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Abstract Background Good wound healing is critical to infection prophylaxis and satisfactory rehabilitation in Total Knee Arthroplasty (TKA). Currently, two techniques, i.e., barbed continuous subcuticular suture without skin adhesive or combined use skin adhesive (n-butyl-2) are being used for superficial wound closure of TKA. While a new skin adhesive (2-octyl) with self-adhesive mesh has been employed as an alternative to conventional surgical skin closure in TKA, its superiority, especially in reducing wound complications and improving wound cosmetic outcomes has not been investigated. This study aimed to compare 2-octyl, n-butyl-2, and no skin adhesive in terms of safety and efficacy in TKA superficial wound closure. Methods We conducted a multicenter, prospective, randomized controlled study in 105 patients undergoing primary TKA between May 2022 and October 2023. Each patient’s knee was randomized to receive 2-octyl, n-butyl-2, or no skin adhesive skin closure with all using barbed continuous sutures in deep tissue. Wounds were followed 1, 3, 5 days, 2, 6 weeks, and 3 months after surgery. Wound discharge, complications, cosmetic outcomes, patient satisfaction, and wound-related costs were compared among these three methods. Results Wound discharge was less in 2-octyl group and n-butyl-2 group than in non-adhesive group at 1 day, with the discharge only being less in 2-octyl group than in the non-adhesive group at day 3 and day 5 days (P 0.05). The 2-octyl group achieved better cosmetic effects than the other two groups in 6 weeks and 3 months (P

A novel insertion device is introduced, designated as the Mango wiggler, designed for synchrotron radiation (SR) imaging that provides a large field of view. This innovative device is constructed from two orthogonal planar wigglers with a small difference in their period lengths, eliciting the phase difference of the magnetic fields to incrementally transitions from 0 to π/2. Such a configuration enlarges the vertical divergence of the light source, as with the horizontal divergence. The appellation `Mango wiggler' derives from the distinctive mango-shaped contour of its radiation field. A comprehensive suite of theoretical analyses and simulations has been executed to elucidate the radiation properties of the Mango wiggler, employing SPECTRA and Mathematica as calculation tools. In conjunction with the ongoing construction of the High Energy Photon Source in Beijing a practical Mango wiggler device has been fabricated for utilization in SR imaging applications. Theoretical analyses were applied to this particular Mango wiggler to yield several theoretical conclusions, and several simulations were performed according to the measured magnetic field results.

Laser-induced projectile impact testing (LIPIT) based on synchrotron imaging is proposed and validated. This emerging high-velocity, high-strain microscale dynamic loading technique offers a unique perspective on the strain and energy dissipation behavior of materials subjected to high-speed microscale single-particle impacts. When combined with synchrotron radiation imaging techniques, LIPIT allows for in situ observation of particle infiltration. Two validation experiments were carried out, demonstrating the potential of LIPIT in the roentgenoscopy of the dynamic properties of various materials. With a spatial resolution of 10 µm and a temporal resolution of 33.4 µs, the system was successfully realized at the Beijing Synchrotron Radiation Facility 3W1 beamline. This innovative approach opens up new avenues for studying the dynamic properties of materials in situ.

Abstract Malus sieversii, commonly known as wild apples, represents a Tertiary relict plant species and serves as the progenitor of globally cultivated apple varieties. Unfortunately, wild apple populations are facing significant degradation in localized areas due to a myriad of factors. To gain a comprehensive understanding of the nutrient status and spatiotemporal variations of M. sieversii, green leaves were collected in May and July, and the fallen leaves were collected in October. The concentrations of leaf nitrogen (N), phosphorus (P), and potassium (K) were measured, and the stoichiometric ratios as well as nutrient resorption efficiencies were calculated. The study also explored the relative contributions of soil, topographic, and biotic factors to the variation in nutrient traits. The results indicate that as the growing period progressed, the concentrations of N and P in the leaves significantly decreased (P P > N. The resorption efficiencies were mainly regulated by nutrient concentrations in fallen leaves. A robust spatial dependence was observed in leaf nutrient concentrations during all periods (70.1–97.9% for structural variation), highlighting that structural variation, rather than random factors, dominated the spatial variation. Nutrient resorption efficiencies (NRE, PRE, and KRE) displayed moderate structural variation (30.2–66.8%). The spatial patterns of nutrient traits varied across growth periods, indicating they are influenced by multifactorial elements (in which, soil property showed the highest influence). In conclusion, wild apples manifested differentiated spatiotemporal variability and influencing factors across various leaf nutrient traits. These results provide crucial insights into the spatiotemporal patterns and influencing factors of leaf nutrient traits of M. sieversii at the permanent plot scale for the first time. This work is of great significance for the ecosystem restoration and sustainable management of degrading wild fruit forests.

Abstract Background The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. Methods We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues from 120 HNSCC patients. A series of in vitro and in vivo experiments were performed to explore the impact of the feedback loop between PFKP and c-Myc on HNSCC progression. Additionally, we explored the therapeutic effects of targeting PFKP and c-Myc in HNSCC using Patient-Derived Organoids (PDO), Cell Line-Derived Xenografts, and Patients-Derived Xenografts. Results Our findings indicated that PFKP is frequently upregulated in HNSCC tissues and cell lines, correlating with poor prognosis. Our in vitro and in vivo experiments demonstrate that elevated PFKP facilitates cell proliferation, angiogenesis, and metastasis in HNSCC. Mechanistically, PFKP increases the ERK-mediated stability of c-Myc, thereby driving progression of HNSCC. Moreover, c-Myc stimulates PFKP expression at the transcriptional level, thus forming a positive feedback loop between PFKP and c-Myc. Additionally, our multiple models demonstrate that co-targeting PFKP and c-Myc triggers synergistic anti-tumor effects in HNSCC. Conclusion Our study demonstrates the critical role of the PFKP/c-Myc positive feedback loop in driving HNSCC progression and suggests that simultaneously targeting PFKP and c-Myc may be a novel and effective therapeutic strategy for HNSCC.

Abstract Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a family of broad substrate specificity serine (Ser)/threonine (Thr) protein kinases that play a crucial role in the Ca2+-dependent signaling pathways. Its significance as an intracellular Ca2+ sensor has garnered abundant research interest in the domain of neurodegeneration. Accumulating evidences suggest that CaMKII is implicated in the pathology of degenerative retinopathies such as diabetic retinopathy (DR), age-related macular degeneration (AMD), retinitis pigmentosa (RP) and glaucoma optic neuropathy. CaMKII can induce the aberrant proliferation of retinal blood vessels, influence the synaptic signaling, and exert dual effects on the survival of retinal ganglion cells and pigment epithelial cells. Researchers have put forth multiple therapeutic agents, encompassing small molecules, peptides, and nucleotides that possess the capability to modulate CaMKII activity. Due to its broad range isoforms and splice variants therapeutic strategies seek to inhibit specifically the CaMKII are confronted with considerable challenges. Therefore, it becomes crucial to discern the detrimental and advantageous aspects of CaMKII, thereby facilitating the development of efficacious treatment. In this review, we summarize recent research findings on the cellular and molecular biology of CaMKII, with special emphasis on its metabolic and regulatory mechanisms. We delve into the involvement of CaMKII in the retinal signal transduction pathways and discuss the correlation between CaMKII and calcium overload. Furthermore, we elaborate the therapeutic trials targeting CaMKII, and introduce recent developments in the zone of CaMKII inhibitors. These findings would enrich our knowledge of CaMKII, and shed light on the development of a therapeutic target for degenerative retinopathy.

