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Abstract Background This study quantitatively analyzed the anatomic structure of the alveolar bone in the maxillary molar region at three potential locations for Temporary Anchorage Device (TAD) placement. Additionally, the study compared the variability in this region across different age groups, sagittal skeletal patterns, vertical facial types, and sexes. Methods In this retrospective cone-beam computed tomography study, the buccal alveolar bone was analyzed in the posterior molar area of 200 patients, the measurement items include buccal alveolar bone height, alveolar bone thickness, interradicular distance, and maxillary retromolar space. Results Buccal alveolar height was greatest in the U56 region. The interradicular space was largest in the U56 region and increased from the alveolar crest to the sinus floor. Buccal alveolar bone thickness was highest in the U67 region and generally increased from the alveolar crest to the sinus floor. The maxillary retromolar space gradually increased from the alveolar crest to the root apex. Conclusions TADs are safest when placed in the buccal area between the maxillary second premolar and the first molar, particularly at the 9 mm plane. The U67 region is the optimal safe zone for TAD placement for maxillary dentition distalization. TADs placement in adolescents can be challenging. Maxillary third molar extraction can be considered for maxillary dentition distalization.

Abstract Compared with teenage patients, adult patients generally show a slower rate of tooth movement and more pronounced alveolar bone loss during orthodontic treatment, indicating the maladaptation of alveolar bone homeostasis under orthodontic force. However, this phenomenon is not well-elucidated to date, leading to increased treatment difficulties and unsatisfactory treatment outcomes in adult orthodontics. Aiming to provide a comprehensive knowledge and further inspire insightful understanding towards this issue, this review summarizes the current evidence and underlying mechanisms. The age-related abatements in mechanosensing and mechanotransduction in adult cells and periodontal tissue may contribute to retarded and unbalanced bone metabolism, thus hindering alveolar bone reconstruction during orthodontic treatment. To this end, periodontal surgery, physical and chemical cues are being developed to reactivate or rejuvenate the aging periodontium and restore the dynamic equilibrium of orthodontic-mediated alveolar bone metabolism. We anticipate that this review will present a general overview of the role that aging plays in orthodontic alveolar bone metabolism and shed new light on the prospective ways out of the impasse.

Abstract Objective This study aims to elucidate the dose‒response relationship between 24-h activity behaviors and body fat percentage (BFP) in Chinese preschool children using a compositional isotemporal substitution model (ISM). Methods In a cross-sectional design, 881 children aged 3–6 from urban and rural areas of Jiangxi Province were sampled. Activity behaviors, including sedentary behavior (SB), low-intensity physical activity (LPA), and moderate- to high-intensity physical activity (MVPA), were measured using accelerometers. Sleep patterns were assessed through questionnaires, and BFP was determined by bioelectrical impedance analysis (BIA). The study employed compositional data analysis (CoDA) and ISM to estimate the impact of reallocating durations of different activity behaviors on BFP. Results Higher BFP was found in urban vs. rural children, decreasing with age. Overweight and obesity rates were 10.6% and 7.6%, respectively, above national averages. MVPA and LPA were negatively correlated with BFP, while SB was positively correlated. A 30-min MVPA reduction significantly increased zBFR, particularly in overweight children. Gender-specific nuances revealed that boys' MVPA negatively influenced zBFP (β = -0.155), P

The interaction between influenza A virus (IAV) and host proteins is an important process that greatly influences viral replication and pathogenicity. PB2 protein is a subunit of viral ribonucleoprotein (vRNP) complex playing distinct roles in viral transcription and replication. BAG6 (BCL2-associated athanogene 6) as a multifunctional host protein participates in physiological and pathological processes. Here, we identify BAG6 as a new restriction factor for IAV replication through targeting PB2. For both avian and human influenza viruses, overexpression of BAG6 reduced viral protein expression and virus titers, whereas deletion of BAG6 significantly enhanced virus replication. Moreover, BAG6-knockdown mice developed more severe clinical symptoms and higher viral loads upon IAV infection. Mechanistically, BAG6 restricted IAV transcription and replication by inhibiting the activity of viral RNA-dependent RNA polymerase (RdRp). The co-immunoprecipitation assays showed BAG6 specifically interacted with the N-terminus of PB2 and competed with PB1 for RdRp complex assembly. The ubiquitination assay indicated that BAG6 promoted PB2 ubiquitination at K189 residue and targeted PB2 for K48-linked ubiquitination degradation. The antiviral effect of BAG6 necessitated its N-terminal region containing a ubiquitin-like (UBL) domain (17-92aa) and a PB2-binding domain (124-186aa), which are synergistically responsible for viral polymerase subunit PB2 degradation and perturbing RdRp complex assembly. These findings unravel a novel antiviral mechanism via the interaction of viral PB2 and host protein BAG6 during avian or human influenza virus infection and highlight a potential application of BAG6 for antiviral drug development.

The proliferation of plug-in electric vehicles (PEVs) advocates a distributed paradigm for coordinating PEV charging. Unlike existing primal-dual decomposition or consensus methods, this paper proposes a cutting-plane-based distributed algorithm considering a peer-to-peer (P2P) communication network, which enables asynchronous coordination among PEVs. First, an equivalent surrogate model is established by exploiting the duality of the original optimization problem, which masks the private information of individual users by equivalent transformation. Then, a cutting-plane based algorithm is derived to solve the surrogate problem in a distributed manner with intrinsic superiority to cope with various asynchrony. Critical implementation issues, including distributed initialization, distributed cutting-plane generation, and localized stopping criteria, are discussed in detail. Numerical tests on IEEE 37- and 123-node feeders with actual data illustrate that the proposed method is resilient to several asynchronies and admits the plug-and-play operation mode. The proposed methodology is expected to provide an alternative path toward the robust protocol for PEV charging.

