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Abstract Infantile Epileptic Spasms Syndrome (IESS) is a severe developmental epileptic encephalopathy that manifests in infancy, significantly impacting the health and quality of life of affected children. The treatment of IESS poses a significant challenge, primarily due to the incomplete understanding of its etiology and pathogenesis. Objective: This study aims to investigate the pathogenic mechanisms of IESS, utilizing metabolomics and proteomics analyses to uncover potential biomarkers for the disease, thereby providing new insights for diagnostic and therapeutic strategies. Cerebrospinal fluid samples from 6 IESS patients and 6 control subjects with benign intracranial hypertension were collected and analyzed using metabolomics and proteomics techniques. Significant differential metabolites and proteins were identified and correlated to determine key proteins associated with specific metabolites. The study then expanded the sample size to 10 per group and validated the identified proteins through ELISA analysis. A total of 24 differential metabolites (12 upregulated and 12 downregulated) and 79 differential proteins (18 upregulated and 61 downregulated) were identified. Metabolomic analysis suggests that linoleic acid is a highly noteworthy differential metabolite in the cerebrospinal fluid of IESS patients. The associated differential protein HLA-A and SEZ6L2 proteins were notably downregulated (p

Abstract Background Chromatin accessibility plays a crucial role in mediating transcriptional dysregulation and heterogeneity in Esophageal Squamous Cell Carcinoma (ESCC). Examining the chromatin accessibility of ESCC at single-cell level is imperative to understand how it activates oncogenes and contributes to the onset and metastasis of ESCC. Methods We performed single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on cancerous and adjacent noncancerous tissues from four ESCC patients who were pathological staged as T1a, T2b, T3b, or T4a, to investigate whether regulatory elements are pivotal in instigating cellular heterogeneity during ESCC metastasis. In conjunction, we integrated these data with 55 scRNA-seq datasets, ChIP-seq or CUT&Tag sequencing data, Hi-C sequencing data, bulk RNA-seq data, and bulk ATAC-seq data from ESCC cell lines to dissect the mechanisms underlying the heterogeneity of ESCC and tumor microenvironment (TME). Results Our study identified enhancer-specific activation within epithelial cells orchestrated by the three-dimensional structure of chromatin that regulates SERPINH1 transcription, and promotes the epithelial-mesenchymal transition (EMT) and metastasis of ESCC. Additionally, chromatin element activation facilitated the expression of TNFSF4 in CD8 + exhausted T cells, thereby activating Tregs. Furthermore, we observed that chromatin accessibility promoted the differentiation of tumor-associated macrophages (TAMs) and cancer associated fibroblasts (CAFs). Conclusions In summary, utilizing multiomics analyses, we have revealed chromatin accessibility maps and illuminated the intricate molecular mechanisms that underlie cellular heterogeneity during ESCC metastasis, offering valuable insights to further advance research on tumor progression and deterioration.

To investigate the effect of naringenin and its glycoside (naringin and narirutin) on foaming, emulsifying and interfacial tension of oat protein and their interaction mechanism, in this study, fluorescence spectra and circular dichroism were used to elucidate the interaction mechanism and protein structure changes of oat protein-flavonoid complex system. The interaction of oat protein-flavonoid complex system was visualized by molecular simulation technique. The results showed that naringenin, naringin, and narirutin significantly improved the foaming and emulsifying properties of oat protein, and reduced the interfacial tension of oat protein, and the effect of glucoside flavonoids was better, namely naringin>narirutin>naringenin. The results of fluorescence and molecular simulation showed that the three flavonoids interact with oat protein mainly through hydrogen bonding and van der Waals force, and the binding constants at room temperature were narirutin (11.05×104 L/mol)>naringenin (6.25×104 L/mol)>naringin (0.23×104 L/mol). The three flavonoids changed the tertiary structure (fluorescence spectral redshift), secondary structure (α-helix decreased, β-folding and random curling increased), and decreased surface hydrophobicity of oat protein, which resulted the and functional properties (foaming and emulsification) of oat protein improved. These results can provide a theoretical reference for selecting suitable flavonoids for oat protein-based products.

This paper primarily investigates the extended state observer design issue for nonlinear Markov jump systems under limited communication bandwidth. In order to achieve reasonable network resource configurations while estimating the system states and total disturbances, a continuous-time dynamic event-triggered strategy is incorporated into the observer design. Accordingly, the transmission of the measured output occurs only when the predefined conditions are satisfied. In contrast to the conventional static triggering strategy, the dynamic event-triggered mechanism enables adaptive threshold adjustment by introducing an internal dynamic variable. In addition, a carefully constructed intermediate variable is considered to indirectly obtain the estimate of the extended state. Then, combining Lyapunov method with stochastic analysis technique, it is proved that the estimation error is exponentially ultimately bounded in mean square under the proposal. At last, a case study of the mass-spring system with four operating modes is presented to illustrate the feasibility of the proposed design approach.

In current clinical practice, various dermal templates and skin substitutes are used to enhance wound healing. However, the role of wound commensal microbiome in regulating scaffold performance and the healing process remains unclear. In this study, we investigated the influence of both natural and synthetic scaffolds on the wound commensal microbiome and wound repair in three distinct models including diabetic wounds, burn injuries, and germ-free (GF) wounds. Remarkably, synthetic electrospun polycaprolactone (PCL) scaffolds were observed to positively promote microbiome diversity, leading to enhanced diabetic wound healing compared to the natural scaffolds Integra® (INT) and MatriDerm® (MAD). In contrast, both natural and synthetic scaffolds exhibited comparable effects on the diversity of the microbiome and the healing of burn injuries. In GF wounds with no detectable microorganisms, a reversed healing rate was noted showing natural scaffold (MAD) accelerated wound repair compared to the open or the synthetic scaffold (PCL) treatment. Furthermore, the response of the wound commensal microbiome to PCL scaffolds appears pivotal in promoting anti-inflammatory factors during diabetic wound healing. Our results emphasize that the wound commensal microbiome, mediated by different scaffolds plays an important role in the wound healing process.

Abstract Relaxor antiferroelectrics are considered promising candidate materials for achieving excellent energy storage capabilities. However, the trade-off between high recoverable energy density and high efficiency remains a major challenge in relaxor antiferroelectrics for practical applications. Herein, guided by phase-field simulation, we propose a strategy of designing polymorphic heterogeneous shell in core-shell dual-phase dielectrics to synergistically control micro and local heterostructures, resulting in comprehensive improvements in breakdown electric field, polarization fluctuation and saturation behaviors. Leveraging the core-shell effect and polarization heterogeneity, an ultrahigh recoverable energy density of 12.7 J cm-3 and an impressive efficiency of 87.2% are achieved in lead-free relaxor antiferroelectrics, making a performance breakthrough in core-shell dielectrics. This work opens up a new avenue to efficiently develop high-performance energy storage dielectrics and is expected to be popularized in other fields.

