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Purpose: This prospective study aims to evaluate the value of [ 18 F]AlF-NOTA-fibroblast activation protein inhibitor (FAPI)-04 positron emission tomography-computed tomography (PET/CT) in predicting molecular subtypes of breast cancer., Methods: The study consecutively recruited patients suspected of having breast cancer from a single center who were prospectively enrolled from July 2023 to May 2024 and underwent [ 18 F]AlF-NOTA-FAPI-04 PET/CT. This study compared the differences in tracer uptake among breast cancers with different adverse prognostic factors and molecular subtypes. The classification performance for each molecular subtype of breast cancer was assessed using a receiver operating characteristic (ROC) curve., Results: Fifty-three participants (mean age, 51 ± 11 years; 52 females) were evaluated. Breast cancer lesions with adverse prognostic factors showed higher tracer uptake. The five different molecular subtypes exhibited varying levels of uptake. The luminal A and luminal B (HER2-negative) subtypes had relatively low uptake, while the luminal B (HER2-positive), HER2-positive, and triple-negative subtypes had relatively high uptake. ROC analysis identified the max standardized uptake value (SUV max ) as a significant classifier (AUC = 0.912, P = 0.0005) for the luminal A subtype, with 100% sensitivity and 83% specificity. For predicting the luminal B (HER2-negative) subtype, SUV max had an AUC of 0.770 (P = 0.0015). SUV max , with an AUC of 0.781 (P = 0.003), was used to identify the triple-negative subtype tumors, resulting in a sensitivity of 100% and specificity of 51%. Lastly, the ROC curve showed the cut-off 15.40 (AUC = 0.921, P < 0.0001) could classify luminal A & luminal B (HER2-negative), and luminal B (HER2-positive) & HER2-positive & triple-negative, yielding a sensitivity of 94% and specificity of 79%., Conclusion: The uptake of [ 18 F]AlF-NOTA-FAPI-04 is significantly correlated with the molecular subtypes of breast cancer, and [ 18 F]AlF-NOTA-FAPI-04 PET/CT is a potential tool for noninvasive identification of luminal A subtypes and guidance of FAP-targeted therapies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Elderly patients with hip fractures are at a greater risk of developing postoperative delirium (POD), which significantly impacts their recovery and overall quality of life. Neuroinflammation is a pathogenic mechanism of POD. Taohong Siwu Decoction (THSWD), known for its ability to promote blood circulation and remove blood stasis, can effectively reduce inflammation in the nervous system. Therefore, the objective of this article is to provide a comprehensive summary of the clinical efficacy of THSWD in the prevention of POD. Additionally, it aims to investigate the underlying mechanism of THSWD in the prevention and treatment of POD using network pharmacology and molecular docking., Methods: We conducted a retrospective analysis of patients with intertrochanteric fractures between January 2016 and October 2021. The patients were divided into two groups: the control and THSWD group. We performed a comparative analysis of hemoglobin (HB), albumin (ALB), C-reactive protein (CRP), blood urea nitrogen (BUN), and the blood urea nitrogen to creatinine ratio (BCR) on two different time points: the day before surgery (D0) and the third day after surgery (D3). Furthermore, we examined the incidence and duration of delirium, as well as the Harris Hip Score (HHS) at 3 months and 12 months post-surgery. Network pharmacology was employed to identify the primary targets and mechanisms of THSWD in the management of delirium. Molecular docking was employed to confirm the interaction between active ingredients and COX-2. Inflammatory cytokines, including cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-α), were measured using the enzyme-linked immunosorbent assay (ELISA). The cognitive status of the patients was assessed using the Mini-Mental State Examination (MMSE) scoring system., Results: Regardless of whether it is in D0 or D3, THSWD treatment can increase HB levels while decreasing BCR. In D3, the THSWD group demonstrated a significant reduction in the expression of CRP and BUN when compared to the control group. However, there were no significant differences in ABL levels, surgery duration, and blood loss between the two groups. Additionally, THSWD treatment requires fewer blood transfusions and can reduce the incidence and duration of POD. The results of the logistic analysis suggest that both CRP levels and BCR independently contribute to the risk of POD. Network pharmacology analysis indicates that THSWD has the potential to prevent and treat POD possibly through inflammatory pathways such as IL-17 signaling pathways and NF-kappa B signaling pathways. Molecular docking validated the interaction between the active ingredient of THSWD and COX-2. Furthermore, THSWD treatment can reduce the levels of COX-2, IL-1β, IL-6, TNF-α, BUN and CRP in the blood of patients with POD, increase HB levels, and enhance MMSE scores. The expression of COX-2 is positively associated with other inflammatory markers (IL-1β, IL-6, TNF-α, and CRP), and inversely associated with MMSE., Conclusion: THSWD has been found to have a preventive and therapeutic effect on POD in intertrochanteric fracture patients possibly through inflammatory pathways. This effect may be attributed to its ability to increase hemoglobin levels and reduce the levels of certain detrimental factors, such as blood urea nitrogen and inflammatory factors., (© 2024. The Author(s).)