Abstract Background 1P36 deletion syndrome is recognized as the most common terminal microdeletion syndrome in humans, characterized by early developmental delay and consequent intellectual disability, seizure disorder, and distinctive facial features. Variable deletion locations may attributed to phenotypic variability. However, the abnormal phenotypes of hematology are rarely reported in 1P36 deletion syndrome patients. Case presentation We present a case of postnatal intellectual disability accompanied by pancytopenia. Copy number variation analysis revealed a pathogenic deletion in 1p36.331p36.32 with a deletion size of 2.21 Mb. Following successful treatment with glucocorticoids, the patient was diagnosed with immuno-related hemocytopenia (IRH). Discussion The patient experienced IRH, an uncommon characteristic of 1p36 deletion syndrome. The deletion fragment of 1p36.33-p36.32, particularly the loss of GNB1 gene, has been associated with the development of pancytopenia. Genotype-phenotype correlations are valuable in identifying the genes responsible for various clinical characteristics of the syndrome by associating phenotypic variation with specific genes located within the chromosome deletion region. Genome sequencing is recommended in cases where clinical manifestations indicate the presence of a genetic disorder but pose diagnostic challenges.

Advanced periodontitis poses a significant threat to oral health, causing extensive damage and loss of both hard and soft periodontal tissues. While traditional therapies such as scaling and root planing can effectively halt the disease’s progression, they often fail to fully restore the original architecture and function of periodontal tissues due to the limited capacity for spontaneous regeneration. To address this challenge, periodontal tissue engineering has emerged as a promising approach. This technology centers on the utilization of biomaterial scaffolds, which function as three-dimensional (3D) templates or frameworks, supporting and guiding the regeneration of periodontal tissues, including the periodontal ligament, cementum, alveolar bone, and gingival tissue. These scaffolds mimic the extracellular matrix (ECM) of native periodontal tissues, aiming to foster cell attachment, proliferation, differentiation, and, ultimately, the formation of new, functional periodontal structures. Despite the inherent challenges associated with preclinical testing, the intensification of research on biomaterial scaffolds, coupled with the continuous advancement of fabrication technology, leads us to anticipate a significant expansion in their application for periodontal tissue regeneration. This review comprehensively covers the recent advancements in biomaterial scaffolds engineered specifically for periodontal tissue regeneration, aiming to provide insights into the current state of the field and potential directions for future research.

Abstract Periodontitis is the sixth most prevalent chronic disease globally and places significant burdens on societies and economies worldwide. Behavioral modification, risk factor control, coupled with cause-related therapy have been the “gold standard” treatment for managing periodontitis. Given that host inflammatory and immunological responses play critical roles in the pathogenesis of periodontitis and impact treatment responses, several adjunctive strategies aimed at modulating host responses and improving the results of periodontal therapy and maintenance have been proposed. Of the many pharmacological host modulators, we focused on non-steroidal anti-inflammatory drugs (NSAIDs), due to their long history and extensive use in relieving inflammation and pain and reducing platelet aggregation. NSAIDs have been routinely indicated for treating rheumatic fever and osteoarthritis and utilized for the prevention of cardiovascular events. Although several efforts have been made to incorporate NSAIDs into the treatment of periodontitis, their effects on periodontal health remain poorly characterized, and concerns over the risk–benefit ratio were also raised. Moreover, there is emerging evidence highlighting the potential of NSAIDs, especially aspirin, for use in periodontal regeneration. This review summarizes and discusses the use of NSAIDs in various aspects of periodontal therapy and regeneration, demonstrating that the benefits of NSAIDs as adjuncts to conventional periodontal therapy remain controversial. More recent evidence suggests a promising role for NSAIDs in periodontal tissue engineering and regeneration.

Abstract Dental pulp stem cells (DPSCs), characterized by easy availability, multi‐lineage differentiation ability, and high proliferation ability, are ideal seed cells for cartilage tissue engineering. However, the epigenetic mechanism underlying chondrogenesis in DPSCs remains elusive. Herein, it is demonstrated that KDM3A and G9A, an antagonistic pair of histone‐modifying enzymes, bidirectionally regulate the chondrogenic differentiation of DPSCs by controlling SOX9 (sex‐determining region Y‐type high‐mobility group box protein 9) degradation through lysine methylation. Transcriptomics analysis reveals that KDM3A is significantly upregulated during the chondrogenic differentiation of DPSCs. In vitro and in vivo functional analyses further indicate that KDM3A promotes chondrogenesis in DPSCs by boosting the SOX9 protein level, while G9A hinders the chondrogenic differentiation of DPSCs by reducing the SOX9 protein level. Furthermore, mechanistic studies indicate that KDM3A attenuates the ubiquitination of SOX9 by demethylating lysine (K) 68 residue, which in turn enhances SOX9 stability. Reciprocally, G9A facilitates SOX9 degradation by methylating K68 residue to increase the ubiquitination of SOX9. Meanwhile, BIX‐01294 as a highly specific G9A inhibitor significantly induces the chondrogenic differentiation of DPSCs. These findings provide a theoretical basis to ameliorate the clinical use of DPSCs in cartilage tissue‐engineering therapies.

Tooth enamel, which is a biological tissue mainly composed of well-aligned hydroxyapatite nanocrystals and an interlaced protein matrix, has remarkable mechanical and aesthetic behaviors. Nevertheless, it is challenging to regenerate enamel naturally, and potential pulp involvement and tooth loss may occur. As the hardest biogenic composite material, enamel has long been regarded as a promising load-bearing material. Thus, understanding the enamel formation process and enamel structural motif mechanisms is important for the design and engineering of high-performance biomimetic composites with high strength and physical resilience. Extensive studies have been conducted on mimicking the microstructure and mechanical properties of tooth enamel, and various enamel-like material synthesis protocols have been developed. In light of the engineering fabrication of enamel-like materials, this review focuses on recent progress in synthetic strategies for enamel-mimetic materials and provides a discussion of the potential applications of these materials.

