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Promoting the efficiency of bone regeneration in bone loss diseases is a significant clinical challenge. Traditional therapies often fail to achieve better therapeutic outcomes and shorter treatment times. However, in recent years, extracellular vesicles (EVs) have gained significant attention due to their exceptional osteogenic function in bone regeneration and superior therapeutic effects compared to traditional cell therapy. EVs have emerged as a promising therapy for tissue defect regeneration due to their various physiological functions, such as regulating the immune response and promoting tissue repair and regeneration. Moreover, EVs have good biocompatibility, low immunogenicity, and long-term stability, and can be improved through pretreatment and other methods. Studies investigating the mechanisms by which extracellular vesicles promote bone regeneration and applying EVs from different sources using various methods to animal models of bone defects have increased. Therefore, this paper reviews the types of EVs used for bone regeneration, their sources, roles, delivery pathways, scaffold biomaterials, and applications. [ABSTRACT FROM AUTHOR]

The ion-intercalation-based rechargeable batteries are emerging as the most efficient energy storage technology for electronic vehicles, grids, and portable devices. These devices require rechargeable batteries with higher energy–density than commercial Li-ion batteries, which are intrinsically limited by specific capacities and electrochemical potentials of transition-metal (M) electrode materials. Over the past decades, a significant number of studies have focused on exploring coordination environments and electronic origins of these materials based on ligand field theory (LFT). However, studies to understand and manipulate the relationship between their local-structural characteristics and electrochemical properties are limited. In this review, we comprehensively discussed how the combining of LFT and first-principles calculations can be used to derive Fermi levels that determine electrochemical potential, crystal field stabilization energy, and anionic redox activity. Based on this, a series of strategies are proposed to improve the phase-stability and energy–density of intercalation-type electrode materials, such as ion-intercalation potential tuning of rigid-band systems and electrode phase stability regulations with different M periods. Two high energy–density cathode materials, M -free LiBCF 2 and Li-free group-VB/VIB MX 2 (X = S, Se), are successfully designed from the aforementioned principles derived. Finally, we also highlight further directions for designing better intercalation-type materials based on LFT and their opportunities/challenges. [ABSTRACT FROM AUTHOR]

The dynamic lane assignment at signalized intersections is a possible countermeasure to address the traffic demand variability problem. However, the operational efficiency is affected by the unfamiliarity of the drivers. This paper evaluates the operational efficiency of the intersections with dynamic lane assignment using field data collected at five intersections in China. A total of 63488 vehicles were captured, which were divided into four groups according to the lanes they drive on: Group 1, the variable approach lane; group 2, the lane adjacent to the variable lane with the same lane-use; group 3, the lane adjacent to the variable lane with different lane-use of the variable lane; and group 4, the lanes with the same lane-use as the variable lane at other approaches of the intersection. The statistical analysis was conducted to identify the difference of saturation flow rate among the four groups. A saturation flow rate adjustment model was established accordingly. Results indicate that the using of the dynamic lane assignment decreases the saturation flow rate of the variable lane and the adjacent lane with different lane-use 22.86% and 9.80%, respectively. For the variable lane, the reduction of the saturation flow rate comes from three aspects: the unequal distribution of traffic (8.9%), the mandatory lane-changing (10.7%), and the lane blockage (4.9%). [ABSTRACT FROM AUTHOR]

A 14-year-old female Mongrel dog presented with multiple, cherry-sized, wellcircumscribed papillary masses on the right upper hard palate and gingival area. Histologically, the masses contained biphasic components composed of hyperplastic squamous epithelium forming papillary fronds, and underlying tortuous dilated ducts and cysts. Immunohistochemistry demonstrated that both squamous and ducts epithelium were pan-Cytokeratin (pCK) positive, but they were negative of Alpha smooth muscle (α-SMA), Vimentin and Protein 53 (P53). Duct epithelial cells were strong positive of Cytokeratin 8 & 18 (CK8&18), Ki-67, and weakly positive of S-100, whereas squamous component were strong positive of Cytokeratin 5&6 (CK5&6). Sialadenoma papilliferum (SP) was diagnosed based on clinical sign, gross and histopathological findings, and biochemistry. [ABSTRACT FROM AUTHOR]

