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Abstract The introduction of antiferroelectric filler AgNbO3 into the polyvinylidene fluoride (PVDF) polymer matrix enhances its energy storage properties of PVDF. However, AgNbO3 and PVDF matrix are incompatible due to their distinct physical and chemical properties, resulting in poor compatibility between the two phases. Surface modification enhances the large difference in physical and chemical properties between the filler and the polymer matrix, and improves the compatibility between the two phases. Silane coupling agents (KH550, KH560), dopamine (DA), and grafted poly(methyl methacrylate) (PMMA) were used to modify the surface of AgNbO3 particles, and the effects of different surface modification methods on the energy storage performance of the composites were studied. The PVDF matrix was introduced with 0.3 wt% AgNbO3 particle filler. The results showed that the amino group in KH550 had the strongest binding with PVDF. The ester group in PMMA has a strong binding with PVDF. The epoxy group in KH560 has a weak binding with PVDF, while the amino group in DA has the worst binding with PVDF. The compatibility of the two phases in AgNbO3@KH550/PVDF composites is the best, and the charge distribution on the surface of the filler is uniform. Under an electric field of 350 kV/mm, the energy storage density is 8.48 J/cm3.

In this study, a novel three-dimensional biofilm electrode reactor (3D-BER) with a graphene oxide (GO)–modified cathode was developed to enhance the denitrification performance of secondary effluent from wastewater treatment plants (SEWTPs). The effects of different hydraulic retention times (HRTs) and currents on the 3D-BER were explored. The results indicated that at the optimal HRT of 4 h and current of 350 mA/m2, the 3D-BER with GO-modified cathode had a higher denitrification rate (2.40 ± 0.1 mg TN/L/h) and less accumulation of intermediate products, especially with 3.34% total nitrogen (TN) molar conversion to N2O. The GO-modified cathode offered a large biocompatible specific surface area and enhanced the conductivity, which favored microbial growth and increased electron transfer efficiency and extracellular enzyme activities. Moreover, the activity of nitrite reductase increased more than that of nitrate reductase to accelerate nitrite reduction, thus facilitating the denitrification process. The proposed 3D-BER provided an effective solution to elevate tertiary denitrification in the SEWTP. HIGHLIGHTS Secondary effluent from wastewater treatment plants are treated by the three-dimensional biofilm electrode reactor (3D-BER) with GO-modified cathode.; The 3D-BER improves the denitrification efficiency at appropriate current and HRT.; A 52.6% N2O greenhouse gas reduction with 3.34% TN molar conversion to N2O was achieved.; The GO-modified 3D-BER enhances denitrifying enzyme activity.;

Lung cancer as a molecularly and histologically high heterogonous disease, there is an urgent need to predict lung cancer patients' responses to anti-cancer treatment, and patient-derived organoids (PDOs) have been recognized as a valuable platform for preclinical drug screening. In this study, we successfully established 26 PDO lines from various subtypes of lung cancers including benign tumor, adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, large-cell carcinoma, and small-cell carcinoma. These PDOs were shown to retain the major genomic and histological characteristics of primary tumors and remain stable during long-term culture. With the help of targeted genomic sequencing, we found that lung cancer that harbors METN375S mutation is selectively sensitive to afatinib, and a combination of afatinib and gemcitabine induced synthetic lethality in PDO and mini-PDX models. In summary, our findings demonstrate the potential of PDO in predicting lung cancer drug response, and reveal a promising strategy for METN375S mutant lung cancer treatment.

BackgroundThe occurrences of occupational stress and sleep disorders are closely related. As a high-risk group of occupational stress, the sleep quality of locomotive engineers is of great significance for road traffic safety. ObjectiveTo explore the direction and degree of occupational stress affecting the sleep quality among locomotive engineers, and to analyze potential mediating and moderating roles of response strategy and overcommitment in the relationship. MethodsFrom July 1st to July 31st, 2022, a total of 6219 locomotive engineers from three locomotive depots of China Railway Lanzhou Group Corporation were selected. We conducted an online survey on occupational stress, overcommitment, response strategy and sleep quality using the Effort-Reward Imbalance, Personal Resources Questionnaire, and Pittsburgh Sleep Quality Index. Single factor analysis and correlation analysis were conducted using SPSS 25.0 software, mediation and moderation models were constructed using the Process V3.3 macro program plugin, and Harman's single factor test was used for common method bias testing. ResultsA total of 6219 questionnaires were distributed, and 5738 valid questionnaires were collected, with an effective response rate of 92.27%. The average locomotive engineers' occupational stress score (1.22±0.29), overcommitment score (16.38±3.55), response strategy score (50.00±10.00), and sleep quality score (11.51±3.95) were calculated. The Pearson correlation analysis results showed that occupational stress was positively correlated with overcommitment and sleep quality (r=0.435, 0.321, P

Abstract Chimeric antigen receptor T (CAR-T) cells have been proposed for HIV-1 treatment but have not yet demonstrated desirable therapeutic efficacy. Here, we report newly developed anti-HIV-1 CAR-T cells armed with endogenic broadly neutralizing antibodies (bNAbs) and the follicle-homing receptor CXCR5, termed M10 cells. M10 cells were designed to exercise three-fold biological functions, including broad cytotoxic effects on HIV-infected cells, neutralization of cell-free viruses produced after latency reversal, and B-cell follicle homing. After demonstrating the three-fold biological activities, M10 cells were administered to treat 18 HIV-1 patients via a regimen of two allogenic M10 cell infusions with an interval of 30 days, with each M10 cell infusion followed by two chidamide stimulations for HIV-1 reservoir activation. Consequently, 74.3% of M10 cell infusions resulted in significant suppression of viral rebound, with viral loads declining by an average of 67.1%, and 10 patients showed persistently reduced cell-associated HIV-1 RNA levels (average decrease of 1.15 log10) over the 150-day observation period. M10 cells were also found to impose selective pressure on the latent viral reservoir. No significant treatment-related adverse effects were observed. Overall, our study supported the potential of M10 CAR-T cells as a novel, safe, and effective therapeutic option for the functional cure of HIV-1/AIDS.

Highlights Hierarchical Fe3O4-Fe@CNFs/Al-Fe3O4-Fe nanocomposites were constructed by in situ growth, vacuum-assisted filtration, and self-reduction methods. The carbon framework, with in situ grown magnetic nanoparticles, supports two-dimensional magnetic nanosheets, achieving excellent electromagnetic performance and good impedance matching. Excellent reflection loss value (− 59.3 dB), broadband wave absorption (5.6 GHz at 2.2 mm thickness), and low radar cross-section value were achieved.