Hydrogels are extracellular-matrix-like biomimetic materials that have wide biomedical applications in tissue engineering and drug delivery. However, most hydrogels cannot simultaneously fulfill the mechanical and cell compatibility requirements. In the present study, we prepared a semi-interpenetrating network composite gel (CG) by incorporating short chain chitosan (CS) into a covalent tetra-armed poly(ethylene glycol) network. In addition to satisfying physicochemical, mechanics, biocompatibility, and cell affinity requirements, this CG easily encapsulated acetylsalicylic acid (ASA) via electrostatic interactions and chain entanglement, achieving sustained release for over 14 days and thus promoting periodontal ligament stem cell (PDLSC) proliferation and osteogenic differentiation. In vivo studies corroborated the capacity of PDLSCs and ASA-laden CG to enhance new bone regeneration in situ using a mouse calvarial bone defect model. This might be attributed to PDLSCs and host mesenchymal stem cells expressing monocyte chemoattractant protein-1, which upregulated M2 macrophage recruitment and polarization in situ, indicating its appealing potential in bone tissue engineering.

Abstract Background Previous studies have demonstrated the effect of socioeconomic status on the health status of the elderly. Nevertheless, the specific dimensions of the effect and the mechanism await further investigation. In this study, socioeconomic status was divided into three dimensions and we used social participation as the mediation variable to investigate the specific path of effect. Methods Using the 2018 Waves of Chinese Longitudinal Healthy Longevity Survey (CLHLS) dataset, a total of 10,197 effective samples of the elderly over 65 years old were screened out. Socioeconomic status included income, education level, and main occupation before retirement. The physical health and mental health of the elderly was measured by the Instrumental Activities of Daily Living Scale and the Minimum Mental State Examination, respectively. The social participation of the elderly was the mediation variable, including group exercise, organized social activities and interacting with friends. Omnibus mediation effect analysis was adopted to examine the mediation effect and mediation analysis was completed using the SPSS PROCESS program. Results First, the results showed that when the income gap between the elderly reached a certain level, there was a significant difference in health status. Significant differences existed in health status amongst with different education levels. There was no sufficient evidence to show that occupation has a significant effect on the physical health. But when the dependent variable was mental health, the effect was significant. Second, group exercise mediated 64.11% (aib = 0.24, 95% CI [0.17,0.3]) and up to 20.44% (aib = 0.12, 95% CI [0.07,0.17]) of the disparity in physical and mental health due to income gap, respectively. And it could mediate the effect up to 56.30% (aib = 0.62, 95% CI [0.52,0.73]) and 17.87% (aib = 0.50, 95% CI [0.4,0.61]) of education on physical and mental health status, respectively. The proportion of relative mediation effect of occupation was up to 28.74% (aib = 0.19, 95% CI [0.13,0.25]) on mental health. Interacting with friends mediated only on the path that the education affected the health status of the elderly. The proportion was up to 33.72% (aib = 0.29, 95% CI [0.16,0.44]). The relative mediation effect of organized social activities on the health gap caused by income or education level gap was significant at some levels. The proportion was up to 21.20% (aib = 0.33, 95% CI [0.26,0.4]). Conclusion The SES of the elderly including relatively large income gap, different education levels and occupational categories could indeed have a significant effect on health status of the elderly, and the reason why this effect existed could be partly explained by the mediation effect of social participation. Policymakers should pay more attention to the social participation of the elderly.

Water and power systems are two national critical infrastructures which support our daily life and economic growth. Both are highly interconnected and complex networks, which consist of various system elements. The core functions of water and power distribution systems are to deliver satisfactory water and electric services to consumers by satisfying the demands at all load points. Besides the factors in the water distribution system itself, power supply may affect the performance of the water distribution system. Therefore, the two systems are in fact physically connected and coupled. The purpose of this study is to develop an appropriate model and an efficient evaluation algorithm to quantify the reliability of the water distribution and power supply system as an integrated Water-Energy Nexus (WEN). This paper proposes a probabilistic reliability evaluation method for the micro-WEN model based on the sequential Monte Carlo Simulation (MCS) procedure. In the proposed evaluation procedure, both mechanical failures and hydraulic analysis are taken into consideration. Case studies are performed based on a representative water-energy nexus system to demonstrate the effectiveness of the proposed method.

A public health crisis in the form of a significant incidence of fatal pulmonary disease caused by repeated use of humidifier disinfectants containing polyhexamethylene guanidine phosphate (PHMG) recently arose in Korea. Although the mechanisms of pulmonary fibrosis following respiratory exposure to PHMG are well described, distant-organ effect has not been reported. In this study, we investigated whether intratracheal administration of PHMG affects liver pathophysiology and metabolism. Our PHMG mouse model showed a significant decrease in liver cholesterol level. An mRNA-seq analysis of liver samples revealed an alteration in the gene expression associated with cholesterol biosynthesis and metabolism to bile acids. The expression of genes involved in cholesterol synthesis was decreased in a real-time PCR analysis. To our surprise, we found that the coordinate regulation of cholesterol and bile acid homeostasis was completely disrupted. Despite the decreased cholesterol synthesis and low bile acid levels, the farnesoid X receptor/small heterodimer partner pathway, which controls negative feedback of bile acid synthesis, was activated in PHMG mice. As a consequence, gene expression of Cyp7a1 and Cyp7b1, the rate-limiting enzymes of the classical and alternative pathways of bile acid synthesis, was significantly downregulated. Notably, the changes in gene expression were corroborated by the hepatic concentrations of the bile acids. These results suggest that respiratory exposure to PHMG could cause cholestatic liver injury by disrupting the physiological regulation of hepatic cholesterol and bile acid homeostasis.

Spin relaxation induced by the interfacial effects in GaN/Al0.25Ga0.75N heterostructures was carefully investigated using a photon-energy-dependent time-resolved Kerr rotation spectrum. The existence of the interfacial localized states with potential fluctuations at the GaN/AlGaN heterointerface leads to photoluminescence peaks showing blue and S-shaped shifts owing to the excitation power and temperature, respectively. Photoexcited electrons in the localized states show a spin relaxation time longer than 1 ns because of the suppression of the D'yakonov–Perel’ (DP) scattering, while the spin relaxation time of free electrons was approximately only 10 ps because of the giant Rashba spin-orbit coupling induced by the interfacial polarization field under the framework of the DP scattering mechanism. Furthermore, it is found that the high electron mobility at the heterointerface results in a long spin diffusion length of 300 nm at high temperatures, which is promising for the development of GaN-based spintronic devices.

