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ObjectivesTo develop a novel automatic delineation model, the Multi-Scale Channel Attention U-Net (MCAU-Net) model, for gallbladder segmentation on CT images of patients with liver cancer.MethodsWe retrospectively collected the CT images from 120 patients with liver cancer, based on which ground truth was manually delineated by physicians. The images and ground truth constitute a dataset, which was proportionally divided into a training set (54%), a validation set (6%), and a test set (40%). Data augmentation was performed on the training set. Our proposed MCAU-Net model was employed for gallbladder segmentation and its performance was evaluated using Dice Similarity Coefficient (DSC), Jaccard Similarity Coefficient (JSC), Positive Predictive Value (PPV), Sensitivity (SE), Hausdorff Distance (HD), Relative Volume Difference (RVD), and Volumetric Overlap Error (VOE) metrics.ResultsOn the test set, MCAU-Net achieved DSC, JSC, PPV, SE, HD, RVD, and VOE values of 0.85 ± 0.22, 0.79 ± 0.23, 0.92 ± 0.14, 0.84 ± 0.23, 2.75 ± 0.98, 0.18 ± 0.48, and 0.22 ± 0.42, respectively. Compared to the control models, U-Net, SEU-Net and TransUNet, the MCAU-Net improved DSC 0.06, 0.04 and 0.06, JSC by 0.09, 0.06 and 0.09, PPV by 0.08, 0.08 and 0.05, SE by 0.05,0.05 and 0.07, and reduced HD by 0.45, 0.28 and 0.41, RVD by 0.07, 0.03 and 0.07, VOE by 0.04, 0.02 and 0.08 respectively. Qualitative results revealed that MCAU-Net produced smoother and more accurate boundaries, closer to the expert delineation, with less over-segmentation and under-segmentation and improved robustness.ConclusionsThe MCAU-Net model significantly improves gallbladder segmentation on CT images. It satisfies clinical requirements and enhances the efficiency of physicians, particularly in segmenting complex anatomical structures.

Summary: Background: Type 1 diabetes (T1D) is an autoimmune disease characterised by the attack of pancreatic β cells by “self” immune cells. Although previous studies demonstrated that B cells contribute to T1D through antigen presentation and autoantibody production, the involvement of different populations of B cells, particularly in the early stages of T1D, has not been fully elucidated. Methods: In this study, we employed single-cell RNA sequencing (scRNA-seq) and flow cytometry to investigate immune cell populations in patients with newly diagnosed T1D, their relative controls and age-matched healthy controls. Phosphoprotein microarray analysis was employed to investigate changes in protein phosphorylation in B cells. Furthermore, we developed a siRNA-based nanomedicine and evaluated its therapeutic potential in the NOD mouse. The integration of scRNA-seq, flow cytometry, phosphoprotein microarrays, and functional assays established a robust framework for understanding and targeting B cell-mediated autoimmunity in T1D. Findings: Using single-cell RNA sequencing, we discovered that patients with T1D exhibited increased humoural immunity in the early stage of T1D. Specifically, the population of naïve B cells increased in patients with newly diagnosed T1D who expressed elevated levels of the AKT kinase coactivator TCL1A. Using a protein phosphorylation microarray, we confirmed that TCL1A knockdown specifically impaired AKT2 phosphorylation and affected B cell survival and proliferation. Notably, we discovered that the naïve B cell population increased and TCL1A expression was upregulated in NOD mice that developed T1D. Both the levels of naïve B cells and TCL1A were strongly associated with glucose intolerance in T1D mice. Importantly, treatment with a siRNA-based nanomedicine targeting Tcl1a mRNA effectively reduced the number of naïve B cells, prevented the loss of pancreatic β cells, and improved glucose intolerance in T1D mice. Interpretation: Using single-cell RNA-seq, we have not only uncovered a naïve B cell specific gene that may contribute to the pathogenesis of T1D but also highlighted the potential of siRNA-based nanomedicine for treating T1D. The clinical translation of these findings offers a new approach for the treatment of T1D. Funding: See Acknowledgements.

Background: Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver condition globally, with its severe form, cirrhosis, leading to liver failure, hepatocellular carcinoma (HCC), and mortality. The causal relationships among them remain unclear. Methods: This study employed a two-sample Mendelian randomization (MR) approach to systematically investigate the causal relationships among inflammatory proteins, non-alcoholic steatohepatitis (NASH), and HCC. We utilized NASH data and HCC data from the FinnGen biobank, and genomic data for 91 circulating inflammatory factors from GWAS database. Bidirectional MR analyses were conducted using the Inverse-Variance Weighted method as the primary analysis, supplemented by MR-Egger and weighted median methods for sensitivity analyses. Additionally, we performed heterogeneity, pleiotropy, and MR-PRESSO tests to assess the robustness of our findings. Results: Forward MR analysis identified five inflammatory factors significantly associated with NASH risk: CCL25 (OR = 0.8703, p = .0159), S100A12 (OR = 0.7582, p = .0204), IL18 (OR = 0.7412, p = .0026), and LIFR (OR = 0.6804, p < .001) showed negative correlations, while CXCL11 (OR = 1.2625, p = .0354) demonstrated a positive correlation. Reverse analysis revealed that NASH significantly influenced the levels of 10 circulating inflammatory factors, including Beta-nerve growth factor (OR = 1.0286, p = .0245), CCL20 (OR = 1.0382, p = .0012), CD5 (OR = 1.0268, p = .0466), CUBD1 (OR = 1.0371, p = .0078), CSF1 (OR = 1.0231, p = .0458), IL-12β (OR = 1.0261, p = .0381), IL-22Rα1 (OR = 0.9722, p = .0311), CCL3 (OR = 1.0372, p = .0013), OPG (OR = 1.0436, p = .0103), and uPA (OR = 1.0320, p = .0054). Further analysis revealed that IL-1α levels were positively associated with HCC risk (OR = 1.5335, p = .0377), while SULT1A1 levels showed a negative correlation (OR = 0.7190, p = .0200). Pleiotropy analyses showed no significant heterogeneity or horizontal pleiotropy for most identified associations, except for OPG (heterogeneity p = .001, MR-PRESSO p < .001) and CUBD1 (MR-PRESSO p < .05) in the reverse analysis of NASH, which warrant cautious interpretation. Conclusion: This study unveils complex bidirectional causal relationships among inflammatory factors, NASH, and HCC. Intervention targeting IL-1α in patients with liver cirrhosis will significantly impact the progression of HCC.

