Insights into the Mechanical Characterization of Mouse Brain Tissue Using Microindentation Testing.

Indentation testing is the most common approach to quantify mechanical brain tissue properties. Despite a myriad of studies conducted already, reported stiffness values vary extensively and continue to be subject of study. Moreover, the growing interest in the relationship between the brain's spatially heterogeneous microstructure and local tissue stiffness warrants the development of standardized measurement protocols to enable comparability between studies and assess repeatability of reported data. Here, we present three individual protocols that outline (1) sample preparation of a 1000-µm thick coronal slice, (2) a comprehensive list of experimental parameters associated with the FemtoTools FT-MTA03 Micromechanical Testing System for spherical indentation, and (3) two different approaches to derive the elastic modulus from raw force-displacement data. Lastly, we demonstrate that our protocols deliver a robust experimental framework that enables us to determine the spatially heterogeneous microstructural properties of (mouse) brain tissue. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Mouse brain sample preparation Basic Protocol 2: Indentation testing of mouse brain tissue using the FemtoTools FT-MTA03 Micromechanical Testing and Assembly System Basic Protocol 3: Tissue stiffness identification from force-displacement data.

FOXF1 reverses lung fibroblasts transdifferentiation via inhibiting TGF-ß/SMAD2/3 pathway in silica-induced pulmonary fibrosis.

Silicosis is one of the most common and severe types of pneumoconiosis and is characterized by lung dysfunction, persistent lung inflammation, pulmonary nodule formation, and irreversible pulmonary fibrosis. The transdifferentiation of fibroblasts into myofibroblasts is one of the main reasons for the exacerbation of silicosis. However, the underlying mechanism of transcription factors regulating silicosis fibrosis has not been clarified. The aim of this study was to investigate the potential mechanism of transcription factor FOXF1 in fibroblast transdifferentiation in silica-induced pulmonary fibrosis. Therefore, a silicosis mouse model was established, and we found that FOXF1 expression level was significantly down-regulated in the silicosis group, and after overexpression of FOXF1 by adeno-associated virus (AAV), FOXF1 expression level was up-regulated, and silicosis fibrosis was alleviated. In order to further explore the specific regulatory mechanism of FOXF1 in silicosis, we established a fibroblasts transdifferentiation model induced by TGF-ß in vitro. In the model, the expression levels of SMAD2/3 and P-SMAD2/3 were up-regulated, but the expression levels of SMAD2/3 and P-SMAD2/3 were down-regulated, inhibiting transdifferentiation and accumulation of extracellular matrix after the overexpressed FOXF1 plasmid was constructed. However, after silencing FOXF1, the expression levels of SMAD2/3 and P-SMAD2/3 were further up-regulated, aggravating transdifferentiation and accumulation of extracellular matrix. These results indicate that the activation of FOXF1 in fibroblasts can slow down the progression of silicosis fibrosis by inhibiting TGF-ß/SMAD2/3 classical pathway, which provides a new idea for further exploration of silicosis treatment.

Microbiota profiling reveals alteration of gut microbial neurotransmitters in a mouse model of autism-associated 16p11.2 microduplication.

The gut-brain axis is evident in modulating neuropsychiatric diseases including autism spectrum disorder (ASD). Chromosomal 16p11.2 microduplication 16p11.2dp/+ is among the most prevalent genetic copy number variations (CNV) linked with ASD. However, the implications of gut microbiota status underlying the development of ASD-like impairments induced by 16p11.2dp/+ remains unclear. To address this, we initially investigated a mouse model of 16p11.2dp/+, which exhibits social novelty deficit and repetitive behavior characteristic of ASD. Subsequently, we conducted a comparative analysis of the gut microbial community and metabolomic profiles between 16p11.2dp/+ and their wild-type counterparts using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC/MS). Our microbiota analysis revealed structural dysbiosis in 16p11.2dp/+ mice, characterized by reduced biodiversity and alterations in species abundance, as indicated by α/ß-diversity analysis. Specifically, we observed reduced relative abundances of Faecalibaculum and Romboutsia, accompanied by an increase in Turicibacter and Prevotellaceae UCG_001 in 16p11.2dp/+ group. Metabolomic analysis identified 19 significantly altered metabolites and unveiled enriched amino acid metabolism pathways. Notably, a disruption in the predominantly histamine-centered neurotransmitter network was observed in 16p11.2dp/+ mice. Collectively, our findings delineate potential alterations and correlations among the gut microbiota and microbial neurotransmitters in 16p11.2dp/+ mice, providing new insights into the pathogenesis of and treatment for 16p11.2 CNV-associated ASD.

