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In this work, we aim to investigate the origin of the magnetic carriers in the lunar crust and the intensity of the ancient dynamo field. The magnetization and depth range of magnetic carriers are studied under a weak and a strong magnetic anomaly in Mare Tranquillitatis and in Oceanus Procellarum, respectively, where the surface ages are 3.6 and 3.3 billion years. A sophisticated three-dimensional amplitude inversion software program from a geophysical survey is used to reconstruct the distributions of magnetization in the lunar crust. Because no globally measured surface magnetic field exists for the Moon, a crustal magnetic anomaly model with a grid resolution of 0.2° is used. The depth range of the magnetic source is fixed by the boundary identified by a relative criterion, which is 20% of the recovered maximum magnetization. The central burial depths of the magnetic carriers are approximately 15 km and 25 km under Reiner Gamma and Mare Tranquillitatis, respectively. The volumes of the two magnetic sources are at scales of 104 and 105 km3, respectively. The aforementioned differences may imply a hotter crust under Reiner Gamma than Mare Tranquillitatis by 3.3 billion years. The results support the view that the magma intrusions magnetized by an ancient magnetic field could be the origin of magnetic anomalies under Reiner Gamma and Mare Tranquillitatis. Compared with previous works, the maximum magnetization of 3 A/m under Reiner Gamma supports the intensity of the field being several microteslas.

With the rapid expansion of artificial light in the global nocturnal environment, the ecological impacts of artificial light at night (ALAN) on plant communities have garnered increasing research interest. However, the role of phyllosphere microorganisms as mediators in the regulation between ALAN and plants remains unclear. In this study, we conducted a field experiment in natural grassland plots, employing two treatments: one with no artificial light at night (control) and another with artificial light at night (ALAN). We then investigated the response of phyllosphere microorganisms in three grassland plant species (Leymus chinensis, Vicia sepium, and Aster altaicus) to ALAN exposure. The results revealed that the constructive species L. chinensis demonstrated a markedly higher diversity of phyllosphere bacteria and fungi compared to V. sepium and A. altaicus and thus had the most abundant microbial community. However, ALAN exposure reduced the diversity of phyllosphere bacteria and fungi in all three plant species to varying degrees. ALAN induced certain changes to the phyllosphere bacterial community composition, particularly manifesting in a reduction in the abundance of beneficial bacteria, including Sphingomonas, Hymenobacter, Methylobacterium-Methylorubrum, and Bacillus. Compared with phyllosphere bacterial communities, the alterations in phyllosphere fungal communities were more sensitive, characterized by a significant decrease in the abundance of certain fungi, including Zymoseptoria, Mycosphaerella, Cladosporium, and Epicoccum. The functional predictions of phyllosphere bacteria and fungi further corroborate these conclusions. In summary, ALAN exposure may suppress the functional capacity of phyllosphere microorganisms in grassland plants while decreasing the probability of fungal pathogen occurrence.

Purpose: The impact of winter moisture on root metabolism and root integrity has potential consequences for the geographical distribution of drought-adapted succulent species and for their long-term performance on green roofs. The interacting effects of soil characteristics and precipitation frequency on root mortality under winter conditions and the potential to grow new roots in spring were evaluated for six Sedum species under controlled conditions. Methods: To test for the impact of soil moisture during winter on root regrowth potential in six Sedum species, we used a combination of two substrates with differing water-holding capacity and four contrasting watering regimes. Specially, for the fine and coarse substrates, total pore volume was 42 and 46 %, respectively, and maximum water-holding capacity (i.e. field capacity) was 0.50 and 0.33 kg water per L, respectively. The four watering treatments involved overhead watering to runoff (approx. 10 mm): once every second week, once a week, three times per week and three times per week with 1 cm standing water in trays from January to March 2019. Results: It was found that winter soil moisture had no major impact on root mortality or root regrowth potential in spring. Root mortality was not affected by watering frequency and regrowth potential showed no directional response to increased watering frequency, although species-specific responses were involved. Root diameter did not differ between the substrates, but there were some differences between the species. Sedum rupestre had on average the thickest roots (0.17 mm), followed by S. acre, S. anglicum and S. sexangulare (0.15–0.16 mm), while S. album and S. hispanicum had the thinnest roots (0.12–0.13 mm). Moreover, effects of watering frequency on root mortality and regrowth potential were not influenced by soil water-holding capacity across species. We concluded that winter soil moisture had no negative effects on root performance within the range of treatments tested here. Conclusions: Root response to transient waterlogging or moist but unsaturated soil may not be an important mechanism for determining the survival and distribution of temperate Sedum species during winter.

The phenomenon of nitrogen deposition resulting in species loss in terrestrial ecosystems has been demonstrated in several experiments. Nitrogen (N) and phosphorus (P), as major nutrients required for plant growth, exhibit ecological stoichiometric coupling in many ecosystems. The increased availability of nitrogen can exacerbate the ecological effects of phosphorus. To reveal the ecological effects of phosphorus under nitrogen-limiting and non-limiting conditions, we conducted a controlled N–P interaction experiment over 5 years in the Hulunbuir meadow steppe, where two nitrogen addition levels were implemented: 0 g N·m-2·a-1 (nitrogen-limiting condition) and 10 g N·m-2·a-1 (nitrogen-non-limiting condition), together with six levels of phosphorus addition (0, 2, 4, 6, 8, and 10 g P·m-2·a-1). The results showed that nitrogen addition (under nitrogen-non-limiting conditions) significantly decreased species diversity in the steppe community, which was exacerbated under phosphorus addition. Under nitrogen-limiting conditions, phosphorus addition had no marked impact on species diversity compared to the control; however, there were substantial differences between different levels of phosphorus addition, exhibiting a unimodal change. Under both experimental nitrogen conditions, the addition of 6 g P·m-2·a-1 was the threshold for affecting the community species diversity. Nitrogen addition reduced the relative biomass of legumes, bunch grasses, and forbs, but substantially increased the relative biomass of rhizomatous grasses. In contrast, phosphorus addition only markedly affected the relative biomass of forbs and rhizomatous grasses, with the former showing a unimodal pattern of first increasing and then decreasing with increasing phosphorus addition level, and the latter exhibiting the opposite pattern. The different responses of rhizomatous grasses and other functional groups to nitrogen and phosphorus addition were observed to have a regulatory effect on the changes in grassland community structure. Phosphorus addition may increase the risk of nitrogen deposition-induced species loss. Both nitrogen and phosphorus addition lead to soil acidification and an increase in the dominance of the already-dominant species, and the consequent species loss in the forb functional group represents the main mechanism for the reduction in community species diversity.

Abstract Microalbuminuria and hyperuricemia management are crucial for the integrated management of hypertensive patients. This retrospective post hoc analysis aims to evaluate the optimal allisartan‐isoproxil‐based combination regimen for hypertensive patients with microalbuminuria or hyperuricemia. A total of 460 hypertensive patients with microalbuminuria and 486 hypertensive patients with hyperuricemia were included in this study. All patients were initially treated with allisartan‐isoproxil for 4 weeks. Thereafter, patients with blood pressure (BP)

Abstract Frozen shoulder (FS) is a common disorder often treated with Tuina, but the mechanisms involved remain unclear. We employed proteomics and phosphoproteomics to investigate the mechanisms associated with the treatment of capsule fibrosis in FS rats. We used a method composed of three weeks of cast immobilization to establish a model of FS. We then administered Tuina once daily for 14 days, evaluated glenohumeral range of motion (ROM), assessed histological changes, and identified differentially expressed proteins (DEPs) using proteomics and phosphoproteomics. This study demonstrated that Tuina could improve glenohumeral ROM and reserve capsule fibrosis in FS rats. Proteomics revealed proteins regulated by Tuina belonging to the PI3K-AKT and ECM receptor interaction signaling pathways. Phosphoproteomics detected differentially phosphorylated proteins regulated by Tuina to be enriched in the MAPK signaling pathway. The combination of proteomics and phosphoproteomics for Protein–Protein Interaction (PPI) network analysis revealed that the phosphorylation of Myh3 and Srsf1 with a node degree larger than the average degree were considered the central regulatory protein modulated by Tuina to reverse capsule fibrosis. Thbs1, Vtn, and Tenascin-W were significantly enriched in PI3K-AKT and ECM receptor interaction signaling pathways and highly expressed in model rats. Tuina resulted in reduced expression of these proteins. Our findings demonstrated some of mechanisms behind the reversal of FS capsule fibrosis following Tuina, a scientific medical therapy for FS patients.