Abstract Background To compare presence and levels of serum cytokines in smokers and non-smokers with periodontitis following periodontal therapy. Methods Thirty heavy smokers and 30 non-smokers with stage III or IV periodontitis were included in this prospective cohort study. Clinical data and blood serum were collected at baseline (T0), after step I-III (T1), and after 12 months step IV periodontal therapy (T2). Cytokine IL-1β, IL-6, IL-8, TNF-α, IL-10, and IP-10 levels were measured using multiplex kit Bio-Plex Human Pro™ Assay. Linear regression models with cluster robust variance estimates to adjust for repeated observations were used to test intra- and intergroup levels for each marker, IL-6 and IL-8 defined as primary outcomes. Results Clinical outcomes improved in both groups following therapy (p

Triterpenoids widely exist in nature, displaying a variety of pharmacological activities. Determining triterpenoids in different matrices, especially in biological samples holds great significance. High-performance liquid chromatography (HPLC) has become the predominant method for triterpenoids analysis due to its exceptional analytical performance. However, due to the structural similarities among botanical samples, achieving effective separation of each triterpenoid proves challenging, necessitating significant improvements in analytical methods. Additionally, triterpenoids are characterized by a lack of ultraviolet (UV) absorption groups and chromophores, along with low ionization efficiency in mass spectrometry. Consequently, routine HPLC analysis suffers from poor sensitivity. Chemical derivatization emerges as an indispensable technique in HPLC analysis to enhance its performance. Considering the structural characteristics of triterpenoids, various derivatization reagents such as acid chlorides, rhodamines, isocyanates, sulfonic esters, and amines have been employed for the derivatization analysis of triterpenoids. This review comprehensively summarized the research progress made in derivatization strategies for HPLC detection of triterpenoids. Moreover, the limitations and challenges encountered in previous studies are discussed, and future research directions are proposed to develop more effective derivatization methods.

Lately, the inclusion of oleogels has emerged as an alternative strategy for the preparation of chocolate. The present study used Lycium barbarum seed oil-based oleogel through a combination of glyceryl monostearate and vegetable wax as gelling factor, and partially replaced cocoa butter for the preparation of chocolate. To further explore the storage stability of the oleogel chocolate, we measured the white index of the chocolate every five days, and also observed the surface morphology of the chocolate using 3D laser focusing microscopy. Then, we characterized the stability of resulting oleogel-chocolate stored at different temperature conditions using differential scanning calorimetry and X-ray diffraction. Our data showed that the polycrystalline morphology of the chocolate changed during storage, and the temperature differences led to variations in white index and surface roughness. The presence of oleogel attenuated the migration of liquid oils and fats in the chocolate system, and increased the stability of the chocolate system as well as relatively improved the frosting phenomenon of the chocolate. This study provides innovative avenue for the preparation of chocolates with lower saturated fatty acid content, higher storage stability, and improved nutritional value.

Background and aimsThe American Heart Association (AHA) recently introduced the Life’s Essential 8 (LE8) to improve cardiovascular health (CVH). However, the association between LE8 and the risk of prediabetes or diabetes is not yet fully understood. Consequently, this study aims to assess the association between CVH, as evaluated by LE8, and the risk of prediabetes and diabetes.Methods and ResultsThis cross-sectional study encompassed 7,739 participants aged ≥20 years from the 2007-2018 National Health and Nutrition Examination Surveys (NHANES). The CVH of participants was evaluated using the LE8, combining four health behaviors and three health factors. Glucose metabolic status categories included normal glucose metabolism, prediabetes including isolated impaired fasting glucose, isolated impaired glucose tolerance, both IFG and IGT, and diabetes. The associations between CVH and prediabetes and diabetes were analyzed using logistic regression, linear regression, restricted cubic splines, and subgroup analyses. Among 7,739 participants, 1,949 had iIFG, 1,165 were diagnosed with iIGT, 799 were IFG+IGT, and 537 were diagnosed with diabetes. After multivariable adjustments, CVH scores were inversely associated with prediabetes and diabetes, with the most robust inverse association observed between IFG+IGT and CVH across all prediabetes subgroups. Of all CVH components not directly in the causal pathway, body mass index (BMI) had the most robust associations with prediabetes and diabetes. Subgroup analyses indicated that the negative correlation between CVH and prediabetes was stronger among those with university or higher education.ConclusionCVH, as defined by LE8, showed a significant negative association with prediabetes and diabetes.

The biodiversity-ecosystem functioning (BEF) relationship is a critical topic in ecological research, as it guides the maintenance of ecosystem functioning in the face of climate change and human disturbance. However, the BEF relationship is complicated by the fact that biodiversity has multiple dimensions, and in particular functional diversity may be strongly correlated with community productivity. But the understanding is still lacking about how different functional traits determine community productivity. The present study tested the relationship between biodiversity and community productivity empirically in a demersal fish community, based on continuous bottom trawl surveys in Haizhou Bay, China from 2013 to 2022. Structural equation modeling (SEM) with composite variables was used to evaluate the relationships among environmental factors, species diversity (SD), functional diversity (FD), community weighted mean traits (CWM), and community productivity (CP), and the roles of different aspects of functional traits were further compared. The results showed that there were considerable heterogeneities in the temporal and spatial distributions of CP, and PCA revealed that the CP was weakly correlated with both species and functional diversity. SEM showed that CWM had the greatest influences on CP (r = 0.63), followed by SD (r = 0.52), and FD had the least impact (r = -0.42). This finding supported the mass ratio hypothesis, indicating that functional traits of dominant species determined community productivity. Environmental factors showed no direct impacts on CP but had indirect effects through biodiversity. Regarding the role of different functional traits, the trait of locomotion was the most important driver of CP in terms of CWM, while the food acquisition was more important than other components in terms of FD. Our study can contribute to an improved comprehension of the BEF linkages in marine fish communities, and serve as a guideline for fisheries management and biodiversity protection in the face of climate changes.

Abstract This paper examines the ethical issues of water environment in the context of river management in practical engineering and technological applications. In particular, three important issues are discussed in this paper referring to two actual engineering cases in ancient and modern China, that is, the construction of ancient Dujiangyan irrigation project in Sichuan, China, and the modern practice of integrated operation of flood control and pollution prevention in Huai River Basin. The three issues include how to consider the trade‐offs between flood control and irrigation, how to balance flood control and contamination prevention related to sudden water pollution incident, and how to ensure the protection of water environments and ecology in rivers under the grand challenges of natural environmental changes and high‐intensity human activities. Finally, this paper concludes by emphasizing the future development of water environmental ethics and its interdisciplinary integration with modern science & technology in smart river management in China.

