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Abstract As the global demand for clean energy continues to rise, wind power has become one of the most important renewable energy sources. However, wind power data often contains a high proportion of dense anomalies, which not only significantly affect the accuracy of wind power forecasting models but may also mislead grid scheduling decisions, thereby jeopardizing grid security. To address this issue, this paper proposes an adaptive threshold robust regression model (RPR model) based on the combination of the Random Sample Consensus (RANSAC) algorithm and polynomial linear regression for wind power data cleaning. The model successfully captures the nonlinear relationship between wind speed and power by extending the polynomial features of wind speed and power, enabling the linear regression model to handle the nonlinearity. By combining the RANSAC algorithm and polynomial linear regression, a robust polynomial regression model is constructed to tackle anomalous data and enhance the accuracy of data cleaning. During the cleaning process, the model first fits the raw data by randomly selecting a minimal sample set, then dynamically adjusts the decision thresholds based on the median of residuals and median absolute deviation (MAD), ensuring effective identification and cleaning of anomalous data. The model’s robustness allows it to maintain efficient cleaning performance even with a high proportion of anomalous data, addressing the limitations of existing methods when handling densely distributed anomalies. The effectiveness and innovation of the proposed method were validated by applying it to real data from a wind farm operated by Longyuan Power. Compared to other commonly used cleaning methods, such as the Bidirectional Change Point Grouping Quartile Statistical Model, Principal Contour Image Processing Model, DBSCAN Clustering Model, and Support Vector Machine (SVM) Model, experimental results showed that the proposed method delivered the best performance in improving data quality. Specifically, the method significantly reduced the average absolute error (MAE) of the wind power forecasting model by 72.1%, which is higher than the reductions observed in other methods (ranging from 37.3 to 52.7%). Moreover, it effectively reduced the prediction error of the Convolutional Neural Network (CNN) + Gated Recurrent Unit (GRU) forecasting model, ensuring high prediction accuracy. The adaptive threshold robust regression model proposed in this study is innovative and has significant application potential. It provides an effective new approach for wind power data cleaning, applicable not only to conventional scenarios with low proportions of anomalous data but also to complex datasets with a high proportion of dense anomalies.

Abstract Cerebral cavernous malformations (CCMs) are hemorrhagic vascular disorders with varied clinical and radiological presentations, occurring sporadically due to MAP3K3 or PIK3CA mutations or through inherited germline mutations of CCM genes. This study aimed to clarify the clinical, genetic, and pathological features of CCMs using a multicenter cohort across three Chinese centers. We analyzed 290 surgical specimens from symptomatic CCM patients, utilizing whole-exome sequencing, droplet digital PCR, and targeted panel sequencing, alongside immunohistology to examine genotypic and phenotypic differences. Among 290 cases, 201 had somatic MAP3K3, PIK3CA, or germline CCM mutations, each associated with distinct clinical parameters: hemorrhage risk (P

Small-animal single-photon emission computed tomography-X-ray computed tomography (SPECT-CT) is an advanced imaging tool for preclinical research of single-photon radiopharmaceuticals. Its detection performance is the foundation of image quality and the reliability of experimental data. This study aims to evaluate the performance of Albira SI SPECT-CT in terms of advisable test range，linearity，stability，deviation of measurement results，related to the radioactive isotope 99mTc，and to explore the authenticity and reliability of the scan results.The Albira SI SPECT-CT was subjected to quarterly quality control using the clinically commonly used single-photon radionuclide 99mTc. The linearity，stability，and deviation of the measurement results were tested，and preliminary attempts were made at small-animal bone metabolism scanning. The device demonstrated a strong linear correlation between radioactivity and measurement results，exhibited high stability，and showed minimal variation when compared to commonly used radioactivity measurement devices.The Albira SI small animal SPECT-CT accurately reflects the distribution of the radioactive activity of the single photon isotope 99mTc，showing excellent imaging of mouse bone metabolism，suitable for preclinical radiopharmaceutical research. The method for evaluating SPECT-CT performance established in this study is expected to provide a reference for the operation of similar equipment.

Abstract Background In the context of public health emergencies, the presence of medical and health talents (MHT) is critically important for support in any country or region. This study aims to analyze the spatial and temporal distributions and evolution of MHT in China and propose strategies and recommendations for promoting a balanced distribution. Methods This research used data from 31 provinces in China to construct a multidimensional index system for measuring the agglomeration level of MHT. The indices include talent agglomeration density (TAD), talent agglomeration scale (TAS), talent agglomeration intensity (TAI), and talent agglomeration equilibrium (TAE). Using provincial data from the years 1982, 1990, 2000, 2010, and 2020, a spatiotemporal analysis of the MHT agglomeration levels was conducted. Furthermore, the regional dynamic distribution of MHT was analyzed using kernel density estimation diagrams. The spatial autocorrelation of MHT was assessed through global and local Moran’s I, and the spatial gap and decomposition of MHT were analyzed using the Dagum Gini coefficient. Results From the temporal level, the TAD and TAI of MHT showed an increasing trend over the studied period, whereas TAS decreased and TAE first increased and then decreased from 1982 to 2020. At the spatial level, the TAD, TAS, TAI, and TAE of MHT exhibited varied patterns among the eastern, central, and western regions of China, showing significant geographical disparities, generally demarcated by the Hu Huanyong Line. The regional dynamic distribution level of MHT in the country and the three regions were expanding. Spatial autocorrelation analysis using global and local Moran’s I for TAD, TAS, TAI, and TAE demonstrated significant regional differences. The Dagum Gini coefficient of TAD, TAS, TAI, and TAE revealed divergent trends in regional disparities, with overall declines in disparities for TAD and TAI, a slight increase for TAS, and fluctuating patterns for TAE. Conclusions From a temporal perspective, the overall number of MHT in China has been increasing annually at the national and provincial levels. From the spatial perspective, TAD, TAS, TAI, and TAE exhibit significant differences among the three regions. Kernel analysis reveals that the distribution differences are gradually expanding in national level and varying in regional level. Moreover, the global and local Moran’s I indices reveal varying spatial autocorrelation for TAD, TAS, TAI, and TAE. The Dagum Gini coefficients of TAD, TAS, TAI, and TAE show different patterns of decomposition.

Abstract Background This study aims to examine the temporal changes in the incidence, prevalence, and disability-adjusted life years (DALYs) of depressive disorders as well as its association with age, period, and birth cohort among Chinese from 1990 to 2021, and forecast the future trends of incidence rates and numbers from 2022 to 2030. Methods Data for analysis were obtained from the Global Burden of Disease (GBD) 2021. Joinpoint analysis was used to calculate the annual percentage change (APC) and average annual percent change (AAPC) to describe the rates of depressive disorders. Age, period, and cohort model was utilized to disentangle age, period, and birth cohort effects on rates of depressive disorders. Bayesian age-period-cohort (BAPC) analysis was capitalized to forecast the incidence rates and numbers for different sexes and age groups from 2022 to 2030. Results The age-standardized incidence (ASIR, AAPC: -0.35 [95%CI: -0.65, -0.04]), prevalence (ASPR, AAPC: -0.20 [95%CI: -0.24, -0.16]), and DAYLs (AAPC: -0.28 [95%CI: -0.51, -0.05]) rates of both sexes showed a downward trend from 1990 to 2021, despite a volatility growth in recent years (APC in 2019–2021 of ASPR: 0.96 [95%CI: 0.70, 1.23]). Females exhibited a higher burden of depressive disorders compared to males but experienced a more rapid rate of reduction changes. The burden of depressive disorders was most owing to the age effect and period effect in recent years. The ASIR was predicted to decrease in the whole population (males in 2030: 1,546.3 per 100,000 people; females in 2030: 2,465.8 per 100,000 people), but in children, adolescents, and the elderly demonstrate unfavorable trends in the future. Conclusion The burden of depressive disorders decreased in China from 1990 to 2021 in terms of age-standardized rates, but increased in recent years. Children, adolescents, and the elderly are the risk groups for future depressive disorders. Considering the large population, the increasing fewer children, and the aging trend, as well as the possible long-term effects of COVID-19 on human psychological burden, more sex-age-sensitive social healthcare programs should be considered in the future to minimize the burden of depressive disorders in China.

