A developed and validated centrifugal ultrafiltration coupled with high performance liquid chromatography-tandem mass spectrometry method for rapid quantification of unbound lenvatinib in human plasma.

In clinical practice, the determination of unbound drug concentration is very important for dose adjustment and toxicity prediction because only the unbound fraction can achieve a pharmacological effect. A fast, sensitive and accurate analytical method of centrifugal ultrafiltration coupled with high performance liquid chromatography-tandem mass spectrometry method was developed and applied to allow the quantification of unbound lenvatinib concentration. The application of linear regression analysis was used to examine the effects of centrifugal force, centrifugal time, and protein content on ultrafiltrate volume (Vu). The results indicated that the centrifugal force and centrifugal time have an influence on Vu that is significantly positive (P < 0.05). This developed method with good linearity (r2 = 0.9996), good accuracy (bias % ≤ 2.24 %), good precision (CV % ≤ 7.10 %), and good recovery (95.46 %-106.46 %) was suitable for routine clinical practice and studies. Particularly, the ultrafiltration membrane had no non-specific binding to lenvatinib. The unbound fractions can be separated in just 15 min. This method was applied to quantify clinical samples and to determine the plasma protein binding and unbound fraction of lenvatinib. This study provides a more effective and promising method for determination of unbound lenvatinib. It could be beneficial to measure the unbound concentration of lenvatinib in personalized medicine and therapeutic drug monitoring in routine clinical practice.

Identification of molecular subtypes based on chromatin regulator-related genes and experimental verification of the role of ASCL1 in conferring chemotherapy resistance to breast cancer.

Objective: The aim of this study was to identify the molecular subtypes of breast cancer based on chromatin regulator-related genes. Methods: The RNA sequencing data of The Cancer Genome Atlas-Breast Cancer cohort were obtained from the official website, while the single-cell data were downloaded from the Gene Expression Omnibus database (GSE176078). Validation was performed using the Molecular Taxonomy of Breast Cancer International Consortium dataset. Furthermore, the immune characteristics, tumor stemness, heterogeneity, and clinical characteristics of these molecular subtypes were analyzed. The correlation between chromatin regulators and chemotherapy resistance was examined in vitro using the quantitative real-time polymerase chain reaction (qRT-PCR) and Cell Counting Kit-8 (CCK8) assays. Results: This study identified three stable molecular subtypes with different prognostic and pathological features. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction analyses revealed that the differentially expressed genes were associated with disease processes, such as mitotic nuclear division, chromosome segregation, condensed chromosome, and specific chromosome region. The T stage and subtypes were correlated with the clinical features. Tumor heterogeneity (mutant-allele tumor heterogeneity, tumor mutational burden, purity, and homologous recombination deficiency) and tumor stemness (RNA expression-based stemness score, epigenetically regulated RNA expression-based stemness score, DNA methylation-based stemness score, and epigenetically regulated DNA methylation-based stemness score) significantly varied between the three subtypes. Furthermore, Western blotting, qRT-PCR, and CCK8 assays demonstrated that the expression of ASCL1 was positively correlated with chemotherapy resistance in breast cancer. Conclusion: This study identified the subtypes of breast cancer based on chromatin regulators and analyzed their clinical features, gene mutation status, immunophenotype, and drug sensitivity. The results of this study provide effective strategies for assessing clinical prognosis and developing personalized treatment strategies.

Constructing 3D Zincophilic Skeleton in Nitrogen-Doped Carbon Hybrid Fibers for Dendrite-Free Zn Anodes.