Abstract In this paper we study Einstein-bumblebee gravity theory minimally coupled with external matter – a phantom/non-phantom (conventional) scalar field, and derive a series of hairy solutions – bumblebee-phantom (BP) and BP-dS/AdS black hole solutions, regular Ellis-bumblebee-phantom (EBP) and BP-AdS wormholes, etc. We first find that the Lorentz violation (LV) effect can change the so-called black hole no-hair theorem and these scalar fields can give a hair to a black hole. If LV coupling constant $$\ell >-1$$ ℓ > - 1 , the phantom field is admissible and the conventional scalar field is forbidden; if $$\ell

Abstract Objectives GPC3 has been recognized as a promising target for immunotherapy in hepatocellular carcinoma (HCC). However, the GPC3-targeted immunotherapies have shown limited therapeutic efficacy. The use of anti-PD-1/PD-L1 monoclonal antibodies in HCC treatment is considerably constrained. Furthermore, there is still a notable lack of understanding concerning the immune landscape in HCC, especially regarding varied GPC3 expression levels. Therefore, thorough exploration of the intricate tumor immune microenvironment at different GPC3 expression levels is essential for guiding and improving HCC treatment strategies. Methods Sixty patients with HCC were enrolled in this study, receiving a first-line treatment that combined anti-angiogenesis targeted drugs and immunotherapy. Immunohistochemistry was used to assess the levels of GPC3 expression. Multiple immunohistochemical markers, such as CD8, PD-1, LAG3, TIGIT, TIM-3, CD103, Claudin18.2, PD-L1, CD4, Foxp3, CD68, CD163, GPC3, CD11C, CD14, CD66b, and HLA-DR, were used to characterize the immune microenvironment and spatial distribution of immune cells in HCC tumors with different levels of GPC3 expression. Cell expression levels and spatial distribution were determined by fluorescence staining and subsequent analysis of fluorescence intensity using the Panoramic Pathology Workstation (Pano ATLAS). This approach facilitated a detailed examination of cell characteristics and spatial information within the samples. Results Based on the result of GPC3 immunohistochemical analysis, patients with strong positive GPC3 expression were classified as high GPC3 expression, while the others were classified as low GPC3 expression. Patients in the low GPC3 expression group had longer overall survival (OS) than in the high group (P = 0.003, HR = 2.9240). Further exploration of the immune microenvironment based on different GPC3 expression levels revealed that in high GPC3 expression group, the proportions of CD8+ T cells(P = 0.0435), TIM-3+ T cells(P = 0.0447), CD103+CD8+ tissue-resident T cells(P = 0.0410), CD11C+CD14−DC cells(P = 0.0497), CD11C+HLA-DR−DC cells(P = 0.0309), CD11C+CD14−HLA-DR−DC cells(P = 0.0233), and CD11C+CD14−CD66b−DC cells(P = 0.0474) were all higher compared to low expression group. At spatial distances of 10 μm, 20 μm, and 30 μm, the levels of CD8+ T cells were higher in the high expression group compared to the low expression group (high vs. low: P = 0.0281, P = 0.0236, P = 0.0220). Conclusions Multiple immunohistochemistry is a powerful technique for exploring the intricate immune microenvironment of hepatocellular carcinoma, enabling the precise identification of diverse cell subsets and their spatial distribution within the tumor microenvironment. This methodology provides valuable insights into the complex interactions and spatial organization of immune cells in the context of hepatocellular carcinoma progression. Low GPC3 expression in HCC patients indicates potential benefits from combined targeted and immunotherapy. Different levels of GPC3 expression levels can predict the effectiveness of targeted combination immunotherapy in HCC patients. Additionally, different GPC3 expression patterns in HCC patients correspond to unique tumor immune microenvironments, which have implications for guiding HCC treatment approaches.

Abstract Accurately estimating particulate organic nitrate under high NOx and oxidizing conditions is critical. This study compared the NOx + ratio, unconstrained Positive Matrix Factorization (PMF), and Multilinear Engine-2 (ME2) methods to estimate particulate organic nitrate in Shanghai across different seasons. The factors associated with organic nitrate, as identified through two receptor methods, exhibited consistent daily patterns in spring, summer, and autumn, although source contributions varied. The NOx + ratio method reported higher organic nitrate levels than the PMF and ME2 methods, likely due to the fixed RON/RAN parameter. Seasonal RON/RAN parameters were optimized based on precursor emissions in Shanghai, achieving values of 3.13 in spring, 2.25 in summer, and 1.88 in autumn. This optimization reduced discrepancies in organic nitrate using the NOx + ratio to 3.2–7.4%. The optimized parameters in this study support the rapid and accurate estimation of organic nitrate during different seasons in urban areas.

Abstract Leaf is the main photosynthetic organ at the seedling stage of rapeseed and leaf size is a crucial agronomic trait affecting rapeseed yield. Understanding the genetic mechanisms underlying leaf size is therefore important for rapeseed breeding. In this study, QTL mapping for three traits related to leaf size, i.e., leaf width (LW), leaf length (LL) and leaf area (LA), was performed using a recombinant inbred line (RIL) population and four QTLs for LW, two QTLs for LL and four QTLs for LA were detected. Transcriptome analysis revealed that differentially expressed genes (DEGs) were enriched in the GO terms related to microtubules, and the expression level of several genes involved in cell division also showed significant differences. Microscopic analysis suggested that the cell number was the main factor regulating leaf size. Combining QTL mapping and RNA sequencing, four promising candidate genes, including BnaA10G0085600ZS, BnaA10G0156900ZS, BnaC03G0441700ZS, and BnaC08G0410600ZS, were proposed to control leaf size by regulating cell division. The results of QTL, transcriptome analysis, and anatomical observation were highly consistent, collectively revealing that genes related to cell division played a crucial role in regulating the leaf size traits in rapeseed. These findings provided further insights into the genetic mechanism of leaf size and built fundamental theory basis for high-density tolerance breeding in rapeseed.

Abstract The genesis of hepatocellular carcinoma (HCC) is closely related to male factors and hyper-activated Ras signals. A transcriptomic database was established via RNA-Seq of HCC (T) and the adjacent precancerous liver tissue (P) of Hras12V transgenic mice (Ras-Tg, HCC model) and the normal liver tissue of wild-type mice (W) of both sexes. Comparative analysis within W, P, and T and correlation expression pattern analysis revealed common/unique cluster-enriched items towards HCC between the sexes. Specifically, the numbers of differentially expressed genes (DEGs) were much higher in females than in males, and tumor suppressor genes, such as p21 Waf1/Cip1 and C6, were significantly higher in the female P. This finding denotes the higher sensitivity of female hepatocytes to the Ras oncogene and, therefore, the difficulty in developing HCC. Moreover, convergence in HCC between the sexes suggests the underlying mechanisms for the ineffectiveness of sex hormone therapies. Additionally, expression pattern analysis revealed that the DEGs and their relevant pathways were either positively or negatively associated with the HCC/Ras oncogene. Among them, the vital role of glutathione metabolism in HCC was established. This work provides a basis for future research on elucidating the underlying mechanisms, selecting the diagnostic biomarker, and planning the clinical therapy in HCC.

Abstract Electric field induced antiferroelectric-ferroelectric phase transition is a double-edged sword for energy storage properties, which not only offers a congenital superiority with substantial energy storage density but also poses significant challenges such as large polarization hysteresis and poor efficiency, deteriorating the operation and service life of capacitors. Here, entropy increase effect is utilized to simultaneously break the long-range antiferroelectric order and locally adjust the fourfold commensurate modulated polarization configuration, leading to a breakthrough in the trade-off between recoverable energy storge density (14.8 J cm−3) and efficiency (90.2%) in medium-entropy antiferroelectrics. The embedding of non-polar phase regions in the incommensurate antiferroelectric matrices, revealing as a mixture of commensurate, incommensurate, and relaxor antiferroelectric polarization configurations, contributes to the diffuse antiferroelectric-ferroelectric phase transition, enhanced phase transition electric field, delayed polarization saturation, and efficient recovery of polarization. This work demonstrates that controlling local diverse antiferroelectric polarization configurations by increasing entropy is an effective avenue to develop high-performance energy storage antiferroelectrics, with implications that can be extended to other materials and functionalities.