Growing quantities of biomass ashes (phyto-ashs) are currently produced worldwide due to the increasing biomass consumption in energy applications. Utilization of phyto-ash in agriculture is environmentally friendly solution. However, mechanisms involving the coordination of carbon metabolism and distribution in plants and soil amendment are not well known. In the present study, tobacco plants were chemically-fertilized with or without 2‰ phyto-ash addition. The control had sole chemical fertilizer; for two phyto-ash treatments, the one (T1) received comparable levels of nitrogen, phophorus, and potassium from phyto-ash and fertilizers as the control and another (T2) had 2‰ of phyto-ash and the same rates of fertilizers as the control. Compared with the control, phyto-ash addition improved the soil pH from 5.94 to about 6.35; T2 treatment enhanced soil available potassium by 30% but no difference of other elements was recorded among three treatments. Importantly, bacterial (but not fungal) communities were significantly enriched by phyto-ash addition, with the rank of richness as: T2 > T1 > control. Consistent with amelioration of soil properties, phyto-ash promoted plant growth through enlarged leaf area and photosynthesis and induced outgrowth of lateral roots (LRs). Interestingly, increased auxin content was recorded in 2 nd and 3 rd leaves and roots under phyto-ash application, also with the rank level as T2 > T1 > control, paralleling with higher transcripts of auxin synthetic genes in the topmost leaf and stronger [ 3 H]IAA activity under phyto-ash addition. Furthermore, exogenous application of analog exogenous auxin (NAA) restored leaf area, photosynthesis and LR outgrowth to the similar level as T2 treatment; conversely, application of auxin transport inhibitor (NPA) under T2 treatment retarded leaf and root development. We demonstrated that phyto-ash addition improved soil properties and thus facilitated carbon balance within plants and biomass accumulation in which shifting auxin distribution plays an important role., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Glial fibrillary acidic protein (GFAP) in serum has been shown as a biomarker of traumatic brain injury (TBI) which is a significant global public health concern. Accurate and rapid detection of serum GFAP is critical for TBI diagnosis. In this study, a time-resolved fluorescence immunochromatographic test strip (TRFIS) was proposed for the quantitative detection of serum GFAP. This TRFIS possessed excellent linearity ranging from 0.05 to 2.5 ng/mL for the detection of serum GFAP and displayed good linearity (Y = 598723X + 797198, R 2 = 0.99), with the lowest detection limit of 16 pg/mL. This TRFIS allowed for quantitative detection of serum GFAP within 15 min and showed high specificity. The intra-batch coefficient of variation (CV) and the inter-batch CV were both < 4.0%. Additionally, this TRFIS was applied to detect GFAP in the serum samples from healthy donors and patients with cerebral hemorrhage, and the results of TRFIS could efficiently discern the patients with cerebral hemorrhage from the healthy donors. Our developed TRFIS has the characteristics of high sensitivity, high accuracy, and a wide linear range and is suitable for rapid and quantitative determination of serum GFAP on-site., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Urine retinol-binding protein 4 (RBP4) has recently been reported as a novel earlier biomarker of chronic kidney disease (CKD) which is a global public health problem with high morbidity and mortality. Accurate and rapid detection of urine RBP4 is essential for early monitor of impaired kidney function and prevention of CKD progression. In the present study, we developed a time-resolved fluorescence immunochromatographic test strip (TRFIS) for the quantitative and rapid detection of urine RBP4. This TRFIS possessed excellent linearity ranging from 0.024 to 12.50 ng/mL for the detection of urine RBP4, and displayed a good linearity (Y = 239,581 × X + 617,238, R 2  = 0.9902), with the lowest visual detection limit of 0.049 ng/mL. This TRFIS allows for quantitative detection of urine RBP4 within 15 min and shows high specificity. The intra-batch coefficient of variation (CV) and the inter-batch CV were both < 8%, respectively. Additionally, this TRFIS was applied to detect RBP4 in the urine samples from healthy donors and patients with CKD, and the results of TRFIS could efficiently discern the patients with CKD from the healthy donors. The developed TRFIS has the characteristics of high sensitivity, high accuracy, and a wide linear range, and is suitable for rapid and quantitative determination of urine RBP4., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Early detection and treatment of breast cancer can significantly reduce patient mortality, and mammogram is an effective method for early screening. Computer-aided diagnosis (CAD) of mammography based on deep learning can assist radiologists in making more objective and accurate judgments. However, existing methods often depend on datasets with manual segmentation annotations. In addition, due to the large image sizes and small lesion proportions, many methods that do not use region of interest (ROI) mostly rely on multi-scale and multi-feature fusion models. These shortcomings increase the labor, money, and computational overhead of applying the model. Therefore, a deep location soft-embedding-based network with regional scoring (DLSEN-RS) is proposed. DLSEN-RS is an end-to-end mammography image classification method containing only one feature extractor and relies on positional embedding (PE) and aggregation pooling (AP) modules to locate lesion areas without bounding boxes, transfer learning, or multi-stage training. In particular, the introduced PE and AP modules exhibit versatility across various CNN models and improve the model's tumor localization and diagnostic accuracy for mammography images. Experiments are conducted on published INbreast and CBIS-DDSM datasets, and compared to previous state-of-the-art mammographic image classification methods, DLSEN-RS performed satisfactorily.