Abstract Background Hylurgus ligniperda, a major international forestry quarantine pest, was recently found to have invaded and posed a serious threat to the Pinus forests of the Jiaodong Peninsula in China. Continuous monitoring and vigilance of the early population is imperative, and rapid molecular detection technology is urgently needed. We focused on developing a single-gene-based species-specific PCR (SS-PCR) method. Results We sequenced and assembled the mitochondrial genome of H. ligniperda to identify suitable target genes. We identified three closely related species for detecting the specificity of SS-PCR through phylogenetic analysis based on 13 protein-coding genes (PCGs). Subsequently, we analyzed the evolution of 13 PCGs and selected four mitochondrial genes to represent slow-evolving gene (COI) and faster-evolving genes (e.g. ND2, ND4, and ND5), respectively. We developed four species-specific primers targeting COI, ND2, ND4, and ND5 to rapidly identify H. ligniperda. The results showed that the four species-specific primers exhibited excellent specificity and sensitivity in the PCR assays, with consistent performance across a broader range of species. This method demonstrates the ability to identify beetles promptly, even during their larval stage. The entire detection process can be completed within 2–3 h. Conclusions This method is suitable for large-scale species detection in laboratory settings. Moreover, the selection of target genes in the SS-PCR method is not affected by the evolutionary rate. SS-PCR can be widely implemented at port and forestry workstations, significantly enhancing early management strategies and quarantine measures against H. ligniperda. This approach will help prevent the spread of the pest and effectively preserve the resources of Chinese pine forests.

Abstract There are more than 170 subtypes of sarcomas (SARC), which pose a challenge for diagnosis and patient management. Relatively simple or complex karyotypes play an indispensable role in the early diagnosis and effective treatment of SARC. The genes related to absorption, distribution, metabolism, and excretion (ADME) of a drug can serve as prognostic biomarkers of cancer and potential drug targets. In this study, a risk score signature was created. The SARC cohort was downloaded from The Cancer Genome Atlas (TCGA) database, and divided into high-risk group and low-risk group according to the median value of risk score. Compared with high-risk group, low-risk group has a longer survival time, which is also verified in osteosarcoma cohort from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. In addition, the relationship between the signature and immunophenotypes, including status of immune cell infiltration and immune checkpoint expression, was explored. Then, we found that high-risk group is in immunosuppressive status. Finally, we verified that PPARD played a role as a carcinogen in osteosarcoma, which provided a direction for targeted treatment of osteosarcoma in the future. Generally speaking, the signature can not only help clinicians predict the prognosis of patients with SARC, but also provide a theoretical basis for developing more effective targeted drugs in the future.

Background Nocturnal blood pressure (BP) is correlated with an increased risk of cardiovascular events and is an important predictor of cardiovascular death in hypertensive patients.Objective Nocturnal BP control is of great importance for cardiovascular risk reduction. This systematic review and meta-analysis aimed to explore the efficacy of angiotensin receptor blockers (ARBs) for nocturnal BP reduction in patients with mild to moderate hypertension.Methods PICOS design structure was used to formulate the data extraction. All statistical calculations and analyses were performed with R.Results Seventy-seven studies with 13,314 participants were included. The overall analysis indicated that nocturnal BP drop varied considerably among different ARBs. Allisartan (13.04 [95% CI (−18.41, −7.68)] mmHg), olmesartan (11.67 [95% CI (−14.12, −9.21)] mmHg), telmisartan (11.11 [95% CI (−12.12, −10.11)] mmHg) were associated with greater reduction in nocturnal systolic BP. In the aspect of the nocturnal-diurnal BP drop ratio, only allisartan was greater than 1. While, the variation tendency of last 4–6 h ambulatory BP was basically consistent with nocturnal BP. Additionally, allisartan showed improvement effect in the proportion of patients with dipping BP pattern.Conclusions This study demonstrates that for patients with mild to moderate hypertension, allisartan, olmesartan and telmisartan have more advantages in nocturnal BP reduction among the ARBs, while allisartan can reduce nighttime BP more than daytime BP and improve the dipping pattern.

In the context of an aging population, the concept of peaceful end-of-life care has gained increasing significance as an essential component of individuals’ fundamental well-being. This underscores the importance of researching and developing hospice care facilities and service systems dedicated to providing a tranquil resting environment. This study focuses on selected hospice care buildings, examining their service model evolution and architectural design. Through case analyses, it explores contemporary hospice care architecture, identifying various types and spatial design features that cater to the end-of-life needs of individuals. The findings guide the design of hospice care buildings in China, emphasizing patient-living areas, medical care zones, and auxiliary functional spaces. This comprehensive approach aims to enhance terminally ill patients’ comfort, serenity, and dignity. Moreover, it aims to provide emotional and post-funeral support to terminally ill patients’ families.

Abstract Introduction Evidence on the willingness of men who have sex with men (MSM) with oral pre-exposure prophylaxis (PrEP) experience, especially those with suboptimal adherence, to take long-acting injectable PrEP (LAI-PrEP) is critical to guide future LAI-PrEP implementation. Objective The objective was to assess the willingness of MSM with oral PrEP experience to take LAI-PrEP. Methods MSM who participated in the China Real-world Study of Oral PrEP (CROPrEP) were enrolled in this study. Information on the willingness of MSM to take LAI-PrEP and potential correlates was collected using a structured online questionnaire. The main outcomes were the willingness of MSM to take LAI-PrEP and its association with HIV-related behaviours, sexually transmitted infections, and oral PrEP history. Logistic regression was used to identify correlates of the willingness of MSM to take LAI-PrEP. Results A total of 612 former CROPrEP participants (FCPs) were included in this study. There were 315 (51.5%) daily oral PrEP (D-PrEP) users and 297 (48.5%) event-driven oral PrEP (ED-PrEP) users at the last follow-up. Most FCPs (77.8%) were willing to take free LAI-PrEP. FCPs with no less than two sexual male partners (aOR = 1.54, [95% CI: 1.04, 2.29], P = 0.031), those with male partners with unknown HIV statuses (aOR = 2.04, [95% CI: 1.31, 3.18], P = 0.002), those with recreational drug use (aOR = 1.58, [95% CI: 1.05, 2.40], P = 0.030), and those with HSV-2 positivity (aOR = 2.15, [95% CI: 1.30, 3.57], P = 0.003) were more willing to take LAI-PrEP, while ED-PrEP users (aOR = 0.66, [95% CI: 0.45, 0.98], P = 0.037) and FCPs with suboptimal oral PrEP adherence (aOR = 0.58, [95% CI: 0.36, 0.94], P = 0.026) were less willing to take LAI-PrEP. Conclusion LAI-PrEP has good prospects for expanding PrEP coverage. However, FCPs with suboptimal oral PrEP adherence are less likely to take LAI-PrEP. Further intervention and implementation efforts are needed to improve the willingness of MSM to use LAI-PrEP, and sexual health should be considered during the discussion about PrEP initiation.