Abstract Background and aim Recent Mendelian randomization and meta analysis suggest a controversial causality between C3-epimer of 25 hydroxyvitamin D3 (C3-epi-D3) and type 2 diabetes mellitus (T2DM). The clinical evidence regarding the impact of C3-epi-D3 on the progression of T2DM is currently insufficient. This study aims to investigate whether C3-epi-D3 has any effect on metabolic disorders of T2DM patients. Methods A total of 1222 patients with T2DM were prospectively enrolled in this study and followed up every 1 to 2 months for 3 to 6 months. Kidney biomarkers, lipids, electrolytes, and 25 hydroxyvitamin D (25-OHD) metabolites were measured as required during follow-up, to investigate the association of C3-epi-D3 levels and %C3-epi-D3 with metabolic disorders, including dyslipidemia, chronic kidney disease (CKD), and calcium-phosphorus metabolic disorder. Results Among these T2DM patients, there were age and seasonal differences in C3-epi-D3 levels (χ 2 = 10.419 and 19.609, P = 0.034 and

Tantalum (Ta) has good potential for bone tissue engineering due to its excellent corrosion resistance and biocompatibility. However, the customization of Ta-based bone repair materials for irregularly shaped bone defects has been challenging due to their high melting point and hardness. In this work, porous tantalum granules (PTaG) were developed for the first time to repair irregularly shaped bone defects, inspired by the natural phenomenon of sand flow. PTaG were designed as a hierarchical porous structure to regulate the mechanical properties and provide a favorable space for inward growth of cells and tissues. Commercial porous titanium granules (PTiG) and Bio-Oss were used as positive controls to explore the potential of PTaG as bone substitute. The morphology, three-dimensional structure, composition, and mechanical properties of PTaG and PTiG were evaluated by SEM, X-Ray 3D imaging system, 3D laser confocal microscope, EDS, XRD, XPS, and nanoindentation. In vitro, cell compatibility and mineralization ability were evaluated for both materials. Furthermore, PTaG, PTiG, and Bio-Oss were filled in the rabbit femoral defect, and micro-CT and histological analysis were performed after 8 weeks. The results showed that the PTaG had the best bone healing effect due to the hierarchical porous structure, excellent three-dimensional connectivity and chemical stability, suitable mechanical properties and surface roughness, good biocompatibility and mineralization osteogenic activity. This work indicates that PTaG may have a positive potential for filling and repairing irregularly shaped bone defects.

Magnesium-based composites with bioactive ceramic particles addition are promising materials for biomedical implant applications. Nevertheless, the agglomeration of bioactive ceramic particles remains a challenge for fabricating high-performance biomedical magnesium-based composites. Herein, a novel high-performance biomedical rare-earth magnesium alloy-based WE43/hydroxyapatite (HA) composite is successfully fabricated via multi-pass friction stir processing (MP-FSP). Systematic investigations reveal that MP-FSP leads to a uniform distribution of HA particles and efficient elimination of defects. The microstructural analysis shows a significant grain refinement in the WE43 alloy from 49.4 μm to 2.4 μm under triple-pass FSP. The mechanical properties of the composite are enhanced significantly under triple-pass FSP, with yield strength, ultimate tensile strength, and elongation reaching 236.2 MPa, 278.6 MPa, and 14.2% respectively. Corrosion resistance is also improved, with a 30% reduction in the corrosion rate in SBF solution compared to the unprocessed alloy. Moreover, the MP-FSP fabricated composites exhibit superior corrosion-wear resistance, characterized by slight abrasive wear compared to the abrasive wear and severe pitting corrosion observed in the base WE43 alloy. These improvements are attributed to the synergistic effects of grain refinement, dispersion strengthening, enhanced interfacial bonding, and texture modification. Overall, these findings provide significant insights into the fabrication of magnesium-based composites for biomedical implant applications, highlighting the effectiveness of MP-FSP in enhancing both mechanical and corrosion-related properties.

Abstract Background This study aimed to understand the vision health status of adolescents in the Western Pacific Region (WPR) using Global Burden of Disease (GBD) data from 1990 to 2019. Methods We conducted a comprehensive analysis of blindness and vision loss using GBD data from 1990 to 2019, analyzed trends in the prevalence and burden of blindness and vision loss over time using joinpoint regression, and analyzed their independent effects on blindness and vision loss in three dimensions using age-period-cohort (APC) modeling. Results The prevalence of blindness and vision loss among adolescents in the WPR showed an increasing trend between 1990 and 2019 (AAPC: 0.56%) and a slight increase in YLD (AAPC: 0.11%). The joinpoint regression showed a decreasing trend after 2017 (AAPC: -2.45%). The prevalence and burden trended downward in most Western Pacific countries, with only China rising significantly (AAPC prevalence: 0.57%). Refractive disorders had the highest prevalence among the subgroups. The risk of blindness and vision loss in adolescents reduced with age but grew later in time and at later birth. In addition, prevalence and burden were generally higher in females than males. Conclusions In the context of a declining global trend in the prevalence and burden of blindness and vision loss among adolescents, there is an increasing trend among adolescents in WPR, with the most pronounced rise in China. This finding has important implications for WPR, suggesting that more attention should be given to adolescent eye health in the region.

X-ray ghost imaging with a crystal beam splitter has advantages in highly efficient imaging due to the simultaneous acquisition of signals from both the object beam and reference beam. However, beam splitting with a large field of view, uniform distribution and high correlation has been a great challenge up to now. Therefore, a dedicated beam splitter has been developed by optimizing the optical layout of a synchrotron radiation beamline and the fabrication process of a Laue crystal. A large field of view, consistent size, uniform intensity distribution and high correlation were obtained simultaneously for the two split beams. Modulated by a piece of copper foam upstream of the splitter, a correlation of 92% between the speckle fields of the object and reference beam and a Glauber function of 1.25 were achieved. Taking advantage of synthetic aperture X-ray ghost imaging (SAXGI), a circuit board of size 880 × 330 pixels was successfully imaged with high fidelity. In addition, even though 16 measurements corresponding to a sampling rate of 1% in SAXGI were used for image reconstruction, the skeleton structure of the circuit board can still be determined. In conclusion, the specially developed beam splitter is applicable for the efficient implementation of X-ray ghost imaging.

Abstract Simultaneous manipulation of multiple degrees of freedom of light lies at the heart of photonics. Nonlinear wavefront shaping offers an exceptional way to achieve this goal by converting incident light into beams of new frequencies with spatially varied phase, amplitude, and angular momenta. Nevertheless, the reconfigurable control over structured light fields for advanced multimode nonlinear photonics remains a grand challenge. Here, we propose the concept of nonlinear geometric phase in an emerging ferroelectric nematic fluid, of which the second-order nonlinear susceptibility carries spin-dependent nonlinearity phase. A case study with photopatterned q-plates demonstrates the generation of second-harmonic optical vortices with spin-locked topological charges by using cascaded linear and nonlinear optical spin-orbit interactions. Furthermore, we present the dynamic tunability of second-harmonic structured light through temperature, electric field, and twisted elastic force. The proposed strategy opens new avenues for reconfigurable nonlinear photonics, with potential applications in optical communications, quantum computing, high-resolution imaging, etc.