Abstract The purpose of this study is to explore the relationship between appearance anxiety and social media use among Chinese adolescents. Using a grounded theory approach, the study conducted two-round online interviews with ten Chinese university students and subsequently constructed a theoretical model of social media appearance anxiety among Chinese young people. The results of the study indicate that social media has a dual impact on appearance anxiety. On one hand, increased social media engagement amplifies appearance anxiety by shaping aesthetic standards and fostering comparative environments. On the other hand, diverse aesthetic perspectives and authentic presentations on social media partially alleviate appearance anxiety by promoting acceptance of unique appearances and boosting self-confidence. It is emphasized in this study that there should be an in-depth understanding of the dual impact and complicated relationship of social media on the daily lives of Chinese adolescents to further develop relevant strategies that promote healthy social media behavior among youth. Furthermore, this study calls for efforts to actively promote the healthy image and psychological well-being of adolescents while alleviating the negative impact of appearance anxiety and overall mental health. Such efforts are needed to ensure a positive and healthy development for the younger generation.

BackgroundEsophageal cancer (EC) is a prevalent malignancy characterized by a low 5-year survival rate, primarily attributed to delayed diagnosis and limited therapeutic options. Currently, early detection of EC heavily relies on endoscopy and pathological examination, which pose challenges due to their invasiveness and high costs, leading to low patient compliance. The detection of DNA methylation offers a non-endoscopic, cost-effective, and secure approach that holds promising prospects for early EC detection.MethodsTo identify improved methylation markers for early EC detection, we conducted a comprehensive review of relevant literature, summarized the performance of DNA methylation markers based on different input samples and analytical methods in EC early detection and screening.FindingsThis review reveals that blood cell free DNA methylation-based method is an effective non-invasive method for early detection of EC, although there is still a need to improve its sensitivity and specificity. Another highly sensitive and specific non-endoscopic approach for early detection of EC is the esophageal exfoliated cells based-DNA methylation analysis. However, while there are substantial studies in esophageal adenocarcinoma, further more validation is required in esophageal squamous cell carcinoma.ConclusionIn conclusion, DNA methylation detection holds significant potential as an early detection and screening technology for EC.

Objective To assess the correlation between the effort–reward imbalance (ERI) and sleep quality among railway locomotive stewards.Design Cross-sectional study.Setting Lanzhou Bureau Group, China Railway, between July and August 2022.Participants Railway locomotive stewards.Primary and secondary outcome measures Sleep quality was assessed using the Pittsburgh Sleep Quality Index Scale (PSQI), categorising scores of >14 as poor, 8–14 as fair and

Abstract Background Physio-psycho-socioeconomical health comprehensively declines during aging, the complexity of which is challenging to measure. Among the complexity, multiple chronic disorders continuously cumulated during aging, further aggravating the challenge. Methods A population-based survey on Comprehensive Ageing Health Assessment was conducted in older adults (age > = 60) enrolled from hospital settings and community settings in 13 working centers in six subnational regions in China. Cross-sectional datasets of 8,093 older participants with approximately complete assessment results were collected for the present analysis. Individual’s multi-disease or multi-symptom was respectively scored by summing coexistent multiple diseases or multiple symptoms by respective weighting efficient for Self-Rated Health (SRH). Individual’s age-dependent health decline was further summed of four SRH-weighted scores for daily function (activity of daily life, ADL), physical mobility (an average of three metrics), cognitive function (mini mental state examination, MMSE) and mental being (geriatric depression scale, GDS) plus multi-disease score (MDS) and multi-symptom score (MSS).Multi-disease patten among 18 diseases or multi-symptom pattern among 15 symptoms was latent-clustered in the older adults, the optimal outcome of which was categorized into high, moderate or low aging-associated clusters, respectively. Percentage distribution was compared between overall health decline score and multi-disease pattern cluster or multi-symptom patten cluster. A new variable of difference between MDS and MSS (hereinafter terming DMM) that displayed linear variation with socioeconomic factors was further fitted using multilevel regression analyses by substantial adjustments on individual confounders (level-1) and subnational region variation (level-2). Results Consistent gradient distribution was shown between health decline and multimorbidity pattern cluster in the older adults. DMM was found linearly varied with personal education attainment and regional socioeconomic status. Using optimally fitted stratification of DMM (DMM interval = 0.02), an independent U-shaped interrelated tendency was shown between health decline, multi-disease and multi-symptom, which could be well explained by regional disparities in socioeconomic status. Conclusion Newly developed metrics for age-dependent health decline and aging-associated multimorbidity patten were preliminarily validated from within. The new variable of optimally fitted categorization of DMM might function as a practical indicator aiding in improving the cost-effectiveness and reduce inequity of healthcare delivery for older adults in developing countries.

Abstract China's economic growth has reached a new plateau. It is no longer appropriate to use the old economic growth model, which relied on labor, land resources, mineral resources, and other economic considerations. Under the background of artificial intelligence, high-quality economic development is an inevitable trend. A new financial paradigm called "digital finance" integrates financial services with information technologies. Digital financial technology is thought to be a crucial foundation for fostering high-quality and sustainable economic and social development since it may offer more economic entities reduced cost of capital and more realistic financial service skills than in traditional financial models. In the era of artificial intelligence, how to reasonably release the momentum of digital finance for China's sustained economic growth has become a hot topic of discussion at this stage. This paper studies the impact of digital finance on the economic efficiency of the energy industry in the context of artificial intelligence. Relevant metrics were also calculated. The findings revealed that: The benchmark regression result of digital finance on the efficiency of the green economy was 0.4685 before adding the main restrictions; the benchmark regression result of digital finance on the efficiency of the green economy was 0.2243 after adding the main constraints. As a result, data finance had a favorable impact on the effectiveness of the green economy.

Abstract Traditional villages are repositories for preserving human artifacts and cultural heritage. An investigation of the spatial distribution characteristics and factors influencing traditional villages in provincial administrative regions can provide new insights regarding the protection of traditional villages and rural development. This study focused on 275 traditional villages in Henan Province. Using ArcGIS and GeoDa software, we analysed the spatial autocorrelation and heterogeneity of the nearest neighbour index, Gini coefficient, Moran’s I, and kernel density of the villages. Additionally, in conjunction with the Python sklearn library and GeoDetector, 15 indicators were selected to construct a decision tree model, spatial lag regression model, and geographic detector. Then the influence and interaction mechanisms of each indicator were analysed. The results revealed that (1) the spatial distribution of traditional villages in Henan Province was clustered and uneven, with a spatial layout comprising “3 high-density areas + 1 medium-density belt”; (2) overall, the number of traditional villages was negatively correlated with altitude, slope, rainfall, population density, proportion of the minority population, and historical-cultural intensity; and (3) the decision tree model results demonstrated that the selected 15 indicators had good predictive ability and that population density was particularly important. The spatial lag regression model results showed that the spatial distribution of traditional villages was positively correlated with distance from rivers, urbanization rate, and tourism resources, and negatively correlated with population density, per capita GRP, historical-cultural intensity, and NDVI. (4) The GeoDetector results indicated that historical-cultural intensity and population density were the two factors with the most significant explanatory power for the spatial differentiation of traditional villages in Henan Province. In terms of interactive factors, population density $$\cap$$ ∩ population was the strongest interactive driving force, followed by population $$\cap$$ ∩ historical-cultural intensity.