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with poor prognosis. Epigenetic dysregulation plays a crucial role in PDAC progression, but its comprehensive landscape and clinical implications remain unclear.MethodsWe integrated single-cell RNA sequencing, bulk RNA sequencing, and clinical data from multiple public databases. Single-cell analysis was performed using Seurat and hdWGCNA packages to reveal cell heterogeneity and epigenetic features. Weighted gene co-expression network analysis (WGCNA) identified key epigenetic modules. A machine learning-based prognostic model was constructed using multiple algorithms, including Lasso and Random Survival Forest. We further analyzed mutations, immune microenvironment, and drug sensitivity associated with the epigenetic risk score.ResultsSingle-cell analysis revealed distinct epigenetic patterns across different cell types in PDAC. WGCNA identified key modules associated with histone modifications and DNA methylation. Our machine learning model, based on 17 epigenetic genes, showed robust prognostic value (AUC >0.7 for 1-, 3-, and 5-year survival) and outperformed existing models. High-risk patients exhibited distinct mutation patterns, including higher frequencies of KRAS and TP53 mutations. Low-risk patients showed higher immune and stromal scores, with increased infiltration of CD8+ T cells and M2 macrophages. Drug sensitivity analysis revealed differential responses to various therapeutic agents between high- and low-risk groups, with low-risk patients showing higher sensitivity to EGFR and MEK inhibitors.ConclusionOur study provides a comprehensive landscape of epigenetic regulation in PDAC at single-cell resolution and establishes a robust epigenetics-based prognostic model. The integration of epigenetic features with mutation profiles, immune microenvironment, and drug sensitivity offers new insights into PDAC heterogeneity and potential therapeutic strategies. These findings pave the way for personalized medicine in PDAC management and highlight the importance of epigenetic regulation in cancer research.

In this study, six types of commercially available water were selected for preparing cold brew coffee to explore the influence of water quality factors on the main components and sensory flavor of the coffee. High-performance liquid chromatography (HPLC) and headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) were used for analysis of the coffee. Physical and chemical indices, volatile and non-volatile components, and sensory evaluation were analyzed and compared, and correlations and principal component analysis (PCA) were performed. It was found that the different types of water had significantly different compositions of major ions. The contents of total phenol, chlorogenic acid, and caffeic acid, as well as antioxidant activity in the cold brew coffee were not significantly affected by the water ions, but they were significantly affected by the extraction concentration, extraction rate, pH, and titratable acid, caffeine, trigonelline, and furan volatile chemical components. The Ca2+, Mg2+, and HCO3− ions in the water were positively correlated with the extraction concentration, extraction rate, and caffeine and trigonelline concentrations in the cold brew coffee (P

Abstract The cytoplasmic pattern recognition receptor, absent in melanoma 2 (AIM2), detects cytosolic DNA, activating the inflammasome and resulting in pro-inflammatory cytokine production and pyroptotic cell death. Recent research has illuminated AIM2’s contributions to PANoptosis and host defense. However, the role of AIM2 in acetaminophen (APAP)-induced hepatoxicity remains enigmatic. In this study, we unveil AIM2’s novel function as a negative regulator in the pathogenesis of APAP-induced liver damage in aged mice, independently of inflammasome activation. AIM2-deficient aged mice exhibited heightened lipid accumulation and hepatic triglycerides in comparison to their wild-type counterparts. Strikingly, AIM2 knockout mice subjected to APAP overdose demonstrated intensified liver injury, compromised mitochondrial stability, exacerbated glutathione depletion, diminished autophagy, and elevated levels of phosphorylated c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). Furthermore, our investigation revealed AIM2’s mitochondrial localization; its overexpression in mouse hepatocytes amplified autophagy while dampening JNK phosphorylation. Notably, induction of autophagy through rapamycin administration mitigated serum alanine aminotransferase levels and reduced the necrotic liver area in AIM2-deficient aged mice following APAP overdose. Mechanistically, AIM2 deficiency exacerbated APAP-induced acute liver damage and inflammation in aged mice by intensifying oxidative stress and augmenting the phosphorylation of JNK and ERK. Given its regulatory role in autophagy and lipid peroxidation, AIM2 emerges as a promising therapeutic target for age-related acute liver damage treatment.

Ultrafast single-shot measurement techniques with high throughput are needed for capturing rare events that occur over short time scales. Such instruments unveil non-repetitive dynamics in complex systems and enable new types of spectrometers, cameras, light scattering, and lidar systems. Photonic time stretch stands out as the most effective method for such applications. However, practical uses have been challenged by the reliance of current time stretch instruments on costly supercontinuum lasers and their fixed spectrum. The challenge is further exacerbated by such a laser’s rigid self-pulsating characteristic, which offers no ability to control the pulse timing. The latter hinders the synchronization of the optical source with the incoming signal—a crucial requirement for the detection of single-shot events. Here, we report the first demonstration of time stretch using electro-optically modulated continuous wave lasers. We do this using diode lasers and modulators commonly used in wavelength-division-multiplexing optical communication systems. This approach offers more cost-effective and compact time stretch instruments and sensors and enables the synchronization of the laser source with the incoming signal. Limitations of this new approach are also discussed, and applications in time stretch microscopy and light scattering are explored.

Summary: Diabetic kidney disease (DKD), the most common cause of kidney failure, is a frequent complication of diabetes and obesity, and yet to date, treatments to halt its progression are lacking. We analyze kidney single-cell transcriptomic profiles from DKD patients and two DKD mouse models at multiple time points along disease progression—high-fat diet (HFD)-fed mice aged to 90–100 weeks and BTBR ob/ob mice (a genetic model)—and report an expanding population of macrophages with high expression of triggering receptor expressed on myeloid cells 2 (TREM2) in HFD-fed mice. TREM2high macrophages are enriched in obese and diabetic patients, in contrast to hypertensive patients or healthy controls in an independent validation cohort. Trem2 knockout mice on an HFD have worsening kidney filter damage and increased tubular epithelial cell injury, all signs of worsening DKD. Together, our studies suggest that strategies to enhance kidney TREM2high macrophages may provide therapeutic benefits for DKD.

In this study, the volatile components in 40 samples of Tartary buckwheat and common buckwheat from 6 major producing areas in China were analyzed. A total of 77 volatile substances were identified, among which aldehydes and hydrocarbons were the main volatile components. Odor activity value analysis revealed 26 aromatic compounds, with aldehydes making a significant contribution to the aroma of buckwheat. Seven key compounds that could be used to distinguish Tartary buckwheat from common buckwheat were identified. The orthogonal partial least squares-discriminant analysis was effectively used to classify Tartary buckwheat and common buckwheat from different producing areas. This study provides valuable information for evaluating buckwheat quality, breeding high-quality varieties, and enhancing rational resource development.

The interaction between Human Leukocyte Antigens (HLA) and peptides is key in cellular immunology and crucial for the development of the immune system and peptide-based drug design. Currently, in the field of machine learning for predicting peptide-HLA (pHLA) binding, the mainstream methods involve neural network-based models that enhance prediction accuracy and efficiency by simulating the interactions between HLA and peptides. Among the peptides binding to class I HLA, most sequences are 9 amino acids in length, therefore, these models mainly consider the binding prediction of peptides with a fixed length of 9. Additionally, most neural network models rely on pseudo-sequence encoding techniques, which are designed based on 34 key positions in the peptide-HLA binding structure. Although this method provides important contextual clues for the model, it may not fully capture the complex interactions between HLA and peptides, thereby affecting prediction accuracy. To address this issue, we introduce a novel pan-specific prediction model, TlcMHCpan, which is capable of handling peptide sequences of varying lengths. It leverages deep learning techniques including Transformer, LSTM, and CNN, and incorporates a self-attention mechanism to enhance feature extraction capabilities. We have conducted a comprehensive evaluation of TlcMHCpan on the latest benchmark dataset provided by the Immune Epitope Database (IEDB). The experimental results show that, out of 38 benchmark datasets, TlcMHCpan achieved the highest AUC score in 11 datasets, with 6 of them being the exclusive top performer.