High-entropy MXenes, as a new emerging class of materials, possess diverse compositions, unexpected physicochemical characteristics, and great potentials for electromagnetic (EM) wave absorption. Herein, two single-to-few-layer high-entropy MXenes, (Mo0.25Cr0.25Ti0.25V0.25)3C2Tx and (Mo0.2Cr0.2Nb0.2Ti0.2V0.2)4C3Tx, were synthesized for the first time. During the exfoliation and delamination processes, the structural, morphological, and compositional evolutions were analyzed, verifying the successful formation of single-to-few-layer two-dimensional MXene nanosheets. Investigations indicate that with the filling content of only 35 wt%, MXene powder filled composites exhibit high-efficiency EM wave absorption performances. The f-(Mo0.25Cr0.25Ti0.25V0.25)3C2Tx possesses the minimum reflection loss (RLmin) of −45.0 dB with the matching thickness of 1.52 mm and the maximum effective absorption bandwidth (EAB) of 5.6 GHz at 1.65 mm thickness. Also, f-(Mo0.2Cr0.2Nb0.2Ti0.2V0.2)4C3Tx can attain an RLmin of −52.8 dB with the thickness of 1.58 mm and an optimum EAB value of 3.6 GHz at 1.50 mm. The satisfactory EM wave absorption efficiency and bandwidth, thin matching thickness, and low filling content prove the lightweight advantage and great application potential of high-entropy MXenes in EM wave absorption. In this work, the high-entropy strategy is applied to tune the EM wave absorption performances for MXenes. Furthermore, high-entropy engineering is expected to provide control and tunability of many other properties, such as electrochemical, catalytic, and mechanical behaviors.

Abstract Background Elliptical excision is the most commonly used method for small benign tumour excision and primary closure. However, elliptical excision remains the topic of debate. The aim of this study was to explore the relationship among postoperative incision, vertex angle, and the length and width of fusiform excision through a mathematical model. Methods We collected data from fusiform circle excisions performed at the author’s hospital (101 cases). The measured values were applied to the mathematical model formula for statistical analysis. Results The functional relationships among the length, width, arc, and angle of the fusiform circle were obtained. The mean apical tangent angle was 100.731°±15.782°, and the mean apical inner angle was 50.366°±7.891°. There was no significant difference between the preoperatively designed arc length preoperative and the postoperative incision length (P

Disulfidptosis, a newly revealed form of cell death, regulated by numerous genes that has been recently identified. The exact role of disulfidptosis in lung adenocarcinoma (LUAD) still uncertain. Objective of this study was to explore potential prognostic markers among disulfidptosis genes in LUAD. By combining transcriptomic information from Gene Expression Omnibus databases and The Cancer Genome Atlas, we identified differentially expressed and prognostic disulfidptosis genes. By conducting least absolute shrinkage and selection operator with multivariate Cox regression, four disulfidptosis genes were selected to create the prognostic signature. The implementation of the signature separated the training and validation cohorts into groups with high- and low-risk. Subsequently, the model was verified by conducting an independent analysis of receiver operating characteristic (ROC) curves. Further comparisons were made between the two risk-divided groups with regards the tumor microenvironment, immune cell infiltration, immunotherapy response, and drug sensitivity. The signature was constructed using four disulfidptosis-related genes: SLC7A11, SLC3A2, NCKAP1, and GYS1. According to ROC curves, the signature was effective for predicting LUAD prognosis. In addition, the prognostic signature correlated with sensitivity to chemotherapeutic agents and the efficacy of immunotherapy in LUAD. Finally, through external validation, we showed that NCKAP1 are correlated with tumor migration, proliferation, and invasion of LUAD cells. GYS1 affects immune cell, especially M2 macrophage infiltration in the tumor microenvironment. The disulfidptosis four-gene model can reliably predict the prognosis of patients diagnosed with LUAD, thereby providing valuable information for clinical applications and immunotherapy.

Abstract Background Breast cancer is the most common cancer affecting women across the world. Tumor endothelial cells (TECs) and malignant cells are the major constituents of the tumor microenvironment (TME), but their origin and role in shaping disease initiation, progression, and treatment responses remain unclear due to significant heterogeneity. Methods Tissue samples were collected from eight patients presenting with breast cancer. Single-cell RNA sequencing (scRNA-seq) analysis was employed to investigate the presence of distinct cell subsets in the tumor microenvironment. InferCNV was used to identify cancer cells. Pseudotime trajectory analysis revealed the dynamic process of breast cancer angiogenesis. We validated the function of small extracellular vesicles (sEVs)-derived protein phosphatase 1 regulatory inhibitor subunit 1B (PPP1R1B) in vitro experiments. Results We performed single-cell transcriptomics analysis of the factors associated with breast cancer angiogenesis and identified twelve subclusters of endothelial cells involved in the tumor microenvironment. We also identified the role of TECs in tumor angiogenesis and confirmed their participation in different stages of angiogenesis, including communication with other cell types via sEVs. Overall, the research uncovered the TECs heterogeneity and the expression levels of genes at different stages of tumor angiogenesis. Conclusions This study showed sEVs derived from breast cancer malignant cells promote blood vessel formation by activating endothelial cells through the transfer of PPP1R1B. This provides a new direction for the development of anti-angiogenic therapies for human breast cancer.

With the improvement of people's living standards and health awareness, the safety of animal-derived food has attracted worldwide attention. Chemical contamination (melamine, veterinary drug residues, food additive residues, etc.) and pathogenic microorganisms are the primary causes of food safety issues in animal-derived food products, potentially threatening human health and socioeconomic development. Therefore, it is essential to establish rapid detection methods for animal-derived food safety. Surface-enhanced Raman spectroscopy (SERS) has the advantages of rapid detection, good selectivity, and high sensitivity. It has shown great application potential in food safety, which has become one of the research hotspots. This paper reviews the application of SERS in the safety of animal-derived food detection and comprehensively introduces the use of SERS to detect melamine, foodborne pathogens, pesticide and veterinary drug residues, and food additives. Furthermore, it prospects the application of SERS technology in rapid residue detection, which would be believed to provide valuable insights into the field of SERS-based food safety evaluation.

A novel biomass-based magnetic nanoparticle (Fe3O4-P-CMC/PAMAM) was synthesized by crosslinking carboxymethyl chitosan (CMC) and poly(amidoamine) (PAMAM), followed by phosphorylation with the incorporation of magnetic ferric oxide nanoparticles. The characterization results verified the successful functionalization and structural integrity of the adsorbents with a surface area of ca. 43 m2/g. Batch adsorption experiments revealed that the adsorbent exhibited a maximum adsorption capacity of 1513.47 mg·g−1 for U(VI) at pH 5.5 and 298.15 K, with Fe3O4-P-CMC/G1.5-2 showing the highest affinity among the series. The adsorption kinetics adhered to a pseudo-second-order model (R2 = 0.99, qe,exp = 463.81 mg·g−1, k2 = 2.15×10−2 g·mg−1·min−1), indicating a chemically driven process. Thermodynamic analysis suggested that the adsorption was endothermic and spontaneous (ΔH° = 14.71 kJ·mol−1, ΔG° = −50.63 kJ·mol−1, 298. 15 K), with increasing adsorption capacity at higher temperatures. The adsorbent demonstrated significant selectivity for U(VI) in the presence of competing cations, with Fe3O4-P-CMC/G1.5-2 showing a high selectivity coefficient. The performed desorption and reusability tests indicated that the adsorbent could be effectively regenerated using 1M HCl, maintaining its adsorption capacity after five cycles. XPS analysis highlighted the role of phosphonate and amino groups in the complexation with uranyl ions, and validated the existence of bimodal U4f peaks at 380.1 eV and 390.1 eV belonging to U 4f7/2 and U 4f5/2. The results of this study underscore the promise of the developed adsorbent as an effective and selective material for the treatment of uranium-contaminated wastewater.

Herein, the morphological characteristics of submarine archipelagic aprons were presented for five guyots, Suda, Arnold, Lamont, Niulang, and Zhinyv, which are over 80 Ma years old and are located in the Marcus–Wake seamount group, northwestern Pacific Ocean. Nearly 28 landslide deposits were recognized using the bathymetry and backscatter intensity data collected from the studied guyots. Landslides and their deposits that surround seamounts are mostly related to the morphology of debris avalanches, scarps, gullies/channels, and bedforms. The morphology of the archipelagic aprons of the studied guyots indicates mutual landslide processes, including slump and distinct debris avalanches arising from a cohesive or cohesionless landslide material flow. The superimposition of debris flows and sedimentation dominates the recent stages of the studied guyots. The archipelagic aprons corresponding to convex-arc-shaped scarps exhibit larger domains compared to the invagination-arc-shaped scarps with similar lateral lengths. The scarp morphologies of the studied guyots are predominantly of the complex-arc shape, indicating multiple landslide events. Parallel and convergent gullies and channels are mostly found on the elongated landslide deposits, whereas divergent and radial gullies and channels are mostly distributed on the fan-shaped aprons. Ubiquitous sediment waves occurred on the bedforms of the distal archipelagic apron across the studied guyots because of sediment creep. Small-scale sediment waves were only observed in the channels on the aprons of the Suda guyot.

