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Freshwater salinization is receiving increasing global attention due to its profound influence on nitrogen cycling in aquatic ecosystems and the accessibility of water resources. However, a comprehensive understanding of the changes in river salinization and the impacts of salinity on nitrogen cycling in arid and semi-arid regions of China is currently lacking. A meta-analysis was first conducted based on previous investigations and found an intensification in river salinization that altered hydrochemical characteristics. To further analyze the impact of salinity on nitrogen metabolism processes, we evaluated rivers with long-term salinity gradients based on in situ observations. The genes and enzymes that were inhibited generally by salinity, especially those involved in nitrogen fixation and nitrification, showed low abundances in three salinity levels. The abundance of genes and enzymes with denitrification and dissimilatory nitrate reduction to ammonium functions still maintained a high proportion, especially for denitrification genes/enzymes that were enriched under medium salinity. Denitrifying bacteria exhibited various relationships with salinity, while dissimilatory nitrate reduction to ammonium bacterium (such as Hydrogenophaga and Curvibacter carrying nirB) were more inhibited by salinity, indicating that diverse denitrifying bacteria could be used to regulate nitrogen concentration. Most genera exhibited symbiotic and mutual relationships, and the highest proportion of significant positive correlations of abundant genera was found under medium salinity. This study emphasizes the role of river salinity on environment characteristics and nitrogen transformation rules, and our results are useful for improving the availability of river water resources in arid and semi-arid regions.

Objectives: Through the reflection of young breast cancer women on their selves and identities, we explored expectations of the wife role that they need to fulfill to return to their families, aimed to provide a reference basis for medical professionals to develop interventions related to cancer family rehabilitation. Methods: Descriptive phenomenological methods and purposive sampling were used. Young breast cancer patients and their spouses were selected for semi-structured face-to-face interviews in the study from March to April 2023 at the department of breast surgery and oncology center of a Class A tertiary hospital in Xuzhou City, China. The interviews were transcribed verbatim and analyzed using Colaizzi’s phenomenological approach. Results: Twenty patients and six spouses were interviewed. The mean patient age was (35.95 ± 3.36) years, and the mean spouse was (37.67 ± 5.28) years. Young breast cancer patients were concerned about three main wife expectations during their treatment and rehabilitation: preserving self-love and self-esteem (paying attention to physical health, embracing the disease, and regaining confidence in female characters); adjustment of conjugal relationships (harmonious and effective couple communication, providing support for marriage and love, and creating a beautiful married life together); assisting in family recovery (relieving stress on spouses from caregiving and finances, and management of daily household chores). Conclusions: The wife role expectations of young breast cancer women and their spouses encompass three core aspects: self, couple, and family. Self-esteem and self-love are the most fundamental expectations of the wife role, while adjusting the couple’s relationship and assistance in family rehabilitation represent higher expectations. This study can help healthcare professionals and cancer families gain a more comprehensive understanding of the wife role expectations for young cancer women, thereby enabling the development of couple-centered interventions to promote patient recovery and enhance the resilience of marriages and families.

Transparent photoresists with a high refractive index (RI) and high transmittance in visible wavelengths have promising functionalities in optical fields. This work reports a kind of tunable optical material composed of titanium dioxide nanoparticles embedded in acrylic resin with a high RI for ultraviolet (UV)-imprint lithography. The hybrid film exhibits a tunable RI of up to 1.67 (589 nm) after being cured by UV light, while maintaining both a high transparency of over 98% in the visible light range and a low haze of less than 0.05%. The precision machining of optical microstructures can be imprinted easily and efficiently using the hybrid resin, which acts as a light guide plate (LGP) to guide the light from the side to the top in order to conserve the energy of the display device. These preliminary studies based on both laboratory and commercial experiments pave the way for exploiting the unparalleled optical properties of nanocomposite resins and promoting their industrial application.

Perimenopausal depression is a subtype of depression and is prevalent among perimenopausal women, which has brought a heavy burden to family and society. The pathogenesis of perimenopausal depression is still unclear, which affects the prevention and treatment of perimenopausal depression to a certain extent. Quercetin is a flavonoid compound, and has estrogenic activity and pharmacological effects such as antioxidant, anti-inflammatory, and neuroprotective effects. This study investigated whether quercetin improved perimenopausal depression-like behaviors and potential mechanism. The results demonstrated that quercetin could alleviate the depression-like behaviors in perimenopausal depression rat model, inhibit astrocyte activation, improve ferroptosis-associated mitochondrial damage (such as mitochondrial pyknosis and mitochondrial cristae reduction) in hypothalamus, increase the expressions of histone 3 lysine 9 acetylation (acetyl-H3K9), ferroptosis-associated protein including glutathione peroxidase 4 (GPX4) and Xc- antiporter (SLC7A11), and reduce the expressions of endoplasmic reticulum stress-related proteins including inositol-requiring enzyme 1 (IRE1α), phosphorylated IRE1α (p-IRE1α), X-box binding protein 1 (XBP1) and glucose-regulated protein 78 (GRP78) in hypothalamus of perimenopausal depression rat model. Furtherly, in vitro study indicated that quercetin could restore histone acetylase (HAT)/histone deacetylase (HDAC) homeostasis through binding to estrogen receptors and increase the expression of acetyl-H3K9, inhibiting ferroptosis through IRE1α/XBP1 pathway in astrocytes of hypothalamus. Our findings demonstrated that acetyl-H3K9 is a crucial target in development of perimenopausal depression, and quercetin exhibited antidepressant effects through modulating acetyl-H3K9 mediated ferroptosis in perimenopausal depression. Quercetin might be the prevention and adjuvant treatment strategy of perimenopausal depression.

Construction Quality Management (CQM) is important for achieving project quality objectives. Currently, CQM is mainly achieved through cyclical inspections and various tests and subsequent analysis of the generated text records. These texts record various construction quality problems (CQPs) that need to be categorized and analyzed by quality managers. However, the current classification and analysis of CQPs is mainly achieved by manual analysis or natural language processing (NLP), the former is time-consuming and labor-intensive, while the latter improves the processing efficiency but is limited by the classification perspective and fails to fully capture the root causes of the CQPs. CQPs text usually describes the problems based on the inspection area, and multiple types of problems may exist simultaneously in each record. The previous classification model of CQPs based on sub-projects can only distinguish the frequent quality problems of sub-projects but cannot analyze the essential characteristics of CQPs, and ignores the comprehensive characteristics of CQPs, such as short text and unbalanced data. Therefore, aiming at the problem of mixed text information and diverse categories of CQPs, this study constructs a TDA-WV-TextCNN model for automatic text categorization by combining the characteristics of unbalanced data and short text of CQPs, taking the actual on-site inspection reports from multiple sources as the data base, and determining the classification labels based on the perspective of CQPs result orientation. The model combines the part-of-speech-based Text Data Augmentation (TDA) method, Word2vec (WV) technique and Text Convolutional Neural Network (TextCNN) algorithm. The results show that the TDA-WV-TextCNN model has a short training time and a high accuracy in short text classification; the part-of-speech-based TDA method expands the small sample data by extracting the core feature words and the word position change, realizing the text data equalization and subsequently improving the accuracy of the model; multiple sources of data increase the diversity of data, redundant text increases the amount of data, both play an important role in improving the performance of the model, so the deletion of duplicate text is related to the model’s demand for the amount of data The research results provide a method to categorize quality reports quickly and accurately, which helps to construct the engineering quality knowledge system.