Abstract Background This study aims to explore the relationship between female reproductive factors (age at first birth (AFB), age at last birth (ALB), gravidity, and number of live birth (NLB)) and prevalence of depression among the US women. Methods The relationship between AFB, ALB, gravidity, and NLB with the prevalence of depression was explored using publicly available data from the National Health and Nutrition Examination Survey 2005–2018. This cross-sectional study included female participants aged 20 years and older, with reproductive factors and depressive symptoms reported by the participants. Depression was evaluated using the Patient Health Questionnaire-9, with a score of ≥ 10 representing major depression disorder. Weighted multivariable logistic regression and restricted cubic splines (RCS) were utilized to explore the association of AFB, ALB, gravidity and NLB with depression. Results In this study of 11,488 US women, 1,332 (11.6%) women had depression. Compared to the reference group of women with AFB under 18 years, the fully adjusted ORs and 95% CIs for depression were 0.83 (95% CI: 0.68–0.99), 0.75 (95% CI: 0.60–0.95), and 0.69 (95% CI: 0.51–0.93) for women with AFB of 21–23, 24–26, and 27–29 years, respectively. Furthermore, women with five or more pregnancies had a significantly higher prevalence of depression compared to those with two or fewer pregnancies (OR = 1.20, 95% CI: 1.01–1.42). RCS models demonstrated linear associations of ALB, gravidity and NLB with the prevalence of depression. Additionally, the RCS analysis revealed a roughly L-shaped relationship between AFB and prevalence of depression. Conclusions Women with later AFB are associated with a decreased prevalence of depression, while multiple pregnancies are associated with an increased prevalence of depression. These findings suggest that reproductive factors should be considered when screening for and developing preventive strategies for depression.

Abstract After the COVID-19 pandemic, fever clinics urgently require rapid nucleic acid tests to enhance their capacity for timely pathogen detection. This study evaluated the analytical performance and clinical utility of the Flash10 SARS-CoV-2 point-of-care test (Flash10 POCT) for detecting SARS-CoV-2 in patients with fever in the adult fever clinic in Beijing Tsinghua Changgung Hospital from August 1 to August 30, 2023. The analytical performance and clinical utility of the Flash10 POCT for detecting SARS-CoV-2 were assessed in 125 patients with fever syndrome in the adult fever clinic. The Flash10 POCT demonstrated an analytical precision of 3.1% for the Ct values of the ORF1ab gene and 2.9% for the Ct values of the N gene in SARS-CoV-2 nucleic acid testing. Furthermore, the Flash10 POCT demonstrated a lower limit of detection (LoD) of 100 copies/mL, with no detected aerosol contamination leakage. Of the 125 patients (median age 61.9 years, 52% male and 48% female), both the Flash10 POCT and RT-PCR tests yielded positive results for 100 patients and negative results for 25 patients (Fisher’s exact test, p

Small animal PET/MRI is an integrated imaging device that combines the high-performance molecular imaging function of PET with the excellent soft tissue contrast function of MRI，offering unique advantages and significant application value in drug development and evaluation，pharmacology，and mechanistic studies of diseases. To verify the feasibility and accuracy of this device in quantitative analysis，this study evaluated the linear detection range，stability，and quantitative performance of the Bruker BioSpec 94/30 USR + PET insert for 18F. High-resolution MRI images were utilized to remove interference from factors such as the gallbladder and blood vessels，ensuring accurate in vivo quantification in animals. The results demonstrate that the Bruker BioSpec 94/30 USR + PET insert small animal PET/MRI system exhibits excellent linearity (R2=0.9992) within the activity range of 1-1500 μCi，good reproducibility，and accurate in vivo quantitative performance. This provides reliable data for subsequent studies utilizing the Bruker BioSpec 94/30 USR + PET insert for in vivo visualization，distribution，metabolism，and pharmacodynamic evaluation of nuclear tracers.

BackgroundMajor depressive disorder (MDD) in adolescents poses a significant threat to physical health. Previous studies have indicated that adolescents with MDD exhibit immune activation.ObjectiveThis study aimed to compare cytokine levels in adolescents with MDD to healthy controls and assess their diagnostic value.MethodsThis cross-sectional study included 58 adolescent patients with depression from Beijing Anding Hospital (outpatients and inpatients) and 40 healthy adolescents recruited from the community. Multiplex cytokine analysis (Luminex xMAP) was used to measure serum levels of several cytokines. Data analysis was performed using SPSS (version 26.0) to compare cytokine levels between adolescents with MDD and healthy controls and assess gender differences. Correlations between cytokine levels and demographic data, clinical features and depressive symptoms were also analyzed. The receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of cytokines.ResultsSerum IL-4, IFN-γ, and TNF-α levels were significantly elevated in MDD group compared with healthy controls (p < 0.05). In MDD group, the age of first onset of depression in females was significantly younger than that in males (p < 0.05), and female serum TNF-α levels were significantly higher than those in males (p < 0.05). BMI and serum IL-4 levels were significantly positively correlated in adolescents with MDD. The area under the ROC curve for serum IL-4 and TNF-α in diagnosing adolescent depression was 0.695 (95% confidence interval [CI]: 0.580 - 0.809; p < 0.05), with a sensitivity of 0.793 and specificity of 0.675.ConclusionCompared with healthy controls, adolescents with depression demonstrated significantly elevated serum cytokine levels, indicating immune activation which were higher in female. Cytokines may have promising diagnostic value in adolescent depression, but further validation with additional indicators is needed.

IntroductionGlobal mining activities have significant impacts on ecosystems, but most studies have focused only on the relationship between soil physicochemical properties and microbial diversity in soils. The present study provides an insight into the effects of mining activities on soil physico-chemical properties and endophytic bacterial community composition in the rhizosphere of three different crops.MethodsMusa basjoo Siebold L., Amygdalus persica L., and Triticum aestivum L. were collected from the inter-root soils and plant roots to determine the soil physicochemical properties and endophytic bacterial communities in the root system.ResultsThe results showed that mining resulted in soil acidification, altered trace element content and increased organic carbon. There was an increase in the Ascomycota and Actinobacteria phylum of crop root bacteria. Interestingly, the chao1 and shannon indices of the root endophytes of the mining crop were significantly elevated compared to the contro (p

Members of the families Thermosynechococcaceae and Thermostichaceae are well-known unicellular thermophilic cyanobacteria and a non-thermophilic genus Pseudocalidococcus was newly classified into the former. Analysis of the codon usage bias (CUB) of cyanobacterial species inhabiting different thermal and non-thermal niches will benefit the understanding of their genetic and evolutionary characteristics. Herein, the CUB and codon context patterns of protein-coding genes were systematically analyzed and compared between members of the two families. Overall, the nucleotide composition and CUB indices were found to differ between thermophiles and non-thermophiles. The thermophiles showed a higher G/C content in the codon base composition and tended to end with G/C compared to the non-thermophiles. Correlation analysis indicated significant associations between codon base composition and CUB indices. The results of the effective number of codons, parity-rule 2, neutral and correspondence analyses indicated that mutational pressure and natural selection primarily account for CUB in these cyanobacterial species, but the primary driving forces exhibit variation among genera. Moreover, the optimal codons identified based on relative synonymous codon usage values were found to differ among genera and even within genera. In addition, codon context pattern analysis revealed the specificity of the sequence context of start and stop codons among genera. Intriguingly, the clustering of codon context patterns appeared to be more related to thermotolerance than to phylogenomic relationships. In conclusion, this study facilitates the understanding of the characteristics and sources of variation of CUB and the evolution of the surveyed cyanobacterial clades with different thermotolerance and provides insights into their adaptation to different environments.