BackgroundChina advocates a health insurance system with social health insurance (SHI) as the main body and private health insurance (PHI) as the supplement. The study of PHI's complementary role in health is conducive to providing evidence for PHI's policy expansion and encouraging the public to participate in PHI, which is insufficient in China.MethodsWe used the three-wave balanced panel data of the China Health and Retirement Longitudinal Survey (CHARLS). Taking the ownership of supplementary PHI as the independent variable and EQ-5D index scores as the dependent variable, the panel instrumental variable (IV) method was used to analyze the impact of participation in PHI on health. We also assessed the heterogeneity of the health effects of PHI between chronic and non-chronic disease groups and between low- and high-income groups.ResultsThe coverage rate of PHI at baseline was 10.53%. The regression results showed that participating in PHI on the basis of SHI could result in an additional 8.21% health gain (p < 0.001). At the same time, PHI had greater health gain for chronic disease population than for healthy population (9.25 vs. 6.24%, p < 0.001), and greater health gain for high-income population than for low-income population (8.32 vs. 5.31%, p < 0.001).ConclusionParticipating in supplementary PHI can effectively enhance the health status of the insured, and has a more significant effect on patients with chronic diseases. The development of PHI should be further supported, while the health inequality in different income groups should be paid attention to.

Dipeptidase 2 (DPEP2) is a dipeptidyl peptidase that plays an important role in the hydrolysis of leukotriene D4 (LTD4) to leukotriene E4 (LTE4). Previous studies have suggested that LTD4 promotes tumor progression and survival in non-small cell lung cancer (NSCLC). Therefore, we hypothesized that DPEP2 may play a pivotal role in this tumor. Given that lung adenocarcinoma (LUAD) is the most common subtype of NSCLC, our study aimed to examine the expression and function of DPEP2 in LUAD. Based on bioinformatics and the analysis of clinical samples, our findings revealed that DPEP2 is highly expressed in normal lung tissues, but downregulated in LUAD tissues, and its expression levels were significantly associated with clinical indicators of tumor grade and prognosis. Pathway enrichment analysis showed that DPEP2 is involved in biological processes such as chemokine signaling pathways, leukocyte trans-endothelial migration, and humoral immune responses in LUAD. In addition, DPEP2 expression was significantly associated with various immune cells, especially monocytes–macrophages. Single-cell transcriptome data further confirmed the expression of DPEP2 dominantly in macrophages from normal lung tissues. Analysis of the TCIA database revealed that high DPEP2 expression is associated with a stronger response to immune checkpoint inhibitors such as CTLA4 and PD1, and determines sensitivity to LUAD therapeutic agents. Furthermore, we found that DPEP2 inhibits the migration and invasion of LUAD cells. Therefore, DPEP2 may serve as a potential immune biomarker and therapeutic target for LUAD, providing novel therapeutic approaches for this disease.

Abstract Backgroud To analyze the morphological changes of the anterior alveolar bone after the retraction of incisors in premolar extraction cases and the relationship between incisor retraction and remodeling of the alveolar base represented by points A and B displacements. Methods Pre- (T0) and post-treatment (T1) lateral cephalograms of 308 subjects in the maxilla and 154 subjects in the mandible who underwent the orthodontic treatment with extraction of 2 premolars in upper or lower arches were included. Alveolar bone width and height in both the maxillary and mandible incisor area were measured at T0 and T1 respectively. By superimposing the T0 and T1 cephalometric tracings, changes of points A and B, and the movement of the incisors were also measured. Then the correlation between incisor movement and the displacements of points A and B was analyzed. Results The alveolar bone width (ABW) showed a significant decrease in both maxilla and mandible (P 0.05). The alveolar bone height (ABH) showed a significant increase in the labial side of maxilla and a significant decrease in the lingual side of maxilla and mandible. A strong positive correlation was verified between incisor movement and position changes of points A and B in both horizontal and vertical directions. Conclusions Anterior alveolar bone width and height generally decreased after orthodontic treatment. Incisor retraction led to significant position changes of points A and B. The decrease of anterior alveolar bone due to significant incisor retraction should be taken into account in treatment planning.

Alzheimer’s disease (AD) is a leading cause of dementia in the elderly, with no effective treatment currently available. Transcranial direct current stimulation (tDCS), a non-drug and non-invasive therapy, has been testified efficient in cognitive enhancement. This study aims to examine the effects of tDCS on brain function in a mouse model of AD. The amyloid precursor protein (APP) and presenilin 1 (PS1) transgenic mice (7–8 months old) were subjected to 20-min anodal and cathodal tDCS (atDCS and ctDCS; 300 μA, 3.12 mA/cm2) for continuous five days. tDCS was applied on the left frontal skull of the animals, targeting on their prefrontal cortex (PFC). Behavioral performances were assessed by open-field, Y-maze, Barnes maze and T-maze paradigms; and their PFC electroencephalogram (EEG) activities were recorded under spontaneous state and during Y-maze performance. Behaviorally, atDCS and ctDCS improved spatial learning and/or memory in AD mice without affecting their general locomotion and anxiety-like behaviors, but the effects depended on the testing paradigms. Interestingly, the memory improvements were accompanied by decreased PFC EEG delta (2–4 Hz) and increased EEG gamma (20–100 Hz) activities when the animals needed memory retrieval during task performance. The decreased EEG delta activities could also be observed in animals under spontaneous state. Specifically, atDCS increased PFC EEG activity in the alpha band (8–12 Hz) for spontaneous state, whereas ctDCS increased that in alpha-beta band (8–20 Hz) for task-related state. In addition, some EEG changes after ctDCS could be found in other cortical regions except PFC. These data indicate that tDCS can reverse the situation of slower brain activity in AD mice, which may further lead to cognitive improvement. Our work highlights the potential clinical use of tDCS to restore neural network activity and improve cognition in AD.