Abstract Epitaxial growth is one of the most commonly used strategies to precisely tailor heterostructures with well-defined compositions, morphologies, crystal phases, and interfaces for various applications. However, as epitaxial growth requires a small interfacial lattice mismatch between the components, it remains a challenge for the epitaxial synthesis of heterostructures constructed by materials with large lattice mismatch and/or different chemical bonding, especially the noble metal-semiconductor heterostructures. Here, we develop a noble metal-seeded epitaxial growth strategy to prepare highly symmetrical noble metal-semiconductor branched heterostructures with desired spatial configurations, i.e., twenty CdS (or CdSe) nanorods epitaxially grown on twenty exposed (111) facets of Ag icosahedral nanocrystal, albeit a large lattice mismatch (more than 40%). Importantly, a high quantum yield (QY) of plasmon-induced hot-electron transferred from Ag to CdS was observed in epitaxial Ag-CdS icosapods (18.1%). This work demonstrates that epitaxial growth can be achieved in heterostructures composed of materials with large lattice mismatches. The constructed epitaxial noble metal-semiconductor interfaces could be an ideal platform for investigating the role of interfaces in various physicochemical processes.

Abstract In recent years, there have been several solutions to medical image segmentation, such as U-shaped structure, transformer-based network, and multi-scale feature learning method. However, their network parameters and real-time performance are often neglected and cannot segment boundary regions well. The main reason is that such networks have deep encoders, a large number of channels, and excessive attention to local information rather than global information, which is crucial to the accuracy of image segmentation. Therefore, we propose a novel multi-branch medical image segmentation network MBSNet. We first design two branches using a parallel residual mixer (PRM) module and dilate convolution block to capture the local and global information of the image. At the same time, a SE-Block and a new spatial attention module enhance the output features. Considering the different output features of the two branches, we adopt a cross-fusion method to effectively combine and complement the features between different layers. MBSNet was tested on five datasets ISIC2018, Kvasir, BUSI, COVID-19, and LGG. The combined results show that MBSNet is lighter, faster, and more accurate. Specifically, for a $$320 \times 320$$ 320 × 320 input, MBSNet’s FLOPs is 10.68G, with an F1-Score of $$85.29\%$$ 85.29 % on the Kvasir test dataset, well above $$78.73\%$$ 78.73 % for UNet++ with FLOPs of 216.55G. We also use the multi-criteria decision making method TOPSIS based on F1-Score, IOU and Geometric-Mean (G-mean) for overall analysis. The proposed MBSNet model performs better than other competitive methods. Code is available at https://github.com/YuLionel/MBSNet .

Abstract Meningioma was the most primary intracranial tumor, but the molecular characteristics and the treatment of malignant meningioma were still unclear. Nine malignant progression-related genes based prognostic signatures were identified by transcriptome analysis between benign meningioma and malignant meningioma. The external dataset GEO136661 and quantitative Real-time Polymerase Chain Reaction were used to verify the prognostic factors. has-miR-3605-5p, hsa-miR-664b-5p, PNRC2, BTBD8, EXTL2, SLFN13, DGKD, NSD2, and BVES were closed with malignant progression. Moreover, Doxorubicin was identified by Connectivity Map website with the differential malignant progression-related genes. CCK-8 assay, Edu assay, wound healing assay, and trans-well experiment were used to reveal that Doxorubicin could inhibit proliferation, migration and invasion of IOMM-Lee Cells.

Triple-negative breast cancer (TNBC), the most aggressive form of breast cancer, presents severe threats to women’s health. Therefore, it is critical to find novel treatment approaches. Ferroptosis, a newly identified form of programmed cell death, is marked by the buildup of lipid reactive oxygen species (ROS) and high iron concentrations. According to previous studies, ferroptosis sensitivity can be controlled by a number of metabolic events in cells, such as amino acid metabolism, iron metabolism, and lipid metabolism. Given that TNBC tumors are rich in iron and lipids, inducing ferroptosis in these tumors is a potential approach for TNBC treatment. Notably, the metabolic adaptability of cancer cells allows them to coordinate an attack on one or more metabolic pathways to initiate ferroptosis, offering a novel perspective to improve the high drug resistance and clinical therapy of TNBC. However, a clear picture of ferroptosis in TNBC still needs to be completely revealed. In this review, we provide an overview of recent advancements regarding the connection between ferroptosis and amino acid, iron, and lipid metabolism in TNBC. We also discuss the probable significance of ferroptosis as an innovative target for chemotherapy, radiotherapy, immunotherapy, nanotherapy and natural product therapy in TNBC, highlighting its therapeutic potential and application prospects.

BackgroundReference intervals (RIs) play an important role in clinical decision-making. However, due to the time, labor, and financial costs involved in establishing RIs using direct means, the use of indirect methods, based on big data previously obtained from clinical laboratories, is getting increasing attention. Different indirect techniques combined with different data transformation methods and outlier removal might cause differences in the calculation of RIs. However, there are few systematic evaluations of this. ObjectiveThis study used data derived from direct methods as reference standards and evaluated the accuracy of combinations of different data transformation, outlier removal, and indirect techniques in establishing complete blood count (CBC) RIs for large-scale data. MethodsThe CBC data of populations aged ≥18 years undergoing physical examination from January 2010 to December 2011 were retrieved from the First Affiliated Hospital of China Medical University in northern China. After exclusion of repeated individuals, we performed parametric, nonparametric, Hoffmann, Bhattacharya, and truncation points and Kolmogorov–Smirnov distance (kosmic) indirect methods, combined with log or BoxCox transformation, and Reed–Dixon, Tukey, and iterative mean (3SD) outlier removal methods in order to derive the RIs of 8 CBC parameters and compared the results with those directly and previously established. Furthermore, bias ratios (BRs) were calculated to assess which combination of indirect technique, data transformation pattern, and outlier removal method is preferrable. ResultsRaw data showed that the degrees of skewness of the white blood cell (WBC) count, platelet (PLT) count, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular volume (MCV) were much more obvious than those of other CBC parameters. After log or BoxCox transformation combined with Tukey or iterative mean (3SD) processing, the distribution types of these data were close to Gaussian distribution. Tukey-based outlier removal yielded the maximum number of outliers. The lower-limit bias of WBC (male), PLT (male), hemoglobin (HGB; male), MCH (male/female), and MCV (female) was greater than that of the corresponding upper limit for more than half of 30 indirect methods. Computational indirect choices of CBC parameters for males and females were inconsistent. The RIs of MCHC established by the direct method for females were narrow. For this, the kosmic method was markedly superior, which contrasted with the RI calculation of CBC parameters with high |BR| qualification rates for males. Among the top 10 methodologies for the WBC count, PLT count, HGB, MCV, and MCHC with a high-BR qualification rate among males, the Bhattacharya, Hoffmann, and parametric methods were superior to the other 2 indirect methods. ConclusionsCompared to results derived by the direct method, outlier removal methods and indirect techniques markedly influence the final RIs, whereas data transformation has negligible effects, except for obviously skewed data. Specifically, the outlier removal efficiency of Tukey and iterative mean (3SD) methods is almost equivalent. Furthermore, the choice of indirect techniques depends more on the characteristics of the studied analyte itself. This study provides scientific evidence for clinical laboratories to use their previous data sets to establish RIs.

It is a widely held view that people rely on incomplete information to find a relationship partner, resulting in non-compensatory choice heuristics. However, recent experimental work typically finds that partner choice follows compensatory choice strategies. To bridge this gap between theory and experimental evidence, we characterize the mate choice problem by distinguishing the information search process from the evaluation process. In an eye-tracking experiment and a MouseLab experiment, we show that people display strong value-directed search heuristics in response to all types of cues and that the magnitude of value-directed searches increases with cue primacy. Cue primacy also explains the interaction effect of cue type and participant sex on the extent of valued-directed search. We further argue that value-directed searching does not necessarily lead to non-compensatory choice rules but may serve compensatory decision-making. Our results demonstrate that people may adopt remarkably smart search heuristics to find an ideal partner efficiently.