The Zn dendrite growth and side reactions are two major issues for the practical use of Zn metal anodes (ZMAs). Herein, an N-doped carbon-based hybrid fiber with the 3D porous skeleton and the zincophilic Cu nanoparticles (denoted as Cu@HLCF) is developed for stable ZMAs. The zincophilic Cu particles in the skeleton work as the active sites to facilitate uniform Zn nucleation. Meanwhile, the abundant pores in the framework of the hybrid fibers provide a large space to relieve the structural stress and suppress the dendrite growth. Moreover, the good mechanical characteristics of the hybrid fiber ensure its high potential applications for flexible electronics. Theoretical analysis results disclose the strong interaction between Zn and Cu sites, and experimental results demonstrate the low voltage hysteresis, high reversibility, and dendrite-free behavior of the Cu@HLCF host for Zn plating/stripping. Moreover, the solid-state Zn-ion battery (ZIB) assembled with a Cu@HLCF/Zn anode shows the prominent flexibility, impressively reliability, and outstanding cycling capability. Therefore, this work not only provides a novel design for the efficient and stable Zn metal anode but also promotes the development of flexible power sources for flexible electronics.

Achieving High-Rate and Stable Sodium-Ion Storage by Constructing Okra-Like NiS2/FeS2@Multichannel Carbon Nanofibers.

Transition metal sulfides (TMSs) are considered as promising anode materials for sodium-ion batteries (SIBs) due to their high theoretical capacities. However, the relatively low electrical conductivity, large volume variation, and easy aggregation/pulverization of active materials seriously hinder their practical application. Herein, okra-like NiS2/FeS2 particles encapsulated in multichannel N-doped carbon nanofibers (NiS2/FeS2@MCNFs) are fabricated by a coprecipitation, electrospinning, and carbonization/sulfurization strategy. The combined advantages arising from the hollow multichannel structure in carbon skeleton and heterogeneous NiS2/FeS2 particles with rich interfaces can provide facile ion/electron transfer paths, ensure boosted reaction kinetics, and help maintain the structural integrity, thereby resulting in a high reversible capacity (457 mA h g-1 at 1 A g-1), excellent rate performance (350 mA h g-1 at 5 A g-1), and outstanding long-term cycling stability (93.5% retention after 1100 cycles). This work provides a facile and efficient synthetic strategy to develop TMS-based heterostructured anode materials with high-rate and stable sodium storage properties.

Rhizoma Alismatis Decoction improved mitochondrial dysfunction to alleviate SASP by enhancing autophagy flux and apoptosis in hyperlipidemia acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas, especially hyperlipidemia acute pancreatitis (HLAP) is the third leading cause of acute pancreatitis which is more severe with a greater incidence of persistent multiorgan failure. HLAP inflicts injury upon the organelles within the acinar cell, particularly mitochondria, the endolysosomal-autophagy system, and is accompanied by senescence-associated secretory phenotype (SASP). RAD, only two consists of Rhizoma Alismatis and Atractylodes macrocephala Rhizoma, which is best known for its ability to anti-inflammatory and lipid-lowering. Nevertheless, the mechanism by which RAD alleviates HLAP remains obscure, necessitating further investigation. PURPOSE: The study aimed to assess the effects of the RAD on HLAP and to elucidate the underlying mechanism in vivo and in vitro, offering a potential medicine for clinical treatment for HLAP. STUDY DESIGN AND METHODS: C57BL/6 mice with hyperlipidemia acute pancreatitis were induced by HFD and CER, then administrated with RAD. AR42J were stimulated by cerulein or conditioned medium and then cultured with RAD. Serums were analyzed to evaluate potential pancreas and liver damage. Furthermore, tissue samples were obtained for histological, and protein investigations by H&E, Oil red staining, and Western blot. In addition, western blot and immunofluorescent staining were utilized to estimate the effect of RAD on mitochondrial function, autophagy flux, and SASP. RESULTS: In vivo, RAD considerably alleviated systemic inflammation while attenuating TC, TG, AMY, LPS, inflammatory cytokines, histopathology changes, oxidative damage, mitochondrial fission, and autophagy markers in HLAP mice. Impaired autophagy flux and mitochondrial dysfunction resulted in a significant enhancement of NLRP3 and IL-1ß in the pancreas. RAD could reverse these changes. In vitro, RAD significantly restored mitochondrial membrane potential and oxidative phosphorylation levels. RAD decreased Beclin-1 and LC3-II expression and increased LAMP-1 and Parkin-Pink expression, which showed that RAD significantly ameliorated HLAP-induced damage to the mitochondria function by suppressing mitochondrial oxidative damage and enhancing autophagy flux and mitophagy to remove the damaged mitochondria. In addition, we found that RAD could up-regulate the expression of BAX, and Bad and down-regulate the expression of p16, and p21, indicating that RAD could promote damaged cell apoptosis and alleviate SASP. CONCLUSIONS: This study revealed that RAD ameliorates mitochondrial function to alleviate SASP through enhancing autophagy flux, mitophagy, and apoptosis which provided a molecular basis for the advancement and development of protection strategies against HLAP.