Grapes are susceptible to mold and decay during postharvest storage, and developing new technologies to extend their storage period has important application value. Photodynamic technology (PDT) in concurrence with carbon dots (CDs) proposes an innovative and eco-friendly preservation strategy. We examined the effects of carbon dots combined with photodynamic treatment on postharvest senescence and antioxidant system of table grape. The compounding of photodynamic technology with a 0.06 g L−1 CDs solution could possibly extend the postharvest storage period of grape berries. Through this strategy, we achieved a decreased rate of fruit rotting and weight loss alongside the delayed deterioration of fruit firmness, soluble solids, and titratable acid. As paired with photodynamic technology, CDs considerably decreased the postharvest storage loss of phenols, flavonoids, and reducing sugars as compared to the control group. Concurrently, it remarkably postponed the build-up of hydrogen peroxide (H2O2), superoxide anion (O2∙−), and malondialdehyde (MDA); elevated the levels of reduced ascorbic acid (AsA) and reduced glutathione (GSH); lowered the levels of dehydroascorbic acid (DHA) and oxidized glutathione (GSSG); raised the ratios of AsA/DHA and GSSH/GSSG; encouraged the activities of superoxide dismutase (SOD) and phenylalanine ammonia-lyase (PAL); and inhibited the activities of polyphenol oxidase (PPO) and lipoxygenase (LOX). Furthermore, it enhanced the iron reduction antioxidant capacity (FRAP) and DPPH radical scavenging capacity of grape berries. CDs combined with photodynamic treatment could efficiently lessen postharvest senescence and decay of grape berry while extending the storage time.

Climate change has led to significant fluctuations in marine ecosystems. As a component of the food web, the trophic diversity and spatiotemporal changes of fish communities are crucial for understanding ecosystems. In recent years, stable isotope analysis has been increasingly used as a comprehensive tool for quantitative assessment of trophic diversity to explore spatiotemporal variations in fish community diversity. This study is based on carbon (δ13C) and nitrogen (δ15N) stable isotope analysis using different biomass-weighted isotope diversity indices, including isotopic divergence index (IDiv), isotopic dispersion index (IDis), isotopic evenness index (IEve), and isotopic uniqueness index (IUni). The overall results indicate that IDis, IEve, and IUni values of fish communities were relatively low, while IDiv was relatively high in the Haizhou Bay ecosystem. IDiv, IDis, IEve, and IUni were lower in autumn than in spring; IDiv and IDis were relatively higher in offshore waters, while IEve and IUni were relatively higher in inshore waters. The changes in species composition and intensive pelagic–benthic coupling in Haizhou Bay may lead to significant spatiotemporal variations in the trophic diversity of fish communities in the area. These findings highlight the importance of incorporating trophic relationships into ecosystem models, which will help to enhance our understanding of the complexity of the trophic structure of fish communities.

Terahertz (THz) spectroscopy has demonstrated significant potential for substance detection due to its low destructiveness and due to the abundance of molecular fingerprint absorption signatures that it contains. However, there is limited research on the fingerprint detection of substances at different temperatures. Here, we propose a THz metamaterial slit array sensor that exploits localized surface plasmons to enhance the electric field within the slit. The transmission peak frequency can be modulated via temperature adjustments. This method enables the detection of molecular absorption characteristics at multiple spectral frequency points, thereby achieving a specific and highly sensitive detection of characteristic analyte fingerprint spectra. Additionally, the sensor supports the detection of substances at multiple temperatures and sensitively identifies changes in their absorption properties as a function of temperature. Our research has employed temperature variation to achieve a highly sensitive and specific detection of trace analytes, offering a new solution for THz molecular detection.

As the main service mode and management mode of socialized service, agricultural production trusteeship services (APTS) are an important way to realize the tight link between farmers and modern agricultural development, which is highly important for ensuring national food security. By constructing a utility model of farmers, this paper deduces the decision-making mechanism of farmers’ APTS from the dual mechanism of natural risk and non-agricultural employment income (NAEI) and uses the survey data of 956 farmers in the three northeastern provinces to verify the empirical results by using multivariate logit (Mlogit) and propensity score matching (PSM) methods. The research shows that natural risk hinders farmers’ choice of the APTS; NAEI has a positive impact on APST, and an increase in NAEI weakens the negative effect of natural risk on the choice of the APTS, and has an enhanced moderating effect. In addition, the scale heterogeneity analysis revealed that the impacts of natural risk and NAEI on farmers of different scales are significantly different. The NAEI adjustment effect has the greatest impact on small-scale farmers, followed by medium-scale farmers. In view of this, the government should stabilize the nonagricultural employment market and improve the nonagricultural employment opportunities of farmers. APTS organizations should transfer natural risks and improve the agricultural insurance system. According to the differences of different scales of farmers, different promotion policies are formulated, and the expansion of management and deepening services is proposed to further promote the development of APTS and consolidate the foundation of food security in China.

Abstract Dietary methionine interventions are beneficial to apoptosis-inducing chemotherapy and radiotherapy for cancer, while their effects on ferroptosis-targeting therapy and immunotherapy are unknown. Here we show the length of time methionine deprivation affects tumoral ferroptosis differently. Prolonged methionine deprivation prevents glutathione (GSH) depletion from exceeding the death threshold by blocking cation transport regulator homolog 1 (CHAC1) protein synthesis. Whereas, short-term methionine starvation accelerates ferroptosis by stimulating CHAC1 transcription. In vivo, dietary methionine with intermittent but not sustained deprivation augments tumoral ferroptosis. Intermittent methionine deprivation also sensitizes tumor cells against CD8+ T cell-mediated cytotoxicity and synergize checkpoint blockade therapy by CHAC1 upregulation. Clinically, tumor CHAC1 correlates with clinical benefits and improved survival in cancer patients treated with checkpoint blockades. Lastly, the triple combination of methionine intermittent deprivation, system xc - inhibitor and PD-1 blockade shows superior antitumor efficacy. Thus, intermittent methionine deprivation is a promising regimen to target ferroptosis and augment cancer immunotherapy.