Flavor components largely depend on microbial activity and environmental conditions during traditional fermented food production. However, the microbial and abiotic contributions to the flavor of Chinese strong-aroma Baijiu (SAB) remain poorly understood. In this study, the composition and functional profiles of the fungal and bacterial communities changed significantly after fourteen days of grain fermentation. Acetilactobacillus jinshanensis, Issatchenkia orientalis and Kazachstani humilis became the dominant species as fermentation proceeded. Pathways related to lipid, protein and secondary metabolite metabolism were enriched during the middle and later stages of grain fermentation. Ethyl caproate, hexyl caproate, and ethyl lactate were identified as the main volatile components in fermented grain. Lactobacillus species were significantly related to volatile components. Compared with fungi, bacterial diversity accounted for 96 % of the variation in volatile components coupled with temperature, acidity and reducing sugar. This work provides insights into the production optimization and flavor enhancement of SAB by optimizing abiotic factors and microbial compositions.

Abstract The adverse pregnancy outcomes, including recurrent spontaneous abortion (RSA), are strongly correlated with water-soluble vitamins, but how to predict RSA occurrence using them remains unsatisfactory. This study aims to investigate the possibility of predicting RSA based on the baseline levels of water-soluble vitamins tested by ultra-liquid chromatography-tandem mass spectrometry. A total of 918 pregnant women was consecutively enrolled in this cross-sectional study. According to the miscarriage numbers, they were divided into normal first pregnancy (NFP, n = 608), once spontaneous abortion (OSA, n = 167), and continuous spontaneous abortion (CSA, n = 143) groups. The Cox proportional-hazards regression model was employed to establish a risk model for predicting RSA. The RSA occurrence was 6.54% in overall pregnant women, with a prevalence of 12.57% in the OSA group and 27.27% in the CSA group. Significant differences were observed in baseline deficiencies of vitamin B3, B5, B6, and B9 among NFP, OSA, and CSA groups (χ2 = 12.191 ~ 37.561, all P 0.05). Our study presents a highly sensitive model based on mass spectrometry assay of baseline levels in B vitamins to predict the RSA occurrence as possible.

Abstract Glioma is the most aggressive intracranial malignancy and is associated with poor survival rates and limited quality of life, impairing neuropsychological function and cognitive competence in survivors. The Proteasome Subunit Alpha Type-5 (PSMA5) is a multicatalytic proteinase complex that has been linked with tumor progression but is rarely reported in glioma. This study investigates the expression pattern, prognostic characteristics, and potential biological functions of PSMA5 in glioma. PSMA5 was significantly overexpressed in 28 types of cancer when compared to normal tissue. Furthermore, elevated levels of PSMA5 were observed in patients with wild-type isocitrate dehydrogenase 1 and exhibited a positive correlation with tumor grade. It was also found to be a standalone predictor of outcomes in glioma patients. Additionally, inhibiting PSMA5-induced cell cycle arrest may provide a therapeutic option for glioma.

Abstract Macrophages serve as the primary immune cell population and assume a pivotal role in the immune response within the damaged cochleae. Yet, the origin and role of macrophages in response to noise exposure remain controversial. Here, we take advantage of Ccr2RFP/+ Cx3cr1GFP/+ dual-reporter mice to identify the infiltrated and tissue-resident macrophages. After noise exposure, we reveal that activated resident macrophages change in morphology, increase in abundance, and migrate to the region of hair cells, leading to the loss of outer hair cells and the damage of ribbon synapses. Meanwhile, peripheral monocytes are not implicated in the noise-induced hair cell insults. These noise-induced activities of macrophages are abolished by inhibiting TLR4 signaling, resulting in alleviated insults of hair cells and partial recovery of hearing. Our findings indicate cochlear resident macrophages are pro-inflammatory and detrimental players in acoustic trauma and introduce a potential therapeutic target in noise-induced hearing loss.

Abstract Background Recently, the C3-epimer of 25-hydroxyvitamin D [C3-epi-25(OH)D] has become a topic of interest among 25-hydroxyvitamin D [25(OH)D] metabolites. Although it can lead to an overestimation of vitamin D storage, its relationship with disease occurrence remains controversial, possibly related to the great extent of tracking of 25(OH)D by C3-epi-25(OH)D over time. This study aimed to investigate the differential performance of C3-epi-25(OH)D3 and its percentage [%C3-epi-25(OH)D3] with respect to 20 common paediatric diseases. Methods This study involved 805 healthy children and adolescents and 2962 patients with common paediatric diseases. We investigated sex, age, and seasonal differences in C3-epi-25(OH)D3 and %C3-epi-25(OH)D3 levels; their variations on 20 common paediatric diseases; and their degree of correlation with 25(OH)D3 levels and various diseases. Results Among the healthy underage participants, C3-epi-25(OH)D3 and %C3-epi-25(OH)D3 changed similarly, with no sex differences. Moreover, their levels were higher in the infant period than in the other periods (t = 5.329–5.833, t = 4.640–5.711, all Padj

Abstract Continuous directed evolution of base editors (BEs) has been successful in bacteria cells, but not yet in mammalian cells. Here, we report the development of a Continuous Directed Evolution system in Mammalian cells (CDEM). CDEM enables the BE evolution in a full-length manner with Cas9 nickase. We harness CDEM to evolve the deaminases of cytosine base editor BE3 and adenine base editors, ABEmax and ABE8e. The evolved cytidine deaminase variants on BE4 architecture show not only narrowed editing windows, but also higher editing purity and low off-target activity without a trade-off in on-targeting activity. The evolved ABEmax and ABE8e variants exhibit narrowed or shifted editing windows to different extents, and lower off-target effects. The results illustrate that CDEM is a simple but powerful approach to continuously evolve BEs without size restriction in the mammalian environment, which is advantageous over continuous directed evolution system in bacteria cells.

Turbulence within the tropical cyclone boundary layer plays a crucial role in the exchange of heat, moisture, and momentum between the surface and the atmosphere. This study investigates the characteristics of coherent structures, specifically streaks and rolls, using large eddy simulations. Our results highlight significant differences across the three radius cases, with smaller radius exhibiting more intense and organized turbulence and streak/roll structures. Our analyses reveal that thermodynamic conditions significantly impact the timing of initial streak/roll development but do not affect their intensity in the steady state. Wind structures closer to the tropical cyclone center lead to stronger and more rapidly developing streaks/rolls, indicating their critical role in determining the intensity and formation of these features. Sensitivity tests on the Coriolis parameter (f) and radial decay parameter of tangential wind (n) show minimal impact on the development of streaks/rolls, suggesting these factors are less influential compared to wind and thermodynamic conditions.

Objective As one of the most crucial information carriers for predicting mineralized geological bodies, exploration geochemical data play a significant role in the identifying and extracting mineralization-associated anomalies as well as in analyzing deep-level mineralization information. Methods Based on the scale invariance and generalized self-similarity characteristics of the spatial distribution of geochemical elements, this paper uses Cu and Au in the 1:50 000 exploratory geochemical data of the Duolong mineral district as an example and conducts a study using fractal/multifractal and singularity theories to identify the spatial distribution patterns of ore-forming elements and extract anomalies. The multifractal spectrum which is derived by the exploratory moment method for the whole study area, the fault buffer zone and the stratigraphic zone, is used to describe the relative enrichment and depletion of elements in the local area and to analyze the local singularity of Cu and Au mineralized elements, so as to identify and extract weak and low anomalies of mineralized elements and delineate potential mineralization zones. Results Both Cu and Au exhibit mineralization-favoured patterns in the Duolong mineral district, with the Cu showing weak enrichment in the region and Au being over-enriched on a local scale. The intersections of the east-west and northeast-trending faults, as well as the Jurassic strata, are identified as the most promising locations for mineralization in this region. Conclusion The spatial distribution of the local singularity index is mapped to characterize the distribution features of Cu and Au geochemical anomalies, therefore, the central and northern regions of the ore district are subsequently identified as potential areas for mineralization.