Lycopene, a carotenoid with numerous physiological benefits, particularly in its Z-isomer form, faces challenges in its application due to low chemical stability. To address this limitation, high internal phase emulsion was successfully synthesized using ovalbumin-chitosan complexes. The aim was to enhance the stability of lycopene including Z-lycopene. The solubility, particle size, ζ-potential and uniformity of the mixture were dependent on pH value and biopolymer proportion. Notably, optimal ovalbumin-chitosan complex formation occurred at pH 2.5 with a ratio of 4:1 resulting in the highest solubility and optimal uniformity which contributed to its superior emulsification properties. Evaluation of encapsulating efficiency and loading amount revealed 98.19% and 1.7661 mg/g respectively for lycopene in ovalbumin-chitosan stabilized emulsions, inhibiting the transformation from Z-lycopene to (all-E)-lycopene. The encapsulated lycopene possessed UV stability where retention rate remained high at 81.86%. The retention rate was up to 65.37% and 41.82% at 45 °C and 80 °C, respectively.

Purpose: To evaluate the occurrence and influencing factors of myopia occurrence in pre-myopia children aged 3–6 years. Methods: This study included 204 pre-myopia (-0.50D-0.50D). The length of macular BM was shorter in Myopia group than that in Non-myopia group (P < 0.001). Baseline SE and the length of macular BM were independent influencing factors which associated with myopia occurrence (OR, 0.031; 95 % CI, 0.008–0.117, P < 0.001 and OR, 0.204; 95 % CI, 0.055–0.763, P = 0.018, respectively) by multivariate binary logistic regression analysis. SE changing process represented the changes of SE, Myopia group had bigger SE changes (P < 0.001). And in the multivariate liner regression analysis, age was the common influencing factor of SE changing process in total participants, Non-myopia group and Myopia group (B = 0.234, P < 0.001; B = 0.078, P = 0.010; B = 0.161, P = 0.046, respectively) Conclusions: Initial SE and the length of macular BM in pre-myopia children aged 3–6 years were the independent factors of the occurrence of myopia. And initial age was the common factor that associated with SE changing process.

A new and highly sensitive voltammetric technique was described in this study for the concurrent detection of endocrine disruptors bisphenol A (BPA) and bisphenol AF (BPAF) based on carbon nanocages (CNCs) and copper oxide nanochains (CuONCs). The CNCs was prepared by the solvothermal method and characterized using various techniques. Utilizing the nanocomposite of CNCs and CuONCs, the voltammetric sensor demonstrated outstanding performance in detecting BPA and BPAF simultaneously with distinct oxidation peaks and increased current peaks. The voltammetric signals have linear relationships with the two bisphenols ranging from 0.500 μM to 100 μM with a detection limit of 0.16 µM for BPA and 0.14 µM for BPAF. The newly designed sensor showed reliable consistency, long-term durability and anti-interference ability, and performed well in analyzing real water samples, indicating great potential for environmental monitoring.

Purpose: To evaluate temporal vascular arcade angle and its influencing factors in myopic children. Methods: It was a retrospective study, we reviewed the records of 119 patients aged 6–10 years with myopia (spherical equivalent refractive error (SER) ≤ -0.05D) in the third year of follow-up in Beijing Hyperopia Reserve Research. We measured temporal vascular arcade angles on the fundus photographs and measured 3-year rate of spherical equivalent(D/year) and axial length (AXL) changes(mm/year). Results: Mean age at initial visit was 7.71±1.20 years and mean SER was -1.32±1.09D. Children were divided into two groups according to the refractive status of children at baseline: Myopia onset group (SER>-0.50D at baseline) (n = 107) and Myopia progression group (SER≤-0.50D at baseline) (n = 12). The mean SER in Myopia progression group was much smaller than Myopia onset group (P < 0.001) and mean AXL in Myopia progression group was much longer than Myopia onset group (P = 0.042). AXL (r=-0.320, P < 0.001), SER change rate (r=-0.209, P = 0.022) and AXL change rate (r=-0.232, P = 0.011) were associated with temporal vascular arcade angle in all participants. In Myopia onset group, AXL (r=-0.317, P < 0.001) and AXL change rate (r=-0.190, P = 0.05) were associated with temporal vascular arcade angle. There were no parameters were associated with temporal vascular arcade angle (all P > 0.05) in Myopia progression group. Only AXL (r=-0.306, P = 0.018) was associated with temporal vascular arcade angle in girls while AXL (r=-0.370, P = 0.004), SER change rate (r=-0.317, P = 0.013) and AXL change rate (r=-0.365, P = 0.004) were all associated with the Angle in boys. Conclusion: Temporal vascular arcade angle was associated with the rate of SER and AXL changes in myopia onset children, and showed gender differences. These may suggest that lamina cribrosa location has different influencing factors in different genders and different stages of myopia development. Due to the small number of people in Myopia progression group, large sample size studies are still needed in the future.

Mangroves are among the most carbon-rich ecosystems in the world. However, they have experienced widespread loss due to climate change and have been reclaimed for coastal cropland and aquaculture ponds. Studying the impact of climate change on the potential distribution and carbon benefits of mangroves is crucial for their conservation and restoration. Currently, there is limited research on the potential distribution of mangroves in China under future climate change scenarios using ensemble models. Furthermore, there is a relative scarcity of studies that apply simulation results to the restoration and protection of mangroves. Therefore, based on 15 dominant mangrove species, we constructed high-precision species distribution models to simulate the potential distribution of mangroves in China during the current period (1981–2010) and predicted their potential distribution under three climate scenarios (SSP1-2.6, SSP3-7.0, and SSP5-8.5) in the late 21st century (2071–2100). Our study showed that 1) the four most crucial drivers of mangrove suitability in China are: air temperature in the coldest quarter, sea surface temperature range, isothermality, and annual precipitation amount. 2) mangroves tend to expand northward by 2–2.5 degrees of latitude in the end of the 21st century. Meanwhile, the potential distribution of Spartina alterniflora is expected to expand rapidly and pose a significant competitive threat to native mangrove species; 3) by restoring coastal cropland and aquaculture ponds to mangroves in the potential mangrove distribution area, the potential carbon stocks of mangroves would increase by 178.22–296.44 % and 170.31–277.13 % compared to the current carbon stocks of mangroves, the annual blue carbon would increase by 242.64–262.70 % compared to the current blue carbon of mangroves. Our research could provide valuable information for the future conservation and restoration of mangroves in China.

This research evaluates the impact of investing in cleaner bonds on funding clean energy initiatives, pivotal for sustainable economic recovery. The study seeks to assess the efficacy of cleaner bonds in fostering environmentally friendly projects and propelling economic growth and applies fuzzy analytical hierarchy process to examine the findings. Findings suggest that cleaner bonds potentially increase clean energy expenditures by an average growth rate of 4.9 % per year, significantly enhancing economic resilience. Additionally, these bonds are shown to accelerate the revitalization of green economies by approximately 17 % annually. The research underscores the role of energy performance contracts as viable alternatives to conventional project financing, through the application of various modelling tools and fuzzy analyses. It also discusses the strategic allocation of public and private funds into cleaner bond investments to accelrate economic sustainability and energy conservation. This study highlights the essential nature of cleaner bonds for entities and environmental groups aiming to secure funding for long-term projects, stressing the importance of expanding the sustainable economy through green bond issuances for eco-friendly and energy-efficient developments. Furthermore, the research recommends implications for stakeholders to diligently consider the legal aspects associated with these investments.

Dendrobium is a precious Chinese herbal medicine, which belongs to the genus Orchidaceae. Ancient records and modern pharmacological research show that Dendrobium has pharmacological effects such as anti-tumor, antioxidant regulating immunity and blood glucose, and anti-aging. Dendrobium contains polysaccharides, alkaloids, bibenzyl, sesquiterpenes, phenanthrene, polyphenols and other types of chemicals. Its pharmacological activity is closely related to these chemical components. For example, dendrobium extracts can achieve anti-tumor effects by inhibiting tumor cell proliferation and metastasis, promoting cell apoptosis and ferroptosis, or increasing cell sensitivity to chemotherapy drugs. It enhances immunity by regulating immune cell activity or cytokine release. In addition, it can alleviate neurodegenerative diseases by protecting nerve cells from apoptotic damage. In recent years, research reports on biologically active compounds in Dendrobium have shown a blowout growth, which makes us realize that it is meaningful to continuously update the research progress on the components and pharmacological regulatory mechanism of this traditional Chinese medicine. By classifying the collected chemical components according to different chemical structures and summarizing their pharmacological mechanisms, we investigated the current research progress of Dendrobium and provide a more comprehensive scientific foundation for the further development and clinical transformation of Dendrobium in the future.