Abstract Binocular stereo vision relies on imaging disparity between two hemispherical retinas, which is essential to acquire image information in three dimensional environment. Therefore, retinomorphic electronics with structural and functional similarities to biological eyes are always highly desired to develop stereo vision perception system. In this work, a hemispherical optoelectronic memristor array based on Ag‐TiO2 nanoclusters/sodium alginate film is developed to realize binocular stereo vision. All‐optical modulation induced by plasmonic thermal effect and optical excitation in Ag‐TiO2 nanoclusters is exploited to realize in‐pixel image sensing and storage. Wide field of view (FOV) and spatial angle detection are experimentally demonstrated owing to the device arrangement and incident‐angle‐dependent characteristics in hemispherical geometry. Furthermore, depth perception and motion detection based on binocular disparity have been realized by constructing two retinomorphic memristive arrays. The results demonstrated in this work provide a promising strategy to develop all‐optically controlled memristor and promote the future development of binocular vision system with in‐sensor architecture.

Abstract Background Gut bacteria are related to colorectal cancer (CRC) and its clinicopathologic characteristics. Objective To develop gut bacterial subtypes and explore potential microbial targets for CRC. Methods Stool samples from 914 volunteers (376 CRCs, 363 advanced adenomas, and 175 normal controls) were included for 16S rRNA sequencing. Unsupervised learning was used to generate gut microbial subtypes. Gut bacterial community composition and clustering effects were plotted. Differences of gut bacterial abundance were analyzed. Then, the association of CRC‐associated bacteria with subtypes and the association of gut bacteria with clinical information were assessed. The CatBoost models based on gut differential bacteria were constructed to identify the diseases including CRC and advanced adenoma (AA). Results Four gut microbial subtypes (A, B, C, D) were finally obtained via unsupervised learning. The characteristic bacteria of each subtype were Escherichia‐Shigella in subtype A, Streptococcus in subtype B, Blautia in subtype C, and Bacteroides in subtype D. Clinical information (e.g., free fatty acids and total cholesterol) and CRC pathological information (e.g., tumor depth) varied among gut microbial subtypes. Bacilli, Lactobacillales, etc., were positively correlated with subtype B. Positive correlation of Blautia, Lachnospiraceae, etc., with subtype C and negative correlation of Coriobacteriia, Coriobacteriales, etc., with subtype D were found. Finally, the predictive ability of CatBoost models for CRC identification was improved based on gut microbial subtypes. Conclusion Gut microbial subtypes provide characteristic gut bacteria and are expected to contribute to the diagnosis of CRC.

Chemical looping combustion (CLC) has emerged as a cost-effective technology for carbon capture at the combustion source. The reactor, being central to the implementation of CLC, primarily adheres to two technological pathways: the dual fluidized bed reactor and the packed bed reactor. However, the intricate interaction between gas-solid reaction flow and heat/mass transfer processes in these reactors gives rise to diverse operational principles at both macroscopic and microscopic levels across various reactor forms and scales, making performance prediction challenging. Consequently, the rational design of CLC reactors poses a significant challenge in advancing this technology to commercial viability. This article offers an extensive review of the prevailing reactor designs in CLC, delving into reactor characteristics, pivotal aspects of the design process, methodologies, and representative studies in the field. The predominant reactor design approaches are categorized into engineering and numerical methods. The former encompasses phenomenological and similarity analysis methods, whereas the latter consists of macroscopic and computational fluid dynamics simulation methods. Each method possesses its theoretical framework, distinctive characteristics, appropriate applications, and respective advantages and limitations. In practical applications, integrating these aspects is essential. For instance, the engineering design, which is less costly but also less precise, is effective for quickly screening numerous potential design scenarios. In contrast, the numerical design, despite its higher computational demand and greater model complexity, offers improved predictive accuracy and is optimal for validating and refining engineering design solutions.

Posterior segment disease acts as a major cause of irreversible visual impairments. Successful treatment of posterior segment disease requires the efficient delivery of therapeutic substances to the targeted lesion. However, the complex ocular architecture makes the bioavailability of topically applied drugs extremely low. Invasive delivery approaches like intravitreal injection may cause adverse complications. To enhance the efficiency, several biomedical engineering systems have been developed to increase the penetration efficiency and improve the bioavailability of drugs at the posterior segments. Advantageously, biodegradable microspheres are found to deliver the therapeutic agents in a controlled fashion. The microspheres prepared from novel biomaterials can realize the prolonged release at the posterior segment with minimum side effects. Moreover, it will be degraded automatically into products that are non-toxic to the human body without the necessity of secondary operation to remove the residual polymer matrix. Additionally, biodegradable microspheres have decent thermoplasticity, adjustable hydrophilicity, controlled crystallinity, and high tensile strength, which make them suitable for intraocular delivery. In this review, we introduce the latest advancements in microsphere production technology and elaborate on the biomaterials that are used to prepare microspheres. We discuss systematically the pharmacological characteristics of biodegradable microspheres and compare their potential advantages and limitations in the treatment of posterior segment diseases. These findings would enrich our knowledge of biodegradable microspheres and cast light into the discovery of effective biomaterials for ocular drug delivery.

Abstract Creating circularly polarized organic afterglow system with elevated triplet energy levels, suppressed non-radiative transitions, and effective chirality, which are three critical prerequisites for achieving blue circularly polarized afterglow, has posed a formidable challenge. Herein, a straightforward approach is unveiled to attain blue circularly polarized afterglow materials by covalently self-confining isolated chiral chromophore within polymer matrix. The formation of robust hydrogen bonds within the polymer matrix confers a distinctly isolated and stabilized molecular state of chiral chromophores, endowing a blue emission band at 414 nm, lifetime of 3.0 s, and luminescent dissymmetry factor of ~ 10−2. Utilizing the synergistic afterglow and chirality energy transfer, full-color circularly polarized afterglow systems are endowed by doping colorful fluorescent molecules into designed blue polymers, empowering versatile applications. This work paves the way for the streamlined design of blue circularly polarized afterglow materials, expanding the horizons of circularly polarized afterglow materials into various domains.

Abstract Objective Osteonecrosis of the femoral head (ONFH) is a severe disease that primarily affects the middle-aged population, imposing a significant economic and social burden. Recent research has linked the progression of non-traumatic osteonecrosis of the femoral head (NONFH) to the composition of the gut microbiota. Steroids and alcohol are considered major contributing factors. However, the relationship between NONFH caused by two etiologies and the microbiota remains unclear. In this study, we examined the gut microbiota and fecal metabolic phenotypes of two groups of patients, and analyzed potential differences in the pathogenic mechanisms from both the microbial and metabolic perspectives. Methods Utilizing fecal samples from 68 NONFH patients (32 steroid-induced, 36 alcohol-induced), high-throughput 16 S rDNA sequencing and liquid chromatography with tandem mass spectrometry (LC-MS/MS) metabolomics analyses were conducted. Univariate and multivariate analyses were applied to the omics data, employing linear discriminant analysis effect size to identify potential biomarkers. Additionally, functional annotation of differential metabolites and associated pathways was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Subsequently, Spearman correlation analysis was employed to assess the potential correlations between differential gut microbiota and metabolites. Results High-throughput 16 S rDNA sequencing revealed significant gut microbial differences. At the genus level, the alcohol group had higher Lactobacillus and Roseburia, while the steroid group had more Megasphaera and Akkermansia. LC-MS/MS metabolomic analysis indicates significant differences in fecal metabolites between steroid- and alcohol-induced ONFH patients. Alcohol-induced ONFH (AONFH) showed elevated levels of L-Lysine and Oxoglutaric acid, while steroid-induced ONFH(SONFH) had increased Gluconic acid and Phosphoric acid. KEGG annotation revealed 10 pathways with metabolite differences between AONFH and SONFH patients. Correlation analysis revealed the association between differential gut flora and differential metabolites. Conclusions Our results suggest that hormones and alcohol can induce changes in the gut microbiota, leading to alterations in fecal metabolites. These changes, driven by different pathways, contribute to the progression of the disease. The study opens new research directions for understanding the pathogenic mechanisms of hormone- or alcohol-induced NONFH, suggesting that differentiated preventive and therapeutic approaches may be needed for NONFH caused by different triggers.