The influences of ocean warming on marine lives have accelerated over the 21st century, greatly altering the structure and function of marine food webs and causing distributional shifts, species invasions, and changes in productivity. It is imperative to clarify the overall ecosystem responses to ocean warming and develop fisheries management strategies adaptive to the ecosystem changes. In this study, the potential impacts of ocean warming on trophic structure, energy flows, and fisheries production of an overexploited ecosystem were examined, and the effectiveness of fisheries management in mitigating warming impacts were also evaluated. We constructed a mass-balance food web model in Haizhou Bay and simulated three climate scenarios (RCPs 2.6, 4.5, and 8.5) along with different levels of fishing pressure, in order to examine the ecosystem responses to the combined changes in fishing and climate changes. Results showed that the total biomass of commercial species and fisheries catches would decline with rising temperature, especially under the RCP8.5 scenario. Ocean warming could induce lower trophic transfer efficiency and decrease energy recycling capacity within the food web, leading to large losses in total biomass and total production. Reducing fishing intensity could help mitigate the negative effects of ocean warming on fisheries productivity, but was insufficient to maintain ecological properties. Moreover, the effectiveness of such alternative measures would be diminished with increased greenhouse gas emissions, especially under the climate scenario of RCP8.5. The findings of this study highlight the need to slow the rise of sea temperature and implement climate-adaptive fisheries management in the future.

Recent progressions in immunotherapy have transformed cancer treatment, providing a promising strategy that activates the immune system of the patient to find and eliminate cancerous cells. Bispecific antibodies, which engage two separate antigens or one antigen with two distinct epitopes, are of tremendous concern in immunotherapy. The bi-targeting idea enabled by bispecific antibodies (BsAbs) is especially attractive from a medical standpoint since most diseases are complex, involving several receptors, ligands, and signaling pathways. Several research look into the processes in which BsAbs identify different cancer targets such angiogenesis, reproduction, metastasis, and immune regulation. By rerouting cells or altering other pathways, the bispecific proteins perform effector activities in addition to those of natural antibodies. This opens up a wide range of clinical applications and helps patients with resistant tumors respond better to medication. Yet, further study is necessary to identify the best conditions where to use these medications for treating tumor, their appropriate combination partners, and methods to reduce toxicity. In this review, we provide insights into the BsAb format classification based on their composition and symmetry, as well as the delivery mode, focus on the action mechanism of the molecule, and discuss the challenges and future perspectives in BsAb development.

AbstractObjectives The scope of lateral neck lymph node dissection (LND) in papillary thyroid carcinoma (PTC) remains controversial. Our research aimed to explore the value of central lymph node metastasis (CLNM) in frozen sections for predicting neck lateral lymph node metastasis (NLLNM) and to guide clinical surgeons in performing surgical lymph node dissection.Patients A total of 275 patients with PTC with suspected ‘Cervical lymph node metastasis (LNM, including CLNM and NLLNM)’ underwent unilateral or bilateral thyroidectomy and an intraoperative frozen diagnosis of central lymph nodes (LNs), as well as central and neck lateral LND. Validity indices and consistency of central LNs in frozen sections were calculated. In total, 216 patients then met the inclusion criteria and were enrolled in the follow-up study. The clinical and pathological data of the patients were retrospectively analyzed. The relationship between the number, metastatic diameter, and the ratio of CLNM to NLLNM was investigated.Results CLNM in frozen and paraffin-embedded sections was associated with NLLNM. Univariate and multivariate analyses revealed the following risk factors for NLLNM metastasis: maximum diameter, total number, and ratio of metastatic LNs. A significant result was obtained when a cut-off value of 2.050 mm for the maximum metastatic diameter, 5.5 in the total number, and 0.5342 for the CLNM ratio level was used. Interaction term analyses showed that the association between the number of CLNM and NLLNM differed according to maximum diameter.Conclusion Central LNs in frozen sections accurately predicted NLLNM. In patients with PTC with >5 CLNMs, ≥2 and ≤5 CLNMs and maximum metastatic diameter > 2 mm, neck lateral LND should be considered. Our findings will facilitate the identification of patients who are likely to benefit from extended lateral neck LND.

Sound vibration, an external mechanical force, has been proven to modulate plant growth and development like rain, wind, and vibration. However, the role of sound on plants, especially on signal response, has been usually neglected in research. Herein, we investigated the growth state, gene expression, and signal response in duckweed treated with soft music. The protein content in duckweed after music treatment for 7 days was about 1.6 times that in duckweed without music treatment. Additionally, the potential maximum photochemical efficiency of photosystem II (Fv/Fm) ratio in duckweed treated with music was 0.78, which was significantly higher in comparison with the control group (P

Background: Target gastrointestinal cancers (GICs), encompassing esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC), originate within a single readily accessible luminal organ system and are diagnosable using endoscopy. However, endoscopy is an invasive procedure with low compliance and no plasma-based DNA methylation assay for the early detection of GICs. Methods: Nine potential DNA methylation markers were identified and evaluated in tissue (n=60) and plasma (n=155) cohorts to select the most suitable markers. A training cohort (n=244) and a validation cohort (n=199), including GICs patients, benign tumors, gastrointestinal polyps, and controls, were enrolled to develop and validate a DNA methylation panel. An independent prospective cohort (n=158) was used to validate the panel's performance and compare it with blood protein tumor markers. Results: Six out of nine candidate methylation markers with excellent discrimination abilities in both tissue and plasma cohorts were selected for the DNA methylation panel. The panel demonstrated high AUC values of 0.937 (EC), 0.968 (GC), and 0.987 (CRC) in training cohort, and achieved AUC values of 0.921 (EC), 0.921 (GC), and 0.959 (CRC) in validation cohort. Notably, it achieved impressive AUC values of 0.971 and 0.843 for identifying stage I GICs in the training and validation cohorts, respectively. In the prospective cohort, the six-marker panel showed comparable AUC values to CEA, AFP, and CA19-9 (0.935, 0.769, 0.663, and 0.668, respectively). Conclusion: This study successfully developed and validated a novel, robust, sensitive, and specific plasma-based DNA methylation panel, offering a promising strategy for the early detection of GICs.

ABSTRACTExtraintestinal pathogenic Escherichia coli (ExPEC) is an important zoonotic pathogen. Recently, ExPEC has been reported to be an emerging problem in pig farming. However, the mechanism of pathogenicity of porcine ExPEC remains to be revealed. In this study, we constructed a transposon (Tn) mutagenesis library covering Tn insertion in over 72% of the chromosome-encoded genes of a virulent and multi-drug resistant porcine ExPEC strain PCN033. By using a mouse infection model, a transposon-directed insertion site sequencing (TraDIS) assay was performed to identify in vivo fitness factors. By comparing the Tn insertion frequencies between the input Tn library and the recovered library from different organs, 64 genes were identified to be involved in fitness during systemic infection. 15 genes were selected and individual gene deletion mutants were constructed. The in vivo fitness was evaluated by using a competitive infection assay. Among them, ΔfimG was significantly outcompeted by the WT strain in vivo and showed defective adhesion to host cells. rfa which was involved in lipopolysaccharide biosynthesis was shown to be critical for in vivo fitness which may have resulted from its role in the resistance to serum killing. In addition, several metabolic genes including fepB, sdhC, fepG, gltS, dcuA, ccmH, ddpD, narU, glpD, malM, and yabL and two regulatory genes metJ and baeS were shown as important determinants of in vivo fitness of porcine ExPEC. Collectively, this study performed a genome-wide screening for in vivo fitness factors which will be important for understanding the pathogenicity of porcine ExPEC.