Objectives. Conventional approaches for patients with nonerosive gastroesophageal reflux disease (NERD) were not satisfactory. This study aimed to evaluate the effectiveness and mechanisms of Chinese herbal medicine Hewei Jiangni Decoction (HWJND) as a novel and promising regimen for NERD. Methods. A total of 128 patients with NERD were randomly assigned to the Treatment group and Control group. The patients from the Treatment group were administered HWJND (81 g) plus dummy omeprazole (20 mg) daily for 8 weeks, and the others were given dummy HWJND granules (81 g) plus omeprazole (20 mg). The clinical efficacy was assessed using the gastroesophageal reflux disease questionnaire (GERD-Q) scale, patient reported outcomes (PRO) scale, and short form health survey 36 (SF-36) scale at week 4. Moreover, its pharmacological and molecular mechanisms were elucidated based on network pharmacology and molecular docking. Results. Due to case shedding and other reasons, 109 patients, including 56 in the Treatment group and 53 in the Control group completed this study. Our results showed that HWJND significantly improved heartburn, regurgitation, epigastric pain, nausea, and sleep disturbance, which led to a significant reduction of GERD-Q scores in NERD patients. In addition, PRO scores of NERD patients with HWJND administration were improved, and sufficient relief of physical role, body pain, general health, social function, and mental health on the SF-36 scale was also observed in patients after HWJND treatment. We further showed that the curative effect of HWJND was close to that of omeprazole, except for the better improvement of general health and social function. What's more, the main active ingredients of HWJND included quercetin, beta-sitosterol, naringenin, baicalein, and kaempferol were retrieved, and the protective effects of HWJND against NERD may be closely related to targets such as TNF, IL6, IL1B, MMP9, CXCL8, and EGFR, which were mainly enriched in IL-17 signaling pathway and TNF signaling pathway. Conclusion. Our findings demonstrate that HWJND is noninferior to oral omeprazole for the treatment of patients with NERD, plays a therapeutic role through multiple targets and diverse pathways, and holds promise for complementary and alternative therapy for the treatment of NERD. This trial is registered with http://www.chictr.org.cn, Chinese Clinical Trials Registry [ChiCTR2200055960]. [ABSTRACT FROM AUTHOR]

• This manuscript summarizes the role of macrophage immunometabolism in NASH, especially the function conversion. • The progress of regulatory factors of macrophage immunometabolism in NASH has been updated. Targeting macrophage immunometabolism become a potential strategy for treating NASH. Nonalcoholic steatohepatitis (NASH), an inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), is characterized by liver steatosis, inflammation, hepatocellular injury and different degrees of fibrosis, and has been becoming the leading cause of liver-related morbidity and mortality worldwide. Unfortunately, the pathogenesis of NASH has not been completely clarified, and there are no approved therapeutic drugs. Recent accumulated evidences have revealed the involvement of macrophage in the regulation of host liver steatosis, inflammation and fibrosis, and different phenotypes of macrophages have different metabolic characteristics. Therefore, targeted regulation of macrophage immunometabolism may contribute to the treatment and prognosis of NASH. In this review, we summarized the current evidences of the role of macrophage immunometabolism in NASH, especially focused on the related function conversion, as well as the strategies to promote its polarization balance in the liver, and hold promise for macrophage immunometabolism-targeted therapies in the treatment of NASH. [ABSTRACT FROM AUTHOR]

Monoclinic natrium superionic conductors (NASICON; Na3Zr2Si2PO12) are well‐known Na‐ion solid electrolytes which have been studied for 40 years. However, due to the low symmetry of the crystal structure, identifying the migration channels of monoclinic NASICON accurately still remains unsolved. Here, a cross‐verified study of Na+ diffusion pathways in monoclinic NASICON by integrating geometric analysis of channels and bottlenecks, bond‐valence energy landscapes analysis, and ab initio molecular dynamics simulations is presented. The diffusion limiting bottlenecks, the anisotropy of conductivity, and the time and temperature dependence of Na+ distribution over the channels are characterized and strategies for improving both bulk and total conductivity of monoclinic NASICON‐type solid electrolytes are proposed. This set of hierarchical ion‐transport algorithms not only shows the efficiency and practicality in revealing the ion transport behavior in monoclinic NASICON‐type materials but also provides guidelines for optimizing their conductive properties that can be readily extended to other solid electrolytes. [ABSTRACT FROM AUTHOR]