Diffusion tensor imaging combined with chemical shift-encoded sequence to quantify the adaptive changes of calf muscles in amateur marathoners.

PURPOSE: Calf muscles play an important role in marathon race, and the incidence of injury is high in this process. This study prospectively quantified diffusion tensor metrics, muscle fat fraction (MFF) and cross-sectional area (CSA) of calf muscles induced by endurance exercise in amateur marathoners, and the potential mechanisms underlying the changes in these parameters were analyzed. METHOD: In this prospective study, 35 marathoners (27 males, 8 females; mean age (standard deviation, SD), 38.92 (4.83) years) and 26 controls (18 males, 8 females; mean age (SD), 38.35 (6.75) years) underwent magnetic resonance imaging (MRI) from September 2022 to March 2023. The diffusion tensor eigenvalues (λ1, λ2, λ3), radial diffusivity (RD), fractional anisotropy (FA), MFF and CSA of calf muscles were compared between marathoners and controls. A binary logistic regression model with gender correction was performed analyze the relationship between marathon exercise and DTI parameters, CSA and MFF of calf muscles. RESULTS: Interobserver agreement was good (κ = 0.71). The results of binary logistic regression model with gender correction showed that the regression coefficients of FA values in anterior group of calf (AC), soleus (SOL), medial gastrocnemius (MG) and lateral gastrocnemius (LG) were negative, and the odds ratios (OR) were 0.33, 0.45, 0.35, 0.05, respectively (P < 0.05). The OR of RD in SOL and λ2 in external group of calf (EC) were relatively higher, 3.74 and 3.26, respectively (P < 0.05). CSA was greater in SOL of marathoners, with an OR value of 1.00(P < 0.05). The MFF in AC and LG was lower in marathoners and OR of two indexes were -0.69 and -0.59, respectively (P < 0.05). CONCLUSIONS: Diffusion tensor imaging (DTI) combined with chemical shift-encoded sequence can noninvasively detect and quantify the adaptive changes of calf muscle morphology, microstructure and tissue composition induced by long-term running training in amateur marathoners.

A multifunctional biomimetic nanoplatform for image-guideded photothermal-ferroptotic synergistic osteosarcoma therapy.

Much effort has been devoted to improving treatment efficiency for osteosarcoma (OS). However, most current approaches result in poor therapeutic responses, thus indicating the need for the development of other therapeutic options. This study developed a multifunctional nanoparticle, PDA-MOF-E-M, an aggregation of OS targeting, programmed death targeting, and near-infrared (NIR)-aided targeting. At the same time, a multifunctional nanoparticle that utilises Fe-MOFs to create a cellular iron-rich environment and erastin as a ferroptosis inducer while ensuring targeted delivery to OS cells through cell membrane encapsulation is presented. The combination of PDA-MOF-E-M and PTT increased intracellular ROS and LPO levels and induced ferroptosis-related protein expression. A PDA-based PTT combined with erastin showed significant synergistic therapeutic improvement in the anti-tumour efficiency of the nanoparticle in vitro and vivo. The multifunctional nanoparticle efficiently prevents the osteoclasia progression of OS xenograft bone tumors in vivo. Finally, this study provides guidance and a point of reference for clinical approaches to treating OS.

The gut metabolite indole-3-propionic acid activates ERK1 to restore social function and hippocampal inhibitory synaptic transmission in a 16p11.2 microdeletion mouse model.