Endoplasmic reticulum stress (ERS) becomes a significant factor in inflammatory bowel disease (IBD), like Crohn's disease (CD) and ulcerative colitis (UC). Our research was aimed at identifying molecular markers to enhance our understanding of ERS and inflammation in IBD, recognizing risk factors and high-risk groups at the molecular level, and developing a predictive model on the grounds of based on ERS-associated genes.This research adopted the least absolute shrinkage and selection operator (LASSO) regression and logistic regression to build a predictive model, and categorized IBD patients into high- and low-risk groups, and then identified four gene clusters. Our key findings included a significant increase in drug target gene expression in high-risk groups, notable discrepancies in immune levels, and functions between high-risk and low-risk groups. Notably, the TAP1 gene emerged as a strong predictor with the highest diagnostic value (area under the curve [AUC] = 0.941). TAP1 encodes proteins required for antigenic peptide transfer across the endoplasmic reticulum (ER) membrane, and its potential as a diagnostic marker and therapeutic target is reflected by its overexpression in IBD tissues.Our study established a new ERS-associated gene model which could forecast the risk, immunological status, and treatment efficacy of patients with IBD. These findings suggest potential targets for personalized therapy and highlight the significance of ERS in the etiology and therapy of IBD. Future studies should explore the therapeutic potential of targeting TAP1 and other ERS-related genes for IBD management.

Evidence shows that tropomodulin 1 (TMOD1) is a powerful diagnostic marker in the progression of several cancer types. However, the regulatory mechanism of TMOD1 in tumor progression is still unclear. Here, we showed that TMOD1 was highly expressed in acute myeloid leukemia (AML) specimens, and TMOD1-silencing inhibited cell proliferation by inducing autophagy in AML THP-1 and MOLM-13 cells. Mechanistically, the C-terminal region of TMOD1 directly bound to KPNA2, and TMOD1-overexpression promoted KPNA2 ubiquitylation and reduced KPNA2 levels. In contrast, TMOD1-silencing increased KPNA2 levels and facilitated the nuclear transfer of KPNA2, then subsequently induced autophagy and inhibited cell proliferation by increasing the nucleocytoplasmic transport of p53 and AMPK activation. KPNA2/p53 inhibitors attenuated autophagy induced by silencing TMOD1 in AML cells. Silencing TMOD1 also inhibited tumor growth by elevating KPNA2-mediated autophagy in nude mice bearing MOLM-13 xenografts. Collectively, our data demonstrated that TMOD1 could be a novel therapeutic target for AML treatment.

This study focuses on conducting friction-stir processing (FSP) on 3 mm thick LA141 alloy using different tools. Under low heat input conditions of 600 rpm and 200 mm/min, the use of the WC-Co cemented carbide tool successfully produced a defect-free stir zone. This stir zone exhibited an ultrafine grain structure resulting from continuous dynamic recrystallization. Additionally, the stir zone introduced massive grain boundaries, nanoscale MgAlLi2 particles, and stacking faults. The stir zone displayed a favorable balance of strength and ductility. The enhanced strength is attributed to the inhibitory effect of nanoscale MgAlLi2 particles, grain boundaries, and Lomer-Cottrell locks on dislocation movement. The improved work hardening ability and ductility can be attributed to the increase in stacking faults, Lomer-Cottrell locks, and deformation twins during deformation. Furthermore, the stir zone showed improved corrosion resistance, characterized by lower corrosion current density and larger polarization resistance. This improvement in corrosion resistance can be attributed to multiple factors. These include the reduced defect density, refined and evenly distributed MgLiAl2 particles that weakened galvanic corrosion effects, and the presence of more stable Li2CO3 and Al2O3 compounds that resulted in a compact and protective film.

Natural basalt can be processed into rod-like basalt fibers (BFs) and flake-like basalt scales (BSs) through high-temperature melting, forming and other processes. BFs and BSs have great application prospects in the field of organic coatings. BFs possess a regular rod-like structure and excellent mechanical properties, which are mainly used to enhance the mechanical properties of organic coatings. BSs possess a relatively irregular flake-like structure, which can form “maze” effects and layered structures to enhance corrosion resistance of organic coatings. However, basalt materials have poor compatibility, adhesion, and dispersion in organic resins due to their chemical inertness, resulting in a weak basalt-resin interface. Basalt-resin interface is an important parameter that determines the service performance of basalt composite coatings. Therefore, it is necessary to improve basalt-resin interface through corresponding strategies, such as chemical etching, chemical grafting and plasma treatment. Firstly, the surface modification strategies for improving basalt-matrix interface were summarized in this paper. Secondly, we discussed the effects of BFs and BSs on corrosion resistance of organic coatings and corrosion protection mechanism of composite coatings. Finally, we reviewed the research progress of modified basalt materials reinforced organic coatings.

With the advantages of eco-friendliness, low cost, and low density, Mg2(Si,Sn) solid solutions are promising candidates for thermoelectric applications. In this work, Sb-doped Mg2Si0.4Sn0.6 bulks were prepared with a combined method of solid-state reaction and high pressure synthesis, followed by spark plasma sintering. Our investigations show that Sb doping optimizes the carrier concentration, while Si/Sn alloying effectively suppresses the lattice thermal conductivity and induces a convergence of the two lowest-lying conduction bands. Additionally, numerous coherent Sn-rich nanoprecipitates are formed within micron-sized grains. All these factors contribute synergistically to improving the thermoelectric properties of Mg2Si0.4Sn0.6. The optimal Mg2(Si0.4Sn0.6)0.985Sb0.015 exhibits a power factor higher than 4 000 μW·m−1·K−2 and a lattice thermal conductivity less than 0.8 W·m−1·K−1 at temperatures higher than 600 K, leading to the highest ZT of 1.61 at 823 K. Current work demonstrates an effective approach to enhancing the thermoelectric performance of n-type Mg2X solid solutions through doping, alloying, and microstructure modification.

Summary: This study investigated whether lower extremity stiffness plays a role in the enhancement of change of direction speed (CODS) and the duration of this enhancement after dynamic loaded warm-up (DLWU). Fifteen badminton athletes underwent DLWU, and CODS, individual muscle and tendon stiffness, and vertical stiffness were measured before DLWU and 6, 12, and 18 min after DLWU. The data were analyzed using ANOVA and covariance analysis. Significant improvements in CODS were found at 6, 12, and 18 min post-DLWU compared to pre-DLWU (p 0.05). CODS improvement lasted up to 18 min after DLWU in badminton athletes, potentially related to increased Achilles tendon stiffness of the dominant leg.

Summary: Platinum-based chemo-resistance is the major issue for the treatment of small cell lung cancer (SCLC). The integrative analysis of multi-omics data is a reliable approach for discovering novel biomarkers associated with chemo-resistance. Here, multi-omics integrative analysis and Cox regression found that higher expression of PCDHB4 was associated with poorer survival of SCLC patients who received chemotherapy. PCDHB4 gene was hypomethylated and upregulated in SCLC, which was validated in the levels of promoter methylation, mRNA, and protein expression. Mechanistically, using bulk RNA-seq data, functional enrichment analysis indicated that higher PCDHB4 expression was associated with lower immune infiltration. The analysis of single-cell RNA-seq (scRNA-seq) found that SCLC cells with PCDHB4 expression exhibited the characteristics of stemness and EMT. In addition, the high expression and hypomethylation of PCDHB4 were also significantly associated with poor survival in lung squamous cell carcinoma. In summary, PCDHB4 is a potential prognostic biomarker of platinum-based chemotherapy in SCLC.