Clear aligners are removable orthodontic appliances that cover the tooth surface. The microbial composition and pH of the inner surface of aligners directly affect the enamel health. In this study, eight subjects who used the same type of clear aligners were instructed to brush their teeth normally and to not clean their aligners until sampling. Saliva and the contents of the inner surface of the aligners (liquid and plaque) were collected at 0 h (T0), 4 h (T4), 8 h (T8), 12 h (T12), and 24 h (T24) after usage, and pH values and microbial compositions were measured. The microbial composition was analyzed with 16S rRNA gene sequencing, and changes were assessed based on operational taxonomic unit abundance. The pH, alpha diversity values, and abundance of specific microbes on the inner surface of the aligners gradually decreased from T0 to T24 (P < 0.05). An insignificant increase in microbial community beta diversity was observed from T0 to T24. Principal component analysis revealed that the microbial composition at T0 was different from at T12 and T24. The relative abundances of phylum Firmicutes (P < 0.01), orders Lactobacillales and Bacteroidales (P < 0.05), and genus Streptococcus and species Streptococcus infantis increased significantly, while those of genera Actinomyces and Rothia and species Rothia aeria decreased significantly at T24 (P < 0.05). These findings reveal that uncleaned aligners might lead to enamel damage, especially after continuous usage for 12 h. Thus, clear aligners should be cleaned after 12 h of usage or at least within 24 h of usage. [ABSTRACT FROM AUTHOR]

Rhombohedral NaZr2(PO4)3 is the prototype of all the NASICON‐type materials. The ionic diffusion in these rhombohedral NASICON materials is highly influenced by the ionic migration channels and the bottlenecks in the channels which have been extensively studied. However, no consensus is reached as to which one is the preferential ionic migration channel. Moreover, the relationships between the Na+ distribution over the multiple available sites, concerted migration, and diffusion properties remain elusive. Using ab initio molecular dynamics simulations, here it is shown that the Na+ ions tend to migrate through the Na1–Na3–Na2–Na3–Na1 channels rather than through the Na2–Na3–Na3–Na2 channels. There are two types of concerted migration mechanisms: two Na+ ions located at the adjacent Na1 and Na2 sites can migrate either in the same direction or at an angle. Both mechanisms exhibit relatively low migration barriers owing to the potential energy conversion during the Na+ ions migration process. Redistribution of Na+ ions from the most stable Na1 sites to Na2 on increasing Na+ total content further facilitates the concerted migration and promotes the Na+ ion mobility. The work establishes a connection between the Na+ concentration in rhombohedral NASICON materials and their diffusion properties. [ABSTRACT FROM AUTHOR]

Background: Myocardial ischemia-reperfusion (MI/R) injury is a significant clinical problem without effective therapy. Unbiased omics approaches may reveal key MI/R mediators to initiate MI/R injury.Methods: We used a dynamic transcriptome analysis of mouse heart exposed to various MI/R periods to identify S100a8/a9 as an early mediator. Using loss/gain-of-function approaches to understand the role of S100a8/a9 in MI/R injury, we explored the mechanisms through transcriptome and functional experiment. Dynamic serum S100a8/a9 levels were measured in patients with acute myocardial infarction before and after percutaneous coronary intervention. Patients were prospectively followed for the occurrence of major adverse cardiovascular events.Results: S100a8/a9 was identified as the most significantly upregulated gene during the early reperfusion stage. Knockout of S100a9 markedly decreased cardiomyocyte death and improved heart function, whereas hematopoietic overexpression of S100a9 exacerbated MI/R injury. Transcriptome/functional studies revealed that S100a8/a9 caused mitochondrial respiratory dysfunction in cardiomyocytes. Mechanistically, S100a8/a9 downregulated NDUF gene expression with subsequent mitochondrial complex I inhibition via Toll-like receptor 4/Erk-mediated Pparg coactivator 1 alpha/nuclear respiratory factor 1 signaling suppression. Administration of S100a9 neutralizing antibody significantly reduced MI/R injury and improved cardiac function. Finally, we demonstrated that serum S100a8/a9 levels were significantly increased 1 day after percutaneous coronary intervention in patients with acute myocardial infarction, and elevated S100a8/a9 levels were associated with the incidence of major adverse cardiovascular events.Conclusions: Our study identified S100a8/a9 as a master regulator causing cardiomyocyte death in the early stage of MI/R injury via the suppression of mitochondrial function. Targeting S100a8/a9-intiated signaling may represent a novel therapeutic intervention against MI/R injury.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03752515. [ABSTRACT FROM AUTHOR]