With the rapid development of the three-dimensional (3D) printing technology in recent decades, precise and personalized manufacturing has been achieved gradually, bringing benefit to biomedical application, especially stomatology clinical practice. So far, 3D printing has been widely applied to prosthodontics, orthodontics, and maxillofacial surgery procedures, realizing accurate, efficient operation processes and promising treatment outcomes. Although the printing accuracy has improved, further exploration is still needed. Herein, we summarized the various additive manufacturing techniques and their applications in dentistry while highlighting the importance of accuracy (precision and trueness).

Most oral diseases originate from biofilms whose formation is originated from the adhesion of salivary proteins and pioneer bacteria. Therefore, antimicrobial materials are mainly based on bactericidal methods, most of which have drug resistance and toxicity. Natural antifouling surfaces inspire new antibacterial strategies. The super wettable surfaces of lotus leaves and fish scales prompt design of biomimetic oral materials covered or mixed with super wettable materials to prevent adhesion. Bioinspired slippery surfaces come from pitcher plants, whose porous surfaces are infiltrated with lubricating liquid to form superhydrophobic surfaces to reduce the contact with liquids. It is believed that these new methods could provide promising directions for oral antimicrobial practice, improving antimicrobial efficacy.

Background: Fetal arrhythmias are common cardiac abnormalities associated with high mortality due to ventricular dysfunction and heart failure, particularly when accompanied by hydrops. Although several types of common fetal tachycardias have been relatively identified medications, such as digoxin, flecainide, and sotalol, there is no first-line drug treatment protocol established for the treatment of various types of fetal tachycardias.Methods: We conducted a network meta-analysis using a Bayesian hierarchical framework to obtain a model for integrating both direct and indirect evidence. All tachycardia types (Total group), supraventricular tachycardia (SVT subgroup), atrial flutter (AF subgroup), hydrops subgroup, and non-hydrops subgroup fetuses were analyzed, and five first-line regimens were ranked according to treatment outcomes: digoxin monotherapy (D), flecainide monotherapy (F), sotalol monotherapy (S), digoxin plus flecainide combination therapy (DF), and digoxin plus sotalol combination therapy (DS). Effectiveness and safety were determined according to the cardioversion rate and intrauterine death rate.Results: The pooled data indicated that DF combination therapy was always superior to D monotherapy, regardless of the tachycardia type or the presence of hydrops: Total, 2.44 (95% CrI: 1.59, 3.52); SVT, 2.77 (95% CrI: 1.59, 4.07); AF, 67.85 (95% CrI: 14.25, 168.68); hydrops, 6.03 (95% CrI: 2.54, 10.68); and non-hydrops, 5.06 (95% CrI: 1.87, 9.88). DF and F had a similar effect on control of fetal tachycardias. No significant differences were observed when comparing S, DS with D therapies across the subgroup analyses for the SVT, hydrops, and non-hydrops groups. No significant differences in mortality risks were among the various treatment regimens for the total group. And no significant differences were found in rates of intrauterine death rates at the same cardioversion amount.Conclusion The flecainide monotherapy and combination of digoxin and flecainide should be considered the most superior therapeutic strategies for fetal tachycardia.Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=288997), identifier (288997).

Grid-side electrochemical battery energy storage systems (BESS) have been increasingly deployed as a fast and flexible solution to promoting renewable energy resources penetration. However, high investment cost and revenue risk greatly restrict its grid-scale applications. As one of the key factors that affect investment cost, the cycle life of battery heavily depends on its charging/discharging actions during the operation, particularly in the presence of uncertain renewable generation. In this context, it is necessary to consider the operation-dependent cycle life of batteries in optimal BESS sizing, which imposes great challenges to the modeling and solving of the planning problems. In this paper, we propose a novel two-level optimal sizing model for grid-scale BESS, considering its operation under uncertainties induced by volatile wind generation. In the lower level, a long-term chronological operation simulation of BESS is processed with an accurate cycle life model of batteries; in the upper level, marginal economic utility analysis and BESS size reforming are conducted to approach the optimal size of BESS. An iterative algorithm is designed to solve the model effectively. The proposed method is verified on a modified IEEE RTS-24 system and a real provincial power grid of China.

Aiming at shortage of metal materials, ceramic is increasingly applied in biomedicine due to its high strength, pleasing esthetics and good biocompatibility, especially for dental restorations and implants, artificial joints, as well as synthetic bone substitutes. However, the inherent brittleness of ceramic could lead to serious complications, such as fracture and disfunction of biomedical devices, which impede their clinical applications. Herein, several toughening strategies have been summarized in this review, including reinforcing phase addition, surface modification, and manufacturing processes improvement. Doping metal and/or non-metal reinforcing fillers modifies toughness of bulk ceramic, while surface modifications, mainly coating, chemical and thermal methods, regulate toughness on the surface layer. During fabrication, optimization should be practiced in powder preparation, green forming and densification processes. Various toughening strategies utilize mechanisms involving fine-grained, stress-induced phase transformation, and microcrack toughening, as well as crack deflection, bifurcation, bridging and pull-out. This review hopes to shed light on systematic combination of different toughening strategies and mechanisms to drive progress in biomedical devices.

Cleft lip and/or palate (CL/P) is a most common craniofacial birth defect which has multifactorial etiology. In our study, we aimed to discover the underlying etiological gene variation in a Chinese family diagnosed as non-syndromic CL/P (NSCL/P). The blood sample of the proband and her parents were detected by whole exome sequencing. The Mendelian inheritance pattern, allele frequency, variation location, function analysis and literature search were applied to filtrate and screen the mutation. Besides, the candidates were confirmed by Sanger sequencing. We meanwhile explored the conservative analysis and protein homology simulation. As a result, a start-lost mutation c.1A > GAtg/Gtg in the Frizzled-6 (FZD6) gene predicting p.Met1 was detected. The variation has not been reported before and was predicted to be harmful. The alteration caused missing of two starting amino acids that are evolutionarily conserved for FZD6 protein. Moreover, the specific structure of the mutant protein obviously changed according to the results of the homologous model. In conclusion, the results suggest c.1A > GAtg/Gtg in the FZD6 (NM_001164616) might be the genetic etiology for non-syndromic CL/P in this pedigree. Furthermore, this finding provided new etiologic information, supplementing the evidence that FZD6 is a strong potential gene for CL/P.