To study the efficiency of flue gas sequestration with enhanced shale gas recovery in quartz slit, Grand Canonical Monte Carlo (GCMC) and Molecular Dynamics (MD) simulations were adopted to investigate the influence of burial depth, formation water content and the injection ratio of flue gas on the recovery efficiency of shale gas (CH4) in quartz slit by flue gas (CO2/N2). The density distribution, loading, adsorption heat and interaction energy of each component were systematically analyzed to reveal their adsorption mechanisms and the recovery efficiency of CH4. It indicates that the loadings of mixed CH4 and N2 (ΓCH4 and ΓN2) exhibit negative correlation with formation water content. With the increasing burial depth, both ΓCH4 and ΓN2 increase at first and then tend to be constant when the burial depth is over 2 400 m. The maximum loading of CO2 (ΓCO2) occurs at the burial depth of 2 400 m. There is a positive correlation of ΓCO2 with formation water content when the burial depth is below 2 400 m, and a negative correlation when the burial depth is over 2 400 m. The recovery efficiency of CH4 (η) reaches the maximum point at the burial depth of 400-600 m, which increases with the increasing mole fraction of CO2 in flue gas, showing that CO2 in flue gas can promote the displacement of CH4 significantly.

Abstract Background Fibrodysplasia ossificans progressiva (FOP) is an ultrarare and disabling genetic disorder of connective tissue characterized by congenital malformation of the great toes, and progressive heterotopic ossification (HO) in soft connective tissues. A gain-of-function mutation of activin A receptor type I (ACVR1) enables ACVR1 to recognize activin A as an agonist with bone morphogenetic protein (BMP) signalling that leads to HO. Previous studies confirmed that activin A stimulates BMP signalling in vitro and drives HO in mouse models of FOP. However, the roles for BMP4 and BMP6 in FOP are supported only by correlative evidence in vitro. Thus, it remains unclear whether the circulating levels of activin A, BMP4 and BMP6 correlate with flare-ups in FOP patients. Hence, we investigated the protein levels of activin A, BMP4 and BMP6 in the serum of FOP patients. Results We recruited 16 untreated FOP patients and 16 age- and sex- matched healthy control subjects in this study. The 16 FOP patients were retrospectively divided into the flare-up group (n = 8) and remission group (n = 8) depending on whether they had flare-ups or worsening of any joint movement in the last 6 months. The serum activin A, BMP4 and BMP6 levels were detected by enzyme-linked immunosorbent assay. The serum activin A, BMP4 and BMP6 levels were slightly higher in FOP patients (median: 434.05 pg/mL, 459.48 pg/mL and 67.84 pg/mL) versus healthy control subjects (median: 364.14 pg/mL, 450.39 pg/mL and 55.36 pg/mL). However, there were no statistically significant differences between the two groups (p > 0.05 for all items), nor were there significant differences between the flare-up and remission groups of FOP (p > 0.05 for all items). Univariate and multivariate logistic regression analyses showed that age, sex, and serum activin A, BMP4 and BMP6 levels were not related to flare-up in FOP patients. Conclusions There were no significant differences in the serum levels of activin A, BMP4 and BMP6 in FOP patients compared with healthy control subjects. Serum activin A, BMP4 and BMP6 proteins might not be the stimulators for FOP flare-up, and may not be biomarkers for FOP diagnosis.

Abstract Purpose To explore pediatric nurses’ challenges and effective coping strategies in caring for dying children. Methods A descriptive qualitative study was adopted. Data were collected using a semi-structured interview with ten nurses from the pediatric, pediatric emergency, and neonatology departments. Results Three themes were generated: stressors, consequences, and coping strategies. Ten sub-themes were generalized: negative emotions; helplessness; questioning rescue behavior; fear of communication; lack of workforce for night rescue; compassion fatigue; burnout; changes in life attitudes; self-regulation; leadership approval and no accountability. Conclusions Through qualitative research, nurses’ challenges and effective coping strategies in caring for dying children were found, which provides information for nurses’ career development and related policy formulation in China. Clinical relevance While there are many articles in China on hospice care, there is little research on the nurses’ experience of caring for dying children. Many studies have mentioned the adverse consequences of caring for dying children in foreign countries, leading to post-traumatic stress disorder (PTSD). However, domestic discussion of such problems is rare, and no corresponding coping strategies exist. This study explores pediatric nurses’ challenges and effective coping strategies in caring for dying children.

Herbal medicine has been widely valued because of its remarkable efficacy and minimal side effects. The quantitative analysis of herbal medicines is essential to ensure their safety and efficacy. The simultaneous detection of multiple quality markers (Q-markers) has emerged as an important approach and trend in herbal medicine quality control. In recent years, non-targeted screening has become an effective strategy for the discovery and identification of unknown compounds. This study developed a non-targeted screening and quantitative analysis strategy to discover, identify and quantify the multiple components that truly represent the efficacy of Wuling capsule. Within this strategy, 18 types of flavonoids were tentatively discovered and identified from Wuling capsule by analyzing mass cleavage pathways, the precise molecular weights of compounds, and comparing the data with a database. Ten types of flavonoids were determined after the comparison of the standards. Additionally, following the evaluation of the regression equation, linear range, limit of detection (LOD), limit of quantitation (LOQ), precision, repeatability, and recovery of the proposed quantitative method, six flavonoids were quantified. This method successfully screened, identified, and quantified the potential active components in Wuling capsule, providing insights for improving the quality control standards in other herbal medicines.

The act of land transfer in rural areas is an important decision-making mechanism for farmers, to enhance resource allocation efficiency and promote capital mobility, and this act is of strategic importance in promoting the level of agricultural scale and mechanization, land system change, and, thus, the sustainable development of livelihoods and production in China. This study aims to explore farmers’ decision-making mechanisms in the process of land transfer in rural areas, by constructing a theoretical framework. Structural equation modeling was used, based on data from a survey of rural families in the Liaoning Province area of Northeastern China. The main findings are as follows: (1) The seven types of exogenous latent variables, including environmental vulnerability, policy, and five main livelihood assets (natural capital, physical capital, financial capital, human capital, and social capital), are intermediary in farmers’ land transfer behavior, which then positively affect farmers’ livelihood outcomes. (2) Among the exogenous latent variables affecting farmers’ land transfer, human assets have the most significant positive effect, followed by social assets and physical assets, family labor force share, frequency of work information exchange, and number of production tools, greatly affect the corresponding variable. (3) Natural assets play the most important role and have a negative effect on farmers’ land transfer decision; contracted area of land per family is the greatest impacted measurable variable of this. The results of the study suggest that the government should strengthen skills training for farmers, improve the land transfer policy system, and provide appropriate subsidies in a regionally targeted manner. Thus, it can promote the transformation of Chinese-style agricultural modernization and achieve rural revitalization.