Abstract Background Effective drug delivery of nanomedicines to targeted sites remains challenging. Given that hypobaric hypoxia and hyperbaric oxygen exposure can significantly change pharmacokinetics of drugs, it is interesting to determine whether they can regulate tissue distribution of nanomedicine, especially in tumor, for enhanced cancer therapy. Results Hypobaric hypoxia exposure improved the pharmacokinetics of paclitaxel-loaded liposomes and facilitated their distribution in the heart and liver, whereas hyperbaric oxygen exposure did not benefit and even impaired the pharmacokinetics and distribution. Particularly, both hypobaric hypoxia and hyperbaric oxygen exposure could not improve the distribution in subcutaneous tumor. Thus, we constructed orthotopic liver tumor model and discussed whether high distribution of the liposomal nanomedicine in the liver, facilitated by hypobaric hypoxia exposure, could ensure their effective accumulation in liver tumor for enhanced cancer therapy. Conclusions The liposomal nanomedicine with adjuvant hypobaric hypoxia exposure significantly inhibited the growth of orthotopic liver tumor for prolonged survival time, achieved by hypobaric hypoxia-promoted accumulation at tumor sites of the liver. It might be the first example of the application of adjuvant intermittent hypobaric hypoxia exposure in treating liver cancer.

Abstract Background The study explores language acquisition in Chinese English as a Foreign Language (EFL) education, where English proficiency is crucial for global opportunities. As China gains prominence, the demand for English skills rises beyond communication to include academic and business success. The Chinese education system emphasizes proficient English writing for further education and professional achievement. This research investigates the complex linguistic context for EFL learners in China, analyzing the intersection of psychological factors, cultural nuances, varied pedagogy, and individual experiences. Methods Structural Equation Modeling (SEM) is utilized for analysis, enabling the creation of a metric set to explore intangibles such as perfectionism, learning self-efficacy, motivation, study habits, cultural influences, and introspection. The research utilizes a diverse sample from multiple universities across different regions of China, incorporating demographic factors to encompass the varied characteristics within the EFL learner community. Results Results reveal that perfectionism (β = 0.30, p

Abstract Green manuring is the process by which vegetative crops are incorporated into the soil, and it plays a good substitutable role in reducing chemical fertilizer applications while enhancing soil fertility. Field experiments were conducted at Lingao City of Hainan Province in 2020 and 2021, to evaluate the effects of in situ incorporation of different green manures (fallow (as control), rice, sesbania, and stylosanthes) on soil physical and chemical properties, nitrogen (N) uptake, grain yield, and the grain anthocyanin content in colored rice. Treatments included colored rice cultivated with previous fallow (T0), with previous rice straw manure (T1), with previous sesbania manure (T2), and with previous stylosanthes manure (T3). The seedlings of the colored rice variety Suixiangheinuo were transplanted 23 days after the incorporation of green manure. Our results indicated that both the grain yield and grain anthocyanin content of colored rice were significantly increased when green manure was incorporated into the soil compared to that of the control. Therein, grain yields of T1, T2, and T3 were increased by an average of 12.7%, 29.0%, and 24.5%, respectively, across 2 years in comparison with those of T0. And grain anthocyanin content in colored rice under T1, T2, and T3 was increased by 7.2%–7.5%, 13.9%–24.2%, and 9.8%–20.6%, respectively. In addition, in situ incorporation of leguminous green manure in the soil significantly increased soil fertility and partial factor productivity for N fertilizer. The above results suggested that colored rice crops should be followed in rotation with leguminous green manure, which was beneficial to increasing both grain yield and grain anthocyanin content of colored rice. This research elucidated that the incorporation of leguminous green manure sustained the production of colored rice in tropical regions, which was beneficial to reconcile the relationship between rice production and environmental protection.

Abstract Nucleic acid amplification testing (NAAT) remains one of the most reliable methods for pathogen identification. However, conventional bulk NAATs may not be sufficiently fast or sensitive enough for the detection of clinically‐relevant pathogens in point‐of‐care testing. Here, we have developed a digital droplet RT‐LAMP (ddRT‐LAMP) assay that rapidly and quantitatively detects the SARS‐CoV‐2 viral E gene in microfluidic drops. Droplet partitioning using ddRT‐LAMP significantly accelerates detection times across a wide range of template concentrations compared to bulk RT‐LAMP assays. We discover that a reduction in droplet diameter decreases assay times up to a certain size, upon which surface adsorption of the RT‐LAMP polymerase reduces reaction efficiency. Optimization of drop size and polymerase concentration enables rapid, sensitive, and quantitative detection of the SARS‐CoV‐2 E gene in only 8 min. These results highlight the potential of ddRT‐LAMP assays as an excellent platform for quantitative point‐of‐care testing.

Abstract Some bacteria, such as Escherichia coli (E. coli) and Salmonella typhimurium (S. typhimurium), have an inherent ability to locate solid tumours, making them a versatile platform that can be combined with other tools to improve the tumour diagnosis and treatment. In anti‐cancer therapy, bacteria function by carrying drugs directly or expressing exogenous therapeutic genes. The application of bacterial imaging in tumour diagnosis, a novel and promising research area, can indeed provide dynamic and real‐time monitoring in both pre‐treatment assessment and post‐treatment detection. Different imaging techniques, including optical technology, acoustic imaging, magnetic resonance imaging (MRI) and nuclear medicine imaging, allow us to observe and track tumour‐associated bacteria. Optical imaging, including bioluminescence and fluorescence, provides high‐sensitivity and high‐resolution imaging. Acoustic imaging is a real‐time and non‐invasive imaging technique with good penetration depth and spatial resolution. MRI provides high spatial resolution and radiation‐free imaging. Nuclear medicine imaging, including positron emission tomography (PET) and single photon emission computed tomography (SPECT) can provide information on the distribution and dynamics of bacterial population. Moreover, strategies of synthetic biology modification and nanomaterial engineering modification can improve the viability and localization ability of bacteria while maintaining their autonomy and vitality, thus aiding the visualization of gut bacteria. However, there are some challenges, such as the relatively low bacterial abundance and heterogeneously distribution within the tumour, the high dimensionality of spatial datasets and the limitations of imaging labeling tools. In summary, with the continuous development of imaging technology and nanotechnology, it is expected to further make in‐depth study on tumour‐associated bacteria and develop new bacterial imaging methods for tumour diagnosis.

BackgroundThe disruption of intracranial fluid dynamics due to large unruptured cerebral arteriovenous malformation (AVM) commonly triggers a domino effect within the central nervous system. This phenomenon is frequently overlooked in prior clinic and may lead to catastrophic misdiagnoses. Our team has documented the world’s first case of so-called AVM Pentalogy (AVMP) induced by a AVM.Clinical presentation and resultA 30-year-old female was first seen 9 years ago with an occasional fainting, at which time a huge unruptured AVM was discovered. Subsequently, due to progressive symptoms, she sought consultations from several prestigious neurosurgical departments in China, where all consulting neurosurgeons opted for conservation treatment due to perceived surgical risks. During the follow-up period, the patient gradually presented with hydrocephalus, empty sella, secondary Chiari malformation, syringomyelia, and scoliosis (we called as AVMP). When treated in our department, she already displayed numerous symptoms, including severe intracranial hypertension. Our team deduced that the hydrocephalus was the primary driver of her AVMP symptoms, representing the most favorable risk profile for intervention. As expected, a ventriculoperitoneal shunt successfully mitigated all symptoms of AVMP at 21-months post-surgical review.ConclusionDuring the monitoring of unruptured AVM, it is crucial to remain vigilant for the development or progression of AVMP. When any component of AVMP is identified, thorough etiological studies and analysis of cascade reactions are imperative to avert misdiagnosis. When direct AVM intervention is not viable, strategically addressing hydrocephalus as part of the AVMP may serve as the critical therapeutic focus.