Carbon-free ammonia and hydrogen have various disadvantages when used individually, which limits their application as clean energies. These disadvantages can be effectively overcome by combining them as ammonia/hydrogen mixtures in a rational manner. In this paper, the combustion of ammonia/hydrogen in oxygen (the basic form of combustion) is experimentally investigated at various experimental conditions. The results display that the laminar burning velocities of ammonia/hydrogen/oxygen mixtures increase with increasing fuel ratios. At P0 = 0.5 atm and φ = 1.0, the laminar burning velocity proliferated from 1.91 m/s to 4.7 m/s with the increase of fuel ratio from 0.5 to 2.0. As the equivalence ratio increases, the laminar burning velocity rises first and then decreases, with the highest point appearing at φ = 0.8. The initial pressure has minimal impact on the laminar burning velocity. At x = 0.5 and φ = 1.0, the laminar burning velocity decreased slightly from 3.16 m/s to 2.96 m/s with the initial pressure increased from 0.1 atm to 1.0 atm. The empirical correlation among the laminar burning velocity versus the equivalence ratio and hydrogen ratio is given, and the laminar burning velocity of ammonia/hydrogen/oxygen under varying hydrogen ratios (0 %–100 %) and equivalence ratios (0.5–1.5) at atmospheric pressure can be well predicted by the empirical equations. NO is the most emitted NOx substance from hydrogen/ammonia combustion. The amount of NO produced decreases gradually with the growing equivalence ratio. The results of this research can be utilized to renew the basic flame data of ammonia/hydrogen mixture and are important for the development and application of ammonia/hydrogen mixtures.

Adeno-associated virus (AAV)-based gene therapy is a clinical stage therapeutic modality for neurological disorders. A common genetic defect in myriad monogenic neurological disorders is nonsense mutations that account for about 11% of all human pathogenic mutations. Stop codon readthrough by suppressor transfer RNA (sup-tRNA) has long been sought as a potential gene therapy approach to target nonsense mutations, but hindered by inefficient in vivo delivery. The rapid advances in AAV delivery technology have not only powered gene therapy development but also enabled in vivo preclinical assessment of a range of nucleic acid therapeutics, such as sup-tRNA. Compared with conventional AAV gene therapy that delivers a transgene to produce therapeutic proteins, AAV-delivered sup-tRNA has several advantages, such as small gene sizes and operating within the endogenous gene expression regulation, which are important considerations for treating some neurological disorders. This review will first examine sup-tRNA designs and delivery by AAV vectors. We will then analyze how AAV-delivered sup-tRNA can potentially address some neurological disorders that are challenging to conventional gene therapy, followed by discussing available mouse models of neurological diseases for in vivo preclinical testing. Potential challenges for AAV-delivered sup-tRNA to achieve therapeutic efficacy and safety will also be discussed.

White light emitting diodes (wLEDs) have been widely used as the green lighting sources. The commercial wLEDs devices are mainly achieved through the combination of blue emission chips and yellow phosphors, which offer advantages of high efficiency and long lifetime. However, the color rendering index (CRI) of traditional wLEDs is low due to the lack of red components. In recent years, with the improvement of the quality of life, a lot of efforts have been paid to improve the performance of wLEDs devices related to CRI, correlated color temperature, light uniformity, luminous flux, etc. In this article, we summarize the recent advances on the optimization of wLEDs toward healthy lighting. Brief introductions on the fundamentals of healthy effect of lighting are presented, followed by discussions of current methods to realize wLEDs devices. Special overviews on strategies for luminescent materials of wLEDs in recent years are presented. The opportunities and challenges in the future development of wLEDs lighting devices are also discussed.

The discharge of microscale gaps for MEMS systems is a serious issue. To reveal the dark discharge characteristics of the microscale gap, electrodes with various gap feature sizes were prepared, and the DC current–voltage characteristics for the electrodes were implemented in atmospheric air. The results showed minor differences in dark discharge current on a nanoampere scale among electrodes with varying gap sizes of micro-protrusions. The current formation mechanism was consistent with the electron avalanche theory. Morphological characterization identified the presence of non-ideal thin-layer trailings at the electrode edges. To evaluate the effect of trailings on the dark discharge characteristics of the microscale gap structures, the electrodes with varying trailing lengths were fabricated. It showed that the current increased exponentially in the presence of long thin-layer trailing. In this case, the breakdown is most pronounced with an effective gap distance of 30 μm and a trailing length of 14.34 μm for the electrodes. For this structure, the dark discharge current was 198 nA at 36 V bias voltage, while the discharge current increased to 50 µA when the bias was increased to 37 V, and stabilized at 100 µA when the bias voltage was higher than 39 V. The rapid increase in current caused by trailing originates from the field emission as judged by the Fowler-Nordheim theory. Simulation results showed that the field strength can reach up to 3.76 × 109 V/m at a thin layer trailing length of 3.5 μm and a bias voltage of 200 V, which matches the conditions for the field emission. By calculating the effective secondary electron emission coefficient, it was found that thin-layer trailing significantly intensifies the ion-enhanced effect, further lowering the threshold for field emission and resulting in a rapid increase in microscale gap current at lower voltages.

Effective management of large basins necessitates pinpointing the spatial and temporal drivers of primary index exceedances and urban risk factors, offering crucial insights for basin administrators. Yet, comprehensive examinations of multiple pollutants within the Yangtze River Basin remain scarce. Here we introduce a pollution inventory for urban clusters surrounding the Yangtze River Basin, analyzing water quality data from 102 cities during 2018–2019. We assessed the exceedance rates for six pivotal indicators: dissolved oxygen (DO), ammonia nitrogen (NH3–N), chemical oxygen demand (COD), biochemical oxygen demand (BOD), total phosphorus (TP), and the permanganate index (CODMn) for each city. Employing random forest regression and SHapley Additive exPlanations (SHAP) analyses, we identified the spatiotemporal factors influencing these key indicators. Our results highlight agricultural activities as the primary contributors to the exceedance of all six indicators, thus pinpointing them as the leading pollution source in the basin. Additionally, forest coverage, livestock farming, chemical and pharmaceutical sectors, along with meteorological elements like precipitation and temperature, significantly impacted various indicators' exceedances. Furthermore, we delineate five core urban risk components through principal component analysis, which are (1) anthropogenic and industrial activities, (2) agricultural practices and forest extent, (3) climatic variables, (4) livestock rearing, and (5) principal polluting sectors. The cities were subsequently evaluated and categorized based on these risk components, incorporating policy interventions and administrative performance within each region. The comprehensive analysis advocates for a customized strategy in addressing the discerned risk factors, especially for cities presenting elevated risk levels.

The Zhuqing vanadium–titanium magnetite is a large deposit recently discovered in the western margin of the Yangtze Block, where the Zhuqing gabbroic intrusion and associated Fe–Ti–V oxide deposits are fund and dated at 1647 ± 39 Ma (MSWD = 0.79) through U–Pb dating of gabbro zircons. The εHf(t) values of zircons are all positive, with an average of 10.7. The average age of the one-stage model age (TDM) is 1661 Ma, which is very close to the diagenetic and metallogenic age 1647 ± 39 Ma (MSWD = 0.79). These new results indicate that the magma source come directly from the mantle. The contents of Al2O3, CaO, and (Na2O + K2O) increases with the increase of SiO2 contents, while, the contents of MgO, TiO2, and Fe2O3 decreases with the increase of SiO2 contents. Mg# is relatively stable with the increase of SiO2 contents. In the primitive mantle-normalized trace element spider diagrams and chondrite-normalized rare earth element patterns, the characteristics of all samples are similar to that of ocean island basalts (OIBs), showing a right inclination curve. Meanwhile the western margin of the Yangtze Block as an essential part of the supercontinent of Colombia, began to extend at 1.7 Ga, lasted to ca. 1.4 Ga, and finally split. These suggest that the Zhuqing gabbroic intrusion and associated Fe–Ti–V oxide deposits with OIB characteristics formed in the Late Paleoproterozoic, which is a response to the breakup of the Colombian supercontinent in the western margin of the Yangtze Block.