Prohibited additives in infant formula severely affect the health of infants. Terahertz (THz) spectroscopy has enormous application potential in analyte detection due to its rich fingerprint information content. However, there is limited research on the mixtures of multiple analytes. In this study, we propose a split ring metasurface that supports magnetic dipole bound states in the continuum (BIC). By breaking the symmetry, quasi-BIC with a high quality (Q) factor can be generated. Utilizing an angle-scanning strategy, the frequency of the resonance dip can be shifted, resulting in the plotting of an envelope curve which can reflect the molecular fingerprint of the analytes. Two prohibited additives found in infant formula, melamine and vanillin, can be identified in different proportions. Furthermore, a metric similar to the resolution in chromatographic analysis is introduced and calculated to be 0.61, indicating that these two additives can be detected simultaneously. Our research provides a new solution for detecting additives in infant formula.

Spectroscopy is a powerful tool to identify the specific fingerprints of analytes in a label-free way. However, conventional sensing methods face unavoidable barriers in analyzing trace-amount target molecules due to the difficulties of enhancing the broadband molecular absorption. Here, we propose a sensing scheme to achieve strong fingerprint absorption based on the angular-scanning strategy on an all-silicon metasurface. By integrating the mid-infrared and terahertz sensing units into a single metasurface, the sensor can efficiently identify 2,4-DNT with high sensitivity. The results reveal that the fingerprint peak in the enhanced fingerprint spectrum is formed by the linked envelope. It exhibits a significant enhancement factor exceeding 64-fold in the terahertz region and more than 55-fold in the mid-infrared region. Particularly, the corresponding identification limit of 2,4-DNT is 1.32 µg cm−2, respectively. Our study will provide a novel research idea in identifying trace-amount explosives and advance practical applications of absorption spectroscopy enhancement identification in civil and military security industries.

Based on the Protection Motivation Theory (PMT), the Psychological Reactance Theory (PRT), and the Theory of Planned Behavior (TPB), we revealed the psychological impact factors of individuals' private car purchase intentions during the new normal of COVID-19. Structural equation modeling (SEM) and Bayesian network (BN) were used to analyzed the car purchase decision-making mechanism. A questionnaire survey was conducted to collect empirical data from April 20th to May 26th of 2020 in China. We investigated 645 participants and analyzed the data. The SEM results showed that conditional value, pro-car-purchasing attitude, and perceived behavioral control, health value, and cost factors have significant direct effects on car purchase intention. According to BN's prediction of purchase intention, the probability of high purchase intention grew by 47.6%, 97.3% and 163.0%, respectively, with perceived behavioral control, pro-car-purchasing attitude, and conditional value shifting from "low" to "medium" and "high". This study provided a new perspective for researchers to explore the purchase intention of cars during the epidemic. Meanwhile, we could provide a reference for the government and enterprises to develop measures related to the automobile market."

Accurate information for consumer phase connectivity in a low-voltage distribution network (LVDN) is critical for the management of line losses and the quality of customer service. The wide application of smart meters provides the data basis for the phase identification of LVDN. However, the measurement errors, poor communication, and data distortion have significant impacts on the accuracy of phase identification. In order to solve this problem, this paper proposes a phase identification method of LVDN based on stepwise regression (SR) method. First, a multiple linear regression model based on the principle of energy conservation is established for phase identification of LVDN. Second, the SR algorithm is used to identify the consumer phase connectivity. Third, by defining a significance correction factor, the results from the SR algorithm are updated to improve the accuracy of phase identification. Finally, an LVDN test system with 63 consumers is constructed based on the real load. The simulation results prove that the identification accuracy achieved by the proposed method is higher than other phase identification methods under the influence of various errors.

Highlights The first study to establish 28 models using machine learning for TB diagnosis. The first TB diagnostic model based on routine, TB-specific and non-specific tests. Cforest model presented excellent performance in discriminating ATB from LTBI.

Abstract Distant metastasis is the main cause of mortality in breast cancer patients. Using the breast cancer genomic data from The Cancer Genome Atlas (TCGA), we identified brain specific Cav2.2 as a critical regulator of metastasis. Cav2.2 expression is significantly upregulated in breast cancer and its higher expression is inversely correlated with survival suggesting a previously unappreciated role of Cav2.2 in breast cancer. Cav2.2 is required for breast cancer migration, invasion, and metastasis. Interestingly, Cav2.2 promotes invadopodia formation and extracellular matrix (ECM) degradation through the stabilization of invadopodia component cortactin in a proteosome-dependent manner. Moreover, deubiquitinating enzyme USP43 mediated the functions of Cav2.2 in cortactin stabilization, invadopodia formation, ECM degradation, and metastasis. Interestingly, Cav2.2 upregulates USP43 expression through NFAT2 dephosphorylation and nuclear localization. Our study uncovered a novel pathway that regulates cortactin expression and invadopodia formation in breast cancer metastasis.

Background: Gastric cancer (GC) is one of the most common malignancies, with a low 5-year survival rate. However, if diagnosed at an early stage, it can be cured by endoscopic treatment and has a good prognosis. While gastrointestinal X-ray and upper endoscopy are used as national GC screening methods in some GC high-risk countries, such as Japan and Korea, their radiation exposure, invasiveness, and high cost suggest that they are not the optimal tools for early detection of GC in many countries. Therefore, a cost-effective, and highly accurate method for GC early detection is urgently needed in clinical settings. DNA methylation plays a key role in cancer progression and metastasis and has been demonstrated as a promising marker for cancer early detection.Aims and methods: This review provides a comprehensive overview of the current status of DNA methylation markers associated with GC, the assays developed for GC early detection, challenges in methylation marker discovery and application, and the future prospects of utilizing methylation markers for early detection of GC. Through our analysis, we found that the currently reported DNA methylation markers related to GC are mainly in the early discovery stage. Most of them have only been evaluated in tissue samples. The majority of non-invasive assays developed based on blood lack standardized sampling protocols, pre-analytical procedures, and multicenter validation, and they exhibit insufficient sensitivity for early-stage GC detection. Meanwhile, the reported GC DNA methylation markers are generally considered pan-cancer markers.Conclusion: Therefore, future endeavors should focus on identifying additional methylation markers specific to GC and establishing non-invasive diagnostic assays that rely on these markers. These assays should undergo multicenter, large-scale prospective validation in diverse populations.