Objective: Unilateral biportal endoscopic (UBE) surgery has recently been used as a minimally invasive procedure for the treatment of lumbar spinal stenosis and is associated with less perioperative blood loss. However, perioperative hidden blood loss (HBL) may be neglected during UBE. This study aimed to examine the volume of HBL and discuss the influential risk factors for HBL during unilateral biportal endoscopic surgery., Methods: From January 2022 to August 2022, 51 patients underwent percutaneous unilateral biportal endoscopic surgery for lumbar spinal stenosis at the Department of Spinal Surgery of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University and were enrolled in this study. The data included general indicators (age, sex and body mass index [BMI]), underlying disease (hypertension and diabetes), laboratory test results (prothrombin time [PT], activated partial thromboplastin time [APTT], fibrinogen [Fbg]), and preoperative and postoperative hematocrit and hemoglobin), related imaging parameters (severity of intervertebral disc [IVD] degeneration and soft tissue thickness of the interlaminar approach), number of operated vertebrae and operation time. Total blood loss (TBL) and HBL during surgical procedures were measured via the Gross formula. Influential factors were further analyzed by multivariate linear regression analysis and t-tests., Results: The mean HBL was 257.89 ± 190.66 mL for single-operation patients and 296.58 ± 269.75 mL for two-operation patients. Patients with lower PT (p = 0.044), deeper tissue thickness (p = 0.047), and diabetes mellitus were determined to have more HBL during UBE. The operation time might also be an important factor (p = 0.047). However, sex (p = 0.265), age (p = 0.771/0.624), BMI (p = 0.655/0.664), APTT (p = 0.545/0.751), degree of degenerated IVD (p = 0.932/0.477), and hypertension (p = 0.356/0.896) were not related to HBL., Conclusion: This study determined the different influential factors of HBL during UBE. PT, tissue thickness, and diabetes mellitus are the independent risk factors that affect HBL incidence. Long PT may decrease the volume of HBL within a certain range. Tissue thickness and diabetes mellitus can lead to an increased volume of HBL., (© 2024 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

The innovative application of Crowd Intelligent Devices (CIDS) in edge networks has garnered attention due to the rapid development of artificial intelligence and computer technology. This application offers users more reliable and low-latency computing services through computation offloading technology. However, the dynamic nature of network terminals and the limited coverage of edge servers pose challenges, such as data loss and service interruption. Furthermore, the high-speed mobility of intelligent terminals in the dynamic edge network environment further complicates the design of computation offloading and service migration strategies. To address these challenges, this paper explores the computation offloading model of cluster intelligence collaboration in a heterogeneous network environment. This model involves multiple intelligences collaborating to provide computation offloading services for terminals. To accommodate various roles, a switching strategy of split-cluster group collaboration is introduced, assigning the cluster head, the alternate cluster head, and the ordinary user are assigned to a group with different functions. Additionally, the paper formulates the optimal offloading strategy for group smart terminals as a Markov decision process, taking into account factors such as user mobility, service delay, service accuracy, and migration cost. To implement this strategy, the paper utilizes the deep reinforcement learning-based CCSMS algorithm. Simulation results demonstrate that the proposed edge network service migration strategy, rooted in groupwise cluster collaboration, effectively mitigates interruption delay and enhances service migration efficiency., (© 2024. The Author(s).)

This paper investigates the prescribed-time event-triggered cluster practical consensus problem for a class of nonlinear multi-agent systems with external disturbances. To begin, to reach the prescribed-time cluster practical consensus, a new time-varying function is introduced and a novel distributed continuous algorithm is designed. Based on the Lyapunov stability theory and inequality techniques, some sufficient conditions are given, ensuring the prescribed-time cluster practical consensus. Moreover, to avoid different clusters' final states overlapping, a virtual leader is considered for each cluster. In this case, an event-triggered distributed protocol is further established and some related conditions are given for achieving prescribed-time cluster practical consensus. Additionally, it is proven that the Zeno behavior can be avioded by choosing parameters appropriately. Finally, some numerical examples are presented to show the effectiveness of the theoretical results.

Disitamab vedotin (RC48) is a novel cleavable antibody-drug conjugate (ADC) that has shown promising preclinical activity in HER2-positive breast cancer. However, real-world data regarding its efficacy and safety is lacking, especially in patients previously treated with trastuzumab and heavily treated patients. This retrospective study aimed to evaluate the effectiveness and safety of RC48 in HER2-positive metastatic breast cancer (MBC) in non-clinical trial settings. Eighty-one patients with metastatic HER2-positive BC who received RC48 in Shandong Cancer Hospital and Institute between September 2021 to November 2022 were included in this study. The primary endpoints were real-world progression-free survival (RWPFS) and objective response rate (ORR), and the secondary endpoints included safety and exploratory subgroup analyses. Results showed that the median RWPFS was 5.9 months, and the ORR was 29.6%, including one patient who achieved complete remission. Two-thirds of the patients had received more than one line of prior anti-HER2 treatment, and 76.6% were exposed to anti-HER2 monoclonal antibodies and tyrosine kinase inhibitors. Patients who received RC48 in ≤3 lines of treatment had significantly longer RWPFS than those who received it in ≥4 lines of treatment. The median RWPFS of RC48 in patients with trastuzumab resistance and refractoriness was 6.5 months and 5.6 months, respectively. The sequence of pyrotinib and RC48 did not influence their total efficacy. To conclude, RC48 exhibited promising efficacy in HER2-positive MBC with manageable toxicity, particularly in patients previously treated with trastuzumab and those who had undergone extensive treatment. RC48 exhibited potent activity for patients regardless of trastuzumab resistance or refractory. The sequence of pyrotinib and RC48 did not influence their total efficacy, indicating no cross-resistance., Competing Interests: None., (AJCR Copyright © 2024.)