Deciphering the antidepressant effects of Rosa damascena essential oil mediated through the serotonergic synapse signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa damascena is an ancient plant with significance in both medicine and perfumery that have a variety of therapeutic properties, including antidepressant, anti-anxiety, and anti-stress effects. Rose damascena essential oil (REO) has been used to treat depression, anxiety and other neurological related disorders in Iranian traditional medicine. However, its precise mechanism of action remains elusive. AIM OF THE STUDY: The aim of this study was to investigate the impact and mechanism underlying the influence of REO on chronic unpredictable mild stress (CUMS) rats. MATERIALS AND METHODS: Gas chromatography-mass spectrometry (GC-MS) technique coupling was used to analyze of the components of REO. A CUMS rat model was replicated to assess the antidepressant effects of varying doses of REO. This assessment encompassed behavioral evaluations, biochemical index measurements, and hematoxylin-eosin staining. For a comprehensive analysis of hippocampal tissues, we employed transcriptomics and incorporated weighting coefficients by means of network pharmacology. These measures allowed us to explore differentially expressed genes and biofunctional pathways affected by REO in the context of depression treatment. Furthermore, GC-MS metabolomics was employed to assess metabolic profiles, while a joint analysis in Metscape facilitated the construction of a network elucidating the links between differentially expressed genes and metabolites, thereby elucidating potential relationships and clarifying key pathways regulated by REO. Finally, the expression of relevant proteins in the key pathways was determined through immunohistochemistry and Western blot analysis. Molecular docking was utilized to investigate the interactions between active components and key targets, thereby validating the experimental results. RESULTS: REO alleviated depressive-like behavior, significantly elevated levels of the neurotransmitter 5-hydroxytryptamine (5-HT), and reduced hippocampal neuronal damage in CUMS rats. This therapeutic effect may be associated with the modulation of the serotonergic synapse signaling pathway. Furthermore, REO rectified metabolic disturbances, primarily through the regulation of amino acid metabolic pathways. Joint analysis revealed five differentially expressed genes (EEF1A1, LOC729197, ATP8A2, NDST4, and GAD2), suggesting their potential in alleviating depressive symptoms by modulating the serotonergic synapse signaling pathway and tryptophan metabolism. REO also modulated the 5-HT2A-mediated extracellular regulated protein kinases-cAMP-response element binding protein-brain-derived neurotrophic factor (ERK-CREB-BDNF) pathway. In addition, molecular docking results indicated that citronellol, geraniol and (E,E)-farnesol in REO may serve as key active ingredients responsible for its antidepressant effects. CONCLUSIONS: This study is the first to report that REO can effectively alleviate CUMS-induced depression-like effects in rats. Additionally, the study offers a comprehensive understanding of its intricate antidepressant mechanism from a multi-omics and multi-level perspective. Our findings hold promise for the clinical application and further development of this essential oil.

Decreased vitamin D bio-availability with altered DNA methylation of its metabolism genes in association with the metabolic disorders among the school-aged children with degree I, II, and III obesity.