BACKGROUND: Microdeletion of the human chromosomal region 16p11.2 (16p11.2 + / - ) is a prevalent genetic factor associated with autism spectrum disorder (ASD) and other neurodevelopmental disorders. However its pathogenic mechanism remains unclear, and effective treatments for 16p11.2 + / -  syndrome are lacking. Emerging evidence suggests that the gut microbiota and its metabolites are inextricably linked to host behavior through the gut-brain axis and are therefore implicated in ASD development. Despite this, the functional roles of microbial metabolites in the context of 16p11.2 + / -  are yet to be elucidated. This study aims to investigate the therapeutic potential of indole-3-propionic acid (IPA), a gut microbiota metabolite, in addressing behavioral and neural deficits associated with 16p11.2 + / - , as well as the underlying molecular mechanisms. RESULTS: Mice with the 16p11.2 + / -  showed dysbiosis of the gut microbiota and a significant decrease in IPA levels in feces and blood circulation. Further, these mice exhibited significant social and cognitive memory impairments, along with hyperactivation of hippocampal dentate gyrus neurons and reduced inhibitory synaptic transmission in this region. However, oral administration of IPA effectively mitigated the histological and electrophysiological alterations, thereby ameliorating the social and cognitive deficits of the mice. Remarkably, IPA treatment significantly increased the phosphorylation level of ERK1, a protein encoded by the Mapk3 gene in the 16p11.2 region, without affecting the transcription and translation of the Mapk3 gene. CONCLUSIONS: Our study reveals that 16p11.2 + / -  leads to a decline in gut metabolite IPA levels; however, IPA supplementation notably reverses the behavioral and neural phenotypes of 16p11.2 + / -  mice. These findings provide new insights into the critical role of gut microbial metabolites in ASD pathogenesis and present a promising treatment strategy for social and cognitive memory deficit disorders, such as 16p11.2 microdeletion syndrome. Video Abstract.

A retrospective cohort study to observe the efficacy and safety of Endoscopic Submucosal Dissection (ESD) with adjuvant radiotherapy for T1a-MM/T1b-SM Esophageal Squamous Cell Carcinoma (ESCC).

BACKGROUND AND AIM: The clinical outcome of endoscopy submucosal dissection with subsequent radiotherapy for esophageal squamous cell carcinoma remain unclear. In this study we aim to investigate the efficacy and safety of endoscopic submucosal dissection with adjuvant radiotherapy in the treatment of superficial esophageal squamous cell carcinoma involving the muscularis mucosae (T1a-MM) or the submucosa < 200 µm (T1b-SM1). METHODS: We analyzed 20 patients with pathologically confirmed T1a-MM or T1b-SM1 esophageal squamous cell carcinoma treated by endoscopic submucosal dissection from 2016 to 2020 in Lihuili Hospital, 9 patients received adjuvant radiotherapy (RT group) and 11 patients received did not (non-RT group). RESULTS: All 20 patients underwent en bloc resection, and both the vertical and horizontal margins were negative. There was no recurrence or lymph node metastasis in the RT group, and no serious complications or death were observed. In the non-RT group, 2 patients had local recurrence and 1 had distant metastasis. None of the 20 patients died of esophageal carcinoma. CONCLUSIONS: Adjuvant radiotherapy following endoscopic submucosal dissection may be a safe and effective method for the treatment of T1a-MM/T1b-SM1 superficial esophageal squamous cell carcinoma.

Simplified Chinese version of the core outcome measures index (COMI) for patients with neck pain: cross-cultural adaptation and validation.