Encapsulated cell technology (ECT) is a targeted delivery method that uses the genetically engineered cells in semipermeable polymer capsules to deliver cytokines. Thus far, ECT has been extensively utilized in pharmacologic research, and shows enormous potentials in the treatment of posterior segment diseases. Due to the biological barriers within the eyeball, it is difficult to attain effective therapeutic concentration in the posterior segment through topical administration of drug molecules. Encouragingly, therapeutic cytokines provided by ECT can cross these biological barriers and achieve sustained release at the desired location. The encapsulation system uses permeable materials that allow growth factors and cytokines to diffuse efficiently into retinal tissue. Moreover, the ECT based treatment can be terminated timely when we need to retrieve the implant, which makes the therapy reversible and provides a safer alternative for intraocular gene therapy. Meanwhile, we also place special emphasis on optimizing encapsulation materials and enhancing preservation techniques to achieve the stable release of growth factors and cytokines in the eyeball. This technology holds great promise for the treatment of patients with dry AMD, RP, glaucoma and MacTel. These findings would enrich our understandings of ECT and promote its future applications in treatment of degenerative retinopathy. This review comprises articles evaluating the exactness of artificial intelligence-based formulas published from 2000 to March 2024. The papers were identified by a literature search of various databases (PubMed/MEDLINE, Google Scholar, Cochrane Library and Web of Science).

Abstract Background It has been demonstrated that experiential service-learning is effective in fields including public health and medicine. Preventive Dentistry is a practical course, and Oral Health Examination and Education is a topic that is suitable for teaching with experiential service-learning. This study describes an example of experiential service-learning in Preventive Dentistry named “Oral Health Examination and Education Project” and also evaluates its effectiveness among dental students. Methods A total of 108 dental students in their fourth year participated in this project in 2022. The project was composed of six sections: theoretical teaching, field investigation, data collection and analysis, investigation report writing and creating oral health education materials, oral health education and students’ evaluation of the project. Results During this project, students learned how to perform surveys related to oral health, wrote an investigation report, created oral health education materials, and provided oral health education for children. Students were demonstrated an improvement in their academic performance for theoretical knowledge related to Oral Health Examination and Education in comparison with the students in the previous year. Over 90% of students expressed their preference for the learning method of experiential service and believed that it helped them to better understand the course material. They also recommended this teaching method for future classes. Conclusions This study indicated that an experiential service-learning approach within this scope was highly beneficial to students because it provided them with the opportunity to understand the practical application of their coursework and obtain valuable experience in the field. This research suggests that oral epidemiology instructors in dental and oral public health programs should pay more attention to incorporate similar experiential projects into their curriculum with the aim of better preparing students for careers in oral public health.

Abstract Background A protostylid is a relatively rare dental developmental aberration characterized as an extra cusp located on the mesial half of the buccal surface of the molars. A protostylid is rarely to be reported due to its low rate of occurrence. This case report describes a patient referred for endodontic treatment due to the presence of a protostylid on the buccal surface of the maxillary first molar that induced apical periodontitis. Case presentation A 53-year-old female reported a 3-month history of pain of chewing with her upper left posterior teeth over 3 months. In the clinical examination, an abraded anomalous cusp-like structure was found on the buccal surface of tooth 26, Cone beam computed tomography (CBCT) revealed a supernumerary cusp with an intact root canal inside, which was fused with the mesiobuccal (MB) root canal in the middle of the root. In addition, extensive periapical radiolucency was observed around tooth 26. The tooth was diagnosed as apical periodontitis, and endodontic treatment was performed. The initial lesion in tooth 26 gradually healed over 1 year of observation. Conclusions To our knowledge, this case is the first to describe the endodontic management of a maxillary first molar with a protostylid and advances our understanding of supernumerary cusps. This case provides a reference for the treatment of protostylid.

Objectives. We aimed to develop a new calculation model for calcium requirements in dialysis patients following parathyroidectomy. Methods. A total of 98 patients with secondary hyperparathyroidism receiving parathyroidectomy from January 2014 to January 2022 were enrolled in this study. Among these patients, 78 were randomly selected for construction of the calcium requirement calculation model, and the remaining 20 patients were selected for model validation. The calcium requirement model estimated the total calcium supplementation for 1 week after surgery using variables with significant relationships in the derivation group by stepwise multiple linear regression analysis. Bias, precision, and accuracy were measured in the validation group to determine the performance of the model. Results. The model was as follows: calcium requirement for 1 week after surgery=33.798–8.929×immediate postoperative calcium+0.190×C-reactive protein–0.125×age+0.002×preoperative intact parathyroid hormone+0.003×preoperative alkaline phosphatase (R2=0.8). The model was successfully validated. Conclusion. We generated a novel model to guide calcium supplementation. This model can assist in stabilizing the serum calcium levels of patients during the early postoperative period. Furthermore, it contributes to the individualized and precise treatment of hypocalcemia in patients following parathyroidectomy.

Abstract Objective We aimed to develop a 5-year overall survival prediction model for patients with oral tongue squamous cell carcinoma based on machine learning methods. Subjects and methods The data were obtained from electronic medical records of 224 OTSCC patients at the PLA General Hospital. A five-year overall survival prediction model was constructed using logistic regression, Support Vector Machines, Decision Tree, Random Forest, Extreme Gradient Boosting, and Light Gradient Boosting Machine. Model performance was evaluated according to the area under the curve (AUC) of the receiver operating characteristic curve. The output of the optimal model was explained using the Python package (SHapley Additive exPlanations, SHAP). Results After passing through the grid search and secondary modeling, the Light Gradient Boosting Machine was the best prediction model (AUC = 0.860). As explained by SHapley Additive exPlanations, N-stage, age, systemic inflammation response index, positive lymph nodes, plasma fibrinogen, lymphocyte-to-monocyte ratio, neutrophil percentage, and T-stage could perform a 5-year overall survival prediction for OTSCC. The 5-year survival rate was 42%. Conclusion The Light Gradient Boosting Machine prediction model predicted 5-year overall survival in OTSCC patients, and this predictive tool has potential prognostic implications for patients with OTSCC.

With the continuous development and progress of society, age estimation based on deep learning has gradually become a key link in human-computer interaction. Widely combined with other fields of application, this paper performs a gradient division of human fall behavior according to the age estimation of the human body, a complete priority detection of the key population, and a phased single aggregation backbone network VoVNetv4 was proposed for feature extraction. At the same time, the regional single aggregation module ROSA module was constructed to encapsulate the feature module regionally. The adaptive stage module was used for feature smoothing. Consistent predictions for each task were made using the CORAL framework as a classifier and tasks were divided in binary. At the same time, a gradient two-node fall detection framework combined with age estimation was designed. The detection was divided into a primary node and a secondary node. In the first-level node, the age estimation algorithm based on VoVNetv4 was used to classify the population of different age groups. A face tracking algorithm was constructed by combining the key point matrices of humans, and the body processed by OpenPose with the central coordinates of the human face. In the secondary node, human age gradient information was used to detect human falls based on the AT-MLP model. The experimental results show that compared with Resnet-34, the MAE value of the proposed method decreased by 0.41. Compared with curriculum learning and the CORAL-CNN method, MAE value decreased by 0.17 relative to the RMSE value. Compared with other methods, the method in this paper was significantly lower, with a biggest drop of 0.51.