State-of-the-art autonomous micro-robotic turtles suffer from various limitations, such as power restrictions that minimize their deployment times. In this paper, an Ionic Polymer Metal Composite (IPMC) actuator-based centimeter-level biomimetic underwater robot was designed and developed as a robotic turtle with self-charging capabilities to overcome such limitations. It could move forward and make turns driven by five IPMCs on the water. The underwater charging station was able to transmit wideband ultrasonic and electromagnetic fields for electromagnetic induction charging. An ultrasonic communication system with one ultrasonic transmitter and two ultrasonic receivers was first fabricated to implement communication between the underwater station and the biomimetic underwater robot for autonomous tracking and rechargeable capabilities. Experiments were carried out to confirm the operation of the biomimetic underwater robot, which verified the centimeter-level rechargeable capabilities and autonomous target tracking features. The micro-robot demonstrated a self-tracking radial displacement error of approximately 6 mm and a charging reliability rate of more than 73%.

Periodontitis is a dysbiotic biofilm-induced and host-mediated inflammatory disease of tooth supporting tissues that leads to progressive destruction of periodontal ligament and alveolar bone, thereby resulting in gingival recession, deep periodontal pockets, tooth mobility and exfoliation, and aesthetically and functionally compromised dentition. Due to the improved biopharmaceutical and pharmacokinetic properties and targeted and controlled drug release, nano-based drug delivery systems have emerged as a promising strategy for the treatment of periodontal defects, allowing for increased efficacy and safety in controlling local inflammation, establishing a regenerative microenvironment, and regaining bone and attachments. This review provides an overview of nano-based drug delivery systems and illustrates their practical applications, future prospects, and limitations in the field of periodontal tissue regeneration.

This paper proposes a new method of realizing multimode OAM beams with almost the same divergence angles. The theoretical relationship between the divergence angle of the OAM beam and its radiation source is presented, and the radiation source distributions for various mode OAM beams with the same divergence angle range are discussed. In order to verify this method, an eight-mode OAM antenna constructed by a bifocal parabolic reflector and dual OAM feeds is designed and simulated. The simulation results show that the divergence angle ranges of 3 dB beamwidth for OAM modes l=±1,±2,±3,±4 are 2.2°,4.6°,2.2°,5.0°,2.4°,4.4°, and 2.6°,4.8°, the divergence angles corresponding to the maximum beam directions are 3.5°,3.6°,3.5°, and 3.8°, respectively, and the maximum difference is within 0.3°.

Abstract III‐nitride wide bandgap semiconductors are favorable materials for developing room temperature spintronic devices. The effective manipulation of spin dynamics is a critical request to realize spin field‐effect transistor (FET). In this work, the dependence of the spin relaxation time on external strain‐induced polarization electric field is investigated in InGaN/GaN multiple quantum wells (MQWs) by time‐resolved Kerr rotation spectroscopy. Owing to the almost canceled two different spin–orbit coupling (SOC), the spin relaxation time as long as 311 ps in the MQWs is obtained at room temperature, being much longer than that in bulk GaN. Furthermore, upon applying an external uniaxial strain, the spin relaxation time decreases sensitively, which originates from the breaking of the SU(2) symmetry. The extracted ratio of the SOC coefficients shows a linear dependence on the external strain, confirming the essential role of the polarization electric field. This effective manipulation of the spin relaxation time sheds light on GaN‐based nonballistic spin FET working at room temperature.

Bone defects caused by injury, disease, or congenital deformity remain a major health concern, and efficiently regenerating bone is a prominent clinical demand worldwide. However, bone regeneration is an intricate process that requires concerted participation of both cells and bioactive factors. Mimicking physiological bone healing procedures, the sustained release of bioactive molecules plays a vital role in creating an optimal osteogenic microenvironment and achieving promising bone repair outcomes. The utilization of biomaterial scaffolds can positively affect the osteogenesis process by integrating cells with bioactive factors in a proper way. A high water content, tunable physio-mechanical properties, and diverse synthetic strategies make hydrogels ideal cell carriers and controlled drug release reservoirs. Herein, we reviewed the current advancements in hydrogel-based drug sustained release systems that have delivered osteogenesis-inducing peptides, nucleic acids, and other bioactive molecules in bone tissue engineering (BTE).

RNA interference (RNAi) is an efficient post-transcriptional gene modulation strategy mediated by small interfering RNAs (siRNAs) and microRNAs (miRNAs). Since its discovery, RNAi has been utilized extensively to diagnose and treat diseases at both the cellular and molecular levels. However, the application of RNAi therapies in bone regeneration has not progressed to clinical trials. One of the major challenges for RNAi therapies is the lack of efficient and safe delivery vehicles that can actualize sustained release of RNA molecules at the target bone defect site and in surrounding cells. One promising approach to achieve these requirements is encapsulating RNAi molecules into hydrogels for delivery, which enables the nucleic acids to be delivered as RNA conjugates or within nanoparticles. Herein, we reviewed recent investigations into RNAi therapies for bone regeneration where RNA delivery was performed by hydrogels.