PURPOSE: The aim of this study was to translate and cross-culturally adapt the Core Outcome Measures Index for (COMI) into a Simplified Chinese version (COMI-SC) and to evaluate the reliability and validity of COMI-SC in patients with neck pain. METHODS: The COMI-neck was translated into Chinese according to established methods. The COMI-neck questionnaire was then completed by 122 patients with a hospital diagnosis of neck pain. Reliability was assessed by calculating Cronbach's alpha and intraclass correlation coefficient (ICC). Construct validity was assessed by correlating the COMI-neck with the Neck Pain and Disability Scale (NPDS), the Neck Disability Index (NDI), the VAS and the Short Form (36) Health Survey (SF-36). Using confirmatory factor analysis to validate the structural, convergent and discriminant validity of the questionnaire. RESULTS: The COMI-neck total scores were well distributed, with no floor or ceiling effects. Internal consistency was excellent (Cronbach's alpha = 0.861). Moderate to substantial correlations were found between COMI-neck and NPDS (r = 0.420/0.416/0.437, P < 0.001), NDI (r = 0.890, P < 0.001), VAS (r = 0.845, P < 0.001), as well as physical function (r = - 0.989, P < 0.001), physical role (r = - 0.597, P < 0.001), bodily pain (r = - 0. 639, P < 0.001), general health (r = - 0.563, P < 0.001), vitality (r = - 0.702, P < 0.001), social functioning (r = - 0.764, P < 0.001), role emotional (r = - 0.675, P < 0.001) and mental health (r = - 0.507, P < 0.001) subscales of the SF-36. An exploratory factor analysis revealed that the 3-factor loading explained 71.558% of the total variance [Kaiser-Mayer-Olkin (KMO) = 0.780, C2 = 502.82, P < 0.001]. CMIN/DF = 1.813, Tucker-Lewis index (TLI) = 0.966 (> 0.9), Comparative Fit Index (CFI) = 0.982 (> 0.9), Normed Fit Index (NFI) = 0.961 (> 0.9), RMSEA = 0.082 (< 0.5) indicating that the model fits well. CONCLUSION: COMI-neck was shown to have acceptable reliability and validity in patients with non-specific chronic neck pain and could be recommended for patients in mainland China. LEVEL OF EVIDENCE: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

mEnrich-seq: methylation-guided enrichment sequencing of bacterial taxa of interest from microbiome.

Metagenomics has enabled the comprehensive study of microbiomes. However, many applications would benefit from a method that sequences specific bacterial taxa of interest, but not most background taxa. We developed mEnrich-seq (in which 'm' stands for methylation and seq for sequencing) for enriching taxa of interest from metagenomic DNA before sequencing. The core idea is to exploit the self versus nonself differentiation by natural bacterial DNA methylation and rationally choose methylation-sensitive restriction enzymes, individually or in combination, to deplete host and background taxa while enriching targeted taxa. This idea is integrated with library preparation procedures and applied in several applications to enrich (up to 117-fold) pathogenic or beneficial bacteria from human urine and fecal samples, including species that are hard to culture or of low abundance. We assessed 4,601 bacterial strains with mapped methylomes so far and showed broad applicability of mEnrich-seq. mEnrich-seq provides microbiome researchers with a versatile and cost-effective approach for selective sequencing of diverse taxa of interest.

Physical activity changes and influencing factors among Chinese pregnant women: a longitudinal study.

OBJECTIVE: Participating in physical activity during pregnancy has benefited a lot from maternal and child health. However, there are few longitudinal studies describing activity patterns and related factors during pregnancy. The aim of this study is to investigate longitudinal physical activity changes and the influencing factors of Chinese pregnant women. METHODS: From January to August 2020, 240 pregnant women were recruited in Hangzhou, China. Physical activity during pregnancy was assessed in the first, second, and third trimesters of pregnancy by using the Pregnancy Physical Activity Questionnaire. RESULTS: The daily energy consumption during first, second, and third trimesters was 20.55, 20.76, 17.19 METs-h/d. The results of repeated-measure analysis of variance and pairwise comparison showed that the total daily energy consumption of physical activity in the third trimester was significantly lower than that in the first and second trimesters, with statistical significance (p < 0.001). The generalized estimation equation showed that education level, pre-pregnancy BMI, gravidity, unnaturally conceived and pre-pregnancy exercise habits were the influencing factors of physical activity during pregnancy (p < 0.05). CONCLUSION: Physical activity levels of pregnant women during different trimester were not optimistic. In order to improve physical activity during pregnancy and promote the health status of both mother and the developing baby, more attention should be paid on pregnant women with low education level, high BMI before pregnancy, primipara, unnaturally conceived and no good exercise habits before pregnancy.