The global burden of controlling and managing diabetes mellitus (DM) is a significant challenge. Despite the advancements in conventional DM therapy, there remain hurdles to overcome, such as enhancing medication adherence and improving patient prognosis. Digital therapeutics (DTx), an innovative digital application, has been proposed to augment the traditional disease management workflow, particularly in managing chronic diseases like DM. Several studies have explored DTx, yielding promising results. However, certain concerns about this innovation persist. In this review, we aim to encapsulate the potential of DTx and its applications in DM management, thereby providing a comprehensive overview of this technique for public health policymakers.

Abstract Background Parkinson’s disease (PD) is a prevalent neurodegenerative disorder worldwide, diagnosed based on classic symptoms like motor dysfunction and cognitive impairments. With the development of various radioactive ligands, positron emission tomography (PET) imaging combined with specific radiolabelling probes has proven to be effective in aiding clinical PD diagnosis. Among these probes, 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl) nortropane ([18F]FECNT) has been utilized as a PET tracer to image dopamine transporter (DAT) integrity in striatal presynaptic dopaminergic terminals. However, the presence of brain-penetrant radioactive metabolites produced by [18F]FECNT may impact the accuracy of PET imaging. In previous research, we developed 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl-1,1,2,2-d4) nortropane ([18F]FECNT-d4), a deuterated derivative with enhanced stability in plasma and the striatum, along with a slower washout rate. In this study, we further investigated the potential of [18F]FECNT-d4 to detect dopaminergic neuron degeneration in Parkinson’s disease. This involved PET imaging in unilaterally-lesioned PD model rats and in vitro autoradiography conducted on postmortem brain sections. Results PET images revealed reduced specific uptake in the ipsilateral striatum of rats stereotactically injected with 6-hydroxydopamine hydrochloride (6-OHDA). Compared to the sham group, the ratio of standardized uptake value (SUV) in the ipsilateral to contralateral striatum decreased by 13%, 23%, and 63% in the mild, moderate, and severe lesioned groups, respectively. Dopaminergic denervation observed in PET imaging was further supported by behavioral assessments, immunostaining, and monoamine concentration tests. Moreover, the microPET results exhibited positive correlations with these measurements, except for the apomorphine-induced rotational behavior test, which showed a negative correlation. Additionally, [18F]FECNT-d4 uptake was approximately 40% lower in the postmortem striatal sections of a PD patient compared to a healthy subject. Furthermore, estimated human dosimetry (effective dose equivalent: 5.06 E-03 mSv/MBq), extrapolated from rat biodistribution data, remained below the current Food and Drug Administration limit for radiation exposure. Conclusion Our findings demonstrate that [18F]FECNT-d4 accurately estimates levels of dopaminergic neuron degeneration in the 6-OHDA-induced PD rat model and effectively distinguishes between PD patients and healthy individuals. This highly sensitive and safe PET probe holds promising potential for clinical application in the diagnosis and monitoring of Parkinson’s disease.

SiC-based composites are widely used as electromagnetic wave absorbers due to their excellent dielectric properties. However, the constraints associated with structural design and the intricacies of the preparation process hinder their broader application. In this study, novel mullite anti-gyroid/SiC gyroid metastructures are designed to integrate the mechanical and electromagnetic wave (EMW) absorption properties of composite materials. Mullite anti-gyroid/SiC gyroid composites are fabricated utilizing a combination of digital light processing (DLP) three-dimensional (3D) printing and precursor infiltration and pyrolysis (PIP) processes. Through the modulation of structural units, the electromagnetic parameters can be effectively regulated, thus improving the impedance matching characteristics of the composites. The structural composites show outstanding EMW absorption properties, with a minimum reflection loss of −54 dB at a thickness of 1.9 mm and an effective absorption bandwidth of 3.20 GHz at a thickness of 2.2 mm. Furthermore, the PIP process significantly enhances the mechanical properties of the composites; compared with those of the mullite/SiC ceramics, the flexural strength of the composites is improved by 3.69–5.85 times (13.28±1.15 MPa vs. (49.05±1.07)–(77.78±3.72) MPa), and the compressive strength is improved by 4.59–13.58 times (8.55±0.90 MPa vs. (39.02±1.63)–(116.13±2.58) MPa). This approach offers a novel and effective method for fabricating structural composites with an expanded range of higher electromagnetic wave absorption properties and improved mechanical properties.

Abstract Background Xenobiotics like pesticide isoproturon (IPU) and heavy metal cadmium (Cd) are environmental contaminants posing serious impacts on ecosystem. Understanding their toxic and accumulative processes is crucial to uncover insightful mechanisms and minimize health risks. However, the joint effect of IPU and Cd on microorganisms in aquatic ecosystems remains elusive. In this study, Chlamydomonas reinhardtii was selected as a model unicellular organism to evaluate the ecotoxicological effects of IPU and Cd, focusing on biological responses, bioaccumulation capacity, and environmental adaptation. Results The combined treatment with IPU (0.24 μmol L−1) and/or Cd (20 μmol L−1) for 60 h can induce acute toxicity to C. reinhardtii, reducing chlorophyll and photosynthetic fluorescence, while increasing oxidative damage manifested by lipid membrane peroxides and electrical conductivity. IPU and Cd were accumulated in C. reinhardtii. Interestingly, IPU accumulation in algae was significantly repressed in the presence of Cd, showing a remarkable decrease of 116.7% compared to the IPU treatment alone. Similarly, the Cd concentration in the cells exposed to IPU was reduced by 23.5% compared to Cd treatment alone. Calculation of the bioconcentration factors revealed lower accumulation values of IPU or Cd in algae under Cd+IPU exposure compared to IPU or Cd stress, suggesting an antagonistic interaction between IPU and Cd during absorption by the algae. Furthermore, the activities and transcriptional expression of enzymatic antioxidants such as SOD and APX were significantly induced by Cd stress, whereas the activities of CAT, APX, and PPO significantly increased elevated by IPU. Conclusions This study provides compelling evidence of the ecotoxicological effects of combined IPU and cadmium contamination on algae, highlighting the potential of algae for bioremediation of environments contaminated with IPU and cadmium. Graphical Abstract

The unique continuous extrusion-based severe plastic deformation approaches were proposed recently to process high-performance magnesium (Mg) alloys, while the in-depth deformation mechanisms under such complicated thermomechanical conditions were not well understood. In the present work, the fundamental deformation behaviors of AZ61 Mg alloy from 25 to 400 °C were firstly examined under uniaxial compression deformation. Then the deformation mechanisms and microstructural characteristics of AZ61 Mg alloy during continuous expansion extrusion forming (CEEF) were systematically investigated by microstructural observations, finite element and cellular automata simulations. The results showed that the continuous evolutions of temperature, larger strain level and complex stress state with strain rate range of 0 ∼ 5.98 s−1 during CEEF brought the distinctive dynamic recrystallization behaviors and texture development in AZ61 Mg alloy, which were different to that of uniaxial compression deformation. In details, a remarkable grain refinement was achieved via CEEF processing due to the simultaneous actions of continuous dynamic recrystallization (CDRX) and discontinuous dynamic recrystallization (DDRX). Gradually enhanced CDRX were observed from center to edge region, which had significant effects on the texture distribution and texture strength. The c-axis of most grains rotated under distinctive shear strain following parabolic metal flow, resulting in stable fiber texture. In addition, the evolution of the internal texture of the alloy led to an obvious increase in the Schmid factor for the activation of basal 〈c + a〉 slip system.