Cyclin-dependent kinase 9 (CDK9) plays a critical role in transcription initiation and is essential for maintaining gene silencing at heterochromatic loci. Inhibition of CDK9 increases sensitivity to immunotherapy, but the underlying mechanism remains unclear. We now report that RNF20 stabilizes LSD1 via K29-mediated ubiquitination, which is dependent on CDK9-mediated phosphorylation. This CDK9- and RNF20-dependent LSD1 stabilization is necessary for the demethylation of histone H3K4, then subsequent repression of endogenous retrovirus, and an interferon response, leading to epigenetic immunosuppression. Moreover, we found that loss of RNF20 sensitizes cancer cells to the immune checkpoint inhibitor anti-PD-1 in vivo and that this effect can be rescued by the expression of ectopic LSD1. Our findings are supported by the observation that RNF20 levels correlate with LSD1 levels in human breast cancer specimens. This study sheds light on the role of RNF20 in CDK9-dependent LSD1 stabilization, which is crucial for epigenetic silencing and immunosuppression. Our findings explore the potential importance of targeting the CDK9-RNF20-LSD1 axis in the development of new cancer therapies., Competing Interests: Competing interests statement:The authors declare no competing interest.

Delayed wound healing is a public issue that imposes a significant burden on both society and the patients themselves. To date, although numerous methods have been developed to accelerate the speed of wound closure, the therapeutic effects are partially limited due to the complex procedures, high costs, potential side effects, and ethical concerns. While some studies have reported that the in-vivo application of Human Parathyroid Hormone (1-34) (hPTH(1-34)) promotes the wound-healing process, the definitive role and underlying mechanisms through which it regulates the behavior of fibroblasts and keratinocytes remains unclear. Herein, hPTH(1-34)'s role in cell migration is evaluated with a series of in-vitro and in-vivo studies, whereby hPTH(1-34)'s underlying mechanism in activating the two types of cells was detected. The in-vitro study revealed that hPTH(1-34) enhanced the migration of both fibroblasts and HaCaT cells. Ras-associated C3 botulinum toxin subunit 1 (Rac1), a classical member of the Rho family, was upregulated in hPTH(1-34)-treated fibroblasts and HaCaT cells. Further study by silencing the expression of Rac1 with siRNA reversed the hPTH(1-34)-enhanced cell migration, thus confirming that Rac1 was involved in hPTH(1-34)-induced cell behavior. In-vivo study on rat wound models confirmed the effects of hPTH(1-34) on fibroblasts and keratinocytes, with increased collagen deposition, fibroblasts accumulation, and Rac1 expression in the hPTH(1-34)-treated wounds. In summary, the present study demonstrated that hPTH(1-34) accelerated wound healing through enhancing the migration of cells through the up-regulation of Rac1 expression., (© 2024. The Author(s).)

Cisplatin (DDP) is a commonly used chemotherapeutic agent for triple negative breast cancer (TNBC), but its efficacy can be limited by chemoresistance. This study aimed to explore the functional mechanism of SR-rich splicing factor 1 (SRSF1) in DDP chemosensitivity of TNBC cells. Levels of SRSF1, circular RNA septin 9 (circSEPT9), and GTP cyclohydrolase-1 (GCH1) in TNBC cells, DDP-resistant cells, and normal cells were determined. Cell viability, half-maximal inhibitory concentration (IC 50 ) value, and proliferation were evaluated. Ferroptosis was determined by assay kits (ferric ion/ROS/MDA/GSH) and Western blot assay (SLC7A11/ACSL4). The genetic binding was analyzed by RNA immunoprecipitation and RNA pull-down assays. SRSF1, circSEPT9, and GCH1 were upregulated in TNBC cells. SRSF1 downregulation reduced IC 50 to DDP of parent and drug-resistant TNBC cells and inhibited cell viability and proliferation, meanwhile, the downregulation reduced GSH/SLC7A11 levels while elevated ferric ion/ROS/MDA/ACSL4 levels, promoting ferroptosis. SRSF1 bound to and upregulated circSEPT9 and circSEPT9 blocked the ubiquitination of GCH1, thereby increasing GCH1 protein level. Overexpression of circSEPT9 and GCH1 attenuated the DDP chemosensitivity of TNBC cells by inhibiting ferroptosis. This study is the first to report the role of SRSF1 inhibitors combined with chemotherapy in TNBC, which provides a promising strategy for the treatment of TNBC. SIGNIFICANCE: Cisplatin (DDP) is a commonly used chemotherapeutic agent for triple negative breast cancer (TNBC), but its efficacy can be limited by chemoresistance. This study aimed to unravel the molecular mechanism of SR-rich splicing factor 1 (SRSF1) in DDP chemosensitivity of TNBC cells., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Amorphous nanomaterials have drawn extensive attention owing to their unique features, while amorphization on noble metal nanomaterials still remains formidably challenging. Herein, we demonstrate a universal strategy to synthesize amorphous Pd-based nanomaterials from unary to quinary metals through the introduction of phosphorus (P). The amorphous Pd-based nanoparticles (NPs) exhibit generally promoted oxygen reduction reaction (ORR) activity and durability compared with their crystalline counterparts. Significantly, the quinary P-PdCuNiInSn NPs, benefiting from the amorphous structure and multimetallic component effect, exhibit mass activities as high as 1.04 A mg Pd -1 and negligible activity decays of 1.8% among the stability tests, which are much better than values for original Pd NPs (0.134 A mg Pd -1 and 28.4%). Experimental and theoretical analyses collectively reveal that the synergy of P-induced amorphization and the expansion of metallic components can considerably lower the free energy changes in the rate-determined step, thereby explaining the positive correlation with the catalytic activity.