Background: Autoimmune diseases are a group of diseases caused by abnormal immune responses to functional body parts. Single-cell RNA-sequencing (scRNA-seq) technology provides transcriptomic information at the single-cell resolution, thus offering a new way to study autoimmune diseases. Most single-cell RNA-seq studies, however, have often focused on one type of autoimmune disease. Methods: We integrated scRNA-seq data from peripheral blood cells of five different autoimmune diseases (IgA nephropathy [IgAN], Kawasaki disease [KD], multiple sclerosis [MS], Sjogren’s syndrome [SS], and systemic lupus erythematosus [SLE]). We performed dimensionality clustering, cellular communication analysis, re-clustering analysis of monocytes, NK cell populations, differential gene expression analysis, and functional enrichment for all immune cells in these data. Results: We integrated the scRNA-seq results of peripheral blood cells from five different autoimmune diseases (IgAN, KD, MS, SS, and SLE). We showed that all samples contained 18 different immune cell subsets, although the cell cluster populations were different among the 5 diseases. Through intercellular communication network analysis, we determined that the signals of classical and non-classical monocytes were significantly enhanced in patients with IgAN and SLE. The signals of naïve B cells were increased in patients KD. Interestingly, the signals of NK and NK-T cells were enhanced in patients with SS, but reduced in patients with IgAN and SLE. Transcriptomic analysis of classical and non-classical monocyte subsets further revealed that pro-inflammatory cytokines and interferon-related genes, including CCL3, IL1B, ISG15, and IFI6, were specifically increased in patients with IgAN and SLE. Unlike monocytes, the number and NK marker genes were decreased in patients with IgAN and KD, but increased in patients with SS. Meanwhile, two NK-T cell subsets were exclusively found in SS. Conclusions: In summary, based on an integration of the single-cell RNA-seq results, we demonstrated changes in the immune cell landscape of five different autoimmune diseases with respect to immune cell subsets, populations, differentially-expressed genes, and the cell-to-cell communication network. Our data provide new insight to further explore the heterogeneity and similarity among different autoimmune diseases.

Background: Transposable elements (TEs) and noncoding sequences are major components of the genome, yet their functional contributions to long noncoding RNAs (lncRNAs) are not well understood. Although many lncRNAs originating from TEs (TE-lncRNAs) have been identified across various organisms, their characteristics and regulatory roles, particularly in insects, remain largely unexplored. This study integrated multi-omics data to investigate TE-lncRNAs in D. melanogaster, focusing on the influence of transposons across different omics levels. Results: We identified 16,118 transposons overlapping with lncRNA sequences that constitute 2119 TE-lncRNAs (40.4% of all lncRNAs) using 256 public RNA-seq samples and 15 lncRNA-seq samples of Drosophila S2 cells treated with heavy metals. Of these, 67.2% of TE-lncRNAs contain more than one TE. The LTR/Gypsy family was the most common transposon insertion. Transposons preferred to insert into promoters, transcription starting sites, and intronic regions, especially in chromosome ends. Compared with lncRNAs, TE-lncRNAs showed longer lengths, a lower conservation, and lower levels but a higher specificity of expression. Multi-omics data analysis revealed positive correlations between transposon insertions and chromatin openness at the pre-transcriptional level. Notably, a total of 516 TE-lncRNAs provided transcriptional factor binding sites through transposon insertions. The regulatory network of a key transcription factor was rewired by transposons, potentially recruiting other transcription factors to exert regulatory functions under heavy metal stress. Additionally, 99 TE-lncRNAs were associated with m6A methylation modification sites, and 115 TE-lncRNAs potentially provided candidate small open reading frames through transposon insertions. Conclusions: Our data analysis demonstrated that TEs contribute to the regulation of lncRNAs. TEs not only promote the transcriptional regulation of lncRNAs, but also facilitate their post-transcriptional and epigenetic regulation.

The impact of the roasting degree on ultra-high-pressure cold brew (UHP) coffee remains unclear, although it has been found that UHP technology accelerates the extraction of cold brew (CB) coffee. Therefore, this study investigated the effects of three different degrees of roasting (light, medium, and dark) on the physicochemical characteristics, volatile and non-volatile components, and sensory evaluation of UHP coffee. Orthogonal partial least-squares-discriminant analysis (OPLS-DA) and principal component analysis (PCA) were used to assess the effects of different roasting degrees. The results showed that most physicochemical characteristics, including total dissolved solids (TDSs), extraction yield (EY), total titratable acidity (TTA), total sugars (TSs), and total phenolic content (TPC), of UHP coffee were similar to those of conventional CB coffee regardless of the degree of roasting. However, the majority of physicochemical characteristics, non-volatile components, including the antioxidant capacity (measured based on DPPH and ABTS) and melanoidin, caffeine, trigonelline, and CGA contents increased significantly with an increase in roasting degree. The sensory evaluation revealed that as the roasting degree rose, the nutty flavor, astringency, bitterness, body, and aftertaste intensities increased, while floral, fruity, and sourness attributes decreased. The HS-SPME-GC/MS analysis showed that most volatile components increased from light to dark roasting. Moreover, 15 representative differential compounds, including hazelnut pyrazine, linalool, butane-2,3-dione, and 3-methylbutanal, were identified by calculating the odor-active values (OAVs), indicating that these contributed significantly to the odor. The PCA showed that the distance between the three roasting degree samples in UHP coffee was smaller than that in CB coffee. Overall, the effect of roasting degrees on UHP coffee was less than that on CB coffee, which was consistent with the results of physicochemical characteristics, volatile components, and sensory evaluation.

In order to predict the hot workability of the material more accurately, this paper takes the hot deformation of IN617B as the example. The activation energy (Q) map, Zener-Hollomon parameter (Z) map, and hot processing map were established based on the hot compression tests conducted at 950–1200 °C and 0.01–5 s−1. It was found that the area with high power dissipation values (denoted by η) in the hot processing map did not match the complete dynamic recrystallization (DRX) region completely. However, the microstructure corresponding to the high η area and low Z and Q area exhibited higher DRX. Therefore, the optimal hot processing region for this alloy was determined to be 1200 °C/0.1 s−1/0.8. Under this parameter, the DRX mechanism of IN617B alloy was dominated by discontinuous dynamic recrystallization (DDRX), supplemented by small amounts of continuous dynamic recrystallization (CDRX) and twinning dynamic recrystallization (TDRX).

[Introduction] Monopile foundation is currently the most widely used support structure for offshore wind farms. For offshore wind farms in the medium water depth area such as Dafeng, Binhai and Sheyang in China, the design waves are very close to the wave breaking limit. Compared with the traveling wave, the focused waves can form an impact force on the pile column in a short time, which is larger than the conventional wave force, and undermines the operational performance and fatigue life of the offshore wind turbines. [Method] In this paper, NREL 5 MW monopile wind turbine model tests were carried out to investigate the hydrodynamic response of large offshore wind turbines to highly nonlinear waves and other harsh waves in combination with the marine environmental conditions of China's eastern coastal wind farms, focusing on exploring the test techniques for monopile wind turbines, and the mechanism of interaction between focused waves and monopiles under the action of focused waves. [Result] The results show that, the horizontal wave force on the pile foundation, which is significantly transient, will suddenly increase when the focused waves act on the monopile foundation, and receive the reverse impact force at the trough of focused wave fluctuation. [Conclusion] The results are of high theoretical value and have engineering prospect for the safe operation of monopile foundation.