Asymmetric catalytic methods for the divergent construction of phosphoryl derivatives are not widely available. Here, the authors show nickel-catalyzed dienylation and enantioselective allenylation of phosphine oxides with high chemo-, regio-, and enantioselectivity.

Abstract Background TIMM8A is a protein-coding gene located on the X chromosome. There is evidence that TIMM8A plays an important role in mitochondrial morphology and fission. Studies have shown that mitophagy and fission could affect the function of immune cells. However, there is currently no research on this gene’s role in cancer occurrence and progression. Methods TIMM8A expression was analyzed via the Tumor Immune Estimation Resource (TIMER) site and UALCAN database. We evaluated the influence of TIMM8A on clinical prognosis using Kaplan-Meier plotter, the PrognoScan database, and Human Protein Atlas (HPA). The correlations between TIMM8A and cancer immune infiltrates were investigated via TIMER. Tumor Immune Dysfunction and Exclusion (TIDE) was used to evaluate the potential of tumor immune evasion. Functions of TIMM8A mutations and 50 genes significantly associated with TIMM8A mutations in breast cancer (BRCA) and uterine corpus endometrial cancer (UCEC) were analyzed by GO and KEGG in LinkedOmics database. Results We investigated the role of TIMM8A in multiple cancers and found that it was significantly associated with poor prognosis in BRCA and UCEC. After analyzing the effect of TIMM8A on immune infiltration, we found Th2 CD4+ T cells might be a common pathway by which TIMM8A contributed to poor prognosis in BRCA and UCEC. Our results suggested that myeloid-derived suppressor cells (MDSC) and tumor-associated M2 macrophages (TAM M2) might be important factors in immune evasion through T cell rejection in both cancers, and considered TIMM8A as a biomarker to predict the efficacy of this therapy in BRCA and UCEC. The results of TIMM8A enrichment analysis showed us that abnormally expressed TIMM8A might affect the mitochondrial protein in BRCA and UCEC. Conclusions Contributed to illustrating the value of TIMM8A as a prognostic biomarker, our findings suggested that TIMM8A was correlated with prognosis and immune infiltration, including CD8+ T cells, Th2 CD4+ T cells, and macrophages in BRCA and UCEC. In addition, TIMM8A might affect immune infiltration and prognosis in BRCA and UCEC by affecting mitophagy. We believed it could also be a biomarker to predict the efficacy of anti-PD-L1 therapy and proposed to improve the efficacy by eliminating MDSC and TAM M2.

The United States, EU members, and Russia share extensive and important interests in Central and Eastern Europe (CEE) in terms of geo-security, energy, and values. The US–EU–Russia trilateral interaction in this region features three characteristics: intensifying security competition between Washington and Moscow; closer transatlantic coordination against Russia; and growing wariness about China’s larger economic footprint. New changes have taken place in the regional distribution of power amid continued China–US competition, increasingly diverging values among the United States, Germany, and CEE countries like Poland and Hungary, and heightening geopolitical tensions between Washington and Germany on the one hand and Russia on the other. China–CEEC (CEE countries) cooperation is also coming under mounting geopolitical pressure, owing to Washington’s containment policy toward China, the EU’s weakening control over the CEE countries, Russia’s shift from a defensive to an offensive posture in response to Western sanctions, the new German government’s values-based diplomacy, and the European Commission’s new China policy. However, the transatlantic world is not a monolith. The EU’s weakening control over CEE countries and Washington’s deteriorating relations with Poland and Hungary are bringing potential opportunities for furthering China–CEEC cooperation. The aforementioned factors merit closer attention as important variables in CEE countries’ China policies.

Objective The objective of this study was to compare the feeding value, meat nutrients and associative effects of a diet comprised of various corn silages inclusion with peanut vine or wheat straw in finishing beef cattle. Methods One hundred and eighty Simmental crossbred beef steers were blocked and assigned to the follow treatments: i) whole plant corn silage-based diet (control, WPCS), ii) mixed forages-based diet (replacing a portion of corn silage with wheat straw, WPCSW), iii) corn stalklage-based diet (CS), and iv) sweet corn stalklage-based diet (SCS). Each group consisted of 5 repeated pens with 9 steers/pen. The diets were formulated to be isonitrogenous and isoenergetic with same forage to concentrate ratio. Experimental diets were fed for 90 d. Results The effective ruminal degradability of dry matter and crude protein were highest for WPCS diet (p0.05). Conclusion The corn silage-based diet exhibited the highest feeding value. The sweet corn stalklage and wheat straw as an alternative to corn silage offered to beef cattle had limited influence on feeding value and meat nutrients. However, the value of a corn stalklage-based diet was relatively poor. To sum up, when the high quality forage resources, such as corn silage, are in short supply, or the growth rate of beef cattle decreases in the later finishing period, the sweet stalklage and wheat straw could be used as a cheaper alternative in feedlot cattle diet without sharp reducing economic benefits.

The competition between base-induced elimination (E2) and bimolecular nucleophilic substitution (SN2) is of significant importance in organic chemistry and is influenced by many factors. The electronic structure calculations for the gas-phase reactions of F− + RY (R = CH3, C2H5, iC3H7, tC4H9, and Y = Cl, I) are executed at the MP2 level with aug-cc-pVDZ or ECP/d basis set to investigate the α-methyl substitution effect. The variation in barrier height, reaction enthalpy, and competition of SN2/E2 as a function of methyl-substitution and leaving group ability has been emphasized. And the nature of these rules has been explored. As the degree of methyl substitution on α-carbon increases, the E2 channel becomes more competitive and dominant with R varying from C2H5, iC3H7, to tC4H9. Energy decomposition analysis offers new insights into the competition between E2 and SN2 processes, which suggests that the drop in interaction energy with an increasing degree of substitution cannot compensate for the rapid growth of preparation energy, leading to a rapid increase in the SN2 energy barrier. By altering the leaving group from Cl to I, the barriers of both SN2 and E2 monotonically decrease, and, with the increased number of substituents, they reduce more dramatically, which is attributed to the looser transition state structures with the stronger leaving group ability. Interestingly, ∆E0‡ exhibits a positive linear correlation with reaction enthalpy (∆H) and halogen electronegativity. With the added number of substituents, the differences in ∆E0‡ and ∆H between Y = Cl and I likewise exhibit good linearity.

Abstract Background In bladder cancer, up to 70% of patients will relapse after resection within 5 years, in which the mechanism underlying the recurrence remains largely unclear. Methods Quantitative real-time PCR, western blot and immunohistochemistry were conducted. The assays of tumor sphere formation and tumor xenograft were further performed to assess the potential biological roles of ATF5 (activating transcription factor 5). Chromatin immunoprecipitation-qPCR and luciferase activity assays were carried out to explore the potential molecular mechanism. A two-tailed paired Student's t-test, χ2 test, Kaplan Meier and Cox regression analyses, and Spearman's rank correlation coefficients were used for statistical analyses. Results ATF5 is elevated in bladder urothelial cancer (BLCA) tissues, especially in recurrent BLCA, which confers a poor prognosis. Overexpressing ATF5 significantly enhanced, whereas silencing ATF5 inhibited, the capability of tumor sphere formation in bladder cancer cells. Mechanically, ATF5 could directly bind to and stimulate the promoter of DVL1 gene, resulting in activation of Wnt/β-catenin pathway. Conclusions This study provides a novel insight into a portion of the mechanism underlying high recurrence potential of BLCA, presenting ATF5 as a prognostic factor or potential therapeutic target for preventing recurrence in BLCA.