The intersection collision warning system (ICWS) is an emerging technology designed to assist drivers in avoiding collisions at intersections. ICWS has an excellent performance in reducing the number of collisions and improving driving safety. Previous studies demonstrated that when visibility was low under fog conditions, ICWS could help drivers timely detect hazardous conflicting vehicles. However, the influences of ICWS on interactive driving behavior at unsignalized intersection between different vehicles have barely been discussed. This study aimed to investigate the patterns of drivers’ interactive behaviors with the assistance of a new kind of ICWS under fog conditions based on Multiuser Driving Simulation. The Multiuser Driving Simulation allowed multiple drivers to operate in the same simulation scenario at the same time, and it could capture drivers’ interactions preferably. Forty-eight licensed drivers completed the driving simulation experiment in three fog conditions (no fog, light fog, and heavy fog) and two warning conditions (warning and no warning), in which the drivers drove in a straight-moving situation at unsignalized intersection with potential collision risks caused by the encounter of two vehicles. The results verified that warning and fog conditions were significant factors that affected the interactive driving behavior in the unsignalized intersection collision avoidance process, including the driver’s decision, TTC of action point, average acceleration (deceleration) rate, and postencroachment time. Compared to conditions without ICWS, the ICWS could help drivers make collision avoidance actions earlier and change the speed more smoothly. In addition, with the help of Multiuser Driving Simulation, associations between decision driving behaviors of vehicles were discussed with caution. The results revealed the decision-making mechanism of drivers in the process of interaction with other drivers. Under the influence of fog, interactive driving processes were fraught with increased risk at unsignalized intersection. However, the ICWS helped drivers interact more harmoniously, safely, and efficiently. The findings shed some light on the further development of ICWS and the study on interactive driving behavior.

The 1:1 and 2:1 cocrystals of isophthalic acid and 2,1,3-benzoselenadiazole have been successfully synthesized and resolved; the noncovalent interactions in the crystal structures have been studied in detail by quantum chemical calculations. In both of the crystal structures, isophthalic acid and 2,1,3-benzoselenadiazole are bound together by a cyclic supramolecular heterosynthon assembled by an O–H···N hydrogen bond and a N–Se···O chalcogen bond. The crystal structures of the 1:1 and 2:1 cocrystals of isophthalic acid and 2,1,3-benzoselenadiazole and the crystal structure of pure isophthalic acid are very similar, which indicates that the [COOH]···[Se−N] cyclic heterosynthon can be an effective alternative to the strong [COOH]2 cyclic homosynthon. The quantum theory of atoms in molecules further recognizes the existence of the hydrogen bond and chalcogen bond. The results of quantum chemical calculations show that the strengths of the π···π stacking interactions in the 1:1 cocrystals of isophthalic acid and 2,1,3-benzoselenadiazole are almost the same as those in the 2:1 cocrystals of isophthalic acid and 2,1,3-benzoselenadiazole, and the strengths of the [COOH]···[Se−N] cyclic heterosynthons (about 9.00 kcal/mol) are less than the strengths of the much stronger [COOH]2 cyclic homosynthons (14.00 kcal/mol). These calculated results are in good agreement with those experimentally observed, demonstrating that, although not as strong as the [COOH]2 cyclic homosynthon, the [COOH]···[Se−N] cyclic heterosynthon can also play a key role in the crystal growth and design.

Micro-motion parameters extraction is crucial in recognizing ballistic missiles with a wideband radar. It is known that the phase-derived range (PDR) method can provide a sub-wavelength level accuracy. However, it is sensitive and unstable when the signal-to-noise ratio (SNR) is low. In this paper, an improved PDR method is proposed to reduce the impacts of low SNRs. First, the high range resolution profile (HRRP) is divided into a series of segments so that each segment contains a single scattering point. Then, the peak values of each segment are viewed as non-stationary signals, which are further decomposed into a series of intrinsic mode functions (IMFs) with different energy, using the ensemble empirical mode decomposition with the complementary adaptive noise (EEMDCAN) method. In the EEMDCAN decomposition, positive and negative adaptive noise pairs are added to each IMF layer to effectively eliminate the mode-mixing phenomenon that exists in the original empirical mode decomposition (EMD) method. An energy threshold is designed to select proper IMFs to reconstruct the envelop for high estimation accuracy and low noise effects. Finally, the least-square algorithm is used to do the ambiguous phases unwrapping to obtain the micro-curve, which can be further used to estimate the micro-motion parameters of the warhead. Simulation results show that the proposed method performs well with SNR at −5 dB with an accuracy level of sub-wavelength.

Bone defects, massive bone defects in particular, is still an issue clinically. Acetylsalicylic acid (ASA), also known as aspirin, has been proven to be conducive for mesenchymal stem cells osteogenic differentiation, which may be benefited for bone regeneration. In order to achieve a more appealing prognosis of bone defect, here we develop a well-defined tetra-PEG hydrogel sealant with rapid gelation speed, strong tissue adhesion, and high mechanical strength. After in-situ encapsulation of aspirin, this drug-loaded tetra-PEG hydrogel possessed a sustained release, anti-inflammation, and osteoinductive properties. In vitro experiments showed that the cell proliferation was slightly facilitated, and the osteogenic differentiation was notably augmented when periodontal ligament stem cells (PDLSCs) were co-incubating with the hydrogel materials. Moreover, in vivo study manifested that the aspirin sustained release system significantly facilitated the PDLSCs mediated bone defect regeneration. Overall, tetra-PEG hydrogel-based aspirin sustained release system is applicable not only for enhancing the osteogenesis capacity of PDLSC but also providing a new thought of bone regenerative therapy.

Abstract Background Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect. Its etiology is complex and it has a lifelong influence on affected individuals. Despite many studies, the pathogenic gene alleles are not completely clear. Here, we recruited a Chinese NSCL/P family and explored the candidate causative variants in this pedigree. Methods We performed whole‐exome sequencing on two patients and two unaffected subjects of this family. Variants were screened based on bioinformatics analysis to identify the potential etiological alleles. Species conservation analysis, mutation function prediction, and homology protein modeling were also performed to preliminarily evaluate the influence of the mutations. Results We identified three rare mutations that are located on a single chromatid (c.2684C > T_p.Ala895Val, c.4350G > T_p.Gln1450His, and c.4622C > A_p.Ser1541Tyr) in GLI2 as candidate causative variants. All of these three mutations were predicted to be deleterious, and they affect amino acids that are conserved in many species. The mutation c.2684C > T was predicted to affect the structure of the GLI2 protein. Conclusion Our results further demonstrate that GLI2 variants play a role in the pathogenesis of NSCL/P, and the three rare missense mutations combined are probably the potential disease‐causing variants in this family.