Obesity is strongly associated with disturbances of vitamin D (VD) metabolites in the animal models. However, the related epidemiological evidence is still controversial, especially the different degrees of obesity children. Hence, in this present representative case-control study, 106 obesity school-age children aged 7-12 years were included and divided into different subgroups as degree I (the age- and sex-specific BMI≥95th percentile, n=45), II (BMI ≥120% percentile, n=34) and III (BMI ≥140% percentile, n=27) obesity groups across the ranges of body mass index (BMI). While the age- and sex-matched subjects without obesity were as the control group. Notably, it was significantly different of body composition, anthropological and clinical characteristics among the above four subgroups with the dose-response relationships (P<.05). Moreover, comparing with the control group, the serum VD concentrations were higher, VD metabolites like 25(OH)D, 25(OH)D3 and 1,25(OH)2D, and related hydroxylases as CYP27A1, CYP2R1 and CYP27B1 were lower in the degree I, II, and III obesity subgroups (P<.05), which were more disorder with the anthropological and clinical characteristics as the obesity was worsen in a BMI-independent manner (P<.05). However, there was a significant increase of CYP27B1 in the degree III obesity group than those in the degree I and II obesity subgroups. Furthermore, the methylation patterns on the genome-wide (Methylation/Hydroxymethylation) and VD metabolism genes (CYP27A1, CYP2R1 and CYP27B1) were negatively correlated with the worse obesity and their related expressions (P<.05). In summary, these results indicated that obesity could affect the homeostasis of VD metabolism related genes such as CYP27A1, CYP2R1, CYP27B1 and etc through abnormal DNA methylation, resulting in the disorders of VD related metabolites to decrease VD bio-availability with the BMI-independent manner. In turn, the lower levels of VD metabolites would affect the liver function to exacerbate the progression of obesity, as the Degree II and III obesity subgroups.

Safe Induction of Acute Inflammation with Enhanced Antitumor Immunity by Hydrogel-Mediated Outer Membrane Vesicle Delivery.

Acute inflammation has the potential for the recruitment of immune cells, inhibiting tumor angiogenesis, metastasis, and drug resistance thereby overcoming the tumor immunosuppressive microenvironment caused by chronic inflammation. Here, an acute inflammation inducer using bacteria outer membrane vesicles (OMVs) loaded in thermal-sensitive hydrogel (named OMVs-gel) for localized and controlled release of OMVs in tumor sites is proposed. OMVs trigger neutrophil recruitment and amplify acute inflammation inside tumor tissues. The hydrogel ensures drastic inflammation is confined within the tumor, addressing biosafety concerns that the direct administration of free OMVs may cause fatal effects. This strategy eradicated solid tumors safely and rapidly. The study further elucidates one of the possible immune mechanisms of OMVs-gel therapy, which involves the assembly of antitumor neutrophils and elastase release for selective tumor killing. Additionally, tumor vascular destruction induced by OMVs-gel results in tumor darkening, allowing for combinational photothermal therapy. The findings suggest that the use of OMVs-gel can safely induce acute inflammation and enhance antitumor immunity, representing a promising strategy to promote acute inflammation application in tumor immunotherapy.

NLRP3 Inflammasome Activation During Acute Negative Pressure Injury in the Middle Ear of Mice.

HYPOTHESIS: The present study was conducted to explore the role of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in mouse otic barotrauma models. BACKGROUND: Previous studies suggest that the NLRP3 inflammasome plays an important role in the pathogenesis of middle ear disease. However, whether middle ear negative pressure injury underlies NLRP3 inflammasome activation remains unclear. METHODS: Wild-type and Nlrp3 -/- mice were randomly assigned to control and pressure injury groups, respectively. Pressure loading was performed using a pressure cabin with the pressure level set to 20 kPa higher than that of the ambient atmosphere. This was achieved in approximately 15 seconds and maintained for 10 minutes. Hematoxylin and eosin staining was performed to detect morphological changes of the middle ear mucosa, tissue IL-1ß was measured via an enzyme-linked immunosorbent assay, and cleaved caspase-1 was detected by Western blot. RESULTS: We found that the maturation of caspase-1 and IL-1ß production in the middle ear significantly increased after otic barotrauma. In Nlrp3 -/- mice, inflammasome activation is downregulated and mucosal hyperplasia is reduced compared with those of wild-type mice during recovery. CONCLUSION: The NLRP3 inflammasome likely plays an important role in the pathogenesis of otic barotrauma. Controlling activation of the NLRP3 inflammasome may promote middle ear recovery after negative pressure injury.