Asymmetric adhesive SIS-based wound dressings for therapeutically targeting wound repair.

Severe tissue injuries pose a significant risk to human health. Conventional wound dressings fall short in achieving effective tissue regeneration, resulting in suboptimal postoperative healing outcomes. In this study, an asymmetric adhesive wound dressing (marked as SIS/PAA/LAP) was developed, originating from acrylate acid (AA) solution with laponite (LAP) nanoparticles polymerization and photo-crosslinked on the decellularized extracellular matrix small intestinal submucosa (SIS) patch. Extensive studies demonstrated that the SIS/PAA/LAP exhibited higher tissue adhesion strength (~ 33 kPa) and burst strength (~ 22 kPa) compared to conventional wound dressings like Tegaderm and tissue adhesive products. Importantly, it maintained favorable cell viability and demonstrated robust angiogenic capacity. In animal models of full-thickness skin injuries in rats and skin injuries in Bama miniature pigs, the SIS/PAA/LAP could be precisely applied to wound sites. By accelerating the formation of tissue vascularization, it displayed superior tissue repair outcomes. This asymmetrically adhesive SIS-based patch would hold promising applications in the field of wound dressings.

Predictive value of magnetic resonance imaging indications of spinal cord swelling for cervical spondylotic myelopathy prognosis.

BACKGROUND: Magnetic resonance imaging (MRI) is the preferred examination approach for patients with suspected cervical spondylotic myelopathy (CSM). OBJECTIVE: To investigate the predictive value of MRI spinal cord swelling on the prognosis of decompression surgery in patients with CSM. METHODS: A retrospective analysis of 115 patients with CSM who underwent decompression surgery was performed. According to whether cervical MRI showed spinal cord swelling, they were divided into a spinal cord swelling group and non-swelling group. The Modified Japanese Orthopaedic Association (MJOA) score, MJOA improvement rate and abnormal spinal cord enhancement rate in the two groups were compared before and after surgery. Multiple linear regression was used to analyse the influencing factors of the MJOA improvement rate. RESULTS: The time from symptom onset to operation (t= 2.400, p= 0.018) and preoperative MJOA score in the spinal cord swelling group were lower than those in the non-swelling group (t= 3.253, p= 0.002). The body mass index (t= 2.895, p= 0.005), anteroposterior diameter of the spinal canal (t= 4.421, p< 0.001), cross-sectional area (t= 3.136, p= 0.002), postoperative improvement rate (t= 4.277, p< 0.001) and proportion of abnormal enhancement of the spinal cord in the swelling group were higher than those in the non-swelling group (χ2= 3.136, p= 0.002). The preoperative MJOA score in the swelling group was lower than that in the non-swelling group (t= 2.583, p= 0.013). A multivariate linear regression model revealed that age and spinal cord swelling were independent predictors of MJOA score improvement, explaining 33.2% of the total variation. CONCLUSION: Patients with CSM with spinal cord swelling have less time from symptoms to surgery, and the degree of preoperative neurological deterioration is more obvious. Spinal cord swelling is an independent predictor of surgical prognosis in patients with CSM.

Machine learning-aided hydrothermal carbonization of biomass for coal-like hydrochar production: Parameters optimization and experimental verification.

Biomass to coal-like hydrochar via hydrothermal carbonization (HTC) is a promising route for sustainability development. Yet conventional experimental method is time-consuming and costly to optimize HTC conditions and characterize hydrochar. Herein, machine learning was employed to predict the fuel properties of hydrochar. Random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGB) models were developed, presenting acceptable prediction performance with R2 at 0.825---0.985 and root mean square error (RMSE) at 1.119---5.426, and XGB outperformed RF and SVM. The model interpretation indicated feedstock ash content, reaction temperature, and solid to liquid ratio were the three decisive factors. The optimized XGB multi-task model via feature re-examination illustrated improved generalization ability with R2 at 0.927 and RMSE at 3.279. Besides, the parameters optimization and experimental verification with wheat straw as feedstock further demonstrated the huge application potential of machine learning in hydrochar engineering.