Background: The COVID-19 pandemic has exposed healthcare workers (HCWs) to serious risk of infection. The aims of our study were to investigate the epidemiological characteristics and risk factors of SARS-CoV-2 infection among HCWs, and evaluate the vaccine effectiveness (VE) during the Omicron pandemic in Shanghai, China. Methods: Active surveillance of COVID-19 was performed among HCWs who worked in Shanghai General Hospital from December 2022 to January 2023. A case-control study was conducted by questionnaire survey to analyse the infection-related risk factors. A retrospective cohort study was explored to evaluate VE against primary infection. Results: During the Omicron outbreak, 2,008 of 2,460 (81.6%) HCWs were infected with SARS-CoV-2. The infection rate was higher in women, younger age groups, nurses and medical technicians. Among the 1,742 participants in the questionnaire, 1,463 (84.0%) were tested positive, and 95.1% of them developed symptoms. Most of the infections (53.0%) were acquired outside the hospital. The risk factors associated with higher odds of infection were working in the emergency department (aOR 3.77, 95% CI 1.69–8.38) and medical examination area (aOR 2.47, 95% CI 1.10–5.51). The protective factors associated with lower odds of infection were previous infection with SARS-CoV-2 (aOR 0.01, 95% CI 0–0.07) and receiving four doses of vaccines (aOR 0.40, 95% CI 0.17–0.97). For frontline HCWs, those who had oral-nasal exposure to coworkers were more likely to be infected (aOR 1.74, 95% CI 1.21–2.51). In VE analysis, the risk of primary infection was lower in HCWs who received the emergency heterologous booster (the fourth dose) during the epidemic (aHR 0.25, 95% CI 0.15–0.40), resulting in an adjusted-VE of 75.1%. Conclusions: In response to future pandemic, it is important for public health policies to aim at protecting HCWs through risk-differentiated infection control measures, strengthening personal protection and recommending vaccination to vulnerable individuals before the arrival of Omicron wave.

Multiple isozymes are encoded in the Caenorhabditis elegans genome for the various sphingolipid biosynthesis reactions, but the contributions of individual isozymes are characterized only in part. We developed a simple but effective reversed-phase liquid chromatography-tandem mass spectrometry (RPLC-MS/MS) method that enables simultaneous identification and quantification of ceramides (Cer), glucosylceramides (GlcCer), and sphingomyelins (SM) from the same MS run. Validating this sphingolipid profiling method, we show that nearly all 47 quantifiable sphingolipid species found in young adult worms were reduced upon RNA interference (RNAi) of sptl-1 or elo-5, which are both required for synthesis of the id17:1 sphingoid base. We also confirm that HYL-1 and HYL-2, but not LAGR-1, constitute the major ceramide synthase activity with different preference for fatty acid substrates, and that CGT-3, but not CGT-1 and CGT-2, plays a major role in producing GlcCers. Deletion of sms-5 hardly affected SM levels. RNAi of sms-1, sms-2, and sms-3 all lowered the abundance of certain SMs with an odd-numbered N-acyl chains (mostly C21 and C23, with or without hydroxylation). Unexpectedly, sms-2 RNAi and sms-3 RNAi elevated a subset of SM species containing even-numbered N-acyls. This suggests that sphingolipids containing even-numbered N-acyls could be regulated separately, sometimes in opposite directions, from those containing odd-numbered N-acyls, which are presumably monomethyl branched chain fatty acyls. We also find that ceramide levels are kept in balance with those of GlcCers and SMs. These findings underscore the effectiveness of this RPLC-MS/MS method in studies of C. elegans sphingolipid biology.

Background and objectives: The efficacy of rituximab (RTX) in treating steroid-resistant Graves’ orbitopathy (GO) has been limitedly studied in Asians. Moreover, RTX has been considered even less for patients with steroid-resistant dysthyroid optic neuropathy (DON) who failed to undergo orbital decompression surgery for physical or financial reasons, or who responded poorly to the procedure. This study aimed to investigate the efficacy of RTX in treating steroid-resistant active moderate-to-severe and sight-threatening GO in a Chinese population. Methods: Data from 28 patients with steroid-resistant GO prescribed a single dose of 500 mg RTX were retrospectively retrieved. Treatment responses and contributing factors were analyzed. Results: The median follow-up time was 22 (8–34) weeks. 23 (82.1 %) patients had a positive objective outcome recommended by the European Group on Graves’ Orbitopathy (EUGOGO), while 25 (92.6 %) had a decrease in 7-item clinical activity score (CAS) by at least 2. Diplopia, visual dysfunction, and MRI-detected T2 relaxation time of the involved extraocular muscles improved significantly at the last follow-up compared to baseline (81.0 % vs. 47.6 %, 38.9 % vs. 16.7 %, and 87.8 (8.64) vs. 75.8 (10.9) ms, respectively; all p values

Radish (Raphanus sativus L.) undergoes texture changes in their phy-chemical properties during the long-term dry-salting process. In our study, we found that during the 60-day salting period, the hardness and crispness of radish decreased significantly. In further investigation, we observed that the collaborative action of pectin methylesterase (PME) and polygalacturonase (PG) significantly decreased the total pectin, alkali-soluble pectin (ASP), and chelator-soluble pectin (CSP) content, while increasing the water-soluble pectin (WSP) content. Furthermore, the elevated activities of cellulase and hemicellulase directly led to the notable fragmentation of cellulose and hemicellulose. The above reactions jointly induced the depolymerization and degradation of cell wall polysaccharides, resulting in an enlargement of intercellular spaces and shrinkage of the cell wall, which ultimately led to a reduction in the hardness and crispness of the salted radish. This study provided key insights and guidance for better maintaining textural properties during the dry-salting process of radish.

ABSTRACT: Eggshell is one of the most important indicators of egg quality, and due to low shell strength, pimple eggs (PE) are more susceptible to breakage, thus causing huge economic losses to the egg industry. At the current time, the molecular mechanisms that regulate the formation of pimple eggs are poorly understood. In this study, uterine tissues of PE-laying hens (n = 8) and normal egg (NE) -laying hens (n = 8) were analyzed by whole transcriptome sequencing, and a total of 619 differentially expressed mRNAs (DE mRNAs), 122 differentially expressed lncRNAs (DE lncRNAs) and 21 differentially expressed miRNAs (DE miRNAs) were obtained. Based on the targeting relationship among DE mRNAs, DE lncRNAs and DE miRNAs, we constructed a competitive endogenous RNA (ceRNA) network including 12 DE miRNAs, 19 DE lncRNAs, and 128 DE mRNAs. Considering the large amount of information contained in the network, we constructed a smaller ceRNA network to better understand the complex mechanisms of pimple egg formation. The smaller ceRNA network network contains 7 DE lncRNAs (LOC107056551, LOC121109367, LOC121108909, LOC121108862, LOC112530033, LOC121113165, LOC107054145), 5 DE miRNAs (gga-miR-6568-3p, gga-miR-31-5p, gga-miR-18b-3p, gga-miR-1759-3p, gga-miR-12240-3p) and 7 DE mRNAs (CABP1, DNAJC5, HCN3, HPCA, IBSP, KCNT1, OTOP3), and these differentially expressed genes may play key regulatory roles in the formation of pimpled eggs in hens. This study provides the overall expression profiles of mRNAs, lncRNAs and miRNAs in the uterine tissues of hens, which provides a theoretical basis for further research on the molecular mechanisms of pimpled egg formation, and has potential applications in improving eggshell quality.