Effects of soil heterogeneity and preferential flow on the water flow and isotope transport in an experimental hillslope.

Soil water movement plays vital roles in hillslope runoff generation and groundwater and surface water interaction. However, there are still knowledge gaps about the impacts of soil heterogeneity and preferential flow on the internal water flow and transport process. In this study, the vertical soil heterogeneity focused on the variations in soil retention capacity, and the consideration of lateral preferential flow emphasized the higher hydraulic conductivity. We combined isotopic tracing and numerical modeling in an artificial hillslope, focusing on monitored processes of the artificial rainfall and isotopic tracing experiment. The results showed that the soil moisture quickly accumulated at the bottom of the hillslope during rainfall events, while the 2H enrichment occurred in the topsoil derived from enriched isotope injection in the second artificial rainfall. The evaporation process slowed down the mixing of new water in the topsoil and old water in the lower layer. We found that the vertical soil heterogeneity had significant influences on the internal water and isotope transport paths within the hillslope. The lateral preferential flow played an important role in the water flux and transport time to the seepage face. The coupling of isotopic tracing, which reflects the water transport and mixing with the hillslope, effectively improved the model simulation and mechanism analysis of hillslope water flow. Our findings provide new insights into the mechanisms governing soil water flow and transport dynamics in hillslopes, taking into account vertical soil heterogeneity and lateral preferential flow.

High mobility group box 1 knockdown inhibits EV71 replication and attenuates cell pyroptosis through TLR4/NF-κB/NLRP3 axis.

Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD) in children. Nowadays, there are still no effective antiviral drugs for EV71 infection. High mobility group box 1 (HMGB1) is reported to be highly expressed in HFMD patients. However, the role and underlying mechanism of HMGB1 in EV71-associated HFMD are still unclear. HMGB1 expression was detected using RT-qPCR and western blot assays. Loss- and gain-function experiments were performed to evaluate the effects of HMGB1 on EV71-infected cells. The virus titer was examined by TCID50. CCK-8 and flow cytometry assays were applied to detect the cell viability and cell cycle. Oxidative stress was determined by relative commercial kits. HMGB1 level was elevated in the serum of EV71-infected patients with HFMD and EV71-induced RD cells. EV71 infection induced the transfer of HMGB1 from the nucleus into the cytoplasm. HMGB1 knockdown inhibited virus replication, viral protein (VP1) expression and promoted antiviral factor expression. In addition, the inhibition of HMGB1 improved cell viability, protected against S phase arrest, and inhibited EV71-induced cell injury and oxidative stress, whereas HMGB1 overexpression showed the opposite effects. In terms of mechanism, HMGB1 overexpression activated the TLR4/NF-κB/NLRP3 signaling pathway and promoted cell pyroptosis. The inhibition of TLR4 and NF-κB reversed the effects of HMGB1 overexpression on virus replication, oxidative stress, and pyroptosis. In conclusion, HMGB1 knockdown inhibits EV71 replication and attenuates pyroptosis through TLR4/NF-κB/NLRP3 axis.

The color/shape/flavor of yam gel with double emulsified microcapsules changed synchronously in 4D printing induced by microwave.

The feasibility of 3D printing the color, aroma and shape changes of yam gel with microwave heating as stimulus and soybean protein isolate-chitosan-maltodextrin complex coacervated microcapsules rich in water-soluble betacyanin and rose essence as stimulus-response materials was discussed. The morphology of microcapsules presented irregular spherical structure, and the surface was relatively smooth and slightly concave. Microwave heating led to the gradual destruction of microcapsules in yam gel, releasing internal pigments and essence, and enhancing the redness and flavor of printed samples. The release of the water phase and oil phase of the microcapsules and the hot-spot expansion effect of the models made the 3D printed bird models bend and deform, realizing the deformation effect of "spreading of wings", which realized a three-response synchronous change in color, shape, and flavor of the printed samples within 45 s. In this study, a variety of 4D printed foods with synchronous changes in sensory characteristics were created, which increased sensory enjoyment on the basis of ensuring the nutritional needs of food.