Ecosystems at the southern edge of the permafrost distribution are highly sensitive to global warming. Changes in soil freeze-thaw cycles can influence vegetation growth in permafrost regions. Extant studies mainly focused on analyzing the differences of vegetation dynamics in different permafrost regions. However, the intrinsic drivers of permafrost degradation on vegetation growth remain elusive yet. Based on the top temperature of permafrost (TTOP) model, we simulated the spatial distribution of permafrost in Northeast China (NEC) from 2001 to 2020. Using the data of the vegetation Net Primary Productivity (NPP), vegetation phenology, climate and permafrost phenology, and analytical methods including partial correlation, multiple linear regression, and path analysis, we explored the response of vegetation growth and phenology to soil freeze-thaw changes and climate change under different degrees of permafrost degradation. Overall, the start date of the growing season (SOS) was very sensitive to the start date of soil thaw (SOT) changes, and multiple regression analyses showed that SOT was the main factor influencing SOS in 41.8% of the NEC region. Climatic factors remain the main factors affecting vegetation NPP in NEC, and the results of partial correlation analysis showed that only 9.7% of the regional duration of soil thaw (DOT) had a strong correlation with vegetation NPP. Therefore, we determined the mechanism responsible for the soil freeze-thaw changes and vegetation growth relationship using the path analysis. The results indicated that there is a potential inhibitory effect of persistent permafrost degradation on vegetation growth. Our findings would contribute to the improvement of process-based models of forest dynamics in the boreal region, which would help to plan sustainable development and conservation strategies in permafrost areas.

Toxin-antitoxin (TA) modules are important mediators of persister cell formation in response to environmental stresses. However, the mechanisms through which persistence is controlled remain poorly understood. Weissella cibaria, a novel probiotic, can enter a persistent state upon exposure to tetracycline stress. This study found that the Bro-Xre TA modules of W. cibaria function as typical tetracycline regulators. The Bro-Xre TA modules were activated when exposed to tetracycline stress, and the released toxin Bro acted on various cellular metabolic processes, including energy, amino acid, and nucleotide metabolism. Among them, the genes related to intracellular energy pathways, such as PTS, EMP, HMP, TCA, and oxidative phosphorylation, were downregulated, leading to reduced ATP synthesis and proton motive force. This metabolic disruption resulted in cells adopting a persistent phenotype, characterized by an increase in cell length in W. cibaria. Additionally, the frequency of persister cells increased under tetracycline stress. These results provide a novel perspective for understanding the mechanism by which TA modules induce persistence in probiotics, allowing them to evade antibiotic stress through metabolic disruption.

ObjectivesWe focus on utilizing the Labyrinth system for the detection of circulating tumor cells (CTCs) in patients with lung nodules. Our aim is to evaluate CTCs isolated through the Labyrinth system as a biomarker for early-stage lung cancer (LC) detection.Methods167 patients with low dose computed tomography (LDCT) diagnostic results for lung nodules and 31 healthy volunteers (HV) were enrolled. Blood samples were processed for CTC detection. LDCT positive (LDCT+) patients underwent surgery and were categorized into those with LC and those with benign lung diseases (BLD) based on their biopsy results. BLD Patients, LDCT negative (LDCT-) patients and HV served as controls. The correlation of CTC counts with LC, BLD, LDCT- and HV was investigated. Receiver operating characteristic (ROC) curves were used to assess the Labyrinth system’s diagnostic potential for early-stage LC.ResultsMedian CTC counts for LC, BLD, LDCT- and HV were 2.7 CTC/mL, 0.6 CTC/mL, 0.4 CTC/mL, 0 CTC/mL, respectively. Statistical analysis indicated CTC counts could distinguish LC from BLD, LDCT- and HV (p-Values < 0.001). Using a cut-off of 1 CTC/mL, the study showed 84.4% sensitivity and 82.4% specificity for LDCT+ patients. Specificity increased to 85.9% for patients with lung nodules and 88.2% for all participants. In conclusion, CTCs detected by the Labyrinth system can serve as a biomarker for early-stage LC detection for patients with lung nodules.ConclusionsCTCs identified by the Labyrinth system are a promising biomarker for early-stage LC detection in clinical practice.

Abstract Background China experienced an overwhelming COVID-19 pandemic from middle December 2022 to middle January 2023 after lifting the zero-COVID-19 policy on December 7, 2022. However, the infection rate was less studied. We aimed to investigate the SARS-CoV-2 infection rate in children shortly after discontinuation of the zero-COVID-19 policy. Methods From February 20 to April 10, 2023, we included 393 children aged 8 months to less than 3 years who did not receive COVID-19 vaccination and 114 children aged 3 to 6 years who received inactivated COVID-19 vaccines based on the convenience sampling in this cross-sectional study. IgG and IgM antibodies against nucleocapsid (N) and subunit 1 of spike (S1) of SARS-CoV-2 (anti-N/S1) were measured with commercial kits (Shenzhen YHLO Biotech, China). Results Of the 393 unvaccinated children (1.5 ± 0.6 years; 52.2% boys), 369 (93.9%) were anti-N/S1 IgG positive. Of the 114 vaccinated children (5.3 ± 0.9 years; 48.2% boys), 112 (98.2%) were anti-N/S1 IgG positive. None of the unvaccinated or vaccinated children was anti-N/S1 IgM positive. The median IgG antibody titers in vaccinated children (344.91 AU/mL) were significantly higher than that in unvaccinated children (42.80 AU/mL) (P

Abstract Background Abnormally expressed BCR/ABL protein serves as the basis for the development of chronic myeloid leukaemia (CML). The F-actin binding domain (FABD), which is a crucial region of the BCR/ABL fusion protein, is also located at the carboxyl end of the c-ABL protein and regulates the kinase activity of c-ABL. However, the precise function of this domain in BCR/ABL remains uncertain. Methods The FABD-deficient adenovirus vectors Ad-BCR/ABL△FABD, wild-type Ad-BCR/ABL and the control vector Adtrack were constructed, and 32D cells were infected with these adenoviruses separately. The effects of FABD deletion on the proliferation and apoptosis of 32D cells were evaluated by a CCK-8 assay, colony formation assay, flow cytometry and DAPI staining. The levels of phosphorylated BCR/ABL, p73, and their downstream signalling molecules were detected by western blot. The intracellular localization and interaction of BCR/ABL with the cytoskeleton-related protein F-actin were identified by immunofluorescence and co-IP. The effect of FABD deletion on BCR/ABL carcinogenesis in vivo was explored in CML-like mouse models. The degree of leukaemic cell infiltration was observed by Wright‒Giemsa staining and haematoxylin and eosin (HE) staining. Results We report that the loss of FABD weakened the proliferation-promoting ability of BCR/ABL, accompanied by the downregulation of BCR/ABL downstream signals. Moreover, the deletion of FABD resulted in a change in the localization of BCR/ABL from the cytoplasm to the nucleus, accompanied by an increase in cell apoptosis due to the upregulation of p73 and its downstream proapoptotic factors. Furthermore, we discovered that the absence of FABD alleviated leukaemic cell infiltration induced by BCR/ABL in mice. Conclusions These findings reveal that the deletion of FABD diminished the carcinogenic potential of BCR/ABL both in vitro and in vivo. This study provides further insight into the function of the FABD domain in BCR/ABL.

Based on the best-track dataset from the Shanghai Typhoon Institute/China Meteorological Administration, the paper provides a comprehensive summary and analysis of tropical cyclone (TC) activities in the Western North Pacific (WNP) and the South China Sea (SCS) for 2022. Using the historical climatology from 1951 to 2020, the anomalous conditions during 2022 in TC frequency, origin locations, tracks, intensity, and duration for the entire ocean basin as well as landfall events in China are examined. Results show that the overall TC frequency is slightly lower than normal, but the multiple TC events have a very high frequency of occurrence. Origin locations of TCs, which mark the starting points of their paths, show a large westward and northward deviation from climatology. Around 40% of the named TCs exhibit a shift in their direction of movement from westerly to easterly. Additionally, comparisons of the means, medians, upper and lower quartiles all indicate that the intensity of TCs in 2022 is generally lower than the climatology, with the duration of TCs at tropical storm intensity or above being shorter than usual. A notable observation is the fewer incidence of TC landfalls in China, but with a geographical concentration in Guangdong Province. These anomalous annual TC activities are influenced by related atmospheric and oceanic environmental conditions modulated by multi-scale climate variability. The findings provide useful information for enhancing disaster mitigation strategies in the Asia-Pacific region.