Abstract Sodium and potassium intake in hypertensive patients in China is not clear. The authors aimed to investigate the distribution of sodium and potassium intake in hypertensive patients in China, and to analyze the relationship between sodium and potassium intake and blood pressure. The study was performed in 130 hospitals from 23 provinces across China from 2016 to 2019. Finally, 9501 hypertensive patients average aged 54 years were included. 24 h urinary sodium and potassium excretion were measured. Distribution of urinary electrolytes were described according to age, gender and region. The association between urinary electrolytes and blood pressure was analyzed by multivariate linear regression. Hypertensive patients exhibited an average 24 h urinary sodium and potassium excretion of 156.7 ± 81.5 mmol/d and 39.2 ± 20.2 mmol/d (equivalent to sodium chloride of 9.2 g/d, potassium chloride of 2.9 g/d), sodium/potassium ratio (median) of 4.14 (2.92,5.73). Urinary electrolytes were lower in women than men (sodium: 171.1 vs 138.7, p

IntroductionIdentifying people at risk of cardiovascular diseases (CVD) is a cornerstone of preventive cardiology. We developed machine learning (ML) algorithms and investigated their performance in predicting patients’ current CVD risk (coronary heart disease and stroke in this study).Materials and methodsWe compared traditional logistic regression (LR) with five ML algorithms LR with Elastic-Net, Random Forest (RF), XGBoost (XGB), Support Vector Machine, Deep Learning, and an Ensemble model averaging predictions from RF, XGB, and Deep Learning for CVD risk prediction using pre-existing patient-level data from a multi-center, cross-sectional study (the Microalbuminuria Screening in Hypertensive Patients Project initiated by the China International Exchange and Promotive Association for Medical and Healthcare) that enrolled 143,043 patients with hypertension from 600 tertiary, secondary, or community hospitals. Each of the five ML algorithms incorporated 18 variables, such as demographics, examinations, comorbidities, and treatment regimens, and were trained and evaluated using 5-fold cross-validation. Predictive accuracy was assessed by the area under the receiver operating curve (AUROC).ResultsPatients’ mean age was 62 ± 12 years and 57% were men. Advanced ML algorithms outperformed the traditional LR model. Particularly, the Ensemble model had superior discrimination with an AUROC of 0.760 than LR (AUC = 0.737) and other tested models.ConclusionWe establishes an Ensemble model that shows better performance in predicting patients’ current CVD risk using routine information compared to the traditional LR model. ML can help physicians design follow-up plans with more accurate results, offering new possibilities for short-term risk prediction and early detection. Further, ML models can be trained with longitudinal data and used to predict long-term CVD risks, thereby informing CVD prevention.

Background and objective Lung cancer has the highest mortality in China. Different treatments are of great significance to the prognosis of patients. By comparing stage Ia non-small cell lung cancer (NSCLC) patients’ survival rates for ablation and for sub-lobectomy, we studied the difference in the effects of the two treatments on patient prognosis. Methods Using the Surveillance, Epidemiology, and End Results (SEER) database, we screened eligible patients with stage Ia NSCLC from January 2004 to December 2015. Then, 228 patients treated with ablation and 228 patients treated with sub-lobotomy were then selected based on propensity score matching. After stratification, matching, and adjustment the Kaplan-Meier analysis was performed to compare the overall survival rates of patients treated with the two procedures. Results The Kaplan-Meier survival analysis showed that there is a significant difference between the ablation group and the sub-lobectomy group (P

N1-methyladenosine methylation (m1A), as an important RNA methylation modification, regulates the development of many tumours. Metabolic reprogramming is one of the important features of tumour cells, and it plays a crucial role in tumour development and metastasis. The role of RNA methylation and metabolic reprogramming in osteosarcoma has been widely reported. However, the potential roles and mechanisms of m1A-related metabolic genes (MRmetabolism) in osteosarcoma have not been currently described. All of MRmetabolism were screened, then selected two MRmetabolism by least absolute shrinkage and selection operator and multifactorial regression analysis to construct a prognostic signature. Patients were divided into high-risk and low-risk groups based on the median riskscore of all patients. After randomizing patients into train and test cohorts, the reliability of the prognostic signature was validated in the whole, train and test cohort, respectively. Subsequently, based on the expression profiles of the two MRmetabolism, we performed consensus clustering to classify patients into two clusters. In addition, we explored the immune infiltration status of different risk groups and different clusters by CIBERSORT and single sample gene set enrichment analysis. Also, to better guide individualized treatment, we analyzed the immune checkpoint expression differences and drug sensitivity in the different risk groups and clusters. In conclusion, we constructed a MRmetabolism prognostic signature, which may help to assess patient prognosis, immunotherapy response.

Toxoplasma gondii infection is a severe health threat that endangers billions of people worldwide. T. gondii utilizes the host cell membrane to form a parasitophorous vacuole (PV), thereby fully isolating itself from the host cell cytoplasm and making intracellular clearance difficult. PV can be targeted and destroyed by autophagy. Autophagic targeting results in T. gondii killing via the fusion of autophagosomes and lysosomes. However, T. gondii has developed many strategies to suppress autophagic targeting. Accordingly, the interplay between host cell autophagy and T. gondii is an emerging area with important practical implications. By promoting the canonical autophagy pathway or attenuating the suppression of autophagic targeting, autophagy can be effectively utilized in the development of novel therapeutic strategies against T gondii. Here, we have illustrated the complex interplay between host cell mediated autophagy and T. gondii. Different strategies to promote autophagy in order to target the parasite have been elucidated. Besides, we have analyzed some potential new drug molecules from the DrugBank database using bioinformatics tools, which can modulate autophagy. Various challenges and opportunities focusing autophagy mediated T. gondii clearance have been discussed, which will provide new insights for the development of novel drugs against the parasite.

IntroductionCutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, and photodynamic therapy (PDT) is a promising modality against cSCC. This study investigated the impact of PDT on the MAPK pathway and cell cycle alternation of cSCC as well as the related molecular mechanisms.MethodExpressing mRNA profile data sets GSE98767, GSE45216, and GSE84758 were acquired from the GEO database. The functions of differently expressed genes (DEGs) were enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Least absolute shrinkage and selection operator (Lasso) analysis were used to establish a diagnosis model based on GSE98767. A correlation analysis and a protein–protein interaction (PPI) network were used to evaluate the relationship between cSCC-PDT-related genes and the MAPK pathway. Single-sample gene set enrichment analysis (ssGSEA) was performed on GSE98767 to estimate MAPK activation and cell cycle activity. Finally, the effect of MAPK activation on the cell cycle was explored in vitro.ResultFour cSCC-PDT-related genes, DUSP6, EFNB2, DNAJB1, and CCNL1, were identified as diagnostic markers of cSCC, which were upregulated in cSCC or LC50 PDT-protocol treatment and negatively correlated with the MAPK promoter. Despite having a smaller MAPK activation score, cSCC showed higher cell cycle activity. The PDT treatment suppressed the G1 to G2/M phase in JNK overexpressed A431 cells.ConclusionCCNL1, DNAJB1, DUSP6, and EFNB2 were identified as potential PDT target genes in cSCC treatment, whose potential therapeutic mechanism was inhibiting the MAPK pathway and inducing cell cycle alternation.

BackgroundACO1 and IREB2 are two homologous cytosolic regulatory proteins, which sense iron levels and change iron metabolism–linked molecules. These two genes were noticeably decreased in kidney renal clear cell carcinoma (KIRC), which confer poor survival. Meanwhile, there is a paucity of information about the mechanisms and clinical significance of ACO1 and IREB2 downregulation in renal cancers.MethodsThe expression profiles of ACO1 and IREB2 were assessed using multiple public data sets via several bioinformatics platforms. Clinical and pathological information was utilized to stratify cohorts for comparison. Patient survival outcomes were evaluated using the Kaplan–Meier plotter, a meta-analysis tool. The correlations of ACO1 and IREB2 with ferroptosis were further evaluated in The Cancer Genome Atlas (TCGA)–KIRC database. Tumor immune infiltration was analyzed using the CIBERSORT, TIMER, and GEPIA data resources. ACO1 antagonist sodium oxalomalate (OMA) and IREB2 inhibitor sodium nitroprusside (SNP) was used to treat renal cancer ACHN cells together with sorafenib.ResultsKIRC patients with low ACO1 or IREB2 contents exhibited a remarkably worse survival rate in contrast with those with high expression in Kaplan–Meier survival analyses. Meanwhile, ACO1 and IREB2 regulate autophagy-linked ferroptosis along with immune cell invasion in the tumor microenvironment in KIRC patients. Blocking the activation of these two genes by their inhibitors OMA and SNP ameliorated sorafenib-triggered cell death, supporting that ACO1 and IREB2 could be participated in its cytotoxic influence on renal cancer cells.ConclusionACO1 and IREB2 downregulation in renal cancers were correlated with cancer aggressiveness, cellular iron homeostasis, cytotoxic immune cell infiltration, and patient survival outcomes. Our research is integral to verify the possible significance of ACO1 and IREB2 contents as a powerful signature for targeted treatment or novel immunotherapy in clinical settings.