Purpose: The residual cancer burden index (RCB) was proposed as a response evaluation criterion in breast cancer patients treated with Neoadjuvant Chemotherapy (NAC). This study evaluated the relevance of RCB with replase-free survival (RFS)., Methods: The clinical data of 254 breast cancer patients who received NAC between 2016 and 2020 were retrospectively collected. The relationship between clinicopathologic factors and RFS was evaluated using Cox proportional hazards regression models. RFS estimates were determined by Kaplan-Meier(K-M) analysis and compared using the log-rank test. Multivariate logistic regression analysis was used to evaluate the risk factors associated with RCB. Receiver operating characteristic (ROC) curves showed the potential of the RCB and MP grading systems as biomarkers for RFS., Results: At a median follow-up of 52 months, 59 patients(23.23%) developed relapse. Multivariate Cox regression showed that older age (P = 0.022), high Pathologic T stage after NAC (P = 0.023) and a high RCB score(P = 0.003) were risk factors for relapse. The outcomes of the multivariate logistic analysis indicated that RCB 0 (pathologic complete response [pCR]) was associated with HER2-positive patients (P = 0.002) and triple-negative breast cancer (TNBC) patients (P = 0.013). In addition, the RCB and MP scoring systems served as prognostic markers for patients who received NAC, and their area under curves (AUCs) were 0.691 and 0.342, respectively., Conclusion: These data suggest that RCB can be equally applied to predict RFS in Chinese patients with NAC. The application of RCB may help guide the selection of treatment strategies., (© 2023. The Author(s).)

The consensus problem of discrete time-varying linear multi-agent systems (MASs) is studied in this paper. First, an event-triggered intermittent control (ETIC) protocol is designed, aided by a class of auxiliary functions. Under this protocol, some sufficient conditions for all agents to achieve consensus are established by constructing an error dynamical system and applying the Lyapunov function. Second, in order to further reduce the communication burden, an improved event triggered intermittent control (I-ETIC) strategy is presented, along with corresponding convergence analysis. Notably, the difference between the two control protocols lies in the fact that the former protocol only determines when to control or not based on the trigger conditions, while the latter, building upon this, designs new event trigger conditions for the update of the controller during the control stage. Finally, two numerical simulation examples are provided to demonstrate the effectiveness of the theoretical results.

Background: The pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) of breast cancer is closely related to a better prognosis. However, there are no reliable indicators to accurately identify which patients will achieve pCR before surgery, and a model for predicting pCR to NAC is required., Methods: A total of 269 breast cancer patients in Shandong Cancer Hospital and Liaocheng People's Hospital receiving anthracycline and taxane-based NAC were prospectively enrolled. Expression profiling using a 457 cancer-related gene sequencing panel (DNA sequencing) covering genes recurrently mutated in breast cancer was carried out on 243 formalin-fixed paraffin-embedded tumor biopsies samples before NAC from 243 patients. The unique personalized panel of nine individual somatic mutation genes from the constructed model was used to detect and analyze ctDNA on 216 blood samples. Blood samples were collected at indicated time points including before chemotherapy initiation, after the 1 st NAC and before the 2 nd NAC cycle, during intermediate evaluation, and prior to surgery. In this study, we characterized the value of gene profile mutation and circulating tumor DNA (ctDNA) in combination with clinical characteristics in the prediction of pCR before surgery and investigated the prognostic prediction. The median follow-up time for survival analysis was 898 days., Results: Firstly, we constructed a predictive NAC response model including five single nucleotide variant (SNV) mutations (TP53, SETBP1, PIK3CA, NOTCH4 and MSH2) and four copy number variation (CNV) mutations (FOXP1-gain, EGFR-gain, IL7R-gain, and NFKB1A-gain) in the breast tumor, combined with three clinical factors (luminal A, Her2 and Ki67 status). The tumor prediction model showed good discrimination of chemotherapy sensitivity for pCR and non-pCR with an AUC of 0.871 (95% CI, 0.797-0.927) in the training set, 0.771 (95% CI, 0.649-0.883) in the test set, and 0.726 (95% CI, 0.556-0.865) in an extra test set. This tumor prediction model can also effectively predict the prognosis of disease-free survival (DFS) with an AUC of 0.749 at 1 year and 0.830 at 3 years. We further screened the genes from the tumor prediction model to establish a unique personalized panel consisting of 9 individual somatic mutation genes to detect and analyze ctDNA. It was found that ctDNA positivity decreased with the passage of time during NAC, and ctDNA status can predict NAC response and metastasis recurrence. Finally, we constructed the chemotherapy prediction model combined with the tumor prediction model and pretreatment ctDNA levels, which has a better prediction effect of pCR with the AUC value of 0.961., Conclusions: In this study, we established a chemotherapy predictive model with a non-invasive tool that is built based on genomic features, ctDNA status, as well as clinical characteristics for predicting pCR to recognize the responders and non-responders to NAC, and also predicting prognosis for DFS in breast cancer. Adding pretreatment ctDNA levels to a model containing gene profile mutation and clinical characteristics significantly improves stratification over the clinical variables alone., (© 2023. The Author(s).)