Recombinant adeno-associated virus (rAAV)-based gene therapy is entering clinical and commercial stages at an unprecedented pace. Triple transfection of HEK293 cells is currently the most widely used platform for rAAV manufacturing. Here, we develop low-cis triple transfection that decreases transgene plasmid use by 10- to 100-fold and overcomes several major limitations associated with standard triple transfection. This new method improves packaging of yield-inhibiting transgenes by up to 10-fold, and generates rAAV batches with reduced plasmid backbone contamination that otherwise cannot be eliminated in downstream processing. When tested in mice and compared with rAAV produced by standard triple transfection, low-cis rAAV shows comparable or superior potency and results in diminished plasmid backbone DNA and RNA persistence in tissue. Mechanistically, low-cis triple transfection relies on the extensive replication of transgene cassette (i.e., inverted terminal repeat-flanked vector DNA) in HEK293 cells during production phase. This cost-effective method can be easily implemented and is widely applicable to producing rAAV of high quantity, purity, and potency.

Background and aim: Prostate cancer is a leading malignant tumor in men, associated with a high rate of mortality. Androgen deprivation therapy is commonly used to treat prostate cancer, which contributes to the progression of castration-resistant prostate cancer (CRPC). The current therapy has a low survival rate in patients with CRPC. Our study aims to develop a novel effective approach for CRPC treatment and improve survival benefits. Experimental procedure: CRPC cell line PC-3-Luc expressing luciferase and the CRPC cell line PC-3-IL6-Luc stably overexpressing IL-6 were used to establish the xenograft tumor mouse model. The tumor was monitored weekly using Bioluminescence imaging. Infiltrated macrophages were quantified by fluorescence-activated cell sorting using flow cytometry. IL6 mRNA level was determined using quantitative real-time PCR. The protein levels of total STAT3 and phosphorylated STAT3 were determined using Western blot. Results and conclusion: Zhoushi Qi Ling decoction (ZQD) treatment significantly reduced PC3 the xenograft tumor progression and the number of infiltrated macrophages when compared with saline treatment. IL6 mRNA level was remarkedly suppressed by ZQD treatment. Notably, the protein level of phosphorylated STAT3 was significantly decreased in PC3 the xenograft tumor treated with ZQD compared to saline treatment. Our findings demonstrated that ZQD treatment significantly reduced the progression of prostate cancer, evidenced by the reduced population of infiltrated macrophages and the inhibition of the IL6/STAT3 pathway.

High hydrostatic pressure can cause common problems such as cracking and leakage in the lining of railway tunnels during operation. A clear understanding of the magnitude and distribution characteristics of hydrostatic pressure in tunnel lining under high-pressure conditions is crucial for optimizing the structural design of tunnel lining. In this study, professional equipment was first selected to measure the lining water pressure of two typical sections of Tunnel A on site, and the pressure distribution characteristics were analyzed; Then, a calculation model of the tunnel under high hydrostatic pressure was established using FLAC3D numerical calculation software. Select several calculation parameters and within a reasonable range of values, select multiple values for each parameter instead of just taking one value to form 60 working conditions, and calculate the corresponding tunnel lining water pressure for each working condition. Analyze the correlation between static water pressure and calculation parameters under various working conditions, propose a preliminary calculation formula for tunnel lining static water pressure, and finally use SPSS statistical calculation software to fit the final calculation formula for lining water pressure. This formula is applicable to the calculation of lining hydrostatic pressure under various parameters and is a universal calculation formula for tunnel lining hydrostatic pressure. Our proposed formula is very consistent with on-site measured data under similar geology conditions, providing a new method for calculating the hydrostatic pressure of tunnel lining.

College students are inevitably online and at risk of becoming addicted. Life history theory provides an explanatory framework for individual differences in Internet addiction, and childhood harshness and unpredictability may be important antecedents. However, it is unclear whether and how childhood harshness and/or unpredictability affect Internet addiction during college. In this study, we recruited 483 Chinese college students and assessed their childhood harshness, unpredictability, self-control, and Internet addiction. The results of path analysis showed that childhood unpredictability was positively associated with Internet addiction among college students and was partially mediated by self-control. The effect of harshness on Internet addiction showed a suppression effect, i.e., the direct effect of harshness on Internet addiction was negative and the indirect effect through self-control was positive. This suggests that the high risk of Internet addiction stems from harshness and unpredictability in childhood, but that the effects of these factors are independent and distinct. Self-control plays an important role in this process, but many internal mechanisms remain to be tested in future research.

Studying the impact of agricultural digitalization (ADT) on the carbon emission intensity of planting industry (PCI) can help promote sustainable development and realize the “dual carbon” goal. Based on the panel data of 31 provinces in China from 2010 to 2020, this study uses the entropy weight method and emission coefficient method to measure the development level of ADT and PCI, respectively. By using the regression analysis method, as well as the robustness test, heterogeneity test, and spatial spillover effect and threshold tests, the impact of ADT on PCI was examined. The results are as follow: (1) PCI is high in the north and low in the south, and the north-south divide is becoming prominent. (2) ADT in China can significantly reduce PCI, as verified through the robustness test. (3) Regional differences exist in the impact of ADT on PCI, with the most significant effect observed in the northeast region, followed by the western and central regions. (4) ADT exerts a significant spatial spillover effect on PCI and an inhibitory effect on PCI of adjacent provinces. (5) The proportion of urban population exerts a threshold effect in the impact of ADT on PCI. When the urban population ratio crosses 69 %, the inhibitory effect of agricultural carbon emissions decreases marginally. Therefore, promoting the green and low-carbon development of the planting industry is highly recommended.

Background: Although workplace violence is prevalent in the healthcare system, the relationship between workplace violence, job satisfaction, and burnout among healthcare workers (HCWs) in mobile cabin hospitals in China during the COVID-19 pandemic has not yet been investigated. This study analyzes the mediating effects of perceived stress and work environment in the relationship between workplace violence, job satisfaction, and burnout. Methods: A cross-sectional study was conducted in December 2022 on 1,199 frontline HCWs working in mobile cabin hospitals in Chongqing, China, during the COVID-19 pandemic. Multiple linear regression and mediation analysis were performed. Results: A positive correlation was observed between workplace violence and burnout (r = 0.420, P