To evaluate the accuracy of the smartwatch in estimating carotid-femoral pulse wave velocity (cfPWV). A cohort of gender-matched volunteers aged 18–80 years were recruited. At the sitting and supine positions, cfPWV was measured alternately by smartwatch and CompliorAnalyse, for each participant, and nine sets of data were collected from each participant with a 60 s interval between measurements. The accuracy of cfPWV measurement for smartwatches was assessed using mean error (ME) and mean absolute error (MAE), while the consistency of the two methods was assessed using the Bland-Altman analysis and concordance class correlation. A total of 347 participants were enrolled. The mean cfPWV was 9.01 ± 2.29 m/s measured by CompliorAnalyse and 9.06 ± 1.94 m/s by smartwatch. The consistency correlation coefficient (CCC) was 0.9045 (95% CI 0.8853–0.9206), the ME was 0.046 ± 0.92, and the MAE was 0.66 (95% CI 0.59–0.73). Bland-Altman analysis showed that the error of 95% samples was in the range between −1.77 m/s and 1.86 m/s. The Kappa value of cfPWV greater than 10 m/s was 0.79, the area under the ROC curve was 0.97 (P < 0.001), sensitivity was 0.90, specificity was 0.93, positive predictive value was 0.83 and negative predictive value was 0.96. Smartwatch can accurately estimate cfPWV to evaluate arterial stiffness. This method is simple and feasible and is suitable for people to actively and early monitor vascular elasticity.

BackgroundMetastatic disease remains the primary cause of death in patients with oral squamous cell carcinoma (OSCC), especially those who use betel nut. The different steps of the metastatic cascade rely on reciprocal interactions between cancer cells and the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are regarded as a significant component in the TME of OSCC. However, the precise mechanisms regulating CAFs in OSCC are poorly understood.MethodsThirteen genes related to the arecoline were analyzed to explore the significant ones involved in arecoline-related OSCC metastasis. The GSE139869 (n = 10) and The Cancer Genome Atlas (TCGA)-OSCC data (n = 361) were mined for the identification of the differentially expressed genes. The least absolute shrinkage and selection operator (LASSO) regression was performed to identify the independent prognostic signatures. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore the functional enrichment of selected genes, and gene set enrichment analysis of cuproptosis-related genes was completed. Spearman’s analysis and Tumor Immune Estimation Resource (TIMER) were used to visualize the correlation between the infiltration of CAFs and the gene expression. The correlation analysis of the cells and different genes, including CAF infiltration and transcripts per million expression, was assessed. The relationship between arecoline and CAFs was confirmed by cell counting kit-8 assay (CCK-8). CancerSEA was searched to identify the single-cell phenotype.ResultArecoline-associated fibrosis-related OSCC differentially expressed genes (AFOC-DEGs), namely, PLAU, IL1A, SPP1, CCL11, TERT, and COL1A2, were screened out and selected from the Gene Expression Omnibus (GEO) database and TCGA database. AFOC-DEGs were highly expressed in OSCC, which led to poor survival of patients. Functional enrichment analysis, protein–protein interaction network construction, and Spearman’s correlation analysis all suggested that AFOC-DEGs were closely associated with cuproptosis. Cellular experiments demonstrated that arecoline stimulation could significantly increase the cell viability of CAFs. Single-sample Gene Set Enrichment Analysis (ssGSEA) results showed that GLS and MTF1 were highly expressed when fibroblasts proliferated at high enrichment levels. In addition, analysis of single-cell sequencing results suggested that OSCC cells with high expression of AFOC-DEGs were associated with OSCC metastasis.ConclusionWe found a close association between arecoline, cuproptosis, and CAFs, which might play an important role in the metastasis of OSCC.

BackgroundThe coronavirus disease (COVID-19) pandemic has impacted HIV prevention strategies globally. However, changes in pre-exposure prophylaxis (PrEP) adherence and HIV-related behaviors, and their associations with medication adherence among men who have sex with men (MSM) PrEP users remain unclear since the onset of the COVID-19 pandemic.MethodsA Retrospective Cohort Study of HIV-negative MSM PrEP users was conducted in four Chinese metropolises from December 2018 to March 2020, assessing the changes in PrEP adherence and HIV-related behaviors before and during the COVID-19. The primary outcome was poor PrEP adherence determined from self-reported missing at least one PrEP dose in the previous month. We used multivariable logistic regression to determine factors correlated with poor adherence during COVID-19.ResultsWe enrolled 791 eligible participants (418 [52.8%] in daily PrEP and 373 [47.2%] in event-driven PrEP). Compared with the data conducted before the COVID-19, the proportion of PrEP users decreased from 97.9 to 64.3%, and the proportion of poor PrEP adherence increased from 23.6 to 50.1% during the COVID-19 [odds ratio (OR) 3.24, 95% confidence interval (CI) 2.62–4.02]. While the percentage of condomless anal intercourse (CAI) with regular partners (11.8 vs. 25.7%) and with casual partners (4.4 vs. 9.0%) both significantly increased. The proportion of those who were tested for HIV decreased from 50.1 to 25.9%. Factors correlated with poor PrEP adherence during the COVID-19 included not being tested for HIV (adjusted odds ratio [aOR] = 1.38 [95% CI: 1.00, 1.91]), using condoms consistently with regular partners (vs. never, aOR = 2.19 [95% CI: 1.16, 4.13]), and being married or cohabitating with a woman (vs. not married, aOR = 3.08 [95% CI: 1.60, 5.95]).ConclusionsIncreased poor PrEP adherence and CAI along with the decrease in HIV testing can lead to an increase in HIV acquisition and drug resistance to PrEP. Targeted interventions are needed to improve PrEP adherence and HIV prevention strategies.

Abstract In this study, we identified the multifaceted effects of atezolizumab, a specific monoclonal antibody against PD-L1, in tumor suppression except for restoring antitumor immunity, and investigated the promising ways to improve its efficacy. Atezolizumab could inhibit the proliferation and induce immune-independent apoptosis of osteosarcoma cells. With further exploration, we found that atezolizumab could impair mitochondria of osteosarcoma cells, resulting in increased release of reactive oxygen species and cytochrome-c, eventually leading to mitochondrial-related apoptosis via activating JNK pathway. Nevertheless, the excessive release of reactive oxygen species also activated the protective autophagy of osteosarcoma cells. Therefore, when we combined atezolizumab with autophagy inhibitors, the cytotoxic effect of atezolizumab on osteosarcoma cells was significantly enhanced in vitro. Further in vivo experiments also confirmed that atezolizumab combined with chloroquine achieved the most significant antitumor effect. Taken together, our study indicates that atezolizumab can induce mitochondrial-related apoptosis and protective autophagy independently of the immune system, and targeting autophagy is a promising combinatorial approach to amplify its cytotoxicity.