Lysine-specific demethylase 1 (LSD1), a critical chromatin modulator, functions as an oncogene by demethylation of H3K4me1/2. The stability of LSD1 is governed by a complex and intricate process involving ubiquitination and deubiquitination. Several deubiquitinases preserve LSD1 protein levels. However, the precise mechanism underlying the degradation of LSD1, which could mitigate its oncogenic function, remains unknown. To gain a better understanding of LSD1 degradation, we conducted an unbiased siRNA screening targeting all the human SCF family E3 ligases. Our screening identified FBXO24 as a genuine E3 ligase that ubiquitinates and degrades LSD1. As a result, FBXO24 inhibits LSD1-induced tumorigenesis and functions as a tumor suppressor in breast cancer cells. Moreover, FBXO24 exhibits an inverse correlation with LSD1 and is associated with a favorable prognosis in breast cancer patient samples. Taken together, our study uncovers the significant role of FBXO24 in impeding breast tumor progression by targeting LSD1 for degradation., Implications: Our study provides comprehensive characterization of the significant role of FBXO24 in impeding breast tumor progression by targeting LSD1 for degradation., (©2023 American Association for Cancer Research.)

Pyrotinib, an irreversible pan-ErbB inhibitor, has been approved for treating HER2-positive advanced breast cancer in China. We conducted a nationwide, prospective observational study to examine the real-world data of pyrotinib-based therapy in this population. Patients from 61 sites across China were included. Pyrotinib-based regimens were prescribed at local physician's discretion. Demographics, treatment patterns, prognosis and safety were evaluated. The primary outcome was real-world progression-free survival (rwPFS). Of 1129 patients, pyrotinib-based therapy was prescribed as first-, second- and third- or later-line treatment in 437 (38.7%), 476 (42.2%) and 216 (19.1%) patients, respectively. Median rwPFS (mrwPFS) was 14.3 (95% CI, 13.3-15.2) months in the total population, with the longest mrwPFS of 17.8 (95% CI, 15.2-24.9) months in the first-line setting, followed by 14.4 (95% CI, 12.9-15.3) months in the second-line setting. Patients with third- or later-line treatment also achieved a mrwPFS of 9.3 (95% CI, 8.4-11.8) months. Patients with trastuzumab- or trastuzumab-pertuzumab-treated disease achieved a mrwPFS of 14.3 and 13.6 months, respectively. Dual HER2 blockade with pyrotinib plus trastuzumab showed a mrwPFS of 16.2 months in the total population, with data not mature in the first-line setting. For patients with baseline brain metastases, the mrwPFS was 11.7 months. The most common adverse event was diarrhea (any grade, 73.5%; grade ≥ 3, 15.3%). In real world, pyrotinib-based therapy shows promising effectiveness in the first-, as well as second- and later-line treatment, with acceptable tolerability. Further investigations regarding front-line use or novel combinations of pyrotinib might facilitate to maximize its anti-tumor potential., (© 2023 UICC.)

Objective: Bacterial culture and drug sensitivity testing have been the gold standard for confirming community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection in breast abscess with a long history. However, these tests may delay treatment and increase the risk of nosocomial infections. To handle and improve this critical situation, this study aimed to explore biomarkers that could facilitate the rapid diagnosis of CA-MRSA infection., Methods: This study for the first time applied label-free quantitative proteomics and non-targeted metabonomics to identify potential differentially expressed proteins (DEPs) and differentially expressed metabolites (DEMs) in breast abscess infected with CA-MRSA compared to methicillin-susceptible S. aureus (MSSA). The two omics data were integrated and analyzed using bioinformatics, and the results were validated using Parallel Reaction Monitoring (PRM). Receiver operating characteristic (ROC) curves were generated to evaluate the predictive efficiency of the identified biomarkers for diagnosing CA-MRSA infection., Results: After using the above-mentioned strategies, 109 DEPs were identified, out of which 86 were upregulated and 23 were downregulated. Additionally, a total of 61 and 26 DEMs were initially screened in the positive and negative ion modes, respectively. A conjoint analysis indicated that the amino acid metabolism, glycosphingolipid biosynthesis, and glycerophospholipid metabolism pathways were co-enriched by the upstream DEPs and downstream DEMs, which may be involved in structuring the related network of CA-MRSA infection. Furthermore, three significant DEMs, namely, indole-3-acetic acid, L-(-)-methionine, and D-sedoheptulose 7-phosphate, displayed good discriminative abilities in early identification of CA-MRSA infection in ROC analysis., Conclusion: As there is limited high-quality evidence and multiple omics research in this field, the explored candidate biomarkers and pathways may provide new insights into the early diagnosis and drug resistance mechanisms of CA-MRSA infection in Chinese women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yin, Cao, Zhang, Li, Sun, Ma, Liu, Li, Yu and Guan.)