With the continuous increase of depth in underground engineering, rock bursts or rock explosions can cause instantaneous shock load and result in rock engineering disasters. To solve these problems, a novel high strength and high toughness (HSHT) bolt steel with constant resistance and large deformation is proposed. This study aims to investigate the dynamic constitutive models and microstructure of HSHT steel under extreme loading conditions. A series of dynamic tension tests were conducted using a Split Hopkinson Tensile Bar (SHTB) system with a high-speed camera. The results revealed that the HSHT steel exhibited a positive strain rate effect. As the strain rate increased from 1000 s−1 to 5000 s−1, the yield strength and ultimate strength of the HSHT steel increased gradually. However, no obvious changes in the uniform elongation. Specifically, the yield strength, tension strength, and uniform elongation of strain rate at 5000 s−1 were 1100 MPa, 1170 MPa, and 30%, respectively. According to the results of the SHTB tests, a modified Johnson-Cook model was proposed. Additionally, we investigated the microstructure of HSHT steel at a high strain rate through microscopic characterization techniques. A large number of fine and deep dimples were observed near the fracture of HSHT steel under dynamic loading. Moreover, the HSHT steel demonstrates a significant presence of nano-twins, which effectively impedes crack propagation both within the grain interior and along grain boundaries. The above findings reveal the relationship between mechanical behavior and microstructure in HSHT steel within dynamic loading conditions, providing valuable insights for the design of HSHT steel in underground engineering.

Introduction We undertook an in-depth investigation of the data pertaining to pancreatic adenocarcinoma (PAAD) to identify potential targets for the development of precision therapies. Material and methods The construction of a protein-protein interaction (PPI) network was based on overlapping differentially expressed genes (DEGs) identified in the GSE16515, GSE32676, and GSE125158 datasets. A subsequent bioinformatic analysis was performed on the interconnected genes within the PPI network, leading to the identification of the central gene, CENPN. In vitro experimentation such as CCK8 and Transwell experiments was employed to elucidate the impact of CENPN expression patterns on PAAD cell proliferation, migration, and invasion. Furthermore, the investigation revealed through comprehensive enrichment analysis that the pivotal signaling pathway associated with CENPN is the p53 signaling pathway. Results Following a comprehensive bioinformatic analysis of 161 concordant differentially expressed genes (DEGs) across three microarray datasets, CENPN emerged as the central gene under investigation. Overexpression of CENPN in pancreatic adenocarcinoma (PAAD) was associated with unfavorable patient outcomes and heightened sensitivity to four PAAD therapies: gemcitabine, docetaxel, paclitaxel, and sunitinib. Reduced CENPN expression impeded PAAD cell proliferation, migration, and invasion; however, these effects were counteracted upon upregulation of CENPN expression. Additionally, CENPN interacted with MDM2, promoting PAAD progression by targeting the p53 signaling pathway. Conclusions The findings of our study substantiate that CENPN is associated with the pathogenesis of PAAD. Consequently, CENPN appears to be a promising candidate for targeted precision therapy in clinical applications.

Skeletal stem cells (SSC) have gained attentions as candidates for the treatment of osteoarthritis due to their osteochondrogenic capacity. However, the immunomodulatory properties of SSC, especially under delivery operations, have been largely ignored. In the study, we found that Pdpn+ and Grem1+ SSC subpopulations owned immunoregulatory potential, and the single-cell RNA sequencing (scRNA-seq) data suggested that the mechanical activation of microgel carriers on SSC induced the generation of Pdpn+Grem1+Ptgs2+ SSC subpopulation, which was potent at suppressing macrophage inflammation. The microgel carriers promoted the YAP nuclear translocation, and the activated YAP protein was necessary for the increased expression of Ptgs2 and PGE2 in microgels-delivered SSC, which further suppressed the expression of TNF-ɑ, IL-1β and promoted the expression of IL-10 in macrophages. SSC delivered with microgels yielded better preventive effects on articular lesions and macrophage activation in osteoarthritic rats than SSC without microgels. Chemically blocking the YAP and Ptgs2 in microgels-delivered SSC partially abolished the enhanced protection on articular tissues and suppression on osteoarthritic macrophages. Moreover, microgel carriers significantly prolonged SSC retention time in vivo without increasing SSC implanting into osteoarthritic joints. Together, our study demonstrated that microgel carriers enhanced SSC reprogramming towards immunomodulatory phenotype to regulate macrophage phenotype transformation for effectively osteoarthritic therapy by promoting YAP protein translocation into nucleus. The study not only complement and perfect the immunological mechanisms of SSC-based therapy at the single-cell level, but also provide new insight for microgel carriers in stem cell-based therapy.

ABSTRACTDigital Light Processing (DLP) technology is a highly effective molding method for creating complex structural parts. However, the low solid content of SiC stereolithography slurry has been found to diminish the mechanical properties of the ceramic, regardless of whether it is sintered by Reactive Melt Infiltration (RMI) or Precursor Infiltration and Pyrolysis (PIP). This poses a significant challenge in improving the mechanical properties of SiC ceramics manufactured through DLP additive manufacturing. In response to this challenge, a novel method of RMI combined with infiltration is proposed in this study. The process involves the filling of the pores of the green body with pyrolytic carbon from PR or pyrolytic SiC from LHBPCS through circular infiltration, effectively increasing the content of SiC in the ceramics after reaction. Notably, the elastic modulus of RM-P2 and RM-L2 samples increased by 37.39% and 33.91%, respectively, demonstrating the potential of this method for preparing ceramics with high SiC content through stereolithography additive manufacturing. This innovative approach holds promise for overcoming the limitations previously associated with SiC ceramics produced through DLP additive manufacturing, opening up new possibilities for the development of high-performance SiC-based components.

In this study, a single zirconium carbide (ZrC) nanoneedle structure oriented in the direction was fabricated by a dual-beam focused ion beam (FIB-SEM) system, and its field emission characteristics and emission current stability were evaluated. Benefiting from controlled fabrication with real-time observation, the ZrC nanoneedle has a smooth surface and a tip with a radius of curvature smaller than 20 nm and a length greater than 2 μm. Due to its low work function and well-controlled morphology, the ZrC nanoneedle emitter, positioned in a high-vacuum chamber, was able to generate a single and collimated electron beam with a current of 1.2 nA at a turn-on voltage of 210 V, and the current increased to 100 nA when the applied voltage reached 325 V. After the treatment of the nanoneedle tip, the field emission exhibited a stable emission for 150 min with a fluctuation of 1.4% and an emission current density as high as 1.4 × 1010 A m−2. This work presents an efficient and controllable method for fabricating nanostructures, and this method is applicable to the transition metal compound ZrC as a field emission emitter, demonstrating its potential as an electron source for electron-beam devices.