Basis with RNA-Seq and WGCNA to explore the effect of Frankincense essential oil on dextran sodium sulfate-induced ulcerative colitis through MAPK/NF-κB signaling.

PURPOSE: Frankincense has been shown in studies to have healing benefits for people with ulcerative colitis (UC). However, its underlying mechanisms have not been fully investigated. The objective of this study was to explore the potential molecular mechanisms of Frankincense essential oil (FREO) in improving dextran sodium sulfate (DSS)-induced UC from multiple perspectives. METHODS: The FREO components were analyzed by GC-MS, and the interactions between the key active components and the mechanism of FREO were determined based on RNA-seq, "quantity-effect" weighting coefficient network pharmacology, WGCNA and pharmacodynamic experiments. The protection of FREO against DSS-induced UC mice was assessed by behavioral and pathological changes through mice. The expression of pro-inflammatory cytokines was measured using enzyme-linked immunosorbent assay. The expression of MAPK and NF-κB-related proteins by the Western Blotting and immunohistochemistry method. RESULTS: Treatment with FREO significantly improved the symptoms of weight loss, diarrhea, stool blood, and colon shortening in UC mice. Reduced intestinal mucosal damage and the degree of inflammatory cell infiltration in the colon. Decreased TNF-α and IL-6 levels in mice's serum and inhibited phosphorylation of ERK, p65 in MAPK and NF-κB signaling. CONCLUSION: FREO may decrease the inflammatory response to reduce the symptoms of UC by modulating the MAPK/ NF-κB pathway. This may be due to the synergistic interaction of the effective ingredient Hepten-2-yl tiglate, 6-methyl-5-, Isoneocembrene A and P-Cymene. This study provides a promising drug candidate and a new concept for the treatment of UC.

Multiple delivery strategies of nanocarriers for myocardial ischemia-reperfusion injury: current strategies and future prospective.

Acute myocardial infarction, characterized by high morbidity and mortality, has now become a serious health hazard for human beings. Conventional surgical interventions to restore blood flow can rapidly relieve acute myocardial ischemia, but the ensuing myocardial ischemia-reperfusion injury (MI/RI) and subsequent heart failure have become medical challenges that researchers have been trying to overcome. The pathogenesis of MI/RI involves several mechanisms, including overproduction of reactive oxygen species, abnormal mitochondrial function, calcium overload, and other factors that induce cell death and inflammatory responses. These mechanisms have led to the exploration of antioxidant and inflammation-modulating therapies, as well as the development of myocardial protective factors and stem cell therapies. However, the short half-life, low bioavailability, and lack of targeting of these drugs that modulate these pathological mechanisms, combined with liver and spleen sequestration and continuous washout of blood flow from myocardial sites, severely compromise the expected efficacy of clinical drugs. To address these issues, employing conventional nanocarriers and integrating them with contemporary biomimetic nanocarriers, which rely on passive targeting and active targeting through precise modifications, can effectively prolong the duration of therapeutic agents within the body, enhance their bioavailability, and augment their retention at the injured myocardium. Consequently, these approaches significantly enhance therapeutic effectiveness while minimizing toxic side effects. This article reviews current drug delivery systems used for MI/RI, aiming to offer a fresh perspective on treating this disease.

Clinicopathological characteristics and prognosis of metaplastic breast cancer versus triple-negative invasive ductal carcinoma: a retrospective analysis.