Selective laser melting (SLM) produces complex physical behaviors. After laser melting, the molten pool condenses with an uneven surface, which influences the next powder spreading process and affects the quality of the final product. This phenomenon is mainly caused by the Marangoni effect, which is generated by the surface tension of the liquid. This paper describes a method to control the surface deformation during the SLM of AlSi10Mg powder. It is assumed that there is a magnetic field (MF) added to the alloy powder generating a Lorentz force in the molten pool (MP). The Lorentz force can decrease the impact of the Marangoni effect and change the velocity field. Our work simulates the AlSi10Mg alloy melting process, and analyzes the physical parameters of the MP with or without an MF. It is found that increasing the MF within a certain range decreases the impact of the Marangoni effect, resulting in a smoother surface.

Self-control is the ability to comply with a request, to postpone acting upon a desire object or goal, and to generate socially approved behavior in the absence of external monitors. Overeating is actually the failure in self-control while feeding. However, little is known about the brain function that allows individuals to consciously control their behavior in the context of food choice. To address this issue, we used functional MRI to measure brain activity among undergraduate young females. Forty-one undergraduate female students participated in the current study. Subjects underwent the food rating task, during which they rated each food item according to their subjective perception of its taste (from Dislike it very much to Like it very much), its long term effect on health (from very unhealthy to very healthy) and decision strength to eat it (from Strong no to Strong yes). Behavioral results indicate the positive correlation between taste rating and its corresponding decision strength to eat, no matter the food is high caloric or low. Moreover, health ratings of high caloric food was negatively correlated with DEBQ-emotional eating, and taste ratings of high caloric food was positively correlated with DEBQ-external eating. Whole brain analysis of fMRI data indicates that BOLD responses in dlPFC were positively correlated with successful self-control; BOLD responses in midcingulate cortex were positively correlated with failed self-control. This study provided direct evidence that dlPFC was involved in self-control in food-related choice.

Repairing tooth defects with dental resin composites is currently the most commonly used method due to their tooth-colored esthetics and photocuring properties. However, the higher than desirable failure rate and moderate service life are the biggest challenges the composites currently face. Secondary caries is one of the most common reasons leading to repair failure. Therefore, many attempts have been carried out on the development of a new generation of antimicrobial and therapeutic dental polymer composite materials to inhibit dental caries and prolong the lifespan of restorations. These new antimicrobial materials can inhibit the formation of biofilms, reduce acid production from bacteria and the occurrence of secondary caries. These results are encouraging and open the doors to future clinical studies on the therapeutic value of antimicrobial dental resin-based restoratives. However, antimicrobial resins still face challenges such as biocompatibility, drug resistance and uncontrolled release of antimicrobial agents. In the future, we should focus on the development of more efficient, durable and smart antimicrobial dental resins. This article focuses on the most recent 5 years of research, reviews the current antimicrobial strategies of composite resins, and introduces representative antimicrobial agents and their antimicrobial mechanisms.

Thermal stress is one of the main sources of micro-electro-mechanical systems (MEMS) devices error. The Wheatstone bridge is the sensing structure of a typical piezoresistive MEMS pressure sensor. In this study, the thermal stress induced by potting adhesive in MEMS pressure sensor was investigated by experiments, calculated by analytics and analyzed by simulations. An experiment system was used to test the sensor at different air pressures and temperatures. The error becomes greater with the decrease in pressure. A set of novel formulas were proposed to calculate the stress–strain on Wheatstone bridge. The error increases with the temperature deviating from 25 °C. A full-scale geometric model was developed, and finite element simulations were performed, to analyze the effect of the stress on MEMS pressure sensor induced by different temperatures and thicknesses of potting adhesive. Simulation results agree well with the experiments, which indicated that there is a 3.48% to 6.50% output error in 0.35 mm potting adhesive at 150 °C. With the thickness of potting adhesive increasing, the variations of output error of the Wheatstone bridge present an N-shaped curve. The output error meets a maximum of 5.30% in the potting adhesive of 0.95 mm and can be reduced to 2.47%, by increasing the potting adhesive to 2.40 mm.

The oral cavity harbors complex microbial communities, which leads to biomaterial-associated infections (BAI) during dental and orthopedic treatments. Conventional antibiotic treatments have met great challenges recently due to the increasing emergency of drug-resistant bacteria. To tackle this clinical issue, antibacterial surface treatments, containing surface modification and coatings, of dental and orthopedic materials have become an area of intensive interest now. Among various antibacterial agents used in surface treatments, metallic agents possess unique properties, mainly including broad-spectrum antibacterial properties, low potential to develop bacterial resistance, relative biocompatibility, and chemical stability. Therefore, this review mainly focuses on underlying antibacterial applications and the mechanisms of metallic agents in dentistry and orthopedics. An overview of the present review indicates that much work remains to be done to deepen the understanding of antibacterial mechanisms and potential side-effects of metallic agents.

Acoustic injection is one of the most dangerous ways of causing micro-electro−mechanical systems (MEMS) failures. In this paper, the failure mechanism of acoustic injection on the microprocessor unit 6050 (MPU6050) accelerometer is investigated by both experiment and simulation. A testing system was built to analyze the performance of the MPU6050 accelerometer under acoustic injection. A MEMS disassembly method was adopted and a MATLAB program was developed to establish the geometric model of MPU6050. Subsequently, a finite element model of MPU6050 was established. Then, the acoustic impacts on the sensor layer of MPU6050 were studied by acoustic−solid coupling simulations. The effects of sound frequencies, pressures and directions were analyzed. Simulation results are well agreed with the experiments which indicate that MPU6050 is most likely to fail under the sounds of 11,566 Hz. The failure mechanism of MPU6050 under acoustic injection is the relative shift of the capacitor flats caused by acoustic−solid resonance that make the sensor detect false signal and output error data. The stress is focused on the center linkage. MPU6050 can be reliable when the sound pressure is lower than 100 dB.