Abstract Background The correlation between epithelial‐mesenchymal transition (EMT) and osteosarcoma (OS) has been widely reported. Integration of the EMT‐related genes to predict the prognosis is significant for investigating the mechanism of EMT in OS. Here, we aimed to construct a prognostic EMT‐related gene signature for OS. Methods Transcriptomic and survival data of OS patients were downloaded from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO). We performed univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and stepwise multivariate Cox regression analysis to construct EMT‐related gene signatures. Kaplan–Meier analysis and time‐dependent receiver operating characteristic (ROC) were applied to evaluate its predictive performance. GSVA, ssGSEA, ESTIMATE, and scRNA‐seq were performed to investigate the tumor microenvironment, and the correlation between IC50 of drugs and ERG score was investigated. Furthermore, Edu and transwell experiments were conducted to assess the malignancy of OS cells. Results We constructed a novel EMT‐related gene signature (including CDK3, MYC, UHRF2, STC2, COL5A2, MMD, and EHMT2) for outcome prediction of OS. According to the signature, patients stratified into high‐ and low‐ERG‐score groups exhibited significantly different prognoses. ROC curves and Kaplan–Meier analysis revealed a promising performance of the signature with external validation. GSVA, ssGSEA, ESTIMATE algorithm, and scRNA‐seq excavated EMT‐related pathways and suggested the correlation between ERG score and immune activation. Notably, the pivotal gene CDK3 was upregulated in OS tissue and positively related to OS cell proliferation and migration. Conclusion Our EMT‐related gene signature might reference OS risk stratification and guide clinical strategies as an independent prognostic factor in OS.

Abstract Understanding the dynamic process of epitaxial microstructure forming in laser additive manufacturing is very important for achieving products with a single crystalline texture. Here, we perform in situ, real-time synchrotron Laue diffraction experiments to capture the microstructural evolution of nickel-based single-crystal superalloys during the rapid laser remelting process. In situ synchrotron radiation Laue diffraction characterises the crystal rotation behaviour and stray grain formation process. With a complementary thermomechanical coupled finite element simulation and molecular dynamics simulation, we identify that the crystal rotation is governed by the localised heating/cooling heterogeneity-induced deformation gradient and recognise that the sub-grain rotation caused by rapid dislocation movement could be the origin of granular stray grains at the bottom of the melt pool.

Abstract Background Wild apple (Malus sieversii) is under second-class national protection in China and one of the lineal ancestors of cultivated apples worldwide. In recent decades, the natural habitation area of wild apple trees has been seriously declining, resulting in a lack of saplings and difficulty in population regeneration. Artificial near-natural breeding is crucial for protecting and restoring wild apple populations, and adding nitrogen (N) and phosphorous (P) is one of the important measures to improve the growth performance of saplings. In this study, field experiments using N (CK, N1, N2, and N3: 0, 10, 20, and 40 g m− 2 yr− 1, respectively), P (CK, P1, P2, and P3: 0, 2, 4, and 8 g m− 2 yr− 1, respectively), N20Px (CK, N2P1, N2P2, and N2P3: N20P2, N20P4 and N20P8 g m− 2 yr− 1, respectively), and NxP4 (CK, N1P2, N2P2, and N3P2: N10P4, N20P4, and N40P4 g m− 2 yr− 1, respectively) treatments (totaling 12 levels, including one CK) were conducted in four consecutive years. The twig traits (including four current-year stem, 10 leaf, and three ratio traits) and comprehensive growth performance of wild apple saplings were analyzed under different nutrient treatments. Results N addition had a significantly positive effect on stem length, basal diameter, leaf area, and leaf dry mass, whereas P addition had a significantly positive effect on stem length and basal diameter only. The combination of N and P (NxP4 and N20Px) treatments evidently promoted stem growth at moderate concentrations; however, the N20Px treatment showed a markedly negative effect at low concentrations and a positive effect at moderate and high concentrations. The ratio traits (leaf intensity, leaf area ratio, and leaf to stem mass ratio) decreased with the increase in nutrient concentration under each treatment. In the plant trait network, basal diameter, stem mass, and twig mass were tightly connected to other traits after nutrient treatments, indicating that stem traits play an important role in twig growth. The membership function revealed that the greatest comprehensive growth performance of saplings was achieved after N addition alone, followed by that under the NxP4 treatment (except for N40P4). Conclusions Consequently, artificial nutrient treatments for four years significantly but differentially altered the growth status of wild apple saplings, and the use of appropriate N fertilizer promoted sapling growth. These results can provide scientific basis for the conservation and management of wild apple populations.

Aim: VDJ001 is a novel recombinant humanized monoclonal antibody against the anti-interleukin-6 receptor. As an analog of tocilizumab, it exhibited improved affinity and in vitro activity. Based on preclinical studies, a first-in-human clinical study was conducted to evaluate the safety, tolerability, and pharmacokinetics of VDJ001.Methods: This is a single-center, randomized, double-blinded, placebo-controlled phase I dose-escalation study conducted in healthy Chinese volunteers. Four cohorts were designed with dosages ranging from 1 to 8 mg/kg. There were equal numbers of female and male volunteers in each cohort. Enrolled subjects randomly received a single intravenous administration of VDJ001 or placebo (VDJ001: placebo = 4:1 in both female and male volunteers). Three sentinel volunteers in the 1 mg/kg cohort were first administered, and the treatment of the other seven volunteers was carried out after a safety assessment on D15. The following cohort was conducted only when the safety profile was evaluated as acceptable on D29 of the previous cohort. Samples for pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity were collected at specified time points and analyzed through validated methods. Adverse events and the results of the examination and laboratory were analyzed to assess the safety profile.Results: All cohorts were carried out according to the protocol. With the escalation of dosage, Cmax increased linearly, and AUC0-t and AUC0-∞ increased in a non-linear manner, while clearance decreased and t1/2 prolonged. Six volunteers who received VDJ001 tested ADA-positive, among whom one participant tested Nab-positive on D57. One volunteer in the placebo group tested ADA-positive but Nab-negative. CRP concentrations were not found to be correlated with the dosage. Both IL-6 and sIL-6R concentrations increased after the administration of VDJ001. All adverse events were mild to moderate in severity. No serious adverse events were reported in this study. No unexpected or clinically significant safety issues were found.Conclusion: The safety and tolerability of VDJ001 are acceptable with a single intravenous dosage of 1∼8 mg/kg. Further clinical trials are warranted.

BackgroundTo develop and compare different AutoML frameworks and machine learning models to predict premature birth.MethodsThe study used a large electronic medical record database to include 715,962 participants who had the principal diagnosis code of childbirth. Three Automatic Machine Learning (AutoML) were used to construct machine learning models including tree-based models, ensembled models, and deep neural networks on the training sample (N = 536,971). The area under the curve (AUC) and training times were used to assess the performance of the prediction models, and feature importance was computed via permutation-shuffling.ResultsThe H2O AutoML framework had the highest median AUC of 0.846, followed by AutoGluon (median AUC: 0.840) and Auto-sklearn (median AUC: 0.820), and the median training time was the lowest for H2O AutoML (0.14 min), followed by AutoGluon (0.16 min) and Auto-sklearn (4.33 min). Among different types of machine learning models, the Gradient Boosting Machines (GBM) or Extreme Gradient Boosting (XGBoost), stacked ensemble, and random forrest models had better predictive performance, with median AUC scores being 0.846, 0.846, and 0.842, respectively. Important features related to preterm birth included premature rupture of membrane (PROM), incompetent cervix, occupation, and preeclampsia.ConclusionsOur study highlights the potential of machine learning models in predicting the risk of preterm birth using readily available electronic medical record data, which have significant implications for improving prenatal care and outcomes.