A review of machine learning applications in life cycle assessment studies.

Life Cycle Assessment (LCA) is a foundational method for quantitative assessment of sustainability. Increasing data availability and rapid development of machine learning (ML) approaches offer new opportunities to advance LCA. Here, we review current progress and knowledge gaps in applying ML techniques to support LCA, and identify future research directions for LCAs to better harness the power of ML. This review analyzes forty studies reporting quantitative assessment with a combination of LCA and ML methods. We found that ML approaches have been used for generating life cycle inventories, computing characterization factors, estimating life cycle impacts, and supporting life cycle interpretation. Most of the reviewed studies employed a single ML method, with artificial neural networks (ANNs) as the most frequently applied approach. Both supervised and unsupervised ML techniques were used in LCA studies. For studies using supervised ML, training datasets were derived from diverse sources, such as literature, lab experiments, existing databases, and model simulations. Over 70 % of these reviewed studies trained ML models with less than 1500 sample datasets. Although these reviewed studies showed that ML approaches help improve prediction accuracy, pattern discovery and computational efficiency, multiple areas deserve further research. First, continuous data collection and compilation is needed to support more reliable ML and LCA modeling. Second, future studies should report sufficient details regarding the selection criteria for ML models and present model uncertainty analysis. Third, incorporating deep learning models into LCA holds promise to further improve life cycle inventory and impact assessment. Finally, the complexity of current environmental challenges calls for interdisciplinary collaborative research to achieve deep integration of ML into LCA to support sustainable development.

Modeling lateral carbon fluxes for agroecosystems in the Mid-Atlantic region: Control factors and importance for carbon budget.

Estimating lateral carbon fluxes in agroecosystems presents challenges due to intricate anthropogenic and biophysical interactions. We used a modeling technique to enhance our comprehension of the determinants influencing lateral carbon fluxes and their significance in agroecosystem carbon budgets. The SWAT-C model was refined by incorporating a dynamic dissolved inorganic carbon (DIC) module, enhancing our ability to accurately quantify total lateral carbon fluxes. This improved model was calibrated using observed data on riverine particulate organic carbon (POC) and dissolved organic carbon (DOC) fluxes, as well as net ecosystem exchange (NEE) data monitored by a flux tower situated in a representative agricultural watershed, the Tuckahoe Watershed (TW) of the Chesapeake Bay's coastal plain. We assessed the losses of POC, DOC, and DIC across five primary rotation types: C (continuous carbon), CS (corn-soybean), CSS (corn-soybean-soybean), CWS (corn-wheat-soybean), and CWSCS (corn-wheat-soybean-corn-soybean). Our study revealed notable variations in the average annual fluxes of POC (ranging between 152 and 198 kg ha-1), DOC (74-85 kg ha-1), and DIC (93-156 kg ha-1) across the five rotation types. The primary influencing factor for annual POC fluxes was identified as sediment yield. While both annual DOC and DIC fluxes displayed a marked correlation with surface runoff across all crop rotation schemes, soil respiration also significantly influenced annual DIC fluxes. Total lateral carbon fluxes (POC + DOC+DIC) constituted roughly 11 % of both net ecosystem production (NEP) and NEE, yet they represented a striking 95 % of net biome production (NBP) in the TW's agroecosystem. Grain yield carbon accounted for 80 % of both NEP and NEE and was nearly seven times that of NBP. Our findings suggest that introducing soybeans into cornfields tends to reduce NEP, NEE, and also NBP. Conversely, integrating winter wheat into the corn-soybean rotation significantly boosted NEP, NEE, and NBP values, with NBP even surpassing the levels in continuous corn cultivation.

Enhanced Polyacrylamide Degradation via OH Radical-Initiated Single-Electron Transfer.