Summary: Background: Current approved chimeric antigen receptor (CAR) T-cell products are autologous cell therapies that are costly and poorly accessible to patients. We aimed to evaluate the safety and antitumor activity of a novel off-the-shelf anti-CD19 CAR-engineered allogeneic double-negative T cells (RJMty19) in patients with relapsed/refractory large B-cell lymphoma. We report the results from a first-in-human, open-label, single-dose, phase 1 study of allogeneic CD19-specific CAR double-negative T (CAR-DNT) cells. Methods: Eligibility criteria included the presence of measurable lesions, at least 2 lines of prior immunochemotherapy, and an ECOG score of 0–1. We evaluated four dose levels (DL) of RJMty19 in a 3 + 3 dose-escalation scheme: 1 × 106, 3 × 106, 9 × 106 and 2 × 107 CAR-DNT cells per kilogram of body weight. All patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide. The primary endpoints were dose-limiting toxicities (DLTs), incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of standard cellular pharmacokinetic parameters, immunogenicity, objective response rates (ORR), and disease control rate (DCR) per Lugano 2014 criteria. Findings: A total of 12 patients were enrolled between 22 July 2022 and 27 July 2023. Among these patients, 66% were classified as stage IV, 75% had an IPI score of 3 or higher, representing an intermediate risk or worse. The maximum tolerated dose was not reached because no DLT was observed. Four patient experienced grade 1 or 2 cytokine release syndrome and dizziness. The most common AEs were hematologic toxicities, including neutropenia (N = 12, 100%), leukopenia (N = 12, 100%), lymphopenia (N = 10, 83%), thrombocytopenia (N = 6, 50%), febrile neutropenia (N = 3, 25%), and anemia (N = 3, 25%). Seven subjects died till the cut-off date, five of them died of disease progression and two of them died of COVID 19. In all patients (N = 12), the ORR was 25% and CRR was 8.3%. DL1 and DL2 patients benefited less from the therapy (ORR: 17%, N = 1; DCR: 33%, N = 2). However, all DL3 patients achieved disease control (N = 3, 100%), and all DL4 patients achieved objective response (N = 3, 100%). Interpretation: Our results demonstrate that CD19-CAR-DNT cells appear to be well tolerated with promising antitumor activity in LBCL patients. Further study of this product with a larger sample size is warranted. This phase 1 study is registered on clinicaltrials.gov (NCT05453669). Funding: Wyze Biotech. Co., Ltd.

Erianin is an important bibenzyl compound in dendrobium and has a wide spectrum of pharmacological properties. Since Erianin was discovered, abundant results have been achieved in the in vitro synthesis, structural modification, and pharmacological mechanism research. Researchers have developed a series of simple and efficient in vitro synthesis methods to improve the shortcomings of poor water solubility by replacing the chemical structure or coating it in nanomaterials. Erianin has a broad anti-tumor spectrum and significant anti-tumor effects. In addition, Erianin also has pharmacological actions like immune regulation, anti-inflammatory, and anti-angiogenesis. A comprehensive understanding of the synthesis, metabolism, structural modification, and pharmacological action pathways of Erianin is of great value for the utilization of Erianin. Therefore, this review conducts a relatively systematic look back at Erianin from the above four aspects, to give a reference for the evolvement and further appliance of Erianin.

Esophageal cancer, known for its high incidence and low five-year survival rate, poses significant treatment challenges. A key aspect of this challenge is the close link between mitochondria and resistance to chemoradiotherapy (CRT). Currently, there is a scarcity of biomarkers for predicting CRT response and prognosis in esophageal cancer. Our study addresses this gap by developing a prognostic model that incorporates mitochondria-related CRT resistance (MRCRTR) genes, including CTSL, TBL1X, CLN8, MMP1, PDPN, and MRPL37. Survival analysis using Kaplan–Meier curves reveals that patients with high MRCRTR scores have lower survival rates than those with low scores. Utilizing a nomogram, we successfully predict the one-, two-, and three-year overall survival rates for esophageal cancer patients. Cox regression analysis confirms the MRCRTR score as an independent prognostic factor. Furthermore, our single-cell and correlation analyses suggested that MRCRTR genes might influence CRT resistance by modulating the immune microenvironment and impacting angiogenesis. Our pan-cancer analysis also indicates the potential applicability of MRCRTR scores to head and neck squamous cell carcinoma. The validation of these findings, conducted with samples from Xiang-ya Hospital, aligns closely with our bioinformatics results. Our study not only explores the role of MRCRTR genes in predicting the prognosis of esophageal cancer but also enhances the understanding of the interplay between CRT, mitochondria, and patient outcomes.

Ulcerative colitis (UC) is a gastrointestinal disease with an unknown etiology that severely affects patients' quality of life. Acupuncture and moxibustion therapies are effective in the treatment of UC, but existing systematic reviews (SRs) and meta-analyses (MAs) on this subject have variable methodological and outcome quality. Therefore, this study aimed to summarize and evaluate the evidence of existing SRs and MAs to provide more reliable evidence for clinical practice. Data were extracted from seven databases through systematic search and evaluated in terms of the methodological quality, reporting quality, risk of bias, and quality of evidence using the AMSTAR-2, PRISMA, ROBIS, and GRADE systems, respectively. Ten studies were finally included, and all of them showed many problems with the overall design and quality of outcomes. Because of the lack of high-quality evidence to support the findings from the existing studies, we should take this conclusion with caution and strictly implement the registration, design, and implementation of trials based on evidence to provide high-quality results in future studies.

The crystal and electronic structures determine a material's physical and chemical properties. Here, using particle swarm optimization method and first-principles calculations, we conducted a systematically investigation on the ordered CuxBey alloys. Two novel stable phase CuxBey (P4¯m2-CuBe3, and I4/mmm-Cu2Be) and five novel metastable CuxBey alloys (F4¯3m-CuBe5, P21/m-CuBe4, P4/mmm-Cu3Be, P4/mmm-Cu4Be, and P4/mmm-Cu5Be) are predicted for the first time. The primary alloying form of ordered CuxBey alloys is the substitution of certain Be atoms for some Cu atoms in the FCC-Cu according to structural study. Obvious valence electrons transfer from Be to Cu and the lattice interstice are observed, which leads to Cu exhibiting negative valence state in CuxBey and Be-rich CuxBey acting as zero-dimensional electrides. Furthermore, these Be-rich CuxBey have good structural stability due to the interaction between interstitial anionic electrons and Be atoms in the Be-tetrahedron. These findings help us in the design and application of CuxBey alloys and related materials.

Summary: Background: Limited data exists on how early-life weight changes relate to metabolic syndrome (MetS) risk in midlife. This study examines the association between long-term trajectories of body mass index (BMI), its variability, and MetS risk in Chinese individuals. Methods: In the Hanzhong Adolescent Hypertension study (March 10, 1987–June 3, 2017), 1824 participants with at least five BMI measurements from 1987 to 2017 were included. Using group-based trajectory modeling, different BMI trajectories were identified. BMI variability was assessed through standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Logistic regression analyzed the relationship between BMI trajectory, BMI variability, and MetS occurrence in midlife (URL: https://www.clinicaltrials.gov; Unique identifier: NCT02734472). Findings: BMI trajectories were categorized as low-increasing (34.4%), moderate-increasing (51.8%), and high-increasing (13.8%). Compared to the low-increasing group, the odds ratios (ORs) [95% CIs] for MetS were significantly higher in moderate (4.27 [2.63–6.91]) and high-increasing groups (13.11 [6.30–27.31]) in fully adjusted models. Additionally, higher BMI variabilities were associated with increased MetS odds (ORs for SDBMI, VIMBMI, and ARVBMI: 2.30 [2.02–2.62], 1.22 [1.19–1.26], and 4.29 [3.38–5.45]). Furthermore, BMI trajectories from childhood to adolescence were predictive of midlife MetS, with ORs in moderate (1.49 [1.00–2.23]) and high-increasing groups (2.45 [1.22–4.91]). Lastly, elevated BMI variability in this period was also linked to higher MetS odds (ORs for SDBMI, VIMBMI, and ARVBMI: 1.24 [1.08–1.42], 1.00 [1.00–1.01], and 1.21 [1.05–1.38]). Interpretation: Our study suggests that both early-life BMI trajectories and BMI variability could be predictive of incident MetS in midlife. Funding: This work was supported by the National Natural Science Foundation of China No. 82070437 (J.-J.M.), the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University of China (No. XJTU1AF-CRF-2022-002, XJTU1AF2021CRF-021, and XJTU1AF-CRF-2023-004), the Key R&D Projects in Shaanxi Province (Grant No. 2023-ZDLSF-50), the Chinese Academy of Medical Sciences & Peking Union Medical College (2017-CXGC03-2), and the International Joint Research Centre for Cardiovascular Precision Medicine of Shaanxi Province (2020GHJD-14).