Abstract Proteinopathies in neurology typically refer to pathological changes in proteins associated with neurological diseases, such as the aggregation of amyloid β and Tau in Alzheimer’s disease, α-synuclein in Parkinson’s disease and multiple system atrophy, and TAR DNA-binding protein 43 in amyotrophic lateral sclerosis and frontotemporal dementia. Interestingly, these proteins are also commonly found in peripheral tissues, raising important questions about their roles in neurological disorders. Multiple studies have shown that peripherally derived pathological proteins not only travel to the brain through various routes, aggravating brain pathology, but also contribute significantly to peripheral dysfunction, highlighting their crucial impact on neurological diseases. Investigating how these peripherally derived proteins influence the progression of neurological disorders could open new horizons for achieving early diagnosis and treatment. This review summarizes the distribution, transportation pathways, and pathogenic mechanisms of several neurodegenerative disease-related pathological proteins in the periphery, proposing that targeting these peripheral pathological proteins could be a promising strategy for preventing and managing neurological diseases.

Abstract Iron alloys, including steels and magnetic functional materials, are widely used in capital construction, manufacturing, electromagnetic technology, etc. However, they face the long-standing challenge of high coefficient of thermal expansion (CTE), limiting the applications in high-precision fields. This work proposes a strategy involving the in-situ formation of a nano-scale lamellar/labyrinthine negative thermal expansion (NTE) phase within the iron matrix to tackle this problem. For example, a model alloy, Fe-Zr10-Nb6, was synthesized and its CTE is reduced to approximately half of the iron matrix. Meanwhile, the alloy possesses a strength-plasticity combination of 1.5 GPa (compressive strength) and 17.5% (ultimate strain), which outperforms other low thermal expansion (LTE) metallic materials. The magnetovolume effect of the NTE phase is deemed to counteract the positive thermal expansion in iron. The high stress-carrying hard NTE phase and the tough matrix synergistically contribute to the high mechanical properties. The interaction between the slip of lamellar microstructure and the slip-hindering of labyrinthine microstructure further enhances the strength-plasticity combination. This work shows the promise of offering a method to produce LTE iron alloys with high mechanical properties.

The objective of this study was to investigate the feasibility of partially replacing NaCl with salty pig bone peptides (SPBP) in the production of low-NaCl sausages (LNS). The impact of varying proportions of SPBP replacing NaCl on sensory attributes, texture characteristics, color variation, pH, yield, moisture content, taste, and volatile profile was examined. The findings indicated that sausages supplemented with 1% NaCl+1% SPBP (1% LNS-SPBP) outperformed the control (supplemented with 2% NaCl) in terms of color, appearance, taste and flavor, while tissue structure was comparable to that of the control group. Additionally, 1% LNS-SPBP significantly enhanced the textural properties of LNS (P

To investigate the solubilization of composite plant protein after co-processing with an industry-scale microfluidizer and pH cycling and to clarify its solubilization mechanism, this paper used rice protein and pea protein as raw materials, a mixed protein solution with a protein ratio of 1:1 and a total protein concentration of 4% were configured. The pH of the mixture was then adjusted to 12 and the solution processed at different pressures in a high-pressure jet mill. The composite protein was then obtained by adjusting the pH of the solution back to neutral. And to characterize the changes in physicochemical properties and structure of composite protein during this process using nitrogen solubility index, particle size, fluorescence spectroscopy, circular dichroism, molecular weight, and other means. Results showed that the nitrogen solubility index of 4% composite protein underwent industry-scale microfluidizer and pH cycling treatment was increased with the increase of pressure, reaching the maximum of 92.67%±0.77% at 120 MPa. The results of scanning electron microscopy and particle size showed that the composite proteins decreased in size and the specific surface area increased after the treatment of the industry-scale microfluidizer. The results of intrinsic fluorescence spectroscopy, surface hydrophobicity, sulfhydryl disulfide bonding, and circular dichroism indicated that the two proteins interacted to form new co-assembly composites. Surface hydrophobicity increased significantly from 4025.33 to 7359.45 (P

Abstract Ferroptosis is of great significance in carcinogenesis as it interconnects with a multiplicity of biological processes. Meanwhile, its function and regulatory role in lung cancer remains ambiguous. In this study, we discovered by WB and IHC that ALYREF has a higher expression in lung adenocarcinoma (LUAD) tissues compared with normal ones. By the direct observation of mitochondria with electron microscopy, we also identified that the knockdown of ALYREF limits the proliferation of LUAD in vitro as well as in vivo and prompts LUAD cells to go through ferroptosis. Mechanistically, our RNA-immunoprecipitation experiment combined with qRT-PCR analysis confirmed that ALYREF could interact with SLC7A11. ALYREF mainly binds to the 3’UTR region of SLC7A11 mRNA, increasing the mRNA stability of SLC7A11 and reducing intracellular Reactive Oxygen Species (ROS) and Methylene diphenyl diamine (MDA) thereby inhibiting ferroptosis and eventually promoting the proliferation and metastasis of LUAD cells. Importantly, our study reveals for the first time that ALYREF can regulate LUAD by inhibiting ferroptosis. Based on the evidences mentioned above, we have good reason to believe that the role of ALYREF as a new oncological factor could be proved and, acting along the ALYREF-SLC7A11-ferroptosis axis, utilized as a promising therapeutic target for LUAD.

Purpose: To use a finite element method to construct a patch-bridge repair model for massive rotator cuff tears (MRCTs) and investigate the effects of different suture methods and knot numbers on postoperative biomechanics. Methods: A finite element model based on intact glenohumeral joint data was used for a biomechanical study. A full-thickness defect and retraction model of the supraspinatus tendon simulated MRCTs. Patch, suture, and anchor models were constructed, and the Marlow method was used to assign the material properties. Three suturing models were established: 1-knot simple, 1-knot mattress, and 2-knot mattress. The ultimate failure load, failure mode, stress distribution of each structure, and other biomechanical results of the different models were calculated and compared. Results: The ultimate failure load of the 1-knot mattress suture (71.3 N) was 5.6 % greater than that of the 1-knot simple suture (67.5 N), while that (81.5 N) of the 2-knot mattress was 14.3 % greater than that of the 1-knot mattress. The stress distribution on the patch and supraspinatus tendon was concentrated on suture perforation. Failure of the bridging reconstruction mainly occurred at the suture perforation of the patch, and the damage forms included cutting-through and isthmus pull-out. Conclusion: A finite element model for the patch-bridging reconstruction of MRCTs was established, and patch-bridging restored the mechanical integrity of the rotator cuff. The 2-knot mattress suture was optimal for patch-bridging reconstruction of MRCTs.

Abstract Background The total burden of migraine includes not only the episodes with headache pain but extends throughout the interictal periods. Interictal symptoms and associated psychological responses may profoundly impact well-being and drive treatment-seeking behavior. Methods A cross-sectional online survey was conducted with participants aged ≥ 18 years, 250 with episodic migraine (EM) and 250 with chronic migraine (CM), having ≥ 4 monthly migraine headache days. All were naïve to galcanezumab or began ≤ 6 months before survey completion. The study evaluated factors associated with the Migraine Interictal Burden Scale (MIBS-4), including social determinants of health and well-being. Multiple linear regression, logistic regression, and random forests (RF) were used to explore predictors of MIBS-4. Results The majority of participants (90%) were female with a mean (standard deviation) age of 40.6 (± 12.0) years and 18.1 (± 12.7) years since the first migraine episode. Sociodemographically, the EM and CM groups were similar. Common comorbidities were anxiety disorder (45%) and depression (44%). Migraine family history was reported in 59% of participants. MIBS-4 was correlated with a number of diverse variables, including well-being, anxiety sensitivity, income, aura symptoms, and the worst migraine pain in the year before starting galcanezumab. Linear and logistic regression identified years since the first symptom, worst migraine attack pain, premonitory symptoms, and income as significant predictors. RF explained more of the variance than multiple linear regression and introduced additional concepts to the prediction of MIBS, identifying well-being (WHO-5 total score), the WHO-5 item “cheerful and in good spirits,” worry about exercise, and fear of missing social obligations as significant predictors. Socioeconomic status and income were also critical explanatory variables for interictal burden (IIB) based on regression modeling and RF. Still, income was the only variable significantly associated with IIB across regression and RF methods. Conclusions Interictal burden should be considered in the medical care of people with migraine. This additional burden is holistic, with psychosocial and socioeconomic elements in addition to residual symptoms. It is essential to consider this when assessing the impact of IIB.

Abstract Background Lung transplantation is the most effective treatment for end-stage lung disease. However, the shortage of donor lungs is a major limitation. Inverted lung transplantation has the potential to expand the donor pool and make suitable donor lungs available to more patients. Case presentation We present the case of a 65-year-old male who developed interstitial lung disease and pulmonary fibrosis. After a comprehensive evaluation, it was determined that the patient met the criteria for a lung transplantation. The patient’s right lung condition was more severe than the left. Based on the allocation system, a suitable left donor lung was assigned to the patient. The patient underwent a left-to-right inverted single-lung transplantation. The transplanted lung gradually regained function postoperatively. Unfortunately, the patient passed away due to multiple organ failure caused by infection two months later. Conclusions In this report, we present a case of left-to-right inverted single-lung transplantation. Based on the preoperative evaluation and the patient’s consent, this surgical approach is feasible. This technique has the potential to broaden the pool of compatible donors and increase the number of recipients.

Abstract Neurodynamic models that simulate how micro-level alterations propagate upward to impact macroscopic neural circuits and overall brain function may offer valuable insights into the pathological mechanisms of schizophrenia (SCZ). In this study, we integrated a neurodynamic model with the classical Contrastive Variational Autoencoder (CVAE) to extract and evaluate macro-scale SCZ-specific features, including subject-level, region-level parameters, and time-varying states. Firstly, we demonstrated the robust fitting of the model within our multi-site dataset. Subsequently, by employing representational similarity analysis and a deep learning classifier, we confirmed the specificity and disorder-related information capturing ability of SCZ-specific features. Moreover, analysis of the attractor characteristics of the neurodynamic system revealed significant differences in attractor space patterns between SCZ-specific states and shared states. Finally, we utilized Partial Least Squares (PLS) regression to examine the multivariate mapping relationship between SCZ-specific features and symptoms, identifying two sets of correlated modes implicating unique molecular mechanisms: one mode corresponding to negative and general symptoms, and another mode corresponding to positive symptoms. Our results provide valuable insights into disorder-specific neurodynamic features and states associated with SCZ, laying the foundation for understanding the intricate pathophysiology of this disorder.

Abstract Background In observational studies, frailty has been strongly associated with mental disorders. However, the mechanisms underlying the association between frailty and mental disorders remain unclear. Methods We conducted a two-sample Mendelian randomization (MR) study to assess the causal relationship between frailty, as measured by the frailty index (FI), and ten common mental disorders. The datasets involved European ancestry individuals and included measurements of the FI (N = 175,226), schizophrenia (SCZ; N = 320,404), major depressive disorder (MDD; N = 143,265), bipolar disorder (N = 337,199), insomnia (N = 462,341), obsessive–compulsive disorder (N = 33,925), anxiety disorders (N = 463,010), autism spectrum disorder (N = 46,351), anorexia nervosa (N = 14,477), opioid-related mental and behavioral disorders (N = 215,650), and mental and behavioral disorders due to use of other stimulants including caffeine (N = 215,570). Results Two-sample MR analyses were performed using inverse variance weighting followed by various sensitivity and validation analyses. Genetically predicted SCZ (odds ratio [OR] = 1.019, 95% confidence interval [CI] 1.005–1.033) and MDD (OR = 1.211, 95% CI 1.092–1.343) had significant causal effects on FI. In the reverse MR analysis, we discovered that MDD was significantly and causally affected by FI (OR = 1.290, 95% CI 1.133–1.469). No causal links were identified between the FI and the other eight common mental disorders. In the Multivariable MR, the estimated MDD effect on FI is comparable to the univariate IVW estimate (OR = 1.298; 95% CI, 1.175 to 1.435), while the estimated SCZ effect on FI fails to be significant compared to the univariate estimate. The results of the sensitivity and validation analyses confirmed stabilization. Conclusions Our study found evidence of a causal relationship between SCZ, MDD, and frailty and explored the underlying mechanisms.

Abstract Acute liver failure (ALF) is a life-threatening clinical syndrome characterized by high-grade inflammation and multi-organ failure. Our previous study shows that targeting the M2 isoform of pyruvate kinase (PKM2) to inhibit macrophage inflammation may be a promising strategy for ALF treatment. however, the mechanism by which PKM2 regulates the inflammatory response is unclear. Here we demonstrate that PKM2 contributes to ALF by modulating NLRP3-mediated pyroptosis activation in liver macrophages. The specific knockout of PKM2 in myeloid cells reduces mortality and alleviates hepatic injury in D-galactosamine/LPS-induced ALF mice. Single-cell transcriptome analysis suggests that NLRP3 inflammasome activation of macrophages involves in ALF, knockout of PKM2 in macrophages reduces the expression of NLRP3, and activation of pyroptosis. Pharmacological inhibition of the PKM2 nuclear translocation, but not glycolytic activity, protects mice from ALF. Pharmacological and genetic inhibition of PKM2 attenuates NLRP3-mediated pyroptosis activation and consequently reduces the release of IL-1β and IL-18 by macrophages. Mechanistically, PKM2 translocates into the nucleus and combines with STAT3, enhancing its phosphorylation and recruitment to the NLRP3 promoter region, thereby increasing NLRP3 expression. This work defines PKM2 acts as an important nonmetabolic regulator of NLRP3 that modulates pyroptosis activation in macrophages and guides future therapeutic strategies development for ALF.

This study aimed to design and evaluate offset straight teeth roller for precise application of granular mineral fertilizer at low rotation speeds. In the first stage, the experiment focused on optimizing the gap length between offset straight-tooth to prevent unintended fertilizer flow and ensure even distribution. In the second stage, additional gaps on the left and right sides of offset straight teeth were compared to a single gap. The results of the comparison showed that adding gaps on the sides improved the discharge rate and the uniformity of distribution. Therefore, offset straight-tooth roller was divided into five sections, each with a length of 12 mm. Discrete Element Method (DEM) simulations showed an actual discharge mass of 148.35 g, producing a slippage rate of 35.9%. Verification using laboratory equipment with offset straight-tooth roller showed a discharge of 150 g of mineral granular fertilizer.

The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77's non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands. Moreover, the lack of pharmaceutical ligands restricts Nur77's therapeutic proof of concept. Herein, we developed a first-in-class Nur77 site B ligand (NB1) that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria. The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode. Importantly, NB1 showed favorable pharmacokinetic profiles and safety, as evidenced by its good oral bioavailability in rats and lack of mortality, bodyweight loss, and pathological damage at the 512.0 mg/kg dose in mice. Furthermore, oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model. Together, our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.

Abstract This multicohort phase II trial (ALTER-G-001; NCT05262335) aimed to assess the efficacy of first-line anlotinib plus chemotherapy for gastrointestinal (GI) cancer patients with unresectable liver metastases. Eligible patients with colorectal cancer (Cohort A) or noncolorectal and nonesophageal GI cancer (Cohort C) received six cycles of anlotinib plus standard chemotherapeutic regimens followed by anlotinib plus metronomic capecitabine as a maintenance therapy. Liver metastasectomy can be performed when liver metastases are converted to resectable lesions. The primary outcome was the investigator-confirmed objective response rate (ORR) in the intention-to-treat population. Among the 47 patients in Cohort A, the ORR was 40.4% (95% CI 26.4–55.7), including 1 with a complete response (CR) and 18 who achieved a partial response (PR). The median progression-free survival (PFS) was 8.7 months (95% CI 7.3-NE), and the median overall survival (OS) was not reached. In Cohort C, 14 of 44 patients achieved a PR, with an ORR of 31.8% (95% CI 18.6–47.6). The PFS and OS were 5.8 months (95% CI 4.8–6.5) and 11.4 months (95% CI 5.8–19.3), respectively. The liver metastasectomy rate in patients with liver-limited disease was 22.7% (5/22) in Cohort A and 6.7% (2/30) in Cohort C. For pancreatic cancer patients, the ORR of the efficacy-evaluable population was 36.0% (9/25), and those with liver-limited metastasis had better survival. Moreover, no new safety concerns emerged. In conclusion, an anlotinib-based first-line regimen demonstrated promising antitumor activity among GI cancer patients with unresectable liver metastases and led to liver metastasectomy in selected patients.

Abstract With the development of the car‐hailing industry, it has become an indispensable way of travel in our lives. Accurate prediction of online car‐hailing demand can provide the basis for real‐time vehicle dispatch and dynamic pricing for online car‐hailing companies. Most previous studies on online car‐hailing demand forecasting have only considered the temporal and spatial factors separately, while the effects of time series and spatial series on online car‐hailing demand have not been considered. In this paper, the temporal, spatial, and weather features of online car‐hailing are analyzed and they are used as input features of the model. In addition, an attention mechanism is added to the model in order to select a small amount of key feature data from a large amount of feature data and give more weight to the key data, and an attention mechanism‐based TCN (Temporal Convolutional Network) prediction model (TCN+Attention) was developed to better highlight the key features that affect the prediction of online car demand and improve the prediction accuracy of online car demand. Finally, taking the data of Ningbo City as an example, the data is divided into 10 min, 15 min, and 30 min time intervals for prediction, and it is combined with other models and with other prediction models (SVR, LightGBM, Random Forest, Stacking Integrated Learning, LSTM, LSTM+ Attention, and TCN) results in comparative analysis. Experiments show that the TCN+Attention model of online car‐hailing demand prediction has higher accuracy compared with other models.

Context Hyperpigmentation, a common skin condition marked by excessive melanin production, currently has limited effective treatment options.Objective This study explores the effects of Tao-Hong-Si-Wu decoction (THSWD) on hyperpigmentation and to elucidate the underlying mechanisms.Materials and methods We employed network pharmacology, Mendelian randomization, and molecular docking to identify THSWD’s hub targets and mechanisms against hyperpigmentation. The Cell Counting Kit-8 (CCK-8) assay determined suitable THSWD treatment concentrations for PIG1 cells. These cells were exposed to graded concentrations of THSWD-containing serum (2.5%, 5%, 10%, 15%, 20%, 30%, 40%, and 50%) and treated with α-MSH (100 nM) to induce an in vitro hyperpigmentation model. Assessments included melanin content, tyrosinase activity, and Western blotting.Results ALB, IL6, and MAPK3 emerged as primary targets, while quercetin, apigenin, and luteolin were the core active ingredients. The CCK-8 assay indicated that concentrations between 2.5% and 20% were suitable for PIG1 cells, with a 50% cytotoxicity concentration (CC50) of 32.14%. THSWD treatment significantly reduced melanin content and tyrosinase activity in α-MSH-induced PIG1 cells, along with downregulating MC1R and MITF expression. THSWD increased ALB and p-MAPK3/MAPK3 levels and decreased IL6 expression in the model cells.Discussion and conclusion THSWD mitigates hyperpigmentation by targeting ALB, IL6, and MAPK3. This study paves the way for clinical applications of THSWD as a novel treatment for hyperpigmentation and offers new targeted therapeutic strategies.

Context The Xihuang pill (XHP) is a traditional Chinese medicine formulation that has been historically used in the prevention and treatment of proliferative breast diseases. However, there is a lack of guidelines that offer recommendations for its clinical use.Objective The task force from the Chinese Guangdong Pharmaceutical Association aims to develop evidence-based guidelines for XHP to prevent and treat proliferative breast diseases.Methods We searched six Chinese and English electronic databases, including the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Wanfang Medical Database, PubMed, and Embase, up to November 1, 2022. Publications (case reports, clinical observation, clinical trials, reviews) on using XHP to treat proliferative breast diseases were manually searched. The search terms were Xihuang pill, hyperplasia of the mammary gland, breast lump, and mastalgia. The writing team developed recommendations based on the best available evidence.Results Treatment should be customized based on syndrome identification. We recommend using XHP for the prevention and treatment of breast hyperplasia disease when a patient presents the following syndromes: concurrent blood stasis syndrome, concurrent phlegm-stasis syndrome, and concurrent liver fire syndrome. Safety indicators, including blood analysis and liver and kidney function monitoring, should be performed regularly during treatment.Conclusions Current clinical evidence suggests that XHP can be used as a standalone treatment or in conjunction with other medications to prevent and manage breast hyperplasia diseases. More randomized controlled studies are warranted to establish high-quality evidence of its use.

The material removal of micro-nano-machining to prepare microtool is too large, and the material needs to be pre-treated. In this paper, the micro removal processing of zirconia material was carried out by corrosion method, and the effects of corrosive liquid concentration, corrosion temperature and corrosion duration on the efficiency of corrosion processing and the degree of material damage were studied and the material removal mechanism was investigated. The results showed that the material removal increased with the increase of corrosion duration at 50% corrosion solution concentration and 200 °C; the average removal was about 38 μm/h. At the same corrosion duration and corrosion temperature, the removal efficiency of the material increased and then levelled off with the increase of corrosion solution concentration, and remained unchanged after 40% concentration. Microstructures with good taper were obtained at 30% etchant concentration and 7 h etching duration. The material corrosion products and the crystalline changes of zirconia after corrosion were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The results show that during the corrosion process, the corrosive solution mainly corrodes the intergranular bonding phase, leading to the formation of lamellar exfoliation. Microtool with nanoscale edges were prepared using focused ion beam (FIB) technology with machining parameters of 30 KeV, 69 nA, 30 KeV, 2.5 nA and 5 KeV, 0.23 nA, respectively. The results of biocompatibility tests showed that the microtool had no significant effect on cell growth. The cell tissue separation experiments showed that the microtool could effectively separate the cell tissues.

Achieving scar-free skin regeneration in clinical settings presents significant challenges. Key issues such as the imbalance in macrophage phenotype transition, delayed re-epithelialization, and excessive proliferation and differentiation of fibroblasts hinder wound healing and lead to fibrotic repair. To these, we developed an active shrinkage and antioxidative hydrogel with biomimetic mechanical functions (P&G@LMs) to reshape the healing microenvironment and effectively promote skin regeneration. The hydrogel's immediate hemostatic effect initiated sequential remodeling, the active shrinkage property sealed and contracted the wound at body temperature, and the antioxidative function eliminated ROS, promoting re-epithelialization. The spatiotemporal release of LMs (ACEI) during the inflammation phase regulated macrophage polarization towards the anti-inflammatory M2 phenotype, promoting progression to the proliferation phase. However, the profibrotic niche of macrophages induced a highly contractile α-SMA positive state in myofibroblasts, whereas the sustained LMs release could regulate this niche to control fibrosis and promote the correct biomechanical orientation of collagen. Notably, the biomimetic mechanics of the hydrogel mimicked the contraction characteristics of myofibroblasts, and the skin-like elastic modulus could accommodate the skin dynamic changes and restore the mechanical integrity of wound defect, partially substituting myofibroblasts' mechanical role in tissue repair. This study presents an innovative strategy for skin regeneration.

In the present work, the medium Mn steel with a strength - ductility product of 49.5 GPa·% was fabricated by a hot rolling, quenching and intercritical annealing process. The excellent mechanical property is attributed to the heterogeneous austenite morphologies, i.e., lath, granular and equiaxed austenite, and the successive TWIP + TRIP effects. The present work especially focus on two aspects: i) the evolution of micro-strain between different morphologies of austenite and ferrite during tensile deformation and its impact on the strain hardening caused by the transformation induced plasticity (TRIP) effect; and ii) the strengthening mechanisms of successive twin induced plasticity (TWIP) and TRIP effects in heterogeneous structures. Under different austenite/ferrite micro-strain interactions, the sequence of TRIP effect is in granular, lath and equiaxed austenite grains. Prior to this, the TWIP effect mainly enhance the strength of austenite, particularly equiaxed grains, which act as a high-strength skeleton structure, postponing the initiation of necking.

The surface/interfacial reactivity of clay is a critical factor influencing the sedimentation of coal slurry water. To achieve efficient sedimentation of coal slurry water, this paper introduces a novel approach that regulates the hydrophobicity of defective active sites in clay minerals. Fe3+-doped kaolinite (Fe3+-Kao) was synthesized by hydrothermal methods. Subsequently, tests were conducted on the adsorption capacity, surface wettability, and agglomeration sedimentation of alkyl amine/ammonium salts (AAS) on Fe3+-Kao surfaces. Fe3+ doping significantly enhances AAS adsorption and alters surface properties from hydrophilic to hydrophobic, promoting kaolinite particle aggregation and sedimentation, thereby improving coal slurry water treatment efficiency. Molecular dynamics (MD) simulations were performed to analyze the statistical adsorption behavior of AAS on Fe3+-Kao surfaces. The simulation results indicate that the mechanism by which Fe3+ doping influences the hydrophobic regulation of kaolinite surfaces is due to the enhanced interfacial interactions between the kaolinite surface and AAS, where the interfacial effects are more pronounced on surfaces closer to the dopant sites. The findings of this research offer valuable insights for future studies on other types of lattice defects in clay minerals, as well as for the development of more efficient treatment chemicals for coal slurry water.

Abstract This study aimed to evaluate the efficacy and safety of dolutegravir plus lamivudine (DTG/3TC) in antiretroviral treatment (ART)-experienced people living with HIV (PLWH). A total of 303 PLWH in Shanghai, China, who switched from triple ART to DTG/3TC between January 2019 and June 2022, with a minimum ART duration of 6 months, were retrospectively enrolled. More than 95% of PLWH maintained viral suppression with no significant changes in CD4 counts 12 months after switching. Patients transitioning from non-tenofovir (TDF)-based regimens demonstrated more pronounced improvements in lipid profiles, while those previously on TDF-based regimens showed greater enhancements in bone metabolism.

Abstract This is a single Institute, prospective cohort study. We enrolled twenty-two postmenopausal women with pelvic organ prolapse planning to undergo vaginal hysterectomy with transvaginal pelvic reconstructive surgery, with or without a concomitant anti-incontinence procedure. Vaginal swabs and urine samples were longitudinally collected at five time points: preoperative consult visit (T1), day of surgery prior to surgical scrub (T2), immediately postoperative (T3), day of hospital discharge (T4), and at the postoperative exam visit (T5). Women experiencing urinary tract infection symptoms provided a sample set prior to antibiotic administration (T6). Microbiome analysis was performed on vaginal and urinary specimens at each time point. Region V3-V5 of the 16S ribosomal RNA gene was amplified and sequenced. DNA samples were analyzed for visit T1, T2, T5 and T6. Six (27.3%) participants developed postoperative urinary tract infection whose vaginal sample at first clinical visit (T1) revealed beta-diversity analysis with significant differences in microbiome structure and composition. Women diagnosed with a postoperative urinary tract infection had a vaginal microbiome characterized by low abundance of Lactobacillus and high prevalence of Prevotella and Gardnerella species. In our cohort, preoperative vaginal swabs can predict who will develop a urinary tract infection following transvaginal surgery for pelvic organ prolapse. ClinicalTrials.gov Identifier: NCT02751073.

Abstract This study aimed to evaluate the association between the triglyceride-glucose (TyG) index and high-sensitivity C-reactive protein-to-albumin ratio (hsCAR) and the prognosis of patients with STEMI and hypertension. A total of 699 patients diagnosed with STEMI and hypertension were included in this study database. Compared to the low TyG index group (

Abstract The intermittency and randomness of photovoltaic power present different characteristics due to seasonal variations, which greatly affects the reliability of power supply. To boost the prediction accuracy of photovoltaic power, a short-term prediction combination model named GSK–BiGRU–XGboost is proposed. First, the Pearson correlation coefficient is adopted to determine highly-correlated meteorological factors to photovoltaic power to construct the input features. Second, the prediction errors of different single models are compared, and the two, i.e., Bidirectional Gated Recurrent Unit (BiGRU) and Extreme Gradient Boosting (XGboost) that have the smallest errors and lowest correlation are selected to construct the combination model. Third, to achieve an appropriate weight coefficient of the model, an improved gaining sharing knowledge-based algorithm (GSK) based on parameter adaption is designed to optimize it effectively. Fourth, seasonal models and year-round model based on GSK–BiGRU–XGboost are compared to reveal the effect of seasonal characteristics. Finally, the influence of historical meteorological data window with different steps is investigated. To verify the performance of GSK–BiGRU–XGboost, it is compared with different single and combination models under different weather conditions. GSK–BiGRU–XGboost achieves a high prediction accuracy of 97.85%, which is 9.46% and 12.43% higher than its member models, respectively. Besides, GSK can lead to a 1.71% improvement in the accuracy.

Abstract Backgrounds Patients with major depressive disorder (MDD) have a high rate of metabolic syndrome (MetS), which could worsen disease progression. One of the most serious progressions in MDD is suicide attempts (SAs). Previous studies have found gender differences in MetS and SAs among MDD patients respectively. Therefore, we aimed to explore gender differences of SAs in first-episode and drug-naïve (FEDN) MDD patients with comorbid MetS. Methods 1718 outpatients with FEDN MDD were recruited. Depression, anxiety and psychotic symptoms were evaluated using the Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA) and Positive and Negative Syndrome Scale (PANSS) positive subscale, respectively. Blood sugar, blood fat, blood pressure and body mass index (BMI) were measured to evaluate MetS. Results 34.4% patients with FEDN MDD were diagnosed as MetS and those subjects with or without MetS differed in the distribution of SAs and gender. In MetS subgroup, 29.5% and 29.7% of male and female subjects had SAs respectively, without significant differences. However, compared with non-suicide attempters, suicide attempters had higher level of blood pressure in female subjects, while there are no differences in any clinical variables in male subjects. Additionally, the influencing factors for SAs differed by gender. The HAMA scores and BMI were variables associated with SAs in male patients while HAMA scores, marital status and systolic blood pressure (SBP) were associated with SAs in female patients. Furthermore, the receiver operating characteristics (ROC) curves, demonstrating the combination all influencing factors by gender, showed good performance and model accuracy. Conclusions In FEDN MDD patients with comorbid MetS, there were no gender differences in SAs. However, clinical characteristics and influencing factors of SAs differed in different gender groups.

Rock blasting technology is crucial for national economic development, particularly resource extraction and infrastructure construction. This paper explores the constitutive relationships in rock blasting, proposing three evolutionary stages: constitutive relationships 1.0, 2.0, and 3.0. These stages focus on contradictory relationships, energy balance, and minimum action theory, respectively. Constitutive relationship 1.0 centers on the interaction between rock and explosive impact loads, emphasizing the offense–defense dynamic. It analyzes the dynamic mechanical response of rock materials under explosive and impact loads, highlighting the conflict and balance between the explosive force and the rock resistance. This stage provides fundamental insights into the behavior of rock materials under high-stress conditions. Constitutive relationship 2.0 approaches the problem from an energy perspective. It treats rocks with significant anisotropy, joints, fractures, bedding, and cavities as complex structural materials. This stage studies the dynamic equilibrium between load input energy and the energy required to destroy the material. By understanding the relationship between structural strength, input energy, dissipated energy, and releasable strain energy, researchers can better predict the response of complex rock structures to explosive loads and improve blasting efficiency. Constitutive relationship 3.0 examines the propagation laws of stress waves under explosive loads and their relationship with medium damage effects. This stage focuses on optimizing energy propagation paths based on the minimum action theory, aiming to maximize the effectiveness of the explosive force while minimizing unwanted damage to the surrounding rock mass. These theories not only reveal the mechanical behavior of rocks under different load conditions but also provide a theoretical basis for optimizing blasting design and improving blasting outcomes. In addition to these theoretical advancements, the integration of artificial intelligence and big data technologies offers a new approach to managing and predicting rock material performance. This paper proposes the concept of rock material engineering genes, which involves establishing a rock gene library to systematically manage the physical and mechanical parameters of rocks. By constructing performance prediction models using advanced data analytics and machine learning algorithms, this approach enhances the accuracy of predicting how different rock types will respond to various engineering applications. Such a comprehensive database has significant implications for resource extraction, geological disaster prevention, and infrastructure construction. The rock material gene library is expected to play an increasingly important role in mineral resource development, geological disaster prevention, and infrastructure construction, thereby promoting the development and application of engineering technology. Its integration with traditional blasting techniques can lead to more efficient and safer methods of rock blasting, ultimately contributing to the advancement of engineering practices and economic development of regions dependent on these technologies. This holistic approach underscores the importance of continued research and technological innovation in rock blasting and material science.

In order to explore the properties differences of rice protein peptides prepared using different enzymatic hydrolysis routes of double enzymes, rice protein was enzymatically hydrolyzed by trypsin (A) and alkaline protease (B) according to different enzymatic hydrolysis routes to obtain five rice protein peptides (A1B1, A1B2, A2B1, A1*B2, A2B1*). The properties of protein peptides including the hydrolysis, basic components, amino acid composition, microstructure, secondary structure, molecular weight distribution, flavor and antioxidant activity in vitro were analyzed. The results indicated that the protein content of A2B1 group was the highest, reaching 90.69% and the peptide content was 72.73%. The hydrolysis degree of five rice protein peptides was greater than 17.60%, the degree of hydrolysis was relatively high, and the microstructure changed from irregular block to sphere. The A1B2 group and A1*B2 group had thicker spheroid walls, A2B1 group and A2B1* group had thinner spheroid walls, and A1B1 group was spheroid fragments. The essential amino acid content of five rice protein peptides was lower than that of rice protein, and the A1B2 group had the highest essential amino acid content. The secondary structure coexisted with a variety of conformations, and the secondary structures of five rice protein peptides were mainly β-turn, and it accounted for 44.62%~47.18%. Most of the enzymatic hydrolysates of five rice protein peptides were polypeptides with low molecular weight, and the polypeptides with molecular weight less than 5 kDa accounted for 92.09%~93.71%. A1B2 samples had the strongest umami and the weakest astringency, and A2B1 samples had the weakest saltiness and bitterness. Compared with A1B1, A1B2 and A1*B2, A2B1 and A2B1* groups had stronger antioxidant activity. Taking together, the quality of A2B1 group was the best based on the evaluation of basic components, peptide content, amino acid composition, flavor and antioxidant activity.

Rice protein peptide has been widely concerned by researchers at home and abroad, because of its high nutritional value, high digestibility, hypoallergenicity and various physiological regulation functions. Based on the research progress of rice protein peptides in recent years, this paper reviews the preparation methods, separation and purification techniques and bitter taste improvement strategies of rice protein peptides. And summarizes the biological activities of rice protein peptides such as antioxidant, blood pressure lowering, immunomodulatory and hypoglycemic activities, introduces its application prospect in the field of food, and prospects the future research direction. The aim is to provide theoretical basis for the development and practical production of rice protein peptide.

Complexes of hesperidin with different plant proteins (rice protein, pea protein, pea/rice complex protein) were prepared by pH-driven method to improve the water solubility, environmental stability, and bioavailability of hesperidin. The complexes were characterized by scanning electron microscopy, dynamically scattered light, and X-ray diffraction. Meanwhile, the high performance liquid chromatography was used to determine the hesperidin content to analyze the environmental stability of complexes and bioavailability of hesperidin. The results showed that three plant proteins were able to improve the water solubility of hesperidin, among which the pea/rice complex protein improved 19.6-fold, and the solubility of hesperidin in water reached 340.78 μg/mL. The environmental stability of hesperidin-pea/rice complex protein complex was basically better than that of single plant protein, in which the heat stabilization was the most effective, and the retention of hesperidin was at 65.09% after heating at 80 ℃ for 2 h. The in vitro digestion results showed that the bioavailability of hesperidin in hesperidin-pea/rice complex protein complex was the highest, which was about 5.22-fold of free hesperidin. This study provided a new idea to enhance the stability and bioavailability of hesperidin and helped to expand the application of hesperidin.

Abstract Prostate cancer (PCa) is one of the most important health problems among elderly men in China, with the increasing aging of the population. A cross-sectional survey was conducted in eastern China from 2022 to 2023. Recruitment included a total of 70,342 participants aged 60 or older. Social demographic information, such as individual factors like age, education levels and behavior habits, physical examination and laboratory tests results were collected. Age-standardized prevalence rates were estimated by a direct method with a standard population. T test and chi-square test were used to compare the statistical differences. Multivariate regression models were used to identify the risk factors of PCa. Overall, the crude and age-standardized PCa prevalence is 0.93% and 0.91%, respectively in eastern China. When we adjusted all the co-variables, it showed that high age, smoking, having a higher BMI and higher CA19-9 were associated with a higher risk for a prostate cancer diagnosis. Faced with the demographic transition, innovative strategies are needed to control and prevent PCa. Conducting early screening among male population in community health service centers in eastern of China, especially among a population with associated risk factors such as high age, obesity, and conducting community-based intervention programs might be helpful to address this increasingly significant health problem.

In the use of Sn58Bi solder alloy, the abnormal enrichment and coarsening of Bi phase in solder joints and the excessive growth of IMC seriously affect its service reliability, among which, the IMC's reaction mechanism and evolution, the influence on the coarsening of the Bi phase within the solder and the coarsening process are not yet clear. The study found that the initial type and morphology evolution of IMC of Sn58Bi/Cu solder joint are influenced by soldering temperature and cooling rate, attributed to the differences in dissolution and diffusion of Cu in Sn58Bi, resulting in different initial appearances of Cu6Sn5 and Cu3Sn; The temperature and cooling rate affect whether Cu6Sn5 and Cu3Sn are directly generated by the reaction of Cu atoms in the substrate or appear through the consumption of Cu3Sn or Cu6Sn5; The cooling rate affects the IMC morphology evolution of top-view; Based on this, it was cleared that Sn58Bi/Cu solder joints follow four interfacial reaction mechanisms. Meanwhile, the evolution of Bi phase in the solder is affected by the growth of IMC in Sn58Bi/Cu, resulting in varying degrees of coarsening. Analysis suggests that the entire coarsening process involves the aggregation, dissolution, and separation of Bi phase. This article elucidates the reaction mechanism of IMC growth at the Sn58Bi/Cu solder joint interface and its influence on the coarsening of Bi phase inside the solder, providing theoretical support for improving the reliability of Sn58Bi solder in the future.

Ferroptosis is a recently discovered form of cell death that is distinct from apoptosis, characterized primarily by the accumulation of intracellular iron and increased levels of lipid peroxidation. Resistance of tumor cells to ferroptosis can promote tumorigenesis and tumor progression. Various compounds can influence tumor development by triggering ferroptosis. Ferroptosis involves complex regulatory mechanisms, with mitochondria serving as both an iron storage and metabolic center, playing a crucial regulatory role in ferroptosis. This review discusses ferroptosis and its three stages and the role of ferroptosis in tumorigenesis, progression, and treatment, as well as the regulatory mechanisms of mitochondria in ferroptosis.

In order to solve the problems of flesh loss in the process of navel orange juice extraction and poor suspension stability of navel orange juice, this study used an industrial-scale microfluidizer system (ISMS) to prepare whole-flesh Gannan navel orange pulp, achieving ultra-fine pulp of Gannan navel orange. The effects of different ISMS processing pressures (0, 60, 90, and 120 MPa) on the physicochemical properties (particle size distribution, rheological properties, micro morphology, suspension stability, color, pH) and nutritional qualities (soluble solids, VC, carotenoids, limonin, naringin content) of Gannan navel orange pulp was investigated. The results showed that the particle size of whole-flesh Gannan navel orange pulp gradually decreased, and D[3,2] decreased from 59.77 μm to 26.47 μm when the ISMS pressure increased from 0 MPa to 120 MPa. The pulp particles were refined and dispersed more evenly. In addition, the apparent viscosity of orange pulp gradually increased, and the consistency coefficient K increased from 0.126 to 0.165. Compared with whole-flesh Gannan navel orange pulp without ISMS processing, when the ISMS processing pressure was 90 MPa, the instability index of navel orange pulp was the smallest, decreasing from 0.504 to 0.374, and the precipitation weight ratio was the highest, increasing from 40.80% to 59.48%, indicating that the suspension stability of the whole-flesh Gannan navel orange pulp was the best at this time. In addition, after ISMS processing, the C* of the whole flesh Gannan navel orange pulp gradually increased, and the overall color of the navel orange pulp became more saturated. Moreover, ISMS processing did not affect its pH and total soluble solid content. With the increase of ISMS processing pressure, the VC content in navel orange pulp increased by 11%, the total carotenoid content increased by 15%, and the limonin content increased by 10% after ISMS processing, but the naringin content remained was not changed. In summary, in order to preserve as much nutrients as possible, 120 MPa was chosen as the optimal pressure. This study shows that ISMS can produce whole-flesh Gannan navel orange pulp with good suspension stability and nutritional quality at the industrial level, providing a new pulping route for the navel orange industry.

In order to solve the problem of rancidity of rice polishing powder and improve its physicochemical properties, the effects of twin-screw extrusion under different extrusion temperatures on the storage stability and nutritional properties of rice polishing powder were studied. Under the optimum extrusion temperature, the rice polishing powder (SR-1, SR-2, SR-3, and SR-4) with different particle sizes was prepared by low temperature impact mill (LTIM) under different air classifier speeds (300, 600, 1200, and 1800 r/min). The effects of the air classifier speed on volatile aroma compounds and physicochemical properties of rice polishing powder were studied. The results showed that the lipase activity of rice polishing powder decreased significantly from 12.94 mg/g to 2.18 mg/g after extrusion treatment. Stored at the 150th day, the fatty acid value of untreated rice polishing powder was 255.57 mg KOH/100 g, while the fatty acid value of the extruded sample was only 121.90 mg KOH/100 g. After extrusion treatment, dietary fiber, γ-aminobutyric acid, and γ-oryzanol in rice polishing powder were also well retained. LTIM promoted the release of volatile aroma compounds in rice polishing powder, and SR-3 had the highest concentration. Based on the partial least square discriminant, 9 differentially labeled components were screened according to the importance projection of variables, and it was confirmed that SR-3 had the strongest flavor. With the decrease of particle size, the specific surface area of rice polishing powder gradually increased, and the bulk density showed a decreasing trend. The whiteness index increased significantly from 66.08 to 76.61. Water absorption ability and solubility increased significantly from 1.77 g/g and 24% to 2.37 g/g and 31%, respectively. Fourier transform infrared spectroscopy analysis showed that LTIM destroyed hydrogen bonds in starch particles, resulting in more free hydroxyl group exposure. The results can provide a theoretical basis and technical support for the processing of high-quality rice polishing powder.

Abstract Fibroblast growth factor 21 (FGF21) is essential for modulating hepatic homeostasis, but the impact of FGF21 on liver graft injury remains uncertain. Here, we show that high FGF21 levels in liver graft and serum are associated with improved graft function and survival in liver transplantation (LT) recipients. FGF21 deficiency aggravates early graft injury and activates arachidonic acid metabolism and regional inflammation in male mouse models of hepatic ischemia/reperfusion (I/R) injury and orthotopic LT. Mechanistically, FGF21 deficiency results in abnormal activation of the arachidonate 15-lipoxygenase (ALOX15)/15-hydroxy eicosatetraenoic acid (15-HETE) pathway, which triggers a cascade of innate immunity-dominated pro-inflammatory responses in grafts. Notably, the modulating role of FGF21/ALOX15/15-HETE pathway is more significant in steatotic livers. In contrast, pharmacological administration of recombinant FGF21 effectively protects against hepatic I/R injury. Overall, our study reveals the regulatory mechanism of FGF21 and offers insights into its potential clinical application in early liver graft injury after LT.

Abstract The severe mismatch between solid bioelectronics and dynamic biological tissues has posed enduring challenges in the biomonitoring community. Here, we developed a reconfigurable liquid cardiac sensor capable of adapting to dynamic biological tissues, facilitating ambulatory cardiac monitoring unhindered by motion artifacts or interference from other biological activities. We employed an ultrahigh-resolution 3D scanning technique to capture tomographic images of the skin on the wrist. Then, we established a theoretical model to gain a deep understanding of the intricate interaction between our reconfigurable sensor and dynamic biological tissues. To properly elucidate the advantages of this sensor, we conducted cardiac monitoring alongside benchmarks such as the electrocardiogram. The liquid cardiac sensor was demonstrated to produce stable signals of high quality (23.1 dB) in ambulatory settings.