to-pay estimates were derived by taking the negative ratio of the coefficients of non-economic and economic attributes. A series of policy simulation analyses were conducted. Results: Two hundred healthcare professionals completed the questionnaire, with 180 valid responses used for analysis. All attributes were statistically significant. Leadership attention and working intensity were the primary factors influencing staff willingness to participate in MDTs, followed by quality assessment and salary subsidies. Significant preference differences were observed between respondents; compared with mid-level staff, senior-level healthcare professionals believed patient engagement would be more helpful in boosting participation. The policy simulation showed that changing leadership attention from "neglect" to "emphasis" would increase the probability of staff choosing to participate in MDTs from 24.4% to 66.98%. Conclusion: Leadership attention was the primary concern for healthcare professionals in MDTs. To effectively motivate staff participation in MDTs, policymakers should adopt a holistic approach that considers work motivation and individual backgrounds, including competitive salary packages and a positive work environment. They should concurrently introduce MDT case complexity measurement tools to optimize resource allocation. Addressing staff members' unique needs and career aspirations by creating targeted training programs, pathways for advancement, and personalized career development plans are also crucial.