BACKGROUND: Metaplastic breast cancer(MBC) is a specific pathological type of invasive breast cancer. There are few studies related to MBC due to its rarity. This study aimed to analyse the differences in clinicopathological characteristics and prognosis between Metaplastic breast cancer and triple-negative invasive ductal carcinoma (TN-IDC). METHODS: We retrospectively compared the clinicopathological characteristics of patients diagnosed with MBC and TN-IDC at the Fourth Hospital of Hebei Medical University between 2011 and 2020 in a 1:2 ratio. The log-rank test was used to compare the two groups' disease-free survival (DFS) and overall survival (OS). For MBCs, we performed univariate and multivariate analyses using the Cox proportional hazards model to determine the characteristics that impacted OS and DFS. RESULTS: A total of 81 patients with MBC and 162 patients with TN-IDC were included in this study. At initial diagnosis, MBC patients had larger tumour diameters(P = 0.03) and fewer positive lymph nodes (P = 0.04). Patients with MBC were more likely to have organ metastases after surgery (P = 0.03). Despite receiving the same treatment, MBC patients had worse DFS (HR = 1.66, 95%CI 0.90-3.08, P = 0.11) and OS (HR = 1.98, 95% CI 1.03-3.81, P = 0.04), and OS was statistically significant. Positive lymph nodes at initial diagnosis were associated with worse DFS (HR = 3.98, 95%CI 1.05-15.12, P = 0.04) and OS (HR = 3.70, 95%CI 1.03-13.34, P = 0.04) for patients with MBC. The efficacy of platinum-based agents is insensitive for MBC patients receiving chemotherapy. In addition, patients treated with preoperative chemotherapy had worse DFS compared to patients treated with postoperative chemotherapy (HR = 3.51, 95%CI 1.05-11.75, P = 0.04). CONCLUSIONS: The clinicopathological characteristics and prognosis of MBC and TN-IDC differ in many ways. Further studies are required to determine suitable treatment guidelines for patients with MBC.

Effect of tumor-infiltrating lymphocytes depending on the presence of postmastectomy radiotherapy on the prognosis in pT1-2N1M0 breast cancer.

Background: Currently, it remains unclear regarding the association between tumor-infiltrating lymphocytes (TILs) and the efficacy of postoperative radiotherapy in primary tumors. Here we attempted to investigate the effect of TILs depending on the presence of postmastectomy radiotherapy (PMRT) on the prognosis in pT1-2N1M0 breast cancer. Methods: The clinical data of pT1-2N1M0 breast cancer patients undergoing mastectomy and axillary lymph node dissection were retrospectively analyzed. The effect of TILs on the prognosis was assessed based on the infiltration degree (low: TILs ≤10%, high: TILs >10%), and then the prognosis of patients with low and high infiltration of TILs was analyzed based on presence or absence of PMRT. Results: Totally 213 patients were eligible for the study, including 162 cases of low infiltration and 51 of high infiltration. High-infiltration patients tended to be ER/PR-negative, HER2-positive, and have high histological grade. The infiltration in triple-negative and HER2-positive subtypes was higher compared with Luminal A subtype. Regarding local-regional recurrence-free survival, recurrence-free survival, and overall survival (OS) rates, the differences were all inapparent whether in high- and low-infiltration patients or in high-infiltration patients with/without PMRT. Compared with those without PMRT, low-infiltration patients with PMRT showed a significantly increased OS rate (92.8% vs. 80.0%, p=0.023). Multivariate analysis further confirmed PMRT as an independent predicator of OS in low-infiltration patients (HR: 0.228, 95%CI: 0.081-0.644, p=0.005). Conclusion: High infiltration of TILs in pT1-2N1M0 breast cancer may be associated with clinicopathological factors. Low-infiltration patients, but not high-infiltration patients, may derive survival benefits from PMRT.

Flavor Characterization of Native Xinjiang Flat Peaches Based on Constructing Aroma Fingerprinting and Stoichiometry Analysis.