Abstract Background Rectal douching (RD) is widely practiced by men who have sex with men (MSM), and is associated with increased risk of HIV infection. However, the mechanism of how RD increases the risk of HIV infection is not well understood, and there is limited data on RD behavior in MSM practicing anal sex in China. We examine the purpose of RD, its timing in relation to anal sex, the types of RD products used, and risky sexual behaviors among MSM reporting anal sex. Methods Between August 2017 and December 2018, a cross-sectional study was conducted among adult MSM in Shenyang, China. Data were collected on demographics, sexual behaviors, and RD for the most recent sexual intercourse by means of interviewer-administered face-to-face questionnaires. Blood samples were collected to test for antibodies to HIV and syphilis. Multivariable logistic regression models were used to assess the risk factors associated with HIV infection. Results A total of 515 eligible MSM participated in this survey (median age: 31 years). During the most recent anal intercourse, 28.3% (146/515) had condomless receptive anal intercourse (CRAI), 21.4% (110/515) practiced serosorting, and more than half (61.6%, 317/515) reported RD before or after anal sex. Of those practicing RD, 96.8% (307/317) conducted RD before sex, while 62.5% (198/317) conducted RD after sex. The douching devices used were primarily shower hoses (85.3%, 262/307), and relatively few MSM used commercial RD products (8.1%, 25/307) before sex. The prevalence of HIV-1 and syphilis was 11.7% and 13.2%, respectively. HIV infection was positively associated with RD, practicing RD before sex, the interaction between RD and CRAI using a shower hose for RD and other risk factors, practicing RD after sex, CRAI, using nitrite inhalants, main sexual role with males as bottom and syphilis infection. Conclusions RD is popular among Chinese MSM. Improper noncommercial RD tools use (such as shower hose), the interaction effect between RD and CRAI associated with HIV infection. Public health workers and the MSM community should publicize scientific knowledge and prevention approaches relating to RD and HIV transmission to MSM. We recommend that further studies should be conducted to understand the detailed mechanism between RD and increased HIV prevalence.

Triple negative breast cancer (TNBC), which has poor prognosis, easily develops drug resistance and metastasizes. In general, those TNBC characteristics are related to a high activation of the epithelial-mesenchymal transition (EMT) pathway, which is inhibited by shikonin (SKN). Therefore, the synergistic therapy of SKN and doxorubicin (DOX) will increase anti-tumor efficacy and reduce metastasis. In this study, we prepared the folic acid-linked PEG nanomicelle (NM) grafted with the DOX (denoted as FPD) to load the SKN. We prepared the SKN@FPD NM according to the effective ratio of dual drugs, where the drug loadings of DOX and SKN were 8.86 ± 0.21% and 9.43 ± 0.13%, with 121.8 ± 1.1 nm of its hydrodynamic dimension and 6.33 ± 0.16 mV of zeta potential, respectively. The nanomaterials significantly slowed down the release of DOX and SKN over 48 h, leading to the release of pH-responsive drugs. Meanwhile, the prepared NM inhibited the activity of MBA-MD-231 cells in vitro. Further in vitro study revealed that the SKN@FPD NM increased the DOX uptake and significantly reduced the metastasis of MBA-MD-231 cells. Overall, these active-targeting NMs improved the tumor-targeting of small molecular drugs and effectively treated TNBC.

Defect engineering and heteroatom doping can significantly enhance the activity of zinc-aluminum layered double hydroxides (ZnAl-LDHs) in photocatalytic CO2 reduction to fuel. However, the in-depth understanding of the associated intrinsic mechanisms is limited. Herein, we systematically investigated Zn vacancies (VZn), oxygen vacancies (VO), and Cu doping on the geometry and electronic structure of ZnAl-LDH using density functional theory (DFT). We also revealed the related reaction mechanism. The results reveal the concerted roles of VO, VZn, and doped-Cu facilitate the formation of the unsaturated metal complexes (Znδ+-VO and Cuδ+-VO). They can localize the charge density distribution, function as new active centers, and form the intermediate band. Simultaneously, the intermediate band of functionalized ZnAl-LDHs narrows the band gap and lowers the band edge location. Therefore, it can broaden the absorption range of light and improve the selectivity of CO. Additionally, the unsaturated metal complex lowers the Gibbs free energy barrier for effective CO2 activation by bringing the d-band center level closer to the Fermi level. The work provided guidance for developing LDH photocatalysts with high activity and selectivity.

BackgroundThe decrease of bone mineral density (BMD) after the intake of Tenofovir disoproxil fumarate (TDF)-based drugs in people living with HIV/AIDS (PLWHA) and HIV-negative key populations under pre-exposure prophylaxis (PrEP) regimen raised concerns. Previous findings on the effects of vitamin D (VD) and calcium supplements and the recovery of BMD loss were inconclusive. The optimal doses of VD and calcium and its supplementary duration remained unknown. Therefore, we conducted a systematic review and meta-analysis to synthesize current evidence on VD and calcium supplements to inform clinical practice.MethodsWe searched PubMed, Web of Science, Cochrane library, and EMBASE databases for all placebo-controlled trials and prospective cohort studies published before March 5, 2021 that investigated VD and calcium supplements in participants taking TDF-based drugs. The keywords calcium, vitamin D, Tenofovir, and BMD were used for the searches. The primary outcome was changes of spine and hip BMD. A subgroup analysis was performed to determine the factors that were related to the effects of VD supplements on BMD. Locally weighted regression (loess) was used to determine the relationships of VD supplements, supplementary duration, and changes of BMD. This study was registered at PROSPERO (No. 42021231000).FindingsSeven eligible studies including 703 participants were included in the analyses. The meta-analysis found that VD and calcium supplementation was related to a significant increase of BMD in the spine and hip [standardized mean difference (SMD) 0.43; 95% CI, 0.25 to 0.61, p = 0.009]. Moreover, positive dose-response relationships were demonstrated between doses of VD and calcium supplements, supplementary duration, and BMD recovery. Patients who took VD with the dose level of 4,000 IU/D obtained the highest BMD improvement (SMD 0.59, 95% CI, 0.43 to 0.74). No side effects were reported on VD and calcium supplementation.InterpretationWe found the VD and calcium supplementation was associated with increases of BMD in participants taking TDF-based drugs. An optimal supplementary dose of 4,000 IU/D for VD was suggested for clinicians. The findings could be used in clinical practice to improve the BMD outcomes in people who were taking TDF-based drugs.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/.

Taurine-upregulated gene 1 (TUG1) is a long noncoding RNA (lncRNA) that has previously been linked to the development and progression of several cancer types. Its expression and mechanistic role in retinoblastoma (RB), however, remains to be established. Herein, we found that RB tissue samples exhibited TUG1 upregulation. RB cell lines similarly exhibited marked TUG1 upregulation. Real-time cellular analysis (RTCA) and colony formation assays were then used to gauge RB cell proliferation, while transwell assays were conducted to assess the metastatic and invasive potential of these cells. In these assays, TUG1 upregulation was found to promote RB cell proliferative, migratory, and invasive activity while inducing the epithelial–mesenchymal transition (EMT). Subsequent quantitative real-time polymerase chain reaction (qPCR) and Western blotting indicated that this lncRNA functions at least in part by influencing the expression of Notch signaling pathway genes, which were downregulated following TUG1 knockdown in RB cells. Together, these data suggested that TUG1 can promote RB cell malignancy via the Notch signaling and EMT pathways, contributing to negative patient outcomes.

ABSTRACT: Background: The radial forearm skin flap (RFSF) was first introduced by the Chinese scholar Guofan Yang and has since been used for nearly 40 years. The many advantages of RFSF have been investigated in this study. Case presentation: In this case, a female patient underwent RFSF surgery in 1979. In 2016 and 2018, two interviews were held to evaluate her subjective postoperative experience. In addition, overall donor site evaluation was conducted based on general health checkups and tests; tests for appearance, tactile sensitivity, muscle strength, and motor function; and CTA. Results: The flap survived well, and the donor site recovered without hand necrosis in the 1970s. In 2018, the patient was in good health condition and expressed her satisfaction with the surgery. The patient did not suffer from any postoperative complications such as diminished sensation of the donor site or donor site dysfunction; in the evaluation of hand and finger function, there was no point where functional reduction of the donor site was noted. CTA revealed compensatory blood supply with enlargement in the diameter of the ulnar and interosseous artery. Conclusion: After a nearly 40-year follow-up, the patient who underwent the first free radial forearm flap transplantation expressed satisfaction with the operative outcomes. The examination showed good results at the recipient site with little donor site deformities and good compensatory blood supply.