We managed to explore the function of HFY-4A, a novel histone deacetylases (HDACs) inhibitor, on breast cancer as well as its potential mechanisms. MCF7 and T47D cells were treated with 0.8, 1.6 or 3.2 μM HFY-4A for 0-72 h, following of which CCK-8, colony formation, EdU staining, flow cytometry, Transwell, and wound healing assays were carried out. Western blot, immunohistochemistry, and ELISA were conducted for assaying the expression of immunogenic cell death (ICD)-related proteins. The interaction between HFY-4A, HDAC1, and tumor suppressor candidate 2 (TUSC2) was evaluated by chromatin immunoprecipitation assay. Further, the function of HFY-4A in breast cancer progression in vivo was evaluated using xenograft mouse models. HFY-4A inhibited the proliferation, migration, and invasion, and induced apoptosis of breast cancer cells in a dose-dependent manner. HFY-4A dose-dependently caused the ICD of breast cancer cells, as evidenced by the significant high levels of high-mobility group box 1 (HMGB1), calreticulin (CRT), heat shock protein 70 (HSP70), and HSP90. Interestingly, HFY-4A could facilitate TUSC2 transcription by promoting acetylation of histones on the TUSC2 promoter. The results of rescue assays revealed that HFY-4A repressed proliferation and mobility, but enhanced apoptosis and ICD through facilitating TUSC2 transcription in breast cancer. In breast cancer xenograft mouse models, HFY-4A was verified to inhibit tumor growth via upregulating TUSC2. HFY-4A could inhibit breast cancer cell proliferation and mobility, and enhanced apoptosis and ICD through facilitating TUSC2 transcription., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Alzheimer's disease (AD) is a common progressive neurodegenerative disease. The Ubiquitin-Protease system (UPS), which plays important roles in maintaining protein homeostasis in eukaryotic cells, is involved in the development of AD. This study sought to identify differential UPS-related genes (UPGs) in AD patients by using bioinformatic methods, reveal potential biomarkers for early detection of AD, and investigate the association between the identified biomarkers and immune cell infiltration in AD., Methods: The differentially expressed UPGs were screened with bioinformatics analyses using the Gene Expression Omnibus (GEO) database. A weighted gene co-expression network analysis (WGCNA) analysis was performed to explore the key gene modules associated with AD. A Single-sample Gene Set Enrichment Analysis (ssGSEA) analysis was peformed to explore the patterns of immune cells in the brain tissue of AD patients. Real-time quantitative PCR (RT-qPCR) was performed to examine the expression of hub genes in blood samples from healthy controls and AD patients., Results: In this study, we identified four UPGs ( USP3 , HECW2 , PSMB7 , and UBE2V1 ) using multiple bioinformatic analyses. Furthermore, three UPGs ( USP3 , HECW2 , PSMB7 ) that are strongly correlated with the clinical features of AD were used to construct risk score prediction markers to diagnose and predict the severity of AD. Subsequently, we analyzed the patterns of immune cells in the brain tissue of AD patients and the associations between immune cells and the three key UPGs. Finally, the risk score model was verified in several datasets of AD and showed good accuracy., Conclusions: Three key UPGs are identified as potential biomarker for AD patients. These genes may provide new targets for the early identification of AD patients., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Multidrug-resistant bacteria are spreading at alarming rates, and despite extensive efforts, no new antibiotic class with activity against Gram-negative bacteria has been approved in over 50 years. LepB inhibitors (LepBi) based on the arylomycin class of natural products are a novel class of antibiotics and function by inhibiting the bacterial type I signal peptidase (SPase) in Gram-negative bacteria. One critical aspect of LepBi development involves optimization of the membrane-anchored lipophilic portion of the molecule. We therefore developed an approach that assesses the effect of this portion on the complicated equilibria of plasma protein binding, crossing the outer membrane of Gram-negative bacteria and anchoring in the bacterial inner membrane to facilitate SPase binding. Our findings provide important insights into the development of antibacterial agents where the target is associated with the inner membrane of Gram-negative bacteria., Competing Interests: The authors declare the following competing financial interest(s): M.F.T.K.Y-C.C., Yuan C., J.J.C. and M.R.D. are employees and shareholders of Genentech, a member of the Roche group. R.I.H., T.C.R. and P.A.S. are shareholders of RQx Pharmaceuticals, Inc., (© 2023 American Chemical Society.)

Background: Although neoadjuvant trastuzumab and pertuzumab (HP)-based regimens are recommended for human epidermal receptor-positive (HER2 +)/lymph node-positive (N +) breast cancer (BC) patients according to NCCN guidelines, it is undeniable that many patients achieved pathological complete response (pCR) after trastuzumab (H)-based regimens without adding pertuzumab to treatment. Patients who specifically benefit from pertuzumab must be identified. The aim of this retrospective study was to evaluate progesterone receptor (PR) status as a predictor of response to the addition of pertuzumab in HER2 + /N + breast cancer., Methods: One hundred forty-two patients who were diagnosed as HER2 + /N + BC without distant metastasis and followed by neoadjuvant HP-based or H-based therapy were retrospectively included. The endpoints were pCR and disease-free survival (DFS) times., Results: In total, the pCR occurred in 25 of 87 patients (28.74%) in group H compared with 32 of 55 (58.18%) in group HP. The results revealed that hormone receptor (HR) status was significantly different on pCR in group HP. The odds of pCR for patients who have HR-positive tumors were 0.160 times (P = 0.011) that for patients with HR-negative tumors by multivariable analysis. Moreover, a similar probability of PR-positive (PR +) patients, whatever estrogen receptor (ER) status was, achieving pCR in group HP was observed. The ROC curves showed different anti-HER2 regimens provide worst predictive value in the PR + cohort (N = AUC = 0.521, 95% CI: 0.348-0.694, P = 0.813) compared with the overall cohort (AUC = 0.644, 95% CI: 0.550-0.738, P = 0.004) and ER + cohort (AUC: 0.559, 95% CI: 0.405-0.713, P = 0.451). And PR status (AUC = 0.760, 95% CI: 0.626-0.894, P = 0.001) had a greater predictive value than ER status (AUC = 0.658, 95% CI: 0.508-0.807, P = 0.048) in group HP. DFS analyses were done on 141 patients. Although ER and PR status did not show significant difference in group HP (P = 0.789 and 0.088, respectively), HP-based therapy contributed to better DFS in the ER - and PR - cohorts (P = 0.035 and 0.015, respectively)., Conclusions: Compared with ER status, PR status might be a more valuable factor predicting the efficacy of adding pertuzumab into neoadjuvant therapy for HER2 + /N + BC. PR + patients benefit little from the addition of pertuzumab., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Microglia-mediated inflammation is a major contributor to the brain damage in cerebral ischemia and reperfusion (I/R) injury, and N6-Methyladenosine (m6A) has been implicated in cerebral I/R injury. Here, we explored whether m6A modification is associated with microglia-mediated inflammation in cerebral I/R injury and its underlying regulatory mechanism using an in vivo mice model of intraluminal middle cerebral artery occlusion/reperfusion (MCAO/R) and in vitro models of primary isolated microglia and BV2 microglial cells subjected to oxygen-glucose deprivation and reoxygenation (OGD/R) were used. We found microglial m6A modification increased and microglial fat mass and obesity-associated protein (FTO) expression decreased in cerebral I/R injury in vivo and in vitro. Inhibition of m6A modification by intraperitoneal injection of Cycloleucine (Cyc) in vivo or transfection of FTO plasmid in vitro significantly alleviated brain injury and microglia-mediated inflammatory response. Through Methylated RNA immunoprecipitation sequencing (MeRIP-Seq), RNA sequencing (RNA-Seq) and western blotting, we found that m6A modification promoted cerebral I/R-induced microglial inflammation via increasing cGAS mRNA stability to aggravate Sting/NF-κB signaling. In conclusion, this study deepens our understanding on the relationship of m6A modification and microglia-mediated inflammation in cerebral I/R injury, and insights a novel m6A-based therapeutic for inhibiting inflammatory response against ischemic stroke., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Multicomponent metallic nanomaterials with unconventional phases show great prospects in electrochemical energy storage and conversion, owing to unique crystal structures and abundant structural effects. In this review, we emphasize the progress in the strain and surface engineering of these novel nanomaterials. We start with a brief introduction of the structural configurations of these materials, based on the interaction types between the components. Next, the fundamentals of strain, strain effect in relevant metallic nanomaterials with unconventional phases, and their formation mechanisms are discussed. Then the progress in surface engineering of these multicomponent metallic nanomaterials is demonstrated from the aspects of morphology control, crystallinity control, surface modification, and surface reconstruction. Moreover, the applications of the strain- and surface-engineered unconventional nanomaterials mainly in electrocatalysis are also introduced, where in addition to the catalytic performance, the structure-performance correlations are highlighted. Finally, the challenges and opportunities in this promising field are prospected.