The flat peach is a high economic value table fruit possessing excellent quality and a unique aroma. This article investigated the quality characteristics and aroma fingerprinting of flat peaches (Qingpan, QP; Ruipan 2, R2; Ruipan 4, R4; Wanpan, WP) from Xinjiang in terms of taste, antioxidant capacity, and volatile aroma compounds using high-performance liquid chromatography (HPLC) and HS-SPME-GC-MS. The results showed that the flat peaches had a good taste and high antioxidant capacity, mainly due to the high sugar-low acid property and high levels of phenolic compounds. This study found that sucrose (63.86~73.86%) was the main sugar, and malic acid (5.93~14.96%) and quinic acid (5.25~15.01%) were the main organic acids. Furthermore, chlorogenic acid (main phenolic compound), epicatechin, rutin, catechin, proanthocyanidin B1, and neochlorogenic acid were positively related to the antioxidant activity of flat peaches. All flat peaches had similar aroma characteristics and were rich in aromatic content. Aldehydes (especially benzaldehyde and 2-hexenal) and esters were the main volatile compounds. The aroma fingerprinting of flat peaches consisted of hexanal, 2-hexenal, nonanal, decanal, benzaldehyde, 2,4-decadienal, dihydro-ß-ionone, 6-pentylpyran-2-one, 2-hexenyl acetate, ethyl caprylate, γ-decalactone, and theaspirane, with a "peach-like", "fruit", and "coconut-like" aroma. Among them, 2,4-decadienal, 2-hexenyl acetate, and theaspirane were the characteristic aroma compounds of flat peaches. The results provide a theoretical basis for the industrial application of the special aroma of flat peaches.

Spatially Confined Fe7S8 Nanoparticles Anchored on a Porous Nitrogen-Doped Carbon Nanosheet Skeleton for High-Rate and Durable Sodium Storage.

Iron sulfides are widely explored as anodes of sodium-ion batteries (SIBs) owing to high theoretical capacities and low cost, but their practical application is still impeded by poor rate capability and fast capacity decay. Herein, for the first time, we construct highly dispersed Fe7S8 nanoparticles anchored on a porous N-doped carbon nanosheet (CN) skeleton (denoted as Fe7S8/NC) with high conductivity and numerous active sites via facile ion adsorption and thermal evaporation combined procedures coupled with a gas sulfurization treatment. Nanoscale design coupled with a conductive carbon skeleton can simultaneously mitigate the above obstacles to obtain enhanced structural stability and faster electrode reaction kinetics. With the aid of density functional theory (DFT) calculations, the synergistic interaction between CNs and Fe7S8 can not only ensure enhanced Na+ adsorption ability but also promote the charge transfer kinetics of the Fe7S8/NC electrode. Accordingly, the designed Fe7S8/NC electrode exhibits remarkable electrochemical performance with superior high-rate capability (451.4 mAh g-1 at 6 A g-1) and excellent long-term cycling stability (508.5 mAh g-1 over 1000 cycles at 4 A g-1) due to effectively alleviated volumetric variation, accelerated charge transfer kinetics, and strengthened structural integrity. Our work provides a feasible and effective design strategy toward the low-cost and scalable production of high-performance metal sulfide anode materials for SIBs.

Novel strategies for controlling nitrite content in prepared dishes: Current status, potential benefits, limitations and future challenges.

Sodium nitrite is commonly used as a multifunctional curing ingredient in the processing of prepared dishes, especially meat products, to impart unique color, flavor and to prolong the shelf life of such products. However, the use of sodium nitrite in the meat industry has been controversial due to potential health risks. Finding suitable substitutes for sodium nitrite and controlling nitrite residue have been a major challenge faced by the meat processing industry. This paper summarizes possible factors affecting the variation of nitrite content in the processing of prepared dishes. New strategies for controlling nitrite residues in meat dishes, including natural pre-converted nitrite, plant extracts, irradiation, non-thermal plasma and high hydrostatic pressure (HHP), are discussed in detail. The advantages and limitations of these strategies are also summarized. Raw materials, cooking techniques, packaging methods, and storage conditions all affect the content of nitrite in the prepared dishes. The use of vegetable pre-conversion nitrite and the addition of plant extracts can help reduce nitrite residues in meat products and meet the consumer demand for clean labeled meat products. Atmospheric pressure plasma, as a non-thermal pasteurization and curing process, is a promising meat processing technology. HHP has good bactericidal effect and is suitable for hurdle technology to limit the amount of sodium nitrite added. This review is intended to provide insights for the control of nitrite in the modern production of prepared dishes.