Hydroxyl (OH) radicals, as common radicals in aqueous environments, play an important role in inducing the degradation reactions of polymers. However, understanding the fundamental mechanisms of radical-induced degradation of polymers at the atomic level remains a formidable challenge. In this study, we employ density functional theory to investigate the geometric and electronic structural properties of polyacrylamide (PAM) in (-CH2CHCONH2-)n (n = 2-6) complexes. Additionally, we explore the degradation mechanism of the n = 4 complex induced by the OH radical. The results indicate that there are three sites for the initial reaction (R1 and R2 are at the ends and R3 is in the middle). The OH radical removes a H atom from the PAM main chain and simultaneously triggers a single-electron-transfer process on the same chain. This process significantly reduces the dissociation energy barrier of the C-C bond in the PAM chain, from ∼90 to ∼20 kcal/mol. Specifically, when the induced reaction occurs at the end of the chain, a series of broken bonds will appear only along the main chain. While it happens in the middle, the broken bonds will exist simultaneously along both the main and side chains. Our results reveal the importance of OH radicals in polymer dissociation, particularly in PAM, and emphasize the degradation mechanism of SET.

Diagnostic accuracy of superb microvascular imaging for detecting intraplaque neovascularization: a systematic review and meta-analysis.

Background: Atherosclerotic plaques can cause carotid artery stenosis, and "vulnerable plaques" can even lead to ischemic stroke. The objective of this study was to assess the accuracy of superb microvascular imaging (SMI) for the detection of carotid intraplaque neovascularization (IPN) in patients with atherosclerotic plaques. Methods: We searched the Cochrane Library, Embase, Medline, and Wanfang databases until January 17, 2023. We included original studies with information on diagnostic accuracy of SMI for the evaluation of carotid IPN. The primary outcome was the accuracy of SMI for detecting carotid IPN. A meta-analysis was performed to estimate the accuracy of each parameter. We used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) to assess the risk of bias for each included article. Meta-regression was performed to determine items that may have contributed to heterogeneity in the sensitivity or specificity of the test. Results: This meta-analysis included 20 studies with 1,589 carotid plaques in 1,225 patients. The analysis showed a sensitivity and specificity of SMI for detecting IPN of 93% [95% confidence interval (CI): 87-96%] and 80% (95% CI: 71-87%), respectively. The risk of bias across the QUADAS-2 domains was low. Only the proportion of dyslipidemia influenced the estimates of sensitivity and specificity. Conclusions: This review suggests that SMI has a good diagnostic performance for detecting carotid IPN. The very high sensitivity with excellent post-test probability indicated that SMI can be recommended to screen for carotid IPN among patients with carotid plaques.

Periostin-targeted SDSSD peptide decorated calcium phosphate nanocomposites incorporation with simvastatin for osteoporosis treatment.

The limited options of anabolic drugs restrict their application potential in osteoporosis treatment, despite their theoretical superiority in therapeutic efficacy over antiresorptive drugs. As a prevailing strategy, nano-delivery systems could offer a wider choice of anabolic drugs. In this study, calcium phosphate nanocomposites incorporated with simvastatin (Sim) with periostin-targeting ability were designed and prepared for osteoporosis treatment. Carboxymethyl dextran (CMD) as an anionic and hydrophilic dextran derivative was used to stabilize CaP. In addition, periosteum-targeted peptide (SDSSD) was further grafted on CMD to achieve the bone targeting function. In a one-step coordination assembly strategy, hydrophobic anabolic agent Sim and SDSSD-CMD graft (SDSSD-CMD) were incorporated into the CaP nanoparticles forming SDSSD@CaP/Sim nanocomposites. The resulting SDSSD@CaP/Sim possesses uniform size, great short-term stability and excellent biocompatibility. Moreover, SDSSD@CaP/Sim exhibited a reduced release rate of Sim and showed slow-release behaviour. As anticipated, the nanocomposites exhibited bone bonding capacity in both cellular and animal studies. Besides, SDSSD@CaP/Sim achieved obviously enhanced osteoporosis treatment effect compared to direct injection of Simin vivo. Therefore, our findings highlight the potential of SDSSD-incorporated and CaP-based nanocomposites as a viable strategy to enhance the therapeutic efficacy of anabolic drugs for osteoporosis treatment.