With the emergence of Artificial Intelligence (AI) 2.0, computers are now equipped with new creative capabilities and are playing an increasingly significant role in design. The use of AI augmentation has the potential to enhance design performance, however, there is limited research on the acceptance of AI-augmented design. The research gap under consideration in this study is addressed by presenting an acceptance model designed for AI-augmented design. This model integrates a range of variables including perceived privacy risk, enjoyment, perceived value, perceived usefulness, perceived ease of use, perceived behavioral control, social influence, and behavioral intention. The proposed model was validated through a questionnaire survey of 249 designers in China.The results reveal that enjoyment, perceived value, perceived ease of use, perceived behavioral control, and social influence have a significant positive impact on users' intention to use AI-augmented design, while perceived privacy risk has a significant negative impact. Perceived value was found to mediate the relationship between enjoyment and behavioral intention, while perceived behavioral control play a mediation role in the relationship between social influence and behavioral intention.In conclusion, this study highlights the variables that influence the acceptance of AI-augmented design and provides valuable insights into the potential benefits and drawbacks of integrating AI technologies in design. The proposed acceptance model serves as a framework for future research in this area and can guide the development of more user-friendly and effective AI-augmented design tools and technologies.

Vestibular schwannomas in pregnancy have rarely been reported, and there is a lack of in-depth discussion on the experience of management of massive acoustic neuromas in pregnancy. Herein, we present a pregnant woman with a giant vestibular schwannoma and obstructive hydrocephalus who presented at 30 weeks of gestation. She was initially misdiagnosed as having a pregnancy-related reaction of headache, dizziness, and vomiting that had occurred 2 months earlier. After observation at home, her symptoms progressed at 30 weeks of gestation, and imaging findings revealed a brain tumor in the CPA region with secondary cerebella tonsil herniation and obstructive hydrocephalus, and she was transferred to our center for treatment. Consequently, we relieved her hydrocephalus with a ventriculoperitoneal shunt (V-P shunt) and used corticosteroids to simulate fetal maturation. After 10 days, her mental condition deteriorated, and her right limb muscle strength gradually decreased until grade 0 (MMT Grading). Finally, under a joint consultation with the Department of Neurosurgery, Obstetrics, and Anesthesiology, she underwent a cesarean section under general anesthesia and first-stage tumor removal at 31 weeks of gestation. Upon discharge, the previously observed neurological deficits, which were reversible and had manifested during her gestational period, had been successfully resolved, and the fetus had been conserved. The neuroimaging confirmed the complete tumor removal, while the neuropathologic examination revealed a vestibular schwannoma. Therefore, we recommend early diagnosis and treatment for these patients, especially people with headaches, vomiting, and sudden hearing loss during pregnancy. Herein, we concluded that our cases provide a valuable experience in the latest acceptable time frame for the operation to prevent irreversible neurological impairment and premature delivery in late pregnancy.

In acid soil, aluminum (Al) toxicity is one of the main factors limiting agricultural output. As is known to all, the cell wall is the first line of defense against metals that serves as a significant target of Al toxicity and also is crucial for Al detoxification. However, nothing is known about how this process is transcriptionally regulated. Here, we describe recent findings to understand the role of two kinds of transcription factors in regulating the cell wall composition and modification in response to Al stress in Arabidopsis thaliana. ANAC017 encodes a NAM, ATAF1/2, and cup-shaped cotyledon 2 (NAC) transcription factor, loss function of ANAC017 enhanced Al tolerance with the decreased Al content and xyloglucan content in the cell wall. Next, we characterized one xyloglucan endotransglucosylase/hydrolase (XTH), XTH31, which is previously reported to participate in Al stress, acted downstream of ANAC017 to regulate Al tolerance in Arabidopsis. In addition, we also identified MYB103, an R2R3-type transcription factor. MYB103 disruption caused Al sensitivity, and myb103 mutants’ xyloglucan had a high O-acetylation level. Additionally, it was discovered that TRICHOME BIREFRINGENCE-LIKE27 (TBL27), which is in charge of xyloglucan’s O-acetylation, functions downstream of MYB103 through the direct binding of the MYB103 to the promoter of the TBL27 to influence Arabidopsis’s sensitivity to Al. In summary, our research showed that two distinct molecular modules modulate Arabidopsis cell wall composition and modification to positively influence Al resistance.

AbstractDelivery of drugs to special locations of ocular lesions, while minimizing systemic and local toxic effects, is recognized as a critical challenge in the ophthalmic practice. The special anatomy and physiology barriers within the eyeball entail effective drug delivery systems. Emerging attempts in drug delivery has led to developments in ocular iontophoresis, which acts as a noninvasive technology to enhance drug penetration using a small electric current. This technique offers greater flexibility to deliver desired drug dose in a controlled and tolerable manner. In previous studies, this technique has been testified to deliver antibiotics, corticoid, proteins and other gene drugs into the eye with the potency of treating or alleviating diverse ophthalmological diseases including uveitis, cataract, retinoblastoma, herpes simplex and cytomegalovirus retinitis (CMVR), etc. In this review, we will introduce the recent developments in iontophoresis device. We also summarize the latest progress in coulomb controlled iontophoresis (CCI), hydrogel ionic circuit (HIC) and EyeGate II delivery system (EGDS), as well as overview the potential toxicity of iontophoresis. We will discuss these factors that affect the efficacy of iontophoresis experiments, and focus on the latest progress in its clinical application in the treatment of eye diseases.

Soil nutrients in desert ecosystems are influenced by various factors, and the presence of moss crust cover plays a significant role in determining the nutritional content of the surface soil. Moss crusts are distributed as patches within desert ecosystems, creating micro-ecosystems. However, the distribution pattern of soil nutrients under moss crust cover and the impact of patch size on soil nutrient content remain unclear. In this study, we assessed the patch size of mosses in field sites within the Gurbantünggüt Desert and investigated the content of total carbon (C), total nitrogen (N), total phosphorus (P), organic carbon (OC), ammonium (NH4+-N), nitrate (NO3–-N), and available phosphorus (AP) in both surface soil and sub surface soil. We employed linear and structural equation models to examine the regulatory effect of moss crust patch size on soil nutrient content. Our findings revealed that the C and N contents were significantly higher in the surface soil compared to the sub surface soil, while the AP content was significantly higher in the sub surface soil than in the surface soil. Additionally, a significant negative correlation was observed between the N content and patch area of the topsoil in 83% of the sample sites. Climate, soil properties, and moss patch size collectively influenced the multifunctionality of both surface soil and sub surface soil. Climatic factors exerted a greater impact on the surface soil, while soil properties and moss patch size had a stronger influence on the sub surface soil. These findings emphasize the variability in nutrient characteristics between the surface and sub surface soils of biocrusts, highlighting the influence of crust patch size on the nutrient characteristics and functions of desert soils. These insights have practical implications for land management and conservation strategies in arid regions, providing valuable knowledge for sustainable resource utilization and environmental preservation.

Abstract Long noncoding RNAs (lncRNAs), widely expressed in mammalian cells, play pivotal roles in osteosarcoma (OS) progression. Nevertheless, the detailed molecular mechanisms of lncRNA KIAA0087 in OS remain obscure. Here, the roles of KIAA0087 in OS tumorigenesis were investigated. KIAA0087 and miR-411-3p levels were detected by RT-qPCR. Malignant properties were assessed by CCK-8, colony formation, flow cytometry, wound healing, and transwell assays. SOCS1, EMT, and JAK2/STAT3 pathway-related protein levels were measured by western blotting. Direct binding between miR-411-3p and KIAA0087/SOCS1 was validated by a dual-luciferase reporter, RIP, and FISH assays. In vivo growth and lung metastasis were evaluated in nude mice. The expression levels of SOCS1, Ki-67, E-cadherin, and N-cadherin in tumor tissues were measured by immunohistochemical staining. Downregulation of KIAA0087 and SOCS1 and upregulation of miR-411-3p were found in OS tissues and cells. Low expression of KIAA0087 was associated with a poor survival rate. Forced expression of KIAA0087 or miR-411-3p inhibition repressed the growth, migration, invasion, EMT, and activation of the JAK2/STAT3 pathway and triggered apoptosis of OS cells. However, the opposite results were found with KIAA0087 knockdown or miR-411-3p overexpression. Mechanistic experiments indicated that KIAA0087 enhanced SOCS1 expression to inactivate the JAK2/STAT3 pathway by sponging miR-411-3p. Rescue experiments revealed that the antitumor effects of KIAA0087 overexpression or miR-411-3p suppression were counteracted by miR-411-3p mimics or SOCS1 inhibition, respectively. Finally, in vivo tumor growth and lung metastasis were inhibited in KIAA0087-overexpressing or miR-411-3p-inhibited OS cells. In summary, the downregulation of KIAA0087 promotes the growth, metastasis, and EMT of OS by targeting the miR-411-3p-mediated SOCS1/JAK2/STAT3 pathway.

In recent years, the research of autonomous driving and mobile robot technology is a hot research direction. The ability of simultaneous positioning and mapping is an important prerequisite for unmanned systems. Lidar is widely used as the main sensor in SLAM (Simultaneous Localization and Mapping) technology because of its high precision and all-weather operation. The combination of Lidar and IMU (Inertial Measurement Unit) is an effective method to improve overall accuracy. In this paper, multi-line Lidar is used as the main data acquisition sensor, and the data provided by IMU is integrated to study robot positioning and environment modeling. On the one hand, this paper proposes an optimization method of tight coupling of lidar and IMU using factor mapping to optimize the mapping effect. Use the sliding window to limit the number of frames optimized in the factor graph. The edge method is used to ensure that the optimization accuracy is not reduced. The results show that the point plane matching mapping method based on factor graph optimization has a better mapping effect and smaller error. After using sliding window optimization, the speed is improved, which is an important basis for the realization of unmanned systems. On the other hand, on the basis of improving the method of optimizing the mapping using factor mapping, the scanning context loopback detection method is integrated to improve the mapping accuracy. Experiments show that the mapping accuracy is improved and the matching speed between two frames is reduced under loopback mapping. However, it does not affect real-time positioning and mapping, and can meet the requirements of real-time positioning and mapping in practical applications.

Aiming at the problem that the model of YOLOv4 algorithm has too many parameters and the detection effect of small targets is poor, this paper proposes an improved helmet fitting detection model based on YOLOv4 algorithm. Firstly, this model improves the detection accuracy of small targets by adding multi-scale prediction and improving the structure of PANet network. Then, the improved depth-separable convolution was used to replace the standard 3 × 3 convolution, which greatly reduced the model parameters without reducing the detection ability of the model. Finally, the k_means clustering algorithm is used to optimize the prior box. The model was tested on the self-made helmet dataset helmet_dataset. Experimental results show that compared with the safety helmet detection model based on Faster RCNN algorithm, the improved YOLOv4 algorithm has faster detection speed, higher detection accuracy and smaller number of model parameters. Compared with the original YOLOv4 model, the mAP of the improved YOLOv4 algorithm is increased by 0.49%, reaching 93.05%. The number of model parameters was reduced by about 58%, to about 105 MB. The model reasoning speed is 35 FPS. The improved YOLOv4 algorithm can meet the requirements of helmet wearing detection in multiple scenarios.

Abstract Background Voriconazole is a second-generation triazole that is used to prevent and treat invasive fungal infections. The purpose of this study was to evaluate the pharmacokinetic equivalency of a test formulation and reference formulation (Vfend®) of Voriconazole. Materials and methods This was a randomized, open-label, single-dose, two-treatment, two-sequence, two-cycle, crossover phase I trial. The 48 subjects were equally divided into 4 mg/kg and 6 mg/kg groups. Within each group, the subjects were randomized 1:1 to the test or reference formulation.. After a 7-day washout period, crossover formulations were administered. The blood samples were collected at 0.5, 1.0, 1.33,1.42,1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0 h later in the 4 mg/kg group, while at 0.5, 1.0, 1.5, 1.75, 2.0, 2.08, 2.17, 2.33, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0 h later in the 6 mg/kg group. The plasma concentrations of Voriconazole were determined by Liquid chromatography-tandem mass spectrometry (LC–MS/MS). The safety of the drug was evaluated. Results The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ in both 4 mg/kg and 6 mg/kg groups were within the prespecified bioequivalence limits between 80 ~ 125%. In the 4 mg/kg groups, 24 subjects were enrolled and completed the study. The mean Cmax was (2.552 ± 0.448) μg/mL, AUC0-t was (11.875 ± 7.157) h*μg/mL and AUC0-∞ was (12.835 ± 9.813) h*μg/mL after a single dose of 4 mg/kg test formulation. The mean Cmax was (2.615 ± 0.464) μg/mL, AUC0-t was (12.500 ± 7.257) h*μg/mL and AUC0-∞ was (13.416 ± 9.485) h*μg/mL after a single dose of 4 mg/kg reference formulation. In the 6 mg/kg groups, 24 subjects were enrolled and completed the study. The mean Cmax was (3.538 ± 0.691) μg/mL, AUC0-t was (24.976 ± 12.364) h*μg/mL and AUC0-∞ was (26.212 ± 14.057) h*μg/mL after a single dose of 6 mg/kg test formulation. The mean Cmax was (3.504 ± 0.667) μg/mL AUC0-t was (24.990 ± 12.455) h*μg/mL and AUC0-∞ was (26.160 ± 13.996) h*μg/mL after a single dose of 6 mg/kg reference formulation. Serious adverse event (SAE) was not observed. Conclusion In both 4 mg/kg group and 6 mg/kg group, equivalent pharmacokinetic characteristics that satisfied the criteria of bioequivalence for both test and reference formulations of Voriconazole. Trial registration NCT05330000 (15/04/2022).

Abstract The relationships between biodiversity-ecosystem functioning (BEF) for microbial communities are poorly understood despite the important roles of microbes acting in natural ecosystems. Dilution-to-extinction (DTE), a method to manipulate microbial diversity, helps to fill the knowledge gap of microbial BEF relationships and has recently become more popular with the development of high-throughput sequencing techniques. However, the pattern of community assembly processes in DTE experiments is less explored and blocks our further understanding of BEF relationships in DTE studies. Here, a microcosm study and a meta-analysis of DTE studies were carried out to explore the dominant community assembly processes and their potential effect on exploring BEF relationships. While stochastic processes were dominant at low dilution levels due to the high number of rare species, the deterministic processes became stronger at a higher dilution level because the microbial copiotrophs were selected during the regrowth phase and rare species were lost. From the view of microbial functional performances, specialized functions, commonly carried by rare species, are more likely to be impaired in DTE experiments while the broad functions seem to be less impacted due to the good performance of copiotrophs. Our study indicated that shifts in the prokaryotic community and its assembly processes induced by dilutions result in more complex BEF relationships in DTE experiments. Specialized microbial functions could be better used for defining BEF. Our findings may be helpful for future studies to design, explore, and interpret microbial BEF relationships using DTE.

In order to avoid traffic accidents caused by driver fatigue, smoking and talking on the phone, it is necessary to design an effective fatigue detection algorithm. Firstly, this paper studies the detection algorithms of driver fatigue at home and abroad, and analyzes the advantages and disadvantages of the existing algorithms. Secondly, a face recognition module is introduced to crop and align the acquired faces and input them into the Facenet network model for feature extraction, thus completing the identification of drivers. Thirdly, a new driver fatigue detection algorithm based on deep learning is designed based on Single Shot MultiBox Detector (SSD) algorithm, and the additional layer network structure of SSD is redesigned by using the idea of reverse residual. By adding the detection of drivers' smoking and making phone calls, adjusting the size and number of prior boxes of SSD algorithm, improving FPN network and SE network, the identification and verification of drivers can be realized. The experimental results showed that the number of parameters decreased from 96.62 MB to 18.24 MB. The average accuracy rate increased from 89.88% to 95.69%. The projected number of frames per second increased from 51.69 to 71.86. When the confidence threshold was set to 0.5, the recall rate of closed eyes increased from 46.69% to 65.87%, that of yawning increased from 59.72% to 82.72%, and that of smoking increased from 65.87% to 83.09%. These results show that the improved network model has better feature extraction ability for small targets.

To tackle the challenges of weak sensing capacity for multi-scale objects, high missed detection rates for occluded targets, and difficulties for model deployment in detection tasks of intelligent roadside perception systems, the PDT-YOLO algorithm based on YOLOv7-tiny is proposed. Firstly, we introduce the intra-scale feature interaction module (AIFI) and reconstruct the feature pyramid structure to enhance the detection accuracy of multi-scale targets. Secondly, a lightweight convolution module (GSConv) is introduced to construct a multi-scale efficient layer aggregation network module (ETG), enhancing the network feature extraction ability while maintaining weight. Thirdly, multi-attention mechanisms are integrated to optimize the feature expression ability of occluded targets in complex scenarios, Finally, Wise-IoU with a dynamic non-monotonic focusing mechanism improves the accuracy and generalization ability of model sensing. Compared with YOLOv7-tiny, PDT-YOLO on the DAIR-V2X-C dataset improves mAP50 and mAP50:95 by 4.6% and 12.8%, with a parameter count of 6.1 million; on the IVODC dataset by 15.7% and 11.1%. We deployed the PDT-YOLO in an actual traffic environment based on a robot operating system (ROS), with a detection frame rate of 90 FPS, which can meet the needs of roadside object detection and edge deployment in complex traffic scenes.

Age-related macular degeneration (AMD) is an ocular disease that leads to progressive photoreceptor death and visual impairment. Currently, the most common therapeutic strategy is to deliver anti-vascular endothelial growth factor (anti-VEGF) agents into the eyes of patients with wet AMD. However, this treatment method requires repeated injections, which potentially results in surgical complications and unwanted side effects for patients. An effective therapeutic approach for dry AMD also remains elusive. Therefore, there is a surge of enthusiasm for the developing the biodegradable drug delivery systems with sustained release capability and develop a promising therapeutic strategy. Notably, the strides made in hydrogels which possess intricate three-dimensional polymer networks have profoundly facilitated the treatments of AMD. Researchers have established diverse hydrogel-based delivery systems with marvelous biocompatibility and efficacy. Advantageously, these hydrogel-based transplantation therapies provide promising opportunities for vision restoration. Herein, we provide an overview of the properties and potential of hydrogels for ocular delivery. We introduce recent advances in the utilization of hydrogels for the delivery of anti-VEGF and in cell implantation. Further refinements of these findings would lay the basis for developing more rational and curative therapies for AMD.

Organic afterglow is a fascinating phenomenon with exceptional applications. However, it encounters challenges such as low intensity and efficiency, and typically requires UV-light excitation and facile intersystem crossing (ISC) due to its spin-forbidden nature. Here, we develop a novel strategy that bypasses the conventional ISC pathway by promoting singlet-triplet transition through the synergistic effects of the intra/intermolecular heavy-atom effect in aromatic crystals, enabling the direct population of triplet excited states from the ground state. The resulting materials exhibit a bright organic afterglow with a remarkably enhanced quantum efficiency of up to 5.81%, and a significantly increased organic afterglow lifetime of up to 157 microseconds under visible light. Moreover, given the high-efficiency visible-light excitable organic afterglow emission, the potential application is demonstrated in lifetime-resolved, color-encoded, and excitation wavelength-dependent pattern encryption. This work demonstrates the importance of the direct population method in enhancing the organic afterglow performance and red-shifting the excitation wavelength, and provides crucial insights for advancing organic optoelectronic technologies that involve triplet states.

The efficient synthesis of myofibrillar protein(MRN)-gallic acid (GAD) complex in ultrasound (UID)-assisted processing is a challenging problem in food manufacturing. In this investigation, the effect of viscosity characteristics on the efficiency of UID processing in MRN-based beverages was analyzed. Both viscosity and surface tension can increase sono-physico-chemical effects on the degradation of terephthalic acid and crystal violet, with surface tension having a more significant effect (negative correlation, R2 = 0.99) than viscosity (positive correlation, R2 = 0.79). The structural indicators and microstructure demonstrated that the reaggregation and refolding of the MRN structure during the modification procedure occurred with relatively small three-dimensional dimensions. Compared to the MRN/GAD4 group, the water contact angle of the MRN/GAD7 system enhanced by 129.44%, leading to greater system stability. The ABTS-scavenging capacity of the system increased by approximately 19.45% due to the increase in viscosity of these two categories.

BackgroundFocal adhesion serves as a bridge between tumour cells and the extracellular matrix (ECM) and has multiple roles in tumour invasion, migration, and therapeutic resistance. However, studies on focal adhesion-related genes (FARGs) in head and neck squamous cell carcinoma (HNSCC) are limited.MethodsData on HNSCC samples were obtained from The Cancer Genome Atlas and GSE41613 datasets, and 199 FARGs were obtained from the Molecular Signatures database. The integrated datasets’ dimensions were reduced by the use of cluster analysis, which was also used to classify patients with HNSCC into subclusters. A FARG signature model was developed and utilized to calculate each patient’s risk score using least extreme shrinkage and selection operator regression analysis. The risk score was done to quantify the subgroups of all patients. We evaluated the model’s value for prognostic prediction, immune infiltration status, and therapeutic response in HNSCC. Preliminary molecular and biological experiments were performed to verify these results.ResultsTwo different HNSCC molecular subtypes were identified according to FARGs, and patients with C2 had a shorter overall survival (OS) than those with C1. We constructed an FARG signature comprising nine genes. We constructed a FARG signature consisting of nine genes. Patients with higher risk scores calculated from the FARG signature had a lower OS, and the FARG signature was considered an independent prognostic factor for HNSCC in univariate and multivariate analyses. FARGs are associated with immune cell invasion, gene mutation status, and chemosensitivity. Finally, we observed an abnormal overexpression of MAPK9 in HNSCC tissues, and MAPK9 knockdown greatly impeded the proliferation, migration, and invasion of HNSCC cells.ConclusionThe FARG signature can provide reliable prognostic prediction for patients with HNSCC. Apart from that, the genes in this model were related to immune invasion, gene mutation status, and chemosensitivity, which may provide new ideas for targeted therapies for HNSCC.

Cooperative perception is crucial for connected automated vehicles in intelligent transportation systems (ITSs); however, ensuring the authenticity of perception data remains a challenge as the vehicles cannot verify events that they do not witness independently. Various studies have been conducted on establishing the authenticity of data, such as trust-based statistical methods and plausibility-based methods. However, these methods are limited as they require prior knowledge such as previous sender behaviors or predefined rules to evaluate the authenticity. To overcome this limitation, this study proposes a novel approach called zero-knowledge Proof of Traffic (zk-PoT), which involves generating cryptographic proofs to the traffic observations. Multiple independent proofs regarding the same vehicle can be deterministically cross-verified by any receivers without relying on ground truth, probabilistic, or plausibility evaluations. Additionally, no private information is compromised during the entire procedure. A full on-board unit software stack that reflects the behavior of zk-PoT is implemented within a specifically designed simulator called Flowsim. A comprehensive experimental analysis is then conducted using synthesized city-scale simulations, which demonstrates that zk-PoT’s cross-verification ratio ranges between 80 % to 96 %, and 80 % of the verification is achieved in 2 s, with a protocol overhead of approximately 25 %. Furthermore, the analyses of various attacks indicate that most of the attacks could be prevented, and some, such as collusion attacks, can be mitigated. The proposed approach can be incorporated into existing works, including the European Telecommunications Standards Institute (ETSI) and the International Organization for Standardization (ISO) ITS standards, without disrupting the backward compatibility.