Morchella is an edible mushroom with medical applciations. To explore the correlation between the texture indices of Morchella and to establish a sensory quality evaluation system, the texture quality characteristics of 214 Morchella germplasm resources from our country were analyzed via the Texture Profile Analysis (TPA) method on a texture analyzer. The research revealed significant differences in the texture quality characteristics of both the pileus and stipe among Morchella populations. After the Kolmogorov–Smirnov test, the six texture characteristics were seen to conform to a normal distribution. According to the correlation analysis, there was a significant correlation between the texture characteristics of the pileus, and a significant positive correlation between the hardness and the gumminess of the stipe (correlation coefficient of 0.96). Additionally, the hardness was negatively correlated with cohesiveness and resilience, with correlation coefficients of −0.51 and −0.38. Variation analysis indicated abundant genetic variation in each characteristic. Furthermore, the coefficient of variation for the characteristics of Morchella sextalata was higher than those of other species. Principal component analysis simplified the texture evaluation indices of Morchella pileus into a palatable factor and cohesive factor, and arranged the texture evaluation indexes of Morchella stipe into toughness–hardness factor and cohesive factor. Through comprehensive evaluation and cluster analysis, 10 Morchella strains were selected for subsequent use as breeding or cultivation materials. By comparing three different methods, the ‘probability grading method’ was determined to be the most suitable evaluation method for the texture quality characteristics of Morchella. The research results established a texture evaluation system for Morchella, offering a reference for selecting and cultivating breeds with superior texture qualities.

Drought stress is a major constraint on plant growth and agricultural productivity. Caffeic acid O-methyltransferase (COMT), an enzyme involved in the methylation of various substrates, plays a pivotal role in plant responses to abiotic stress. The involvement of COMTs in drought response, particularly through the enhancement of lignin and melatonin biosynthesis, remains poorly understood. In this study, LcCOMT was firstly proposed to be associated with the biosynthesis of both lignin and melatonin, as demonstrated through sequence comparison, phylogenetic analysis, and conserved motif identification. In vitro enzymatic assays revealed that LcCOMT effectively methylates N-acetylserotonin to melatonin, albeit with a higher Km value compared to caffeic acid. Site-directed mutagenesis of residues Phe171 and Asp269 resulted in a significant reduction in catalytic activity for caffeic acid, with minimal impact on N-acetylserotonin, underscoring the specificity of these residues in substrate binding and catalysis. Under drought conditions, LcCOMT expression was significantly upregulated. Overexpression of LcCOMT gene in Arabidopsis plants conferred enhanced drought tolerance, characterized by elevated lignin and melatonin levels, increased chlorophyll and carotenoid content, heightened activities of antioxidant enzymes peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD), and reduced malondialdehyde (MDA) and hydrogen peroxide (H2O2) accumulation. This study is among the few to demonstrate that COMT-mediated drought tolerance is achieved through the simultaneous promotion of lignin and melatonin biosynthesis. LcCOMT represents the first functionally characterized COMT in Apiaceae family, and it holds potential as a target for genetic enhancement of drought tolerance in future crop improvement strategies.

Abstract Senescent cancer cells are endowed with high immunogenic potential that has been leveraged to elicit antitumor immunity and potentially complement anticancer therapies. However, the efficacy of live senescent cancer cell‐based vaccination is limited by interference from immunosuppressive senescence‐associated secretory phenotype and pro‐tumorigenic capacity of senescent cells. Here, a senescent cancer cell‐based nanovaccine with strong immunogenicity and favorable potential for immunotherapy is reported. The biomimetic nanovaccine integrating a senescent cancer cell membrane‐coated nanoadjuvant outperforms living senescent cancer cells in enhancing dendritic cells (DCs) internalization, improving lymph node targeting, and enhancing immune responses. In contrast to nanovaccines generated from immunogenic cell death‐induced tumor cells, senescent nanovaccines facilitate DC maturation, eliciting superior antitumor protection and improving therapeutic outcomes in melanoma‐challenged mice with fewer side effects when combined with αPD‐1. The study suggests a versatile biomanufacturing approach to maximize immunogenic potential and minimize adverse effects of senescent cancer cell‐based vaccination and advances the design of biomimetic nanovaccines for cancer immunotherapy.

Accumulated evidence has supported the probiotic activity of Leuconostoc mesenteroides (L. mesenteroides) which can yield beneficial metabolites via fermentation. Here, bovine milk rich in phenylalanine（PHE) was used as a source for fermentation of L. mesenteroides. The complexes of PHE with bacterial phenylalanine hydroxylase (PheH) at two temperatures were revealed via molecular dynamics simulation. Two carbon hydrogen bonds and a Pi-Alkyl T-shaped interaction were newly formed at an active site of the PheH-PHE complex. The PheH interacted with two different hydrogen atoms in an amine of PHE via conventional hydrogen bonds at 37 °C, a temperature that accelerated the milk fermentation of L. mesenteroides. Twenty-eight metabolites including various neurotransmitters in fermented milk were identified and quantified by liquid chromatography coupled to quadrupole ion trap (Q-Trap) tandem mass spectrometry. Ex ovo injection of milk ferments into the yolk sac of chicken embryos enhanced a rising temperature-induced increase in heartbeats towards the normal resting level. The neurotransmitter-rich milk ferments hold potential for using to adjust energy metabolism, referred from heart rates, during fluctuating temperature conditions.

Abstract Essential amino acids (EAA) and microRNAs (miRs) control biological activity of a cell. Whether EAA regulates the activity of miR has never been demonstrated. Here, as proof‐of‐concept, a tryptophan (Trp, an EAA) complex containing Argonaute 2 (Ago2) and miRs including miR‐193a (Trp/Ago2/miR‐193a) is identified. Trp binds miR‐193a‐3p and interacts with Ago2. Trp/Ago2/miR‐193a increases miR‐193a‐3p activity via enhancing Argonaute 2 (Ago2) RNase activity. Other miRs including miR‐103 and miR‐107 in the Trp complex enhance miR‐193a activity by targeting the same genes. Mechanistically, the Trp/Ago2/miR‐193a complex interacts with Trp‐binding pockets of the PIWI domain of Ago2 to enhance Ago2 mediated miR activity. This newly formed Ago2/Trp/miR‐193a‐3p complex is more efficient than miR‐193a‐3p alone in inhibiting the expression of targeted genes and inhibiting colon cancer liver metastasis. The findings show that Trp regulates miR activity through communication with the RNA‐induced silencing complexes (RISC), which provides the basis for tryptophan based miR therapy.

Objective: To conduct a meta-analysis of the effectiveness and safety of ginkgo biloba extract combined with donepezil hydrochloride vs. donepezil for the treatment of vascular dementia (VaD).Methods: Four English databases (PubMed, EMBASE, Web of Science, Cochrane Library) and four Chinese databases [the China National Knowledge Infrastructure Wanfang DATA, the Chongqing VIP Database (VIP), China Biomedical Database (CBM)] were manually searched for literature published from dates of the inception of the databases to September 2023. The randomized controlled trials (RCTs) of ginkgo biloba extract with donepezil hydrochloride vs. donepezil for the treatment of VaD were included. Relevant literature was screened, and the data in the included studies were extracted for quality assessment according to the Risk of bias tool.Results: A total of 1,309 participants were enrolled in the 15 RCTs. Of these, 656 participants were in the experimental group (ginkgo biloba extract combined with donepezil) and 653 participants were in the control group (donepezil).The results showed that combination therapy was superior to donepezil alone, and there were statistically significant differences in several outcomes including RR in change for total effective rate (1.28, 95% confidence intervals 1.20, 1.38, p < 0.001), MD in change for Mini-Mental State Examination score (2.98, 95%CI 2.31, 3.65, p < 0.001), Barthel Index score (8.55,95%CI 1.11, 15.99, p = 0.024), Activity of Daily Living Scale (ADL)score (10.11,95% CI 7.16,13.07,p < 0.001).Conclusion: Ginkgo biloba extract combined with donepezil dramatically improved the total effective rate, MMSE, BI and ADL scores, and decreased homocysteine (HCY), plasma viscosity (PV), whole blood viscosity at high cut (BVH) and whole blood viscosity at low cut (BVL) in VaD patients, while the effect on mean flow velocity and pulse index (PI) of middle cerebral artery (MCA) is not obvious. However, more relevant high-quality RCTs are needed to validate these results.Systematic Review Registration: Identifier CRD42023474678.