The gut is home to a large number of intestinal microbiota that play an important role in the metabolism and immune system of the host. A growing body of evidence suggests that a high-fat diet is closely associated with many metabolic disorders, including fatty liver and type 2 diabetes. According to reports, Tartary buckwheat extract has a positive effect on intestinal microbiota in animals. The effects of Tartary buckwheat on biochemical indexes and intestinal microflora in mice were studied. Tartary buckwheat protein (FGP), Tartary buckwheat resistant starch (FGS) and Tartary buckwheat flour (FGF) alleviated organ damage in mice and lowered the atherosclerotic index (AI) in plasma. Otherwise, principal coordinate analysis (PCoA) showed that intestinal bacterial structure of FGF were separated apparently from other groups. The Firmicutes/Bacteroidetes (F/B) value of the high-fat (HF)-FGF group was significantly lower than that of the HF-FGP and HF-FGS groups. FGF significantly increases the abundance of beneficial bacteria such as Bifidobacterium, while decreasing the abundance of lipopolysaccharide (LPS)-producing bacteria. Observation of blood lipid metabolism parameters and analysis of the intestinal microbiota suggested that FGF can be more effective than FGP and FGS to reduce the effects of a high-fat diet in mice, restoring the blood parameters to values similar of those in mice fed a low-fat diet. FGF may be used to prevent or treat blood lipid metabolism disorders and intestinal microbiota disorders in mice fed a high-fat diet.

Hemerocallis L. possesses abundant germplasm resources and holds significant value in terms of ornamental, edible, and medicinal aspects. However, the quality characteristics vary significantly depending on different varieties. Selection of a high-quality variety with a characteristic aroma can increase the economic value of Hemerocallis flowers. The analytic hierarchy process (AHP) is an effective decision-making method for comparing and evaluating multiple characteristic dimensions. By applying AHP, the aromatic character of 60 varieties of Hemerocallis flowers were analyzed and evaluated in the present study. Headspace solid-phase microextraction gas chromatography–mass spectrometry (HS-SPME-GC-MS) was employed to identify volatile components in Hemerocallis flowers. Thirteen volatile components were found to contribute to the aroma of Hemerocallis flowers, which helps in assessing their potential applications in essential oil, aromatherapy, and medical treatment. These components include 2-phenylethanol, geraniol, linalool, nonanal, decanal, (E)-β-ocimene, α-farnesene, indole, nerolidol, 3-furanmethanol, 3-carene, benzaldehyde and benzenemethanol. The varieties with better aromatic potential can be selected from a large amount of data using an AHP model. This study provides a comprehensive understanding of the characteristics of the aroma components in Hemerocallis flowers, offers guidance for breeding, and enhances the economic value of Hemerocallis flowers.

The high manufacturing cost of sulfoaluminate cement (SAC) has limited its application for a long time. The addition of solid waste in raw material can solve this problem and provide an effective method for green manufacturing of cement. In this study, ferrite-rich SAC (FSAC) clinker was calcined using red mud (RM) in combination with limestone, bauxite and anhydrite. The effects of anhydrite and desulfurization gypsum (DSG) on the hydration and mechanical properties of cement were evaluated. Results show that RM-based FSAC can be calcined at 1300 °C, and the hydration process is closely related to the varieties and quantities of the calcium sulfate set regulator. Anhydrite promotes the early compressive strength of cement minimally, but it can increase the strength to 94.61 MPa in 3 days. DSG can increase the strength to 30 MPa in 4 h, but the strength shrinkage occurs in the later stage. The reaction between different gypsum with water is the most significant effect on the hydration properties of cement. The cement prepared by anhydrite (12 wt%), DSG (3 wt%) and clinker (85 wt%) has the characteristics of fast mechanical strength development in the early hydration and continuous development after 1 day, which proves that the preparation of ferrite-rich sulfoaluminate cement using red mud and DSG is feasible.

[Introduction] Most of the completed offshore wind farms in the world are located in shallow water (water depth < 30 m), mainly based on fixed foundations such as monopiles. With the increasingly mature wind power technology, offshore wind power gradually shifts towards the trend of large unit, and the foundation diameter of single-pile offshore wind turbines will also increase as the wind turbine become larger. The environmental loads and soil conditions are becoming more and more stringent. The study on pile-soil interaction of large-diameter monopile offshore wind turbines has become one of the key technical issues of offshore wind power technology. [Method] The impact of different pile-soil models on the dynamic response of large monopile offshore wind turbines in shallow water areas with 10 MW large offshore wind turbines was studied. [Result] The results show that the macro element method considers the nonlinear stiffness and plasticity, thus the sum of power spectral density near the characteristic frequency of the macro element method is large, which demonstrates the great advantages of the macro element method over other traditional pile-soil models. [Conclusion] The study of this paper has far-reaching theoretical value and engineering application prospects for the overall safe operation of wind turbine.

Abstract Background The synthesis and secretion of renin in juxtaglomerular (JG) cells are closely regulated by the blood pressure. To date, however, the molecular identity through which JG cells respond to the blood pressure remains unclear. Results Here we discovered that Piezo1, a mechanosensitive ion channel, was colocalized with renin in mouse kidney as well as As4.1 cells, a commonly used JG cell line. Activation of Piezo1 by its agonist Yoda1 induced an intracellular calcium increase and downregulated the expression of renin in these cells, while knockout of Piezo1 in JG cells abolished the effect of Yoda1. Meanwhile, mechanical stress using microfluidics also induced an intracellular calcium increase in wildtype but not Piezo1 knockout JG cells. Mechanistically, we demonstrated that activation of Piezo1 upregulated the Ptgs2 expression via the calcineurin-NFAT pathway and increased the production of Ptgs2 downstream molecule PGE2 in JG cells. Surprisingly, we discovered that increased PGE2 could decreased the renin expression through the PGE2 receptor EP1 and EP3, which inhibited the cAMP production in JG cells. In mice, we found that activation of Piezo1 significantly downregulated the renin expression and blood pressure in wildtype but not adeno-associated virus (AAV)-mediated kidney specific Piezo1 knockdown mice. Conclusions In summary, these results revealed that activation of Piezo1 could downregulate the renin expression in JG cells and mice, subsequently a reduction of blood pressure, highlighting its therapeutic potential as a drug target of the renin-angiotensin system.

In this study, tartary buckwheat combined with compound strains was fermented to make sourdough and applied to improve frozen dough. The results showed that the compound bacteria had a certain synergistic effect, and the bacterial colony growth in tartary buckwheat substrate was better than single bacteria, especially in LF+WC group, the lactic acid bacteria growth rate was the fastest, and a large amount of fructose (11.82 mmol/kg) and EPS (3.132 g/kg) were generated after 12 h fermentation. In addition, the binding water content of tartary buckwheat sourdough in LF+WC group decreased by 0.48%, content of non-flowing water and free water increased by 0.18% and 0.3%, respectively, the glutenin subunit degradation was less, α-helix and β-rotation content decreased by 0.43% and 2.34%, respectively, after 13 weeks of freezing. So that gluten can maintain a more uniform and regular network structure. Therefore, LF+WC tartary buckwheat sourdough has good antifreezing protection effect.

Tartary buckwheat contains more valuable nutrients than common buckwheat, but it also contains allergenic proteins that induce allergic reactions through an IgE-mediated response. Our study demonstrated that fermentation by Pediococcus pentosaceus degrades allergenic proteins in Tartary buckwheat, as confirmed by HPLC-MS/MS analysis of polypeptides. Our results showed significant degradation of the protein after 16 h of Pediococcus pentosaceus fermentation (PP16), leading to a reduction in IgE-binding activity. Comparison with unfermented Tartary buckwheat (UTB) peptides yielded 2042 fragments, of which 756 fragments associated with allergenic proteins were upregulated. Among them, the expression of 213 fragments was reduced by 71.83%. By performing bioactivity prediction on potential allergenic peptide fragments, we identified six peptide fragments derived from Fagt 1, potentially contributing to the residual allergenicity in PP16. These suggest that Pediococcus pentosaceus fermentation can effectively destroy allergen epitopes and mitigate the allergenicity of Tartary buckwheat.

Lithium metal batteries (LMBs) with ultra-high theoretical energy densities are regarded as excellent candidates for the next energy storage devices. Unfortunately, there are many factors can cause the temperature of LMBs to exceed a safe range and trigger thermal runaway. Countless effort has been invested in designing safe components of batteries to realize the application of LMBs. However, most studies only focus on one single aspect since there is no uniform metrics for evaluating the safety of LMBs. Herein, this review comprehensively summarizes all the trigger factors of thermal runaway and proposes the complete safety metrics of LMBs. A comprehensive overview of the development of safe LMBs is provided to discuss the gap between studies and practical applications. Finally, the future directions of academic research are proposed according to the challenges existing in current studies.

The frequency and severity of drought events are increasing under a changing climate, trees of different stand ages respond differently to drought events, which has a great impact on the stability of forest ecosystems. In this study, we measured radial growth (RG) in cored trees from 49 forests including young stands (20–30a) and middle-aged stands (31–50a) of Pinus sylvestris var. mongolica plantations in a semi-arid area of western Liaoning, China. We evaluated the response of RG of P. sylvestris to long-term climate, and calculate three response indicators: resistance (Rt), recovery (Rc) and resilience (Rs), so as to measure the growth response of trees to drought events. Results showed that a negative correlation was detected between RG of young stands and the monthly highest temperature (MHT) in April and May. Positive correlations were found between RG of young stands and the monthly lowest temperature (MLT) across periods from September to November, when RG of young stands was also positively correlated with Palmer Drought Severity Index (PDSI) across whole-years. There was a positive correlation between RG of middle-aged stands and MLT in September, and PDSI from June to December. After the first drought event, most pine trees recovered their RG (Rc > 1, Rs > 1). However, after three consecutive drought events, Rt, Rc, and Rs of pine trees decreased significantly (p

Winter wheat is one of the major cereal crops globally and one of the top three cereal crops in China. The precise forecasting of the yield of winter wheat holds significant importance in the realms of agricultural management and ensuring food security. The use of multi-temporal remote sensing data for crop yield prediction has gained increasing attention. Previous research primarily focused on utilizing remote sensing data from individual or a few growth stages as input parameters or integrated data across the entire growth period. However, a detailed analysis of the impact of different temporal combinations on the accuracy of yield prediction has not been extensively reported. In this study, we optimized the temporal sequence of growth stages using interpolation methods, constructed a yield prediction model incorporating the enhanced vegetation index (EVI) at different growth stages as input parameters, and employed a random forest (RF) algorithm. The results indicated that the RF model utilizing the EVI from all the temporal combinations throughout the growth period as input parameters accurately predicted the winter wheat yield with an R2 of the calibrated dataset exceeding 0.58 and an RMSE less than 1284 kg/ha. Among the 1023 yield models tested in this study with ten different growth stage combinations, the most accurate temporal combination comprised five stages corresponding to the regreening, erecting, jointing, heading, and filling stages, with an R2 of 0.81 and an RMSE of 1250 kg/ha and an NRMSE of 15%. We also observed a significant decrease in estimation accuracy when the number of growth stages was fewer than five and a certain degree of decline when the number exceeded five. Our findings confirmed the optimal number and combination of growth stages for the best yield prediction, providing substantial insights for winter wheat yield forecasting.

Besides improving the generator torque and blade pitch controller, incorporating additional control actuations, such as a vibration absorber and active ballast, into the floating offshore wind turbine (FOWT) system is also promising for the motion mitigation of FOWTs. This work aims to study the catenary mooring length re-configuration effect on the dynamic behaviours of semi-submersible FOWTs. The mooring length re-configuration mentioned here is achieved by altering the mooring length with winches mounted on the floating platform, which is in a period of minutes to hours, so that the mooring tensions could be adjusted to reduce the aerodynamic load induced platform mean pitch. Control designs for both single mooring line and multiple mooring lines have been described and studied comparatively. In order to assess the motion mitigation performance of the proposed mooring line length re-configuration methods, fully coupled numerical simulations under different environmental cases have been conducted. Results indicate that the catenary mooring length re-configuration is able to reduce the platform pitch motion by up to 15.8% under rated condition, while careful attention must be paid to the scenarios where the catenary moorings become taut, which may lead to large load variations.

Upon careful examination, numerous wind turbine collapses can be attributed to the failure of the tower bolts. Nowadays, the Schmidt–Neuper algorithm is extensively accepted in wind turbine tower bolt design. It is not advisable to utilize the finite-element method, notwithstanding the effect of the flange gap. To quantitatively investigate the influence of flange gaps on bolt fatigue, a nonlinear finite-element model of a flange segment incorporating bolt pretension and contact elements is herein proposed. Three distinct types of flange gaps are defined intentionally. It is possible to determine the nonlinear relationship between the wall load and bolt internal force. The fatigue damage of bolts was thus computed using the obtained nonlinear curve. Comparing with the results with those of Schmidt–Neuper method revealed the bolt fatigue damage is susceptible to a specified flange gap.

Abstract Background Surgery is an important adjuvant treatment for tuberculous empyema(TE). We thus conducted a single arm-clinical retrospective study of stage II-III TE patients who underwent uniportal video-assisted thoracic surgery (Uni-VATS) over a 5-year period to evaluate the efficacy and safety of surgery on TE, so as to provide the evidence for the optimal clinical strategies. Methods Patients diagnosed as TE with withdrawal of anti-tuberculosis-VATS were retrospectively enrolled from January 2016 to December 2021. All patients were followed up untill 12 months after withdrawal of anti-tuberculosis treatment (ATT). Clinical characteristics and surgical details were observed and analyzed to evaluate the efficacy and safety of the minimally invasive surgery. Results Totally 439 cases met included criteria were enrolled, no deaths were reported. The mean operative time was 2.6 (1.9, 4.3) hours and the mean intraoperative blood loss was 356 (240, 940) ml. Blood transfusion was performed in 20.50% (90/439) of patients and additional pneumonectomy was occurred in 9.89%(37/439)of patients .The mean postoperative drainage time was 12 (7, 49) days and the mean hospital stay was 6 (4,12) days. All stage II TE achieved complete lung re-expansion after surgery while 84.22%(315/374) of stage III achieved complete lung re-expansion, p 0.00. 15.78% (59/374) of stage III TE achieved incomplete re-expansion, 4 of which underwent a second decortication by Uni-VATS. Recurrences rate was 2.96% (13/439), including 11 cases of early recurrence and 2 cases of late recurrence at TE stage III, 5 of which underwent a second decortication by Uni-VATS. Conclusion Uni-VATS is highly effective safe and minimally invasive for patients with TE, which could be recommended as the mainstream operation in areas with high TB burden.

Excessive reactive oxygen species (ROS) can cause oxidative damage and lead to various metabolic disease. Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) is a new kind of protein-rich functional food, the protein in which has been proved to have good antioxidant capacity. In this study, in order to further explore the antioxidant mechanism of Tartary buckwheat protein, 4 peptides (CR-8, LR-8, GK-10 and SR-12) were isolated and identified from it. H2O2 was used to induce oxidative damage to Caco-2 cells to evaluate antioxidant capacity of these peptides. The results of superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and mitochondrial membrane potential etc. showed that these peptides have superior antioxidant capacity. CR-8 has the best antioxidant capacity. In order to further clarify the antioxidant mechanism of CR-8, metabolomics was used to analyze related metabolites and metabolic pathways. The results showed that after CR-8 intervention, the content of metabolites such as L-acetyl carnitine has increased. This indicated that CR-8 can improve the antioxidant capacity of damaged cells by intervening in multiple metabolic pathways. This also revealed the anti-oxidant mechanism of tartary buckwheat protein. In conclusion, it provided a theoretical basis for further studying the activity of tartary buckwheat portein and utilizing buckwheat resources.

Origami design has been a popular research field for decades, generating inspiration for various structural applications. The shift from paper to more practical materials such as plate-like metals is materialized by surrogate folds such as compliant hinges. Therefore, it is critical to explore the kinematic and dynamic characteristics of these joints. In this paper, a comparative numerical study of the folding/unfolding performance of three notch-type compliant joints, namely groove, elliptical holes, and rectangular holes is presented. Indicators including stress contour, load-deformation, moment-angle, and stiffness-angle are selected to evaluate the performance of joints with different geometric parameters, especially the hysteretic behaviors of the joints. The results illustrate that the geometric parameters of the plate and joint are well correlated with these performance indicators. The transition behaviors of the folding/unfolding stiffness of all joints are associated with a certain regime of rotational angles. Besides, the performances of all studied joints are benchmarked against the much-popularized outside LET joint, from which their deformation modes are recognized. Finally, considering various performance aspects, the groove joint is recognized as the most suitable for the folding of a planar plate.

Multi-label classification has been extensively researched and utilized for several decades. However, the performance of these methods is highly susceptible to the presence of noisy data samples, resulting in a significant decrease in accuracy when noise levels are high. To address this issue, we propose a robust ranking support vector machine (Rank-SVM) method that incorporates manifold regularized matrix factorization. Unlike traditional Rank-SVM methods, our approach integrates feature selection and multi-label learning into a unified framework. Within this framework, we employ matrix factorization to learn a low-rank robust subspace within the input space, thereby enhancing the robustness of data representation in high-noise conditions. Additionally, we incorporate manifold structure regularization into the framework to preserve manifold relationships among low-rank samples, which further improves the robustness of the low-rank representation. Leveraging on this robust low-rank representation, we extract a resilient low-rank features and employ them to construct a more effective classifier. Finally, the proposed framework is extended to derive a kernelized ranking approach, for the creation of nonlinear multi-label classifiers. To effectively solve this non-convex kernelized method, we employ the augmented Lagrangian multiplier (ALM) and alternating direction method of multipliers (ADMM) techniques to obtain the optimal solution. Experimental evaluations conducted on various datasets demonstrate that our framework achieves superior classification results and significantly enhances performance in high-noise scenarios.

Background: To investigate the underlying molecular mechanisms of radiofrequency hyperthermia (RFH)-enhanced direct chemotherapy of pancreatic cancers. Method: Rat ductal PaCa cell line DSL-6A/C1 and orthotopic pancreatic cancers of Lewis rats were divided into four study groups with various treatments: i) phosphate-buffered saline (PBS) as a control; ii) RFH alone; iii) intratumoral chemotherapy alone (gemcitabine); and (iv) combination therapy of gemcitabine plus intratumoral RFH at 42 ​°C for 30 ​min. In the in-vitro confirmation experiments, the viability and apoptosis of DSL-6A/C1 cells in each treatment group were evaluated using cell live/dead staining, flow cytometry, and Western blot. In the in vivo validation experiments, related proteins were evaluated by immunohistochemistry (IHC) staining of tumors. Results: Of the in-vitro experiments, the lowest cell viability and more apoptotic cells were shown in the group with combination therapy compared to other treatments. Western blot data showed elevated Bax/Bcl-2, Caspase-3, and HSP70 expressions in DSL cells with combination therapy, compared to other treatments. Of the in vivo experiments, IHC staining detected the significantly increased expressions of HSP70, IL-1β, TNF-ɑ, Bax, and Caspase-3 in pancreatic cancer tissues of the animal group treated by combination therapy of gemcitabine with RFH. Conclusion: Molecular imaging-guided interventional RFH can significantly enhance the chemotherapeutic effect on pancreatic cancers via potential molecular mechanisms of up-regulating Bax/caspase-3-dependent apoptosis pathways.

Abstract Background Refractory pneumothorax combined with diffuse emphysematous changes is an intractable problem requiring surgical treatment. Traditional bullectomy may result in long-term air leakage and has a risk of early recurrence. Pleurectomy is an effective pleurodesis procedure, which appears to be more suitable for these cases. We conducted this study to present our experience with this procedure. Methods We collected the clinical data of 14 patients who underwent subtotal pleurectomy via video-assisted thoracic surgery (VATS) in our institution from November 2016 to October 2021. All patients had undergone complete preoperative examinations and met the indications for pleurectomy. Regular follow-up was conducted after surgery. Results The study population was composed of 11 males and 3 females, with an average age of 52.4 ± 19.0 years. Subtotal pleurectomy via VATS was successfully performed in all patients, with no conversion to open surgery. The average operation time was 82.5 ± 23.4 min (range 45–120 min), intraoperative blood loss was 92.9 ± 37.1 mL (range 50–200 mL), postoperative hospital stay was 5.0 ± 4.8 days (range 2–19 days), and chest tube duration time was 22.1 ± 13.0 days (range 5–49 days). No major complication occurred except for one case in which reoperation was performed due to massive postoperative hemorrhage. The mean follow-up time was 24.8 ± 17.0 months (range 6–60 months); no recurrence was noted. Conclusions Subtotal pleurectomy via VATS is a satisfactorily effective procedure for preventing pneumothorax recurrence.

Fibroblast growth factor 18(FGF18) is a member of the fibroblast growth factor family (FGFs). FGF18 is a class of bioactive substances that can conduct biological signals, regulate cell growth, participate in tissue repair and other functions, and can promote the occurrence and development of different types of malignant tumors through various mechanisms. In this review, we focus on recent studies of FGF18 in the diagnosis, treatment, and prognosis of tumors in digestive, reproductive, urinary, respiratory, motor, and pediatric systems. These findings suggest that FGF18 may play an increasingly important role in the clinical evaluation of these malignancies. Overall, FGF18 can function as an important oncogene at different gene and protein levels, and can be used as a potential new therapeutic target and prognostic biomarker for these tumors.

Abstract 4D printing of metallic shape‐morphing systems can be applied in many fields, including aerospace, smart manufacturing, naval equipment, and biomedical engineering. The existing forming materials for metallic 4D printing are still very limited except shape memory alloys. Herein, a 4D printing method to endow non‐shape‐memory metallic materials with active properties is presented, which could overcome the shape‐forming limitation of traditional material processing technologies. The thermal stress spatial control of 316L stainless steel forming parts is achieved by programming the processing parameters during a laser powder bed fusion (LPBF) process. The printed parts can realize the shape changing of selected areas during or after forming process owing to stress release generated. It is demonstrated that complex metallic shape‐morphing structures can be manufactured by this method. The principles of printing parameters programmed and thermal stress pre‐set are also applicable to other thermoforming materials and additive manufacturing processes, which can expand not only the materials used for 4D printing but also the applications of 4D printing technologies.

Abstract Targeted photodynamic therapy (TPDT) is considered superior to conventional photodynamic therapy due to the enhanced uptake of photosensitizers by tumor cells. In this paper, an amphiphilic and asymmetric cyclo-Arg-Gly-Asp-d-Tyr-Lys(cRGDyK)-conjugated silicon phthalocyanine (RSP) was synthesized by covalently attaching the tripeptide Arg-Gly-Asp (RGD) to silicone phthalocyanine in the axial direction for TPDT of triple-negative breast cancer (TNBC). RSP was characterized by spectroscopy as a monomer in physiological buffer. Meanwhile, the modification of RSP with RGD led to a high accumulation of the photosensitizer in TNBC cells overexpressing ανβ3 integrin receptors which can bind RGD, greatly reducing the risk of phototoxicity. In vitro photodynamic experiments showed that the IC50 of RSP was 295.96 nM in the 4T1 cell line, which caused significant apoptosis of the tumor cells. The tumor inhibition rate of RSP on the orthotopic murine TNBC achieved 74%, while the untargeted photosensitizer exhibited no obvious tumor inhibition. Overall, such novel targeted silicon phthalocyanine has good potential for clinical translation due to its simple synthesis route, strong targeting, and high therapeutic efficacy for TPDT treatment of TNBC.

ObjectivesThis paper takes the perspective of user cognition to explore the current situation and influencing factors of the cruise ships' appearance brand images.MethodsBased on the hierarchical clustering method, experiments are designed that allow users to observe the appearance of sample cruise ships and reassess the brand belonging to each ship. The experimental data is then collected and statistically analyzed using SPSS（statistical product and service solutions）software.ResultsThe research results show that there are three kinds of the current situation about cruise ship's appearance brand image: most cruise ship have good appearance brand image; Among them, the development of the appearance brand image of mass cruise and luxury cruise are far better than that of professional cruise. And because of the continuity of appearance of the same brand and the difference of the appearance of the different brand, cruise ship's appearance brand image presents a chaotic situation of image crossing or faulting.ConclusionsThe appearance brand images of cruise ships are generally well constructed. The poor appearance brand images of cruise ships (such as some professional cruise ships) are objectively due to the lack of a typical appearance or family characteristics among ships, as well as the homogenization of appearance across brands. Subjectively, the aesthetics and objectives of cruise users will affect the value of the appearance brand image.

This study mainly focused on a strategy for reducing acrylamide(AM) content in wheat breads by combining Lactobacilli and Saccharomyces cerevisiae in sourdough, in comparison with natural fermentation. The results showed that acrylamide levels in breads using sourdough were much lower (102.02–129.37 μg/kg) than control group (204.79 μg/kg). The pH value of sourdough directly influenced the formation of acrylamide in breads (P

Abstract Background IgA nephropathy (IgAN) is the most common primary glomerulonephritis globally. Increasing evidence suggests the importance of host immunity in the development of IgAN, but its dynamics during the early stage of IgAN are still largely unclear. Results Here we successfully resolved the early transcriptomic changes in immune cells of IgAN by conducting single-cell RNA-sequencing (scRNA-seq) with peripheral blood mononuclear cells. The differentially expressed genes (DEGs) between control and IgAN were predominantly enriched in NK cell-mediated cytotoxicity and cell killing pathways. Interestingly, we discovered that the number and cytotoxicity of NK cells are significantly reduced in IgAN patients, where both the number and marker genes of NK cells were negatively associated with the clinical parameters, including the levels of urine protein creatinine ratio (UPCR), serum galactose-deficient IgA1 and IgA. A distinctive B cell subset, which had suppressed NFκB signaling was predominantly in IgAN and positively associated with disease progression. Moreover, the DEGs of B cells were enriched in different viral infection pathways. Classical monocytes also significantly changed in IgAN and a monocyte subset expressing interferon-induced genes was positively associated with the clinical severity of IgAN. Finally, we identified vast dynamics in intercellular communications in IgAN. Conclusions We dissected the immune landscape of IgAN at the single-cell resolution, which provides new insights in developing novel biomarkers and immunotherapy against glomerulonephritis.

Additive manufacturing of metallic glass has attracted great attentions from researchers owing to the prospect of free-form fabricating high-performance bulk amorphous alloy parts. The characteristics of additive manufacturing from points to tracks, tracks to layers, and layers to parts are suitable for forming complex bulk metallic glass parts, which are difficult to achieve with other processing technologies. Herein, the forming principles used in metallic glass additive manufacturing are reviewed, with an emphasis on the manufacturing processes, material systems, forming part properties and potential applications. The properties of forming bulk metallic glass via selective laser melting, laser-directed energy deposition, and laser foil printing technologies are summarized. In addition, certain newly explored metallic glass additive manufacturing technologies, such as fused filament fabrication, ultrasonic consolidation, thermal spraying, and pneumatic injection, are briefly introduced. Finally, the trends in metallic glass additive manufacturing and perspectives for this emerging field are discussed.

Although cold brew coffee is becoming increasingly popular among consumers, the long coffee extraction time is not conducive to the further development of the market. This study explored the feasibility of ultrahigh pressure (UHP) to shorten the time required for preparing cold brew coffee. The effects of pressure and holding time on the physicochemical characteristics and sensory evaluation of UHP-assisted cold brew coffee were also determined. The extraction yield; total dissolved solid, total phenol, and melanoid content; antioxidant capacity; and trigonelline and chlorogenic acid contents of UHP-assisted cold brew coffee increased as the pressure increased. The extraction yield and the total dissolved solid, total phenol, total sugar, and chlorogenic acid and trigonelline contents were higher when the holding time was longer. The HS-SPME-GC/MS analysis demonstrated that the furan, aldehyde, and pyrazine contents in coffee increased as the pressure and holding time increased. The pressure did not significantly impact the concentrations of volatile components of esters and ketones in coffee samples. However, the increase in holding time significantly increased the ester and ketone contents. The sensory evaluation results revealed that as pressure rose, the intensities of nutty, fruity, floral, caramel, and sourness flavors increased, whereas bitterness and sweetness decreased. Longer holding time increased nutty, caramel, sour, bitter, sweet, and aftertaste flavors. Principal component analysis (PCA) results indicated that holding time is a more crucial factor affecting the physiochemical indices and flavor characteristics of coffee. UHP can shorten the preparation time of cold brew coffee. Pressure and holding time significantly affected the physiochemical indices and volatile components of UHP-assisted cold brew coffee. UHP-assisted cold brew coffee had lower bitterness, higher sweetness, and a softer taste than conventional cold brew coffee.

Abstract Background In recent years, the incidence of pulmonary aspergilloma has increased. The harm of aspergilloma is life-threatening massive hemoptysis, and the conventional treatment is surgical treatment. However, whether the antifungal treatment after surgery is required and the course of treatment before and after surgery are still unclear. Methods In this study, patients with pulmonary aspergilloma confirmed pathologically after surgery will be selected as subjects to conduct a single-center, randomized, parallel grouping, prospective, 2-year clinical study. Through regular visits, the recurrence of aspergillus infection, quality of life, lung function indicators, safety of antifungal therapy and other indicators were recorded to evaluate the recurrence risk of aspergillus infection and safety of antifungal agents. Cox proportional risk regression model was used to analyze the influencing factors of antifungal therapy on aspergillus infection recurrence after aspergillus bulbectomy. Cox multiple regression model was used for optimal model fitting, and regression coefficient (β), relative risk (RR) and 95% confidence interval of RR were calculated. Discussion The study will explore whether antifungal therapy could improve the quality of life, reduce the recurrence of aspergillus infection, and ultimately improve the prognosis of patients with aspergilloma. The study results will provide high-quality evidence-based medical evidence for the formulation, revision and optimization of international and domestic clinical guidelines and expert consensus on chronic aspergillus lung disease, effectively improve the clinical treatment effect of aspergilloma, and form the latest concept of diagnosis and treatment of aspergilloma. Trial registration: The trial was registered on the Chinese Clinical Trial Registry website ( https://www.chictr.org.cn/showprojen.aspx?proj=33231 ). Registration number: ChiCTR1800019990.

Targeted photodynamic therapy (TPDT) based on the photosensitizers responsive for tumor microenvironment is promising because of the better anti-tumor effect and less phototoxicity against normal tissue than the traditional PDT. Nanoparticle-based stimuli-responsive photosensitizers have been widely explored for TPDT. Based on the acidic microenvironments in solid tumors, an ultrasmall pH-responsive silicon phthalocyanine nanomicelle (PSN) (smaller than 10[Formula: see text]nm) was designed for selective PDT of tumor. PSN had high drug loading efficacy (more than 28%) and exhibited morphological transitions, enhanced fluorescence and improved singlet oxygen yield under acidic environments. PSN was renal clearable and could rapidly accumulate and be retained at tumor sites, achieving a tumor-inhibiting effect better than phthalocyanine micelle without pH response. Tumors of mice treated with PSN for PDT were completely ablated without recurrence. Thus, we have developed a phthalocyanine-based pH-responsive micelle with excellent tumor targeting ability, which is expected to realize the selective PDT of tumor.

The effects of cinnamaldehyde microcapsules on the concentration of cinnamaldehyde and its metabolites in plasma, urine, and feces, the antioxidant capacity, and the intestinal flora in male C57/BL6 mice were evaluated by oral administration for 7 weeks. Microencapsulation significantly increased the contents of cinnamaldehyde, cinnamyl alcohol, and methyl cinnamate in plasma and decreased those in urine and feces excretion (p

Background: A 3-year prospective study was conducted to evaluate the efficacy of Xpert MTB/RIF (Xpert) in the diagnosis of pleural tuberculosis (pTB) on contrast -enhanced ultrasound (CEUS)-guided pleural biopsy specimens. Method: Patients suspected with pTB were prospectively enrolled to receive CEUS-guided biopsy. Specimens (pleural tissue and fluid) were submitted for Xpert and other routine examinations. Surgical thoracoscopy was performed on undiagnosed cases. Result: A total of 316 patients were enrolled, including 280 cases of pTB (definite 195, possible 85) and 36 cases of non-pTB. The sensitivity of Xpert was 69.64% (195/280) in biopsy specimens, which was significantly higher than that in pleural effusion specimens (p < 0.01). In 195 definite cases, the highest sensitivity of 100% (195/195) and NPV of 29.75% (36/121) were achieved by Xpert on biopsy specimens. Xpert-positive results were obtained in 149 culture-negative cases and 90 histopathological MTB PCR-negative cases. The incidence of necrosis by CEUS in Xpert-positive pTB was significantly higher than that in Xpert-negative pTB (χ2 = 72.41; p < 0.01). No serious complications occurred. Conclusion: Xpert achieved highly diagnostic sensitivity in pTB through CEUS-guided biopsy sampling, especially on necrotic lesions, which was proven to be efficient, minimally invasive and safe.

Abstract Objective To evaluate the accuracy and safety of contrast-enhanced ultrasound (CEUS) guided biopsy in the diagnosis of radiologically determined pleural based lesions. Method A prospective study was conducted on patients with radiologically determined pleural based lesions. Patients who met the inclusion criteria received pleural biopsy guided by CEUS to obtain specimens, followed by histomathological and microbiological examinations. After treatment and follow-up, surgical thoracoscopy was performed on cases with undefinite diagnosis. Result A total of 460 patients were finally included. CEUS showed internal necrosis in 72.17% cases and obvious peripheral vessels in 55.43% cases, both of which were significantly higher than the conventional ultrasound imaged (p

Rong Xiang et al. analyze the expression of non-coding genes encoded peptides in publicly-available proteomics data from five cancer types and matched controls. They identify peptides from non-coding genes including DGCR9 and RHOXF1P3 that are upregulated in tumors compared to controls, suggesting that non-coding gene-encoded peptides may be a source of neoantigens in some cancers.

Cyanine is a meritorious fluorogenic core for the construction of fluorescent probes and its phototherapeutic potential has been enthusiastically explored as well. Alternatively, the covalent conjugation of cyanine with other potent therapeutic agents not only boosts its therapeutic efficacy but also broadens its therapeutic modality. Herein, we summarize miscellaneous cyanine–therapeutic agent conjugates in cancer theranostics from literature published between 2014 and 2020. The application scenarios of such theranostic cyanine conjugates covered common cancer therapeutic modalities, including chemotherapy, phototherapy and targeted therapy. Besides, cyanine conjugates that serve as nanocarriers for drug delivery are introduced as well. In an additional section, we analyze the potential of these conjugates for clinical translation. Overall, this review is aimed to stimulate research interest in exploring unattempted therapeutic agents and novel conjugation strategies and hopefully, accelerate clinical translation in this field.

Based on a high-pressure servo static and dynamic true triaxial test machine (tawz-500/300), uniaxial and true triaxial tests of AC-25C asphalt mixtures under different heat moisture coupling treatments were performed, and the triaxial compressive strength value was determined by mathematical treatment. The test results show that in the range of 20–60 °C, the uniaxial and triaxial compressive strength of the AC-25C asphalt mixture decreases with increasing drying and soaking environment temperature. In the temperature range of 20–40 °C, the drying temperature sensitivity and soaking temperature sensitivity of the asphalt mixture with compressive strength and failure strain value as indices are the maximum. The increase in the intermediate principal stress can improve the triaxial compressive strength, and the increase reaches the maximum when the environmental treatment temperature is 40 °C. The maximum stress ratio is in the range of σ2/σ3 = 0.25 to σ2/σ3 = 0.5. The failure forms of uniaxial tension and triaxial tension are mainly caused by tensile stress. The influence of temperature, humidity and stress ratio on triaxial failure strength is analysed. The relationship between the failure strength and temperature coefficient k is established using a variety of failure criteria, which can provide an experimental and theoretical basis for the mechanical analysis of asphalt mixtures under complex stress states.