In order to reduce the impacts of configuration change in complex product design, a dynamic optimization method for configuration change in complex product design is proposed. First, a network model for characteristic relationships of complex product (CPCR) is built to describe the configuration scheme of complex product, with characteristics as nodes and relationships between characteristics in the configuration scheme as edges. Then, the impacts of change to different types of characteristics on other characteristics are analyzed to reveal the impact process of configuration change in complex product design. Next, according as the effects of change on upstream and downstream characteristics can be optimized and cannot be optimized, the dynamic optimization method for configuration change in complex product design is put forth, which integrates dynamic optimization for upstream characteristic changes and dynamic search of downstream characteristic changes. Finally, a practical application of the proposed method and a comparison of the proposed method with existing ones are suggested to verify the validity and applicability. [ABSTRACT FROM AUTHOR]

The genetic control of plant architecture is a promising approach to breed desirable cultivars, particularly in ornamental flowers. In this study, the F1 population (142 seedlings) derived from Lagerstroemia fauriei (non-dwarf) × L. indica ‘Pocomoke’ (dwarf) was phenotyped for six traits (plant height (PH), internode length (IL), internode number, primary lateral branch height (PLBH), secondary lateral branch height and primary branch number), and the IL and PLBH traits were positively correlated with the PH trait and considered representative indexes of PH. Fifty non-dwarf and dwarf seedlings were pooled and subjected to a specific-locus amplified fragment sequencing (SLAF-seq) method, which screened 1221 polymorphic markers. A total of 3 markers segregating between bulks were validated in the F1 population, with the M16337 and M38412 markers highly correlated with the IL trait and the M25207 marker highly correlated with the PLBH trait. These markers provide a predictability of approximately 80% using a single marker (M25207) and a predictability of 90% using marker combinations (M16337 + M25207) in the F1 population, which revealed that the IL and the PLBH traits, especially the PLBH, were the decisive elements for PH in terms of molecular regulation. Further validation was performed in the BC1 population and a set of 28 Lagerstroemia stocks using allele-specific PCR (AS-PCR) technology, and the results showed the stability and reliability of the SNP markers and the co-determination of PH by multiple genes. Our findings provide an important theoretical and practical basis for the early prediction and indirect selection of PH using the IL and the PLBH, and the detected SNPs may be useful for marker-assisted selection (MAS) in crape myrtle. [ABSTRACT FROM AUTHOR]

In principle, thermoelectric materials with superior performance require high lattice symmetry and heavy components integrated in semiconductors. Cu 6 WSnSe 8 , isostructural to kiddcreekite Cu 6 WSnS 8 , possesses the characteristics for being a promising thermoelectric material, including narrow band-gap, high crystal symmetry, heavy constituent elements, and complex crystal structure. In this work, the thermoelectric transport properties of pristine and copper-deficient Cu 6 WSnSe 8 were investigated. The extremely low hole mobility restricts Cu 6 WSnSe 8 as an excellent thermoelectric parent despite the fact that Cu-deficiency can increase the electrical conductivity and boost the power factor of Cu 5.94 WSnSe 8 by four times than that of pristine Cu 6 WSnSe 8. Combined with density functional theory calculations and X-ray photoelectron spectra analysis, we conclude that the extremely low hole mobility derives from the charge localization around W cations. Due to charge transfer and redistribution, the high valence state W6+ seizes electrons from Se2−, and thus localizing carriers. [Display omitted] • Kiddcreekite-type Cu 6 WSnSe 8 has been synthesized by mild solid-state reaction method at 773 K. • Cu-deficiency can significantly increase the electrical conductivity and boost the power factor. • The presence of W blocks the hole transport and results in ultralow hole mobility. [ABSTRACT FROM AUTHOR]

High-throughput analysis of the ion transport pathways is critical for screening fast ion conductors. Currently, empirical methods, such as the geometric analysis and bond valence site energy (BVSE) methods, are respectively used for the task. Geometric analysis method can only extract geometric and topological pathway properties without considering the interatomic interactions, while the BVSE method alone does not yield a geometric classification of the sites and interstices forming the pathway. Herein, we propose a highly efficient and informative method to identify interstices and connecting segments constructing an ion transport network by combining topological pathway network and BVSE landscape, which enables to obtain both the geometry and energy profiles of nonequivalent ion transport pathways between adjacent lattice sites. These pathways can be further used as the input for first-principles nudged elastic band calculations with automatically generated chains of images. By performing high-throughput screening of 48,321 Li-, Na-, Mg- and Al-containing ionic compounds from the Inorganic Crystal Structure Database based on the filter combining geometric analysis and BVSE methods, we obtain 1,270 compounds with connected ionic migration pathways of suitable sizes and low migration energy barriers, which include both previously reported fast ion conductors, and new promising materials to be explored further. Image, graphical abstract [ABSTRACT FROM AUTHOR]