Objective: High sensitivity cardiac troponin (hs-cTn) may be useful to monitor residual risk in secondary prevention. Our objective was to study the correlations and comparative associations with mortality of four hs-cTn assays in US adults with known cardiovascular disease (CVD). Methods: We studied 1,211 adults with a history of CVD who participated in the National Health and Nutrition Examination Survey (NHANES) 1999–2004. Using stored samples, we measured hs-cTnT (Roche) and three hs-cTnI assays (Abbott, Siemens, and Ortho). Outcomes were all-cause and CVD mortality, with follow-up through December 31, 2019. Results: Mean age was 64 years, 48 % were female, and 80 % identified as non-Hispanic White. Pearson's correlation coefficients between hs-cTn assays ranged from 0.67 to 0.85. There were 848 deaths (365 from CVD). Among adults with a history of prior non-fatal CVD, each hs-cTn assay (log-transformed, per 1-SD) was independently associated with CVD death (HRs ranging from 1.55 to 2.16 per 1-SD, all p-values

In this work, a new pyrylium derivatization-assisted liquid chromatography-mass spectrometry (LC-MS) method was developed for metabolite profiling of the glutathione anabolic pathway (GAP) in cancer tissues and cells. The pyrylium salt of 6,7-dimethoxy-3-methyl isochromenylium tetrafluoroborate (DMMIC) was used to label the amino group of metabolites, and a reductant of dithiothreitol (DTT) was employed to stabilize the thiol group. By combining DMMIC derivatization with LC-MS, it was feasible to quantify the 13 main metabolites on the GAP in complex biological samples, which had good linearity (R2 = 0.9981−0.9999), precision (interday precision of 1.6%–19.0% and intraday precision of 1.4%–19.8%) and accuracy (83.4%–115.7%). Moreover, the recovery assessments in tissues (82.5%–107.3%) and in cells (98.1%–118.9%) with GSH-13C2, 15N, and Cys-15N demonstrated the reliability of the method in detecting tissues and cells. Following a methodological evaluation, the method was applied successfully to investigate difference in the GAP between the carcinoma and para-carcinoma tissues of esophageal squamous cell carcinoma (ESCC) and the effect of p-hydroxycinnamaldehyde (CMSP) on the GAP in KYSE-150 esophageal cancer cells. The results demonstrate that the developed method provides a promising new tool to elucidate the roles of GAP in physiological and pathological processes, which can contribute to research on drugs and diseases.

Microstructures and mechanical properties of Mg-6Gd-xY-0.5Zr (wt.%, x = 0, 0.5, 1 and 3) alloys with different conditions (solution-treated and 200 °C peak-aged) are investigated. Species of precipitates in Mg-6Gd-0.5Zr alloys are modified by Y addition. In 0Y, 0.5Y and 1Y alloys, β′ precipitates and tentacle-like structures with specific crystallographic directions around β′ body are the main phases. The crystallographic directions of tentacle-like structures are {112‾0}Mg. When 3Y is added, β′ and β1 precipitates become the main phases. Except that, the size and area number density of β′ precipitate are also influenced by adding Y. With Y addition, the size of β′ precipitate is refined, and its area number density increases. This phenomenon has been explained by theoretical method in this paper. According to the study, Mg-6Gd-1Y-0.5Zr alloy with good combination properties is developed. The yield strength, ultimate tensile strength and elongation of Mg-6Gd-1Y-0.5Zr alloy are 164.4 MPa, 280.6 MPa and 16.1 %, respectively. The strengthening precipitates in the peak-aged Mg-6Gd-Y-0.5Zr alloys are β′ precipitates, and the strengthening effect of the β′ precipitates on the yield strength of the Mg-Gd-(Y)–Zr alloys with low Gd/Y content is more obvious than the Mg-Gd-(Y)–Zr alloys with high Gd/Y content.

Objective: Joint stiffness results from the coupling of the nervous system and joint mechanics, and thus stiffness is a comprehensive representation of joint stability. It has been reported that moxibustion can alleviate general weakness and fatigue symptoms and subsequently may influence joint stiffness. This study investigated whether moxibustion could enhance knee joint stiffness in recreational athletes pre- and post-fatigue. Methods: Eighteen participants were randomized into intervention (5 males: 20.6 ± 1.5 yr; 4 females: 20.8 ± 1.5 yr) and control groups (5 males: 19.4 ± 0.9 yr; 4 females: 20.5 ± 0.6 yr). The intervention group received indirect moxibustion applied to acupoints ST36 (bilateral) and CV4 for 30 min every other day for 4 consecutive weeks. The control group maintained regular exercise without moxibustion. Peak torque (PT) of right knee extensor, relaxed and contracted muscle stiffness (MS) of vastus lateralis, and knee extensor musculoarticular stiffness (MAS) was assessed with an isokinetic dynamometer (IsoMed 2000), myometer, and free oscillation technique, respectively. Measurements were taken at three time points: pre-intervention, post-intervention/pre-fatigue, and post-fatigue. Results: MAS (P = 0.006) and PT (P = 0.007) in the intervention group increased more from pre-to post-intervention compared with the control group. Post-fatigue MAS (P = 0.016) and PT (P = 0.031) increased more in the intervention group than in the control group. Conclusion: Moxibustion enhanced PT and knee MAS, suggesting that this intervention could be used in injury prevention and benefit fatigue resistance in young recreational athletes.

To improve the reliability of power supply, this paper proposes a hierarchical and partitioned planning strategy for closed-loop devices in low-voltage distribution network. Based on the geographic location and load situation of the distribution network area, an improved KMeans partition method is used to partition the area in the upper layer. In the lower layer, an intelligent algorithm is adopted to decide the numbers and placement locations of mobile low-voltage contact boxes and mobile seamless closed-loop load transfer devices in each partition with the goal of the highest closed-loop safety, the greatest improvement in annual power outage amount and the lowest cost. Finally, the feasibility and effectiveness of the proposed strategy are proved by an example.

Introduction: Inherent or acquired resistance to paclitaxel (PTX) is a pivotal challenge for chemotherapy treatment of multidrug-resistant (MDR) breast cancer. Although various targeted drug-delivery systems, including nanoparticles and liposomes, are effective for MDR cancer treatment, their efficacy is restricted by immunosuppressive tumor microenvironment (TME). Methods: Ginsenosides Rg3 was used to formulate unique Rg3-based liposomes loaded with PTX to establish Rg3-PTX-LPs, which were prepared by the thin-film hydration method. The stability of the Rg3-PTX-LPs was evaluated by particle size analysis through dynamic light scattering. The active targeting effect of Rg3-based liposomes was examined in an MCF-7/T xenograft model by an in a vivo imaging system. To evaluate the antitumor activity and mechanism of Rg3-PTX-LP, MTT, apoptosis assays, TAM regulation, and TME remodeling were performed in MCF-7/T cells in vitro and in vivo. Results: Rg3-PTX-LPs could specifically distribute to MCF7/T cancer cells and TME simultaneously, mainly through the recognition of GLUT-1. The drug resistance reversing capability and in vivo antitumor effect of Rg3-PTX-LPs were significantly improved compared with conventional cholesterol liposomes. The TME remodeling mechanisms of Rg3-PTX-LPs included inhibiting IL-6/STAT3/p-STAT3 pathway activation to repolarize protumor M2 macrophages to antitumor M1 phenotype, suppressing myeloid-derived suppressor cells (MDSCs), decreasing tumor-associated fibroblasts (TAFs) and collagen fibers in TME, and promoting apoptosis of tumor cells. Hence, through the dual effects of targeting tumor cells and TME remodeling, Rg3-PTX-LPs achieved a high tumor inhibition rate of 90.3%. Conclusion: Our multifunctional Rg3-based liposome developed in the present study offered a promising strategy for rescuing the drug resistance tumor treatment.