Objectives: The purpose of this study was to determine the independent risk factors for bone metastasis in breast cancer and to establish a nomogram to predict the risk of bone metastasis in early stages through clinicopathological characteristics and hematological parameters., Methods: We selected 1042 patients with breast cancer from the database of Shandong Cancer Hospital for retrospective analysis, and determined independent risk factors for bone metastatic breast cancer (BMBC). A BMBC nomogram based on clinicopathological characteristics and hematological parameters was constructed using logistic regression analysis. The performance of the nomograph was evaluated using the receiver operating characteristic (ROC) and calibration curves. The clinical effect of risk stratification was tested using Kaplan-Meier analysis., Results: BMBC patients were found to be at risk for eight independent risk factors based on multivariate analysis: age at diagnosis, lymphovascular invasion, pathological stage, pathological node stage, molecular subtype, platelet count/lymphocyte count, platelet count * neutrophil count/lymphocyte count ratio, Systemic Immunological Inflammation Index, and radiotherapy. The prediction accuracy of the BMBC nomogram was good. In the training set, the area under the ROC curve (AUC) was 0.909, and in the validation set, it was 0.926, which proved that our model had good calibration. The risk stratification system can analyze the risk of relapse in individuals into high- and low-risk groups., Conclusion: The proposed nomogram may predict the possibility of breast cancer bone metastasis, which will help clinicians optimize metastatic breast cancer treatment strategies and monitoring plans to provide patients with better treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tian, Li, Wang, Sun, Zhang and Yu.)

Some triple-negative breast cancer (TNBC) patients evaluated as Miller-Payne 4 with ypN0 after neoadjuvant chemotherapy (NACT) who have better prognoses should avoid escalation of therapy. We aim to identify these patients by evaluating pretherapeutic spatial distributions of immunophenotypes. Our retrospective study in patients with TNBC assessed as Miller-Payne grade 4/5 with ypN0 showed that Miller-Payne 4 with ypN0 group had poorer 5-year disease-free survival (DFS, 63.8% vs. 83.0%, p = 0.003) and the 5-year overall survival (OS, 71.0% vs. 85.5%, p = 0.007) than Miller-Payne 5 with ypN0 group. High TILs were significantly associated with better DFS and OS in patients with Miller-Payne 4 and ypN0 (both p = 0.016). Spatially, detected by multiplexed ion beam imaging by the time of flight combined with proteomics, tumors assessed as Miller-Payne 4 and ypN0 with good prognosis exhibited an inflamed phenotype, with dominant CD8+ T cells on tumor center, few scattered CD68+ myeloid-derived cells far away from T cells, and deposit of increased activated molecules of lymphocyte. While those with poor prognoses presented excluded phenotypes, with few CD8+ T cells restricted to invasive margins and a high density of CD14 + CD68 + CD11c + myeloid cells. A good classifier model based on 29 spatial immunophenotypes was established by the random forest algorithm (AUC = 0.975), for identifying patients with Miller-Payne 4 and ypN0 who had favorable prognoses. We also observed similar signatures in patients with Miller-Payne 5 and ypN0. Taken together, spatial immunophenotypes may assess the prognosis in TNBC patients with Miller-Payne 4 and ypN0 after NACT., (© 2023. The Author(s).)

Nebulized lipid nanoparticles (LNPs) have been considