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Abstract Maximizing materials utilization efficiency via enhancing their reconfigurability and multifunctionality offers a promising avenue in addressing the global challenges in sustainability. To this end, significant efforts have been made in developing reconfigurable multifunctional smart materials, which can exhibit remarkable behaviors such as morphing and self-healing. However, the difficulty in efficiently manipulating and controlling matter at the building block level with manageable cost and complexity, which is crucial to achieving superior responsiveness to environmental clues and stimuli, has significantly hindered the further development of such smart materials. Here we introduce a concept of Robo-Matter, which can be activated and controlled through external information exchange at the building block level, to enable a high-level of controllability, mutability and versatility for reconfigurable multifunctional smart materials. Using specially designed micro-robot building blocks with symmetry-breaking active motion modes, tunable anisotropic interactions, and interactive coupling with a programmable spatial-temporal dynamic light field, we demonstrate an emergent Robot-Matter duality, which enables a spectrum of desirable behaviors spanning from matter-like properties such as ultra-fast self-assembly and adaptivity, to robot-like properties including active force output, smart healing, smart morphing and infiltration. Our work demonstrates a promising direction for designing next-generation smart materials and large-scale robotic swarms.

【Objective】The effects of operation parameters of multi-rotor plant protection unmanned aerial vehicle (UAV) at different growth stages of maize on deposition quality and the control efficacy of Spodoptera frugiperda were compared to select the optimal operation parameters, with an aim to provide scientific basis for precise pesticide application of S. frugiperda.【Method】DJI T20 six-rotor plant protection UAV was used as the research object, the operation parameters including flight altitude, flight speed and nozzle type were tested for optimization of deposition distribution at the trumpet stage and heading stage of maize, and the population decline rate and control effect of S. frugiperda 7 d after the application of pesticides were investigated.【Result】At trumpet stage of maize, when a SX110015VS nozzle operated at a flight speed of 4 m/s and at a flight altitude of 2.5 m above the maize canopy, the maximum normalized average droplet deposition was 0.45 μL/cm2. When a SX110015VS nozzle operated at a flight speed of 4 m/s and a flight altitude of 1.5 m, both average droplet coverage and average droplet density were the highest, which were 44.92 drops/cm2 and 9.31%, respectively. At heading stage of maize, the normalized average droplet deposition, average droplet coverage and average droplet density were the highest when a SX110015VS nozzle operated at a flight speed of 4 m/s and a flight altitude of 2.5 m, which were 0.50 μL/cm2, 82.92 drops/cm2 and 7.67%, respectively.【Conclusion】The actual occurrence level of pests should be taken into consideration in the selection of operation parameters at trumpet stage and heading stage of maize. The highest droplet deposition was achieved when the UAV flew at a speed of 4 m/s, an altitude of 2.5 m and a nozzle type of SX110015VS, the corrected control efficiency was more than 85% after 7 days of application.

As the hallmark of cancer, genetic and phenotypic heterogeneity leads to biomarkers that are typically tailored to specific cancer type or subtype. This specificity introduces complexities in facilitating streamlined evaluations across diverse cancer types and optimizing therapeutic outcomes. In this study, we comprehensively characterized the radiological patterns underlying liver cancer (LC) by integrating radiomics profiles from computed tomography (CT) images of hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and colorectal cancer liver metastases (CRLM) through unsupervised clustering analysis. We identified three distinct radiomics clusters, displaying heterogeneity in prognosis. Subsequently, we formulated a shared prognosticator, the liver cancer radiomics signature (LCRS), by discovering and manifesting connectivity among radiomics phenotypes using GGI strategy. We validated that the LCRS is independent prognostic factor after adjusting for clinic-pathologic variables (all P

Abstract Introduction The United States Centers for Disease Control and Prevention (CDC) advises testing individuals for COVID-19 after exposure or if they display symptoms. However, a deeper understanding of demographic factors associated with testing hesitancy is necessary. Methods A US nationwide cross-sectional survey of adults with risk factors for developing severe COVID-19 (“high-risk” individuals) was conducted from August 18–September 5, 2023. Objectives included characterizing demographics and attitudes associated with COVID-19 testing. Inverse propensity weighting was used to weight the data to accurately reflect the high-risk adult US population as reflected in IQVIA medical claims data. We describe here the weighted results modeled to characterize demographic factors driving hesitancy. Results In the weighted sample of 5019 respondents at high risk for severe COVID-19, 58.2% were female, 37.8% were ≥ 65 years old, 77.1% were White, and 13.9% had a postgraduate degree. Overall, 67% were Non-testers (who indicated that they were unlikely or unsure of their likelihood of being tested within the next 6 months); these respondents were significantly more likely than Testers (who indicated a higher probability of testing within 6 months) to be female (60.2 vs. 54.1%; odds ratio [OR] [95% confidence interval (CI)], 1.3 [1.1‒1.4]), aged ≥ 65 years old (41.5 vs. 30.3%; OR [95% CI] compared with ages 18‒34 years, 0.6 [0.5‒0.7]), White (82.1 vs. 66.8%; OR [95% CI], 1.4 [1.1‒1.8]), and to identify as politically conservative (40.9 vs. 18.1%; OR [95% CI], 2.6 [2.3‒2.9]). In contrast, Testers were significantly more likely than Non-testers to have previous experience with COVID-19 testing, infection, or vaccination; greater knowledge regarding COVID-19 and testing; greater healthcare engagement; and concerns about COVID-19. Conclusions Older, female, White, rural-dwelling, and politically conservative high-risk adults are the most likely individuals to experience COVID-19 testing hesitancy. Understanding these demographic factors will help guide strategies to improve US testing rates.

Abstract Background Vitamin D deficiency is common in pregnancy, however, its effects has not been fully elucidated. Here, we conducted targeted metabolomics profiling to study the relationship. Methods This study enrolled 111 pregnant women, including sufficient group (n = 9), inadequate group (n = 49) and deficient group (n = 53). Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabonomics were used to characterize metabolite profiles associated with vitamin D deficiency in pregnancy. Results Many metabolites decreased in the inadequate and deficient group, including lipids, amino acids and others. The lipid species included fatty acyls (FA 14:3, FA 26:0; O), glycerolipids (MG 18:2), glycerophospholipids (LPG 20:5, PE-Cer 40:1; O2, PG 29:0), sterol lipids (CE 20:5, ST 28:0; O4, ST 28:1; O4). Decreased amino acids included aromatic amino acids (tryptophan, phenylalanine, tyrosine) and branched-chain amino acids (valine, isoleucine, leucine), proline, methionine, arginine, lysine, alanine, L-kynurenine,5-hydroxy-L-tryptophan, allysine. Conclusions This targeted metabolomics profiling indicated that vitamin D supplementation can significantly affect lipids and amino acids metabolism in pregnancy.

Aiming at the issues of complexity, high investment costs, limited heating efficiency improvement, high failure rate, and poor reliability of traditional intermediate and high frequency electromagnetic heating systems, we propose a pipeline-type power-frequency electromagnetic coupling heating device. This device is designed based on transformer principles and utilizes Maxwell's equations and Fourier's heat conduction equation theory to achieve high efficiency and uniform heating. By performing three-dimensional transient field analysis of the heating device, parameters such as the voltage of the primary winding and the secondary winding (pipeline) are calculated to validate the feasibility of the heating scheme. To further enhance the economic efficiency of the heating device, the magnetic induction strength of the core with different hollow sizes is investigated. From this, the optimal hollow radius of the core structure was determined, achieving a saving ratio of approximately 36.52 %. Temperature field analysis of the heating device demonstrated that setting the fluid inside the pipeline to a certain water flow rate can achieve efficient heating of the fluid. Additionally, for applications requiring power regulation, a multi-layer winding-based power regulation method is proposed. Calculations show that this method achieves a heating efficiency exceeding 98 % under four different power settings. Compared to mid- and high-frequency electromagnetic coupling heating and electrode boiler heating methods, the heating efficiency increases by 1.39 % and 8 %, respectively. The proposed pipeline-style power-frequency electromagnetic coupling heating device does not require a boiler body, power electronic components, or even a high-power electrical transformer, thus significantly reducing costs compared to mid-frequency electromagnetic heating devices and electrode boilers, greatly enhancing economic efficiency. The study results suggest that energy output can be managed as needed, reducing the impact of loading and unloading on the local power grid and equipment, demonstrating strong practicality. This provides a new effective heating approach for industrial production of hot water and steam, centralized heating in urban and rural areas, and thermal power plants.

Objective: Traumatic brain injury (TBI) is among the leading causes of death and disability globally. Identifying and assessing the risk of in-hospital mortality in traumatic brain injury patients at an early stage is challenging. This study aimed to develop a model for predicting in-hospital mortality in TBI patients using prehospital data from China. Methods: We retrospectively included traumatic brain injury patients who sustained injuries due to external forces and were treated by pre-hospital emergency medical services (EMS) at a tertiary hospital. Data from the pre-hospital emergency database were analyzed, including demographics, trauma mechanisms, comorbidities, vital signs, clinical symptoms, and trauma scores. Eligible patients were randomly divided into a training set (241 cases) and a validation set (104 cases) at a 7:3 ratio. Least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were employed to identify independent risk factors. Analyzed the discrimination, calibration, and net benefit of the nomogram across both groups. Results: 17.40 % (42/241) of TBI patients died in the hospital in the training set, while 18.30 % (19/104) in the validation set. After analysis, chest trauma (odds ratio [OR] = 4.556, 95 % confidence interval [CI] = 1.861–11.152, P = 0.001), vomiting (OR = 2.944, 95%CI = 1.194–7.258, P = 0.019), systolic blood pressure (OR = 0.939, 95%CI = 0.913–0.966, P

IntroductionThe association between a plant-based diet and weight loss and atherosclerotic cardiovascular disease (ASCVD) has not been fully elucidated. We performed a pooled analysis and Mendelian randomization (MR) analysis to investigate this question.MethodsWe searched for randomized controlled trials on the effects of a plant-based diet on weight loss compared with a non-plant-based diet. In addition, a two-sample MR study was conducted. IVs were obtained from the genome-wide association studies (GWAS) on the exposures, and we obtained summary statistics on the outcomes. The inverse-variance weighted (IVW) method was used as the main analysis and other MR methods were performed as supplementary analyses.ResultsIndividuals on the plant-based diet lost more weight than the non-plant-based diet group (WMD −0.96 kg; 95% CI: −1.32 to −0.60). Population conditions and energy restriction were identified as the study-level factors that influenced the pooling results in the subgroup analyses. Increased consumption of raw vegetables was significantly associated with lower BMI (IVW, β −0.35, 95% CI: −0.62 to −0.08, p = 0.012) and lower risk of obesity (IVW, OR 0.11, 95% CI: 0.01 to 0.99, p = 0.048), coronary heart disease (IVW, OR 0.44, 95% CI: 0.21 to 0.92, p = 0.029) and myocardial infarction (IVW, OR 0.39,95% CI: 0.15 to 0.98, p = 0.045) and a higher HDL-C (IVW, β 0.47, 95% CI: 0.24 to 0.70, p = 4×10−5).DiscussionThe present findings suggest that raw vegetable intake is beneficial for weight loss and prevention of ASCVD.

BackgroundBeinaglutide, whose active ingredient is rhGLP-1, has been widely used as a pharmacological therapy for T2DM. We explored the safety and pharmacokinetics of beinaglutide in Chinese overweight/obese volunteers to lay a foundation for clinical applications of beinaglutide as an anti-obesity drug.MethodsAn open-label, single center, multiple ascending dose phase I clinical trial was conducted in 16 overweight/obese Chinese volunteers. The plasma concentrations of beinaglutide were determined by a validated ELISA method and the pharmacokinetic parameters were estimated via non-compartmental analysis methods. Adverse events were also recorded.ResultsBeinaglutide sequentially multiple dosing (three times daily) at different doses were generally well tolerated, without serious AEs leading to discontinuation of the trial. After multiple subcutaneous injections of different doses (0.1, 0.14 and 0.2 mg), the average blood concentration of beinaglutide with or without baseline correction showed a similar trend among different dose groups on different study days. After reaching the peak concentration around 15 min, it began to decrease, and the median of Tmax and Tmax,adj was 10–15 min. The exposure in vivo increased in proportion to the dosage increment, demonstrating linear pharmacokinetic characteristics. There were no statistically significant differences in the main PK parameters and no accumulation of beinaglutide after multiple dosing. After multiple subcutaneous injections, a gender difference was observed, while no differences in BMI were found under the grouping conditions.ConclusionThe safety profile and pharmacokinetic properties support further development and clinical applications of beinaglutide as an anti-obesity drug.Systematic Review Registration[https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BPEI&selectaction=Edit&uid=U00050YQ&ts=2&cx=wy0ioj].

Abstract Cell migration is crucial for numerous physiological and pathological processes. A cell adapts its morphology, including the overall and nuclear morphology, in response to various cues in complex microenvironments, such as topotaxis and chemotaxis during migration. Thus, the dynamics of cellular morphology can encode migration strategies, from which diverse migration mechanisms can be inferred. However, deciphering the mechanisms behind cell migration encoded in morphology dynamics remains a challenging problem. Here, we present a powerful universal metric, the Cell Morphological Entropy (CME), developed by combining parametric morphological analysis with Shannon entropy. The utility of CME, which accurately quantifies the complex cellular morphology at multiple length scales through the deviation from a perfectly circular shape, is illustrated using a variety of normal and tumor cell lines in different in vitro microenvironments. Our results show how geometric constraints affect the MDA-MB-231 cell nucleus, the emerging interactions of MCF-10A cells migrating on collagen gel, and the critical transition from proliferation to invasion in tumor spheroids. The analysis demonstrates that the CME-based approach provides an effective and physically interpretable tool to measure morphology in real-time across multiple length scales. It provides deeper insight into cell migration and contributes to the understanding of different behavioral modes and collective cell motility in more complex microenvironments.

Fabric defect detection is a crucial step of quality control in textile enterprises. The use of computer vision inspection technology in the textile industry is key to achieving intelligent manufacturing. This study sought to determine the progress made and future research directions in intelligent fabric surface defect detection by comprehensively reviewing published literature in terms of algorithms, datasets, and detection systems. Initially, the detection methods are classified as traditional and learning-based methods. The traditional methods are subdivided into model, spectral, statistical, and structural approaches. Learning-based methods are categorized into classical machine learning methods and deep learning methods. The principles, model performance, detection rate, real-time performance, and applicability of deep learning methods are highlighted and compared. In addition, the strengths and weaknesses of all the approaches are elaborated. The use of fabric defect datasets and deep learning frameworks is analyzed. Public datasets and commonly used frameworks are collated and organized. The application of existing fabric inspection systems on the market is outlined. Fabric defect types are systematically named and analyzed. Finally, future research directions are discussed to provide guidance for researchers in related fields.

As urbanization accelerates, the management of urban solid waste poses increasingly intricate challenges. Traditional urban metrics, such as GDP and per capita consumption rates, have become inadequate for accurately reflecting the realities of waste generation; moreover, the linear correlation between these metrics and waste production is progressively diminishing. Consequently, this study introduces a novel methodology leveraging nighttime light remote sensing data to enhance the precision of urban solid waste production forecasts. By processing remote sensing data to mitigate noise and integrating it with conventional urban datasets, an innovative index system and predictive model were developed. Using Beijing as a case study, the gradient boosting regression algorithm yielded a prediction accuracy of 92%. Furthermore, in light of the substantial costs associated with waste recovery route planning and site selection for treatment facilities, this research further devised a location and distribution framework for waste treatment centers based on high-precision predictions of waste production while employing multi-objective evolutionary algorithms (MOEAs) alongside the non-dominated sorting genetic algorithm II (NSGA-II) for optimization. Distinct from prior studies, this study suggests that service point waste quantities are not fixed values but rather adhere to a normal distribution within specified ranges and thus provides a more realistic simulation of fluctuations in waste production while enhancing both the robustness and predictive accuracy of the model. In conclusion, by incorporating nighttime light remote sensing data along with advanced machine learning techniques, this study markedly improves forecasting accuracy for waste production while offering effective optimization strategies for site selection and recovery route planning—thereby establishing a robust data foundation aimed at refining urban solid waste management systems.

The 3D mesh fabric is a key component of automotive seat ventilation systems as it has good compression resistance and creates channels to provide effective circulating airflow. The dimensional inconsistency of fabric sheets by laser cutting to be integrated into car seats and their unrecoverable dimension changes in subsequent cushioning applications are challenging problems. A typical commercialized 3D mesh fabric was observed to shorten and widen under compression, showing an auxetic behavior in the length–thickness section. This counterintuitive partial auxetic behavior accounts for the dimensional variation. A full-size finite element (FE) model of the fabric was established to simulate the complex fabric deformation based on the precise geometry of a unit cell obtained by X-ray micro-computed tomography (μCT) scanning. The FE simulation reproduced the planar dimension change process of the fabric. The underlying mechanism of partial auxeticity was revealed from the global to local analysis, including fabric global deformation, unit meshes deformation and unit cell geometric structure change. It was shown that buckling of initially post-buckled spacer monofilaments drives in-plane movements of monofilament loops to cause partial auxetic behavior. The partial auxeticity weakens in the compression process due to the gradual intercontact and densification of spacer monofilaments. Different constraints on monofilament loops from adjacent unit cells and multifilament inlays make the deformation uneven in the plane of fabric. It is important to fully analyze the dimensional change, especially the partial auxetic deformation, of the 3D mesh fabric under compression for its practical applications.

ObjectiveTo systematically evaluate the efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) on language function in patients with non-fluent aphasia post-stroke.MethodsWe selected randomized clinical trials (RCT) that involved stroke patients with non-fluent aphasia, whose intervention was rTMS vs. no therapy or other therapy. Two researchers autonomously reviewed the literature based on the specified criteria for inclusion and exclusion and completed the process of data extraction, data verification, and quality evaluation. Meta-analysis was performed using RevMan 5.41 and Stata MP 172, while the assessment of risk of bias was carried out utilizing the Risk of Bias version 2 tool (RoB2)3.ResultsThe meta-analysis involved 47 RCTs, encompassing 2,190 patients overall. The indexes indicated that rTMS has the potential to decrease the severity of non-fluent aphasia in stroke patients, including improvement of the capability of repetition, naming, and spontaneous language. The determination of BDNF in the serum of patients was also increased. In addition, rTMS reduced the likelihood of depression in stroke patients.ConclusionTo summarize the relevant studies, rTMS has significant effects on improving the language abilities of stroke patients suffering from non-fluent aphasia, including the abilities of repetition, naming, and spontaneous language.

ABSTRACTStaphylococcus aureus (S. aureus) is a leading cause of bacteremia and blood stream infections. Methicillin-resistant S. aureus (MRSA) that first appeared in 1961 often caused hospital-acquired infections (HAIs) and community-acquired infections (CAIs) and was associated with high mortality rate. Accurate and rapid point-of-care testing (POCT) of MRSA is crucial for clinical management and treatment of MRSA infections, as well as the prevention and control of HAIs and CAIs. Here, we reported a novel extraction-free dual HiFi-LAMP assay for discriminative detection of methicillin-susceptible S. aureus and MRSA. The dual HiFi-LAMP assay can detect 30 copies/reaction of nuc and mecA genes with detection limits of 147 and 158 copies per 25 µL reaction, respectively. A retrospective clinical evaluation with 107 clinical S. aureus isolates showed both sensitivity and specificity of 100%. A prospective clinical evaluation with 35 clinical samples revealed a specificity of 100% and a sensitivity of 92.3%. The dual HiFi-LAMP assay can detect almost all S. aureus samples (141/142; 99.3%) within 20 min, implying that the entire HiFi-LAMP assay (including sample process) can be completed within 40 min, extremely significantly shorter than 3–5 days by the traditional clinical microbial culture and antibiotic susceptibility testing. The novel extraction-free dual HiFi-LAMP assay can be used as a robust POCT tool to promote precise diagnosis and treatment of MRSA infections in hospitals and to facilitate surveillance of MRSA at hospital and community settings.IMPORTANCEMethicillin-resistant Staphylococcus aureus (MRSA) was associated with high mortality rate and listed as a “priority pathogen” by the World Health Organization. Accurate and rapid point-of-care testing (POCT) of MRSA is critically required for clinical management and treatment of MRSA infections. Some previous LAMP-based POCT assays for MRSA might be questionable due to their low specificity and the lack of appropriate evaluation directly using clinical samples. Furthermore, they are relatively tedious and time-consuming because they require DNA extraction and lack multiplex detection capacity. Here, we reported a novel extraction-free dual HiFi-LAMP assay for discriminative detection of MRSA and methicillin-susceptible S. aureus. The assay has high specificity and sensitivity and can be completed within 40 min. Clinical evaluation with real clinical samples and clinical isolates showed excellent performance with 100% specificity and 92.3%–100% sensitivity. The novel extraction-free assay may be a robust POCT tool to promote precise diagnosis of MRSA infections and facilitate surveillance of MRSA at hospital and community settings.

Abstract Background Physical exercise is the first-line intervention for prediabetes, and metformin is the most widely used oral insulin-sensitizing agent. Moreover, intermuscular adipose tissue (IMAT) directly affects insulin resistance by helping maintain glucose homeostasis. Here, we evaluated the effects of moderate aerobic exercise and/or metformin on histological IMAT parameters in non-streptozotocin-induced prediabetes. Methods Male Wistar rats with prediabetes fed a high-fat diet and high-sugar drinks were randomly assigned to high-fat diet (PRE), metformin (MET), moderate aerobic exercise (EXE), combined therapy (EMC), or EMC + compound-c (EMA) groups for 4 weeks. Multimodal magnetic resonance imaging (MRI) was then performed, and tissue-specific inflammation and energy and lipid metabolism were evaluated in IMAT. Results The EXE group had lower inflammatory factor levels, lipid metabolism, and mitochondrial oxidative stress, and shorter IMAT adipocyte diameters than the MET group. The MET group exhibited lower IL-1β and Plin5 expression than the PRE group. Furthermore, the IMAT of the EMC group had lower TNF-α and phosphorylated NF-κB levels and higher GLUT1 and GLUT4 expression than the PRE group. Multimodal MRI revealed significant changes in transverse-relaxation time 2, apparent diffusion coefficient, and fractional anisotropy values in the IMAT and muscles, as well as lower IMAT% values in the EXE and EMC groups than in the MET and PRE groups. Conclusion Moderate aerobic exercise training can effectively improve IMAT function and structure via the AMP-activated protein kinase pathway in prediabetes. Combining metformin with moderate aerobic exercise might elicit modest synergy, and metformin does not counterbalance the beneficial effects of exercise.

In the last decade, unmanned aerial vehicles (UAVs) for plant protection have rapidly developed worldwide as a new method for pesticide application, especially in China and other Asian countries. To improve the deposition quality in UAV applications, adding appropriate types of spray adjuvants into pesticide solutions is one of the most effective ways to facilitate droplet deposition and control efficacy. At present, research on spray adjuvants for UAVs are mainly based on droplet drift and laboratory tests. Few studies have been conducted on the physicochemical properties of spray adjuvants and the effects of droplet deposition characteristics. To explore the properties of four different kinds of spray adjuvants (Mai Fei, Bei Datong, G-2801, and Agrospred 910) and the deposition characteristics of spray adjuvants on litchi leaves, an automatic surface tension meter, a contact angle measuring device, an ultraviolet visible spectrophotometer, and a DJI AGRAS T30 plant protection UAV was used to measure the surface tension, contact angle, and droplet deposition characteristics on litchi under UAV spraying operations. The results showed that the addition of spray adjuvants could significantly reduce the surface tension of the solution. The surface tension value of the solution after adding the spray additives was reduced by 53.1–68.9% compared with the control solution. Among them, the Agrospred 910 spray adjuvant had the best effect on reducing the surface tension of the solution. The contact angle of the control solution on the litchi leaves varied from 80.15° to 72.76°. With the increase in time, the contact angle of the spray adjuvant solution gradually decreased, the Agrospred 910 spray adjuvant had the best effect, and the contact angle decreased from 40.44° to 20.23° after the droplets fell on the litchi leaves for 60 s. The adjuvant solutions increased the droplet size, but the uniformity of the droplet size decreased. The Dv0.5 of different spray solutions ranged from 97.3 to 117.8 μm, which belonged to the fine or very fine droplets, and the Dv0.5 of adjuvants solutions were significantly greater than that of the control solution. The RSs of adjuvant solutions were very similar and ranged from 0.92 to 0.96, all of which were significantly greater than the result of the control solution (0.57). Compared with the deposition of the control solution, the Mai Fei, Bei Datong, and G-2801 solutions clearly increased spray deposition, with total depositions of 0.776, 0.705, and 0.721 μL/cm2, which are all greater than the total deposition of the control solution of 0.645 μL/cm2. The addition of tank-mixed adjuvants could effectively increase the uniformity of the spray deposition, and all the average CVs of adjuvant solutions were lower than 96.86%. On the whole, Mai Fei performed best in increasing the spray deposition and promoting penetration, followed by Bei Datong and G-2801. Meanwhile, the test can also provide a reference for improving the utilization rate of UAV pesticide applications.

Ultrasound technology has been extensively used as one of the efficient and economic methodology to achieve the desired outcomes in many applications by harnessing the physico-chemical effects of acoustic cavitation. However, the cavitation-associated effects, primarily determined by the oscillatory dynamics of cavitation bubbles, are considerably complex and still remain poorly understood. The main objective of this study was to perform a numerical analysis of the acoustic cavitation (i.e., the cavitation dynamics, the resultant temperature, pressure and chemical yields within collapsing bubbles), particularly focusing on the influence of the interactions between bubbles. A comprehensive model was developed to simulate the acoustic cavitation dynamics via combining the influences of mass transfer, heat conduction and chemical reactions as well as the interaction effects between bubbles. The results demonstrated that only the large bubble exerts a greater impact on the small one in a two-bubble system. Specifically, within parameter ranges covered this study, there are noticeable decreases in the expansion ratio of the small bubble, the resultant temperature, pressure and molar yields of free radicals, hence weakening the cavitation intensity and cavitation- associated physico-chemical effects. Moreover, the influences of the interactions between bubbles were further assessed quantitatively under various parameters, such as the ultrasound amplitude PA and frequency f, the distance between bubbles d0, the initial radius of the large bubble R20, as well as the liquid properties (e.g., surface tension σ and viscosity μ). It was found that the suppression effect can be amplified when subjected to ultrasound with an increased PA and/or a decreased f, probably due to a stronger cavitation intensity under this condition. Additionally, the suppression effect is also enhanced with a decrease in d0, σ and μ, but with R20 increasing. This study can contribute to deepening knowledge about acoustic cavitation and the resultant physical and/or chemical effects, potentially further facilitating the ultrasound-assisted various applications involving acoustic cavitation.

Summary: Background: Currently, the diagnostic testing for the primary origin of liver metastases (LMs) can be laborious, complicating clinical decision-making. Directly classifying the primary origin of LMs at computed tomography (CT) images has proven to be challenging, despite its potential to streamline the entire diagnostic workflow. Methods: We developed ALMSS, an artificial intelligence (AI)-based LMs screening system, to provide automated liver contrast-enhanced CT analysis for distinguishing LMs from hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), as well as subtyping primary origin of LMs as six organ systems. We processed a CECT dataset between January 1, 2013 and June 30, 2022 (n = 3105: 840 HCC, 354 ICC, and 1911 LMs) for training and internally testing ALMSS, and two additional cohorts (n = 622) for external validation of its diagnostic performance. The performance of radiologists with and without the assistance of ALMSS in diagnosing and subtyping LMs was assessed. Findings: ALMSS achieved average area under the curve (AUC) of 0.917 (95% confidence interval [CI]: 0.899–0.931) and 0.923 (95% [CI]: 0.905–0.937) for differentiating LMs, HCC and ICC on both the internal testing set and external testing set, outperformed that of two radiologists. Moreover, ALMSS yielded average AUC of 0.815 (95% [CI]: 0.794–0.836) and 0.818 (95% [CI]: 0.790–0.842) for predicting six primary origins on both two testing sets. Interestingly, ALMSS assigned origin diagnoses for LMs with pathological phenotypes beyond the training categories with average AUC of 0.761 (95% [CI]: 0.657–0.842), which verify the model's diagnostic expandability. Interpretation: Our study established an AI-based diagnostic system that effectively identifies and characterizes LMs directly from multiphasic CT images. Funding: National Natural Science Foundation of China, Guangdong Provincial Key Laboratory of Medical Image Processing.

Background: Although previous studies have shown an association between prenatal exposure to perfluorinated and polyfluoroalkyl substances (PFAS) and neurodevelopmental disorders in children, the results have been inconsistent. We summarize studies on the association between prenatal PFAS exposure and neurodevelopment in children in order to better understand the relationship. Objective: We conducted a meta-analysis of prenatal PFAS exposure and developmental outcomes associated with intellectual, executive function and behavioral difficulty in children to explore the relationship between prenatal exposure to perfluorinated and polyfluoroalkyl substances (PFAS) and neurodevelopmental disorders in children. Methods: We searched for articles published up to August 3, 2023, included and quantified original studies on PFAS and child Intelligence Quotient (IQ), executive function and behavioral difficulty during pregnancy, and systematically summarized articles that could not be quantified. Conclusion: There is evidence of sex-specific relationship between PFAS exposure and children's PIQ. We found that PFOS [β = −1.56, 95% CI = −2.96, − 0.07; exposure = per 1 ln (ng/ml) increase], PFOA [β = −1.87, 95% CI = −3.29, − 0.46; exposure = per 1 ln (ng/ml) increase], PFHxS [β = −2.02, 95% CI = −3.23, − 0.81; exposure = per 1 ln (ng/ml) increase] decreased performance IQ in boys, but PFOS [β = 1.56, 95% CI = 0.06, 3.06; exposure = per 1 ln (ng/ml) increase] increased performance IQ in girls. PFAS are associated with executive function impairments in children, but not related to behavioral difficulty in children.

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.

Abstract The stacking of twisted two-dimensional (2D) layered materials has led to the creation of moiré superlattices, which have become a new platform for the study of quantum optics. The strong coupling of moiré superlattices can result in flat minibands that boost electronic interactions and generate interesting strongly correlated states, including unconventional superconductivity, Mott insulating states, and moiré excitons. However, the impact of adjusting and localizing moiré excitons in Van der Waals heterostructures has yet to be explored experimentally. Here, we present experimental evidence of the localization-enhanced moiré excitons in the twisted WSe2/WS2/WSe2 heterotrilayer with type-II band alignments. At low temperatures, we observed multiple excitons splitting in the twisted WSe2/WS2/WSe2 heterotrilayer, which is manifested as multiple sharp emission lines, in stark contrast to the moiré excitonic behavior of the twisted WSe2/WS2 heterobilayer (which has a linewidth 4 times wider). This is due to the enhancement of the two moiré potentials in the twisted heterotrilayer, enabling highly localized moiré excitons at the interface. The confinement effect of moiré potential on moiré excitons is further demonstrated by changes in temperature, laser power, and valley polarization. Our findings offer a new approach for localizing moiré excitons in twist-angle heterostructures, which has the potential for the development of coherent quantum light emitters.

Background: Polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) can both contribute to adverse maternal and neonatal outcomes. There is relatively limited research on the outcomes for women who have a history of both PCOS and GDM. Our study attempt to explore how the presence of comorbid PCOS affects pregnancy outcomes in women with GDM. Methods: Our study was a retrospective study of women diagnosed with GDM through a 75 g oral glucose tolerance test (OGTT) at our hospital from January 1, 2021, to December 31, 2022. We divided the participants into two groups, group +GDM/+PCOS and group +GDM/-PCOS, based on their history of PCOS. We compared clinical variables, delivery details and neonatal complications between the two groups. Results: Among the 149 women enrolled in the study with GDM, a total of 44 women were diagnosed with PCOS. Women with GDM and PCOS have higher plasma glucose level at 120 minutes (PG120) level (9.17 mmol/L vs 8.59 mmol/L, p = 0.001). The incidence of postpartum hemorrhage is higher in women with history of GDM and PCOS (2.9% vs 22.7%, p < 0.01). On regression analysis, plasma glucose level at 60 minutes (PG60) level (odds ratio (OR) 6.341, 95% confidence interval (CI) 1.69~23.76, p = 0.006) and PCOS (OR 36.105, 95% CI 3.89~335, p = 0.002) were identified as independent risk factors for postpartum hemorrhage. We also found that infants born to mothers with PCOS and GDM had lower Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) scores at 1 minute after birth (p < 0.01). PCOS was also an independent risk factor for lower 1-minute APGAR scores on regression analysis (β = –0.296, t = –3.852, p < 0.001). Conclusions: Women who co-presented with GDM and PCOS had worse postprandial blood glucose levels, higher rates of postpartum hemorrhage, and lower 1-minute APGAR scores in newborns. The management of PCOS should be promptly initiated, with close monitoring of blood glucose levels throughout pregnancy, and timely implementation of intervention measures to optimize obstetric and neonatal outcomes.

As infectious diseases have a severe impact on the individual survival and competitive ability of host species in grassland communities, competition between relevant species may have different consequences, potentially influencing the species composition of grassland communities and the functioning of grassland ecosystems. Understanding the impact of infectious diseases on competition is thus crucial for the health management of grassland ecosystems. How do infectious diseases affect the competitive coexistence of grassland plant species? In this study, by drawing on Tilman’s multispecies competition model and incorporating the spread characteristics of grassland plant diseases, we built three spatial competition models of two grass species subject to infectious diseases, and we analyzed the invasion conditions of infectious diseases and how they impact the population dynamics and competitive consequences of the species. Our model revealed the following: (1) Diseases with high transmission rates and low virulence are more likely to invade populations, while the presence of non-host species is detrimental to disease invasion. (2) Disease promotes the coexistence of competing species, breaking down the original competition–compromise trade-off mechanism for species coexistence and greatly expanding the range of parameters within which the two species can coexist. (3) Pathogen infections indirectly weaken the suppression of inferior species by dominant species, which is similar to the cascade effect seen in trophic interactions. Our findings highlight the importance of disease in species coexistence and grassland biodiversity maintenance.

This study presents a method for analyzing dimethomorph residues in lychee using QuEChERS extraction and HPLC-MS/MS. The validation parameters for this method, which include accuracy, precision, linearity, and recovery, indicate that it meets standard validation requirements. Following first-order kinetics, the dissipation dynamic of dimethomorph in lychee was determined to range from 6.4 to 9.2 days. Analysis of terminal residues revealed that residues in whole lychee were substantially greater than those in the pulp, indicating that dimethomorph residues are predominantly concentrated in the peel. When applied twice and thrice at two dosage levels with pre-harvest intervals (PHIs) of 5, 7, and 10 days, the terminal residues in whole lychee ranged from 0.092 to 1.99 mg/kg. The terminal residues of the pulp ranged from 0.01 to 0.18 mg/kg, with the residue ratio of whole lychee to pulp consistently exceeding one. The risk quotient (RQ) for dimethomorph, even at the recommended dosage, was less than one, indicating that the potential for damage was negligible. This study contributes to the establishment of maximum residue limits (MRLs) in China by providing essential information on the safe application of dimethomorph in lychee orchards.

Babao Dan capsule (BBDC) is a state secrecy traditional Chinese medicine patent prescription (TCMPP) that is widely used for hepatobiliary and urinary diseases. However, its quality uniformity evaluation (QUE) is lacking. It is necessary to develop a novel and multi–dimensional QUE strategy for BBDC based on chemical properties and bioactivities. An ultrahigh performance liquid chromatography–triple quadrupole–mass spectrometry (UHPLC–QQQ–MS/MS) was developed to quantify 14 compounds, and a QUE strategy was to assess intra–batch and inter–batches consistency. Furthermore, the anti-inflammatory activities were measured in vitro by RAW264.7 cell and NF-κB-RE-luc HEK293 cell. The results indicated that 14 compounds from 16 samples (10 batches) were accurately quantified. And the intra–batch consistency values were less than or equal to 20.1%, whereas the largest inter–batches consistency value was 167.5% of glycocholic acid. 10 batches were divided into three categories to distinction inter–batches differences. BBDC had anti-inflammatory activities including inhibition of LPS–induced NO production and TNF α–activated luciferase counts. The NO inhibition difference of 10 batches was 10.87 μM and accounted for 49.8%. Briefly, the anti-inflammatory activities of 10 batches were different, but the dynamic trends within the same batch were similar, which was supported by luciferase counts. And the correlation was confirmed that the main compounds related to anti-inflammatory in BBDC were bile acids and saponins. Hence, a QUE strategy for BBDC was proposed to improve quality and ensure efficacy. This strategy can be utilized as a reference for consistency evaluations of TCMPPs.

Abstract Singlet fission (SF) is an appealing process where one photoexcited singlet transforms to two triplets, which can overcome thermalization energy loss and improve solar cell efficiency. However, it remains unclear how intermolecular coupling, which is subject to molecular stacking, controls SF pathways and dynamics. Here, we prepared polymorph rubrene single crystals with different stacking geometries, including orthorhombic (Orth.), triclinic (Tri.), and monoclinic (Mono.) phases. By micro‐area ultrafast spectroscopy, we find that Orth. and Tri. phases with closer π‐π stacking exhibit co‐existing coherent and incoherent SF channels while loosely stacked Mono. phase shows only incoherent SF. Furthermore, incoherent SF is thermally activated in Orth. but barrierless in Mono. and Tri. phases. Quantum mechanical calculation reveals that different electronic coupling strength in different phases leads to different SF dynamics. This study demonstrates that molecular stacking governs SF dynamics through electronic coupling, providing guidance for designing efficient SF materials via crystal structural engineering.

High entropy alloy (HEA) films offer excellent mechanical properties due to their random solid solution structure. However, their large grain boundary volume fraction can cause thermal instability, resulting in phase decomposition that affects their high-temperature performance. Nevertheless, it remains an interesting question whether phase decomposition can be used as a processing tool to create new HEA materials. In this study, AlCrFeCoNiCu0.5 HEA thin films were fabricated and annealed at 500 °C for up to 72 h. The 72-hour annealed thin film exhibited a 30 % increase in mechanical properties, exceeding most other HEA thin films. Characterization using X-ray and electron microscopy revealed a decomposition-induced phase transformation, which produced four new phases, including Cu-rich FCC phase, Cr-rich BCC phase, and ordered B2 phase of AlNi and FeCo. The enhanced mechanical properties were due to back stress strengthening and BCC + B2 phase strengthening. The 72-hour annealed thin film also showed excellent thermal stability through a new round of annealing, exhibiting a low variation in microstructure and chemical composition after being annealed at 500 °C for 100 h.

Objective: Transcriptional complex activity drives the development and function of pancreatic islet cells to allow for proper glucose regulation. Prior studies from our lab and others highlighted that the LIM-homeodomain transcription factor (TF), Islet-1 (Isl1), and its interacting co-regulator, Ldb1, are vital effectors of developing and adult β-cells. We further found that a member of the Single Stranded DNA-Binding Protein (SSBP) co-regulator family, SSBP3, interacts with Isl1 and Ldb1 in β-cells and primary islets (mouse and human) to impact β-cell target genes MafA and Glp1R in vitro. Members of the SSBP family stabilize TF complexes by binding directly to Ldb1 and protecting the complex from ubiquitin-mediated turnover. In this study, we hypothesized that SSBP3 has critical roles in pancreatic islet cell function in vivo, similar to the Isl1::Ldb1 complex. Methods: We first developed a novel SSBP3 LoxP allele mouse line, where Cre-mediated recombination imparts a predicted early protein termination. We bred this mouse with constitutive Cre lines (Pdx1- and Pax6-driven) to recombine SSBP3 in the developing pancreas and islet (SSBP3ΔPanc and SSBP3ΔIslet), respectively. We assessed glucose tolerance and used immunofluorescence to detect changes in islet cell abundance and markers of β-cell identity and function. Using an inducible Cre system, we also deleted SSBP3 in the adult β-cell, a model termed SSBP3Δβ-cell. We measured glucose tolerance as well as glucose-stimulated insulin secretion (GSIS), both in vivo and in isolated islets in vitro. Using islets from control and SSBP3Δβ-cell we conducted RNA-Seq and compared our results to published datasets for similar β-cell specific Ldb1 and Isl1 knockouts to identify commonly regulated target genes. Results: SSBP3ΔPanc and SSBP3ΔIslet neonates present with hyperglycemia. SSBP3ΔIslet mice are glucose intolerant by P21 and exhibit a reduction of β-cell maturity markers MafA, Pdx1, and UCN3. We observe disruptions in islet cell architecture with an increase in glucagon+ α-cells and ghrelin+ ε-cells at P10. Inducible loss of β-cell SSBP3 in SSBP3Δβ-cell causes hyperglycemia, glucose intolerance, and reduced GSIS. Transcriptomic analysis of 14-week-old SSBP3Δβ-cell islets revealed a decrease in β-cell function gene expression (Ins, MafA, Ucn3), increased stress and dedifferentiation markers (Neurogenin-3, Aldh1a3, Gastrin), and shared differentially expressed genes between SSBP3, Ldb1, and Isl1 in adult β-cells. Conclusions: SSBP3 drives proper islet identity and function, where its loss causes altered islet-cell abundance and glucose homeostasis. β-Cell SSBP3 is required for GSIS and glucose homeostasis, at least partially through shared regulation of Ldb1 and Isl1 target genes.

Abstract Conopomorpha sinensis Bradley is a destructive pest that causes severe economic damage to litchi and longan. Previous C. sinensis research has focused on population life tables, oviposition selectivity, pest population prediction, and control technology. However, there are few studies on its mitogenome and phylogenetic evolution. In this study, we sequenced the whole mitogenome of C. sinensis by the third-generation sequencing, and analyzed the characteristics of its mitogenome by comparative genome. The complete mitogenome of C. sinensis is a typical circular and double-stranded structure. The ENC-plot analyses revealed that natural selection could affect the information of codon bias of the protein-coding genes in the mitogenome of C. sinensis in the evolutionary process. Compared with 12 other Tineoidea species, the trnA-trnF gene cluster of tRNA in the C. sinensis mitogenome appears to have a new arrangement pattern. This new arrangement has not been found in other Tineoidea or other Lepidoptera, which needs further exploration. Meanwhile, a long AT repeated sequence was inserted between trnR and trnA, trnE and trnF, ND1 and trnS in the mitogenome of C. sinensis, and the reason for this sequence remains to be further studied. Furthermore, the results of phylogenetic analysis showed that the litchi fruit borer belonged to Gracillariidae, and Gracillariidae was monophyletic. The results will contribute to an improved understanding of the complex mitogenome and phylogeny of C. sinensis. It also will provide a molecular basis for further research on the genetic diversity and population differentiation of C. sinensis.

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 Background Ezetimibe is a new class of antihyperlipidemic agent indicated for the prevention of atherosclerosis disease and for the treatment of hypercholesterolemia. Information on the pharmacokinetic profiles of ezetimibe tablet in healthy Chinese volunteers are lacking, and regulatory requirements necessitate a bioequivalence study of ezetimibe tablet versus Ezetrol® in China. Methods A single-dose randomized, open-label, two-group, two-period crossover study was conducted in 59 healthy Chinese volunteers under fasting or fed conditions to assess the bioequivalence between two preparations. Eligible participants were randomly divided into fasted and fed groups. Blood samples were collected at specified time intervals, and the plasma concentrations of ezetimibe and ezetimibe glucuronide were determined by a validated liquid chromatography-tandem mass spectrometry (LC–MS/MS) method. PK and bioavailability parameters were estimated via non-compartmental methods. Adverse events were also recorded. Results Fifty-nine healthy volunteers were enrolled in the study. The main pharmacokinetic parameters of total ezetimibe in the plasma of the ezetimibe tablet (10 mg) and the Ezetrol® (10 mg) after a single fasting administration: Cmax were (65.73 ± 47.14), (71.32 ± 51.98) ng·mL− 1; Tmax were 1.75, 1.25 h; T½ were (17.09 ± 13.22), (17.35 ± 12.14) h; AUC0-t were (643.34 ± 400.77), (668.49 ± 439.57) h·ng·mL− 1; AUC0-∞ were (706.36 ± 410.92), (734.23 ± 468.26) h·ng·mL− 1. The main pharmacokinetic parameters of total ezetimibe in plasma of ezetimibe tablet (10 mg) and Ezetrol® (10 mg) after a fed administration: Cmax were (83.38 ± 38.95), (84.74 ± 34.62) ng·mL− 1; Tmax were 2.50, 2.50 h; T½ were (22.56 ± 12.68), (19.80 ± 15.59) h; AUC0-t were (494.21 ± 208.65), (536.69 ± 209.11) h·ng·mL− 1; AUC0-∞ were (573.74 ± 252.74), (604.75 ± 247.13) h·ng·mL− 1. The main pharmacokinetic parameters Cmax, AUC0-t, and AUC0-∞ of the two drugs were analyzed by variance analysis after logarithmic transformation. The total ezetimibe under fasting state with 90% confidence intervals (CIs) were 85.29 ~ 97.19, 90.41% ~ 104.38%, and 90.81 ~ 106.05%; total ezetimibe in fed state were 86.36% ~ 109.17, 84.96% ~ 96.40, and 85.32% ~ 101.0%. The 90% CIs of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ of Ezetrol® and ezetimibe tablet both fasting and fed conditions fell within the conventional bioequivalence criteria of 0.80–1.25. Both Cmax and AUC met the predetermined criteria for assuming bioequivalence. No severe adverse events were observed. Conclusions The test ezetimibe tablet and Ezetrol® were determined to be bioequivalent under both fasting and fed conditions in Chinese people. Trial registration Clinicaltrials, NCT05681247 (retrospectively registered in 11/01/ 2023).

Context Ellagic acid (EA) is a phenolic constituent in certain fruits and has largely been recognized for its role as an antioxidant compound.Objective To evaluate the effect of EA on beryllium sulphate-induced splenic toxicity in rats.Materials and methods Male Sprague-Dawley rats were divided into four groups. The first group was used as control. Group 2 was exposed to BeSO4 (12 mg/kg, b.w.). Groups 3 and 4 were treated with EA (100 and 300 mg/kg, b.w.) daily for 6 weeks after exposing to BeSO4 (12 mg/kg, b.w.). Various biochemical and molecular biomarkers were assessed in blood and spleen.Results BeSO4-intoxicated rats showed significant higher WBC (6.74 ± 0.20 × 109/L vs. 11.02 ± 1.31 × 109/L, p

ABSTRACT: Objectives: Refractory cytomegalovirus reactivation (RCR) after allo–hematopoietic stem cell transplantation (HSCT) is associated with poor outcomes. Current studies for the risk factors and survival of patients with post-transplantation RCR remain limited. Methods: 163 patients with Cytomegalovirus (CMV) reactivation undergoing allo-HSCT in Jiangsu Province hospital from Jan 2013 to Dec 2020 were analyzed retrospectively. Results: Multivariate analysis revealed that highest CMV viremia>1 × 104copies/mL (hazard ratio [HR] 16.895, 95% confidence interval [CI] 3.394–84.109, P = 0.001) and platelet count at Day 90 of more than 87.3 × 109/L (HR 0.381, 95% CI 0.154–0.945, P = 0.037) were independent risk factors affecting RCR. As for prognosis of patients with CMV reactivation, results showed that patients with RCR had higher risk of non-relapse mortality (NRM) (39.5% vs. 22.5%, P = 0.045), and RCR was an independent risk factor for NRM (HR 2.216, 95% CI 1.137–4.317, P = 0.019). There was no significance between patients with or without RCR in terms of overall survival (OS) (50.7% vs. 55.6%, P = 0.281) and relapse-free survival (RFS) (43.6% vs. 52.0%, P = 0.179). The landmark analysis showed that patients with RCR had higher NRM (P = 0.01), worse OS (P = 0.02), and RFS (P =0.01) within 100 days after transplantation. Patients with hemorrhagic cystitis (40.9% vs. 64.5%, P =0.028) and who developed viremia>1 × 105copies/mL (43.4% vs. 58.4%, P = 0.033) were associated with worse OS. Conclusion: Factors such as higher viral load, thrombocytopenia, and ATG used in conditioning therapy increased the incidence of RCR. Patients with RCR had worse NRM, OS, and RFS within 100 days after transplantation.

Oral submucous fibrosis is a chronic, inflammatory and potentially malignant oral disease. Local delivery of triamcinolone to lesion site is a commonly used therapy. The existing methods for local drug delivery include topical administration and submucosal injection. However, in the wet and dynamic oral microenvironment, these methods have drawbacks such as limited drug delivery efficiency and injection pain. Therefore, it is urgently needed to develop an alternative local drug delivery system with high efficiency and painlessness. Inspired by the structure of band-aid, this study proposed a novel double-layered mucoadhesive microneedle patch for transmucosal drug delivery. The patch consisted of a mucoadhesive silk fibroin/tannic acid top-layer and a silk fibroin microneedle under-layer. When applying the annealing condition for the medium content of β-sheets of silk fibroin, the microneedles in under-layer displayed both superior morphology and mechanical property. The mechanical strength of per needle (0.071N) was sufficient to penetrate the oral mucosa. Sequentially, the gelation efficiency of silk fibroin and tannic acid in top-layer was maximized as the weight ratio of tannic acid to silk fibroin reached 5:1. Moreover, in vitro results demonstrated the double-layered patch possessed undetectable cytotoxicity. The sustained release of triamcinolone was observed from the double-layered patch for at least 7 days. Furthermore, compared with other commercial buccal patches, the double-layered patch exhibited an enhanced wet adhesion strength of 37.74 kPa. In addition, ex vivo mucosal tissue penetration experiment confirmed that the double-layered patch could reach the lamina propria, ensuring effective drug delivery to the lesion site of oral submucous fibrosis. These results illustrate the promising potential of the drug-loaded mucoadhesive microneedle patch for the treatment of oral submucous fibrosis.

BackgroundAlthough clinically, Alzheimer’s disease (AD) and vascular dementia (VaD) are the two major types of dementia, it is unclear whether the biophotonic activities associated with cognitive impairments in these diseases share common pathological features.MethodsWe used the ultraweak biophoton imaging system (UBIS) and synaptosomes prepared by modified percoll method to directly evaluate the functional changes in synapses and neural circuits in AD and VaD model animals.ResultsWe found that biophotonic activities induced by glutamate were significantly reduced and spectral blueshifted in synaptosomes and brain slices. These changes could be partially reversed by pre-perfusion of the ifenprodil, a specific antagonist of the GluN2B subunit of N-methyl-D-aspartate receptors (NMDARs).ConclusionOur findings suggest that AD and VaD pathology present similar but complex changes in biophotonic activities and transmission at synapses and neural circuits, implying that communications and information processing of biophotonic signals in the brain are crucial for advanced cognitive functions.

Introduction: Langerhans cell histiocytosis (LCH) is a rare disease that usually occurs in children

The utilization of assisted reproductive technologies (ART) is on the rise, resulting in a growing population of ART-conceived offspring. The health concerns of this unique population have attracted significant attention. During ART procedures, gametes and early-stage embryos are exposed to various non-physiological conditions, such as manipulation, culture media, and cryopreservation, which may disrupt embryonic development and potentially impact the health of offspring. Notably, the potential impact of ART on neurodevelopment and its association with an increased risk of neurodevelopmental disorders (NDD) later in life remains a subject of debate. This review aims to summarize the current research advancements concerning the effects of ART on neurodevelopment, specifically focusing on the evidence of the relationship between ART, epigenetic modifications, and NDD, including autism spectrum disorder, intellectual disability, attention deficit hyperactivity disorder, and cerebral palsy. Future studies should prioritize large sample sizes, rigorous adjustment for confounding factors, and the use of interdisciplinary approaches to effectively monitor the neurodevelopmental outcomes of ART-conceived children.

Keypoints 1. A replicative and integrative Di-CRISPR platform was promising in generating an efficient xylose-utilizing Saccharomyces cerevisiae strain. 2. The functional activity of chimeric xylanases was demonstrated in direct hemicellulose-to-ethanol conversion. 3. The feasibility of an accessory enzymatic system of cellulase for simultaneous saccharification and co-fermentation from pretreated C4 grass was evaluated.

Proposed mechanisms underlying the salutary effects of ADAM17 deficiency on diabetic cardiomyopathy. ADAM17 deficiency increases autophagosome formation and improves autophagic flux via reducing ACE2 shedding, activating AMPK pathway, and promoting TFEB nuclear translocation, which reduces the apoptotic response in cardiomyocytes and attenuates left ventricular remodeling and dysfunction in DCM of mice.

In contrast with well-established dearomatization protocols such as the Birch reduction, sigmatropic rearrangement-based dearomatizations are a less-explored but potentially effective route to saturated compounds. Here, the authors show a [5,5]-rearrangement-enabled dearomatization of aryl sulfoxides.

In order to explore the stress-strain characteristics and microstructure evolution of Cu/Al composite plate during corrugated rolling, a three-dimensional finite element model was established. The accuracy of the model was verified by rolling experiments. The compressive stress, shear stress, and equivalent strain at the characteristic position of rolling deformation zone were extracted and their distribution characteristics were analyzed. In addition, the morphology of the bonding interface and mass fraction of Al on Cu plate side were characterized by scanning electron microscopy. The results show that when the reduction rate is 50%, the compressive stress reaches the maximum value (1 306.28 MPa), and the equivalent strain reaches the maximum at the front waist near the outlet. The corrugated rolling process produces three rolling zones, which promotes the surface metal rupture and the outflow of fresh metal, and facilitates the bonding of dissimilar metals. The mass fraction of Al at multiple positions on the Cu plate side at outlet exceeds 40%. The front waist of Cu plate bears severe deformation, and is obviously thinner than the back waist.

The moiré intralayer excitons in the twisted WSe2/WSe2 homobilayers superlattices were successfully observed and confirmed the existence of moiré intralayer excitons.

The present study describes the development of a highly effective approach for determining the residue distribution and dissipation of trifloxystrobin and tebuconazole, and their risk assessment in brown rice, husk, straw, and grain using high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS). The current study provides considerable novel information regarding the safe utilization of a mixture of trifloxystrobin and tebuconazole in paddy production. The samples demonstrated a range of mean recoveries between 72% and 86%, with a 1.1–9.2% relative standard deviation (RSD). The limits of quantification (LOQ) and half-lives (t1/2) for brown rice, husk, straw, and grain were, respectively, established to be 0.001–0.01 mg/kg and 4.1–7.7 days. The concentrations of terminal residues in the brown rice, husk, straw, and grain were, respectively, found to be 0.02–0.05, 0.03–0.11, 0.02–0.07, and 0.02–0.05 mg/kg after being treated twice at 168.75 g a.i./ha with 21 and 28 days of pre-harvest intervals (PHIs). Trifloxystrobin and tebuconazole presented a non-negligible chronic risk to human subjects, as evidenced by a risk quotient (RQ) value of less than 1.

Proteolysis-targeting chimera (PROTAC) technology is a groundbreaking therapeutic approach with significant clinical potential for degrading disease-inducing proteins within targeted cells. However, challenges related to insufficient target selectivity raise concerns about PROTAC toxicity toward normal cells. To address this issue, researchers are modifying PROTACs using various approaches to enhance their target specificity. This review highlights innovative optically controlled PROTACs as anti-cancer therapies currently used in clinical practice and explores the challenges associated with their efficacy and safety. The development of optically controlled PROTACs holds the potential to significantly expand the clinical applicability of PROTAC-based technology within the realm of drug discovery.