The primary goal of bone tissue engineering is to fabricate scaffolds that can provide a microenvironment similar to that of natural bone. Therefore, various scaffolds have been designed to replicate the bone structure. Although most tissues exhibit complicated structures, their basic structural unit includes stiff platelets arranged in a staggered micro-array. Therefore, many researchers have designed scaffolds with staggered patterns. However, relatively few studies have comprehensively analyzed this type of scaffold. In this review, we have analyzed scientific research pertaining to staggered scaffold designs and summarized their effects on the physical and biological properties of scaffolds. Compression tests or finite element analysis are typically used to evaluate the mechanical properties of scaffolds, and most studies have performed experiments in cell cultures. Staggered scaffolds improve mechanical strength and are beneficial for cell attachment, proliferation, and differentiation in comparison with conventional designs. However, very few have been studied in vivo experiments. Additionally, studies on the effect of staggered structures on angiogenesis or bone regeneration in vivo, particularly in large animals, are required. Currently, with the prevalence of artificial intelligence (AI)-based technologies, highly optimized models can be developed, resulting in better discoveries. In the future, AI can be used to deepen our understanding on the staggered structure, promoting its use in clinical applications.

Introduction: To investigate the effects of an orthokeratology lens on the tear film and tarsal glands and myopia control in children with unilateral myopia using an intelligent analysis model.Methods: We retrospectively reviewed the medical records from November 2020 to November 2022 of 68 pediatric patients with unilateral myopia in Fujian Provincial Hospital who had been wearing an orthokeratology lens for more than 1 year. The 68 myopic eyes were included in the treatment group, while the 68 healthy, untreated contralateral eyes were included in the control group. Tear film break-up times (TBUTs) were compared between the two groups at various intervals, and an intelligent analysis model was used to compare the deformation coefficients of 10 meibomian glands in the central area and the different positions of the glands in the two groups after 12 months of treatment. Changes in axial length and equivalent spherical power were also compared between the groups before and after 12 months of treatment.Results: In the treatment group, TBUTs differed significantly between 1 and 12 months after treatment, although no significant differences from baseline were observed at 3 or 6 months. No significant differences in TBUTs were observed at any time point in the control group. After 12 months of treatment, significant between-group differences were observed for glands 2, 3, 4, 5, 6, 7, 8, and 10 (numbered from the temporal to nasal regions). The treatment group also exhibited significant differences in deformation coefficients at different detection positions in the central region, with glands 5 and 6 exhibiting the highest deformation coefficients. Increases in axial length and equivalent spherical power were significantly greater in the control group than in the treatment group after 12 months of treatment.Discussion: Wearing orthokeratology lenses at night can effectively control myopia progression in children with unilateral myopia. However, long-term use of these lenses may lead to meibomian gland deformation and impact tear film function, and the extent of deformation may vary at different positions in the central region.

Abstract Objective We and others have previously demonstrated that the size-selection enrichment method could remarkably improve fetal fraction (FF) in the early gestational age (GA, 12–13 weeks), suggesting that 9 or 10 weeks should not be used as a threshold for GA in size-selection noninvasive prenatal screening (NIPS). Here, we assessed whether this method was reliable for detecting fetal chromosomal aneuploidy at the earliest GA (6–8 weeks). Methods Size-selection NIPS for fetal chromosomal aneuploidy was applied to 208 pregnancy plasma samples (102 male and 106 female fetuses), while the 169 pregnancy samples with male fetuses also underwent standard NIPS. Multivariable linear regression models were used to evaluate the association between fold-change of FF and experimental factors. Results The sensitivity of the cell-free DNA (cfDNA) test in detecting aneuploidy was 100% when screened with FF enrichment, whereas the sensitivity of the same patients was only 62.5% (5/8) without FF enrichment. In the 102 pregnancy samples with male fetuses, FF increased from 6.1% to 15.7%, and the median increase in FF was 2.8-fold with enrichment. Moreover, there was a trend toward an increasing success rate of the cfDNA test from 6 to 13 weeks of gestation, especially when the test success rate reached 100% after 7 weeks with FF enrichment. Multivariate linear regression analysis demonstrated that a lower initial FF, shorter cfDNA size, increased body mass index (BMI), and later GA were all independent predictors of a higher fold-change of FF. Compared with ≤ 120 bp cfDNA fragments, the mean fold-change of FF differences was 0.820 for 121–125 bp, 0.229 for 126–130 bp, − 0.154 for 131–135 bp, − 0.525 for 136–140 bp and − 0.934 for > 140 bp (P trend 125 bp. These results were statistically significant after adjusting for confounding factors in the models for fold-change of FF. Conclusions The FF enrichment method is a reasonable strategy to detect fetal chromosomal aneuploidy in early pregnancy loss with reduced false negatives and increased test success rate after 7 weeks of GA and should be recommended for patients with early pregnancy loss.

Abstract Background With the continuous improvement of people's living standards, the incidence of hyperuricemia (HUA) is increasing globally. The prevalence of HUA ranged in terms of region, race, and age. This study aims to investigate the changes in the prevalence of HUA in clients of health examination in Eastern China between 2009 and 2019. Methods Chinese men and women aged 20–79 years (n = 4847 in the 2009 group and n = 12,188 in 2019 group) who had received health examinations were enrolled. Serum uric acid (UA) levels and biochemical parameters, including fasting blood-glucose (FBG), triglyceride (TG), total cholesterol (CHOL), high-density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine (Cr) and blood urea nitrogen (BUN) were evaluated. The prevalence of HUA in different age groups were measured, and the correlation of biochemical parameters with HUA were analyzed. Results The prevalence of HUA was 18.7% in the 2019 group, which was significantly higher than that in 2009 (11.1%). In females, the prevalence of HUA was significantly higher in 2019 than 2009 for age groups of 20–29 and 30–39 years. In male population, 2019 participants had significantly higher age-specific prevalence for all age groups than 2009 participants. Young men aged 20–29 years became the main population of HUA in the 2019 participants, whereas middle-aged men aged 40–49 years had the highest prevalence of HUA in the 2009 participants. The prevalence rates of HUA in all BMI groups in 2019 participants were significantly higher than those in 2009 participants. Spearmen’s correlation analysis and Logistic regression analysis indicated that BMI was positively correlated with HUA. The receiver-operating characteristic curve (ROC) analysis showed BMI > 24.48 kg/m2 and BMI > 23.84 kg/m2 displayed good capacities to discriminate the population with HUA from those without HUA in 2009 and 2019 participants, respectively. Conclusions In recent 10 years, the prevalence of HUA was increased rapidly in Chinese adults, especially in males. In 2019, the young male group (20–29 years old) replaced the middle-aged male group (40–49 years old) in 2009 as the leading age group for male HUA. BMI was positively correlated with HUA, and might be a potential risk factors to predict HUA.

Release of α-synuclein aggregates by neurons instigates spread of pathology in synucleinopathies, but the mechanism remains unclear. Here the authors show that neuronally generated α-synuclein aggregates accumulate within neuronal lysosomes and are released via SNARE-dependent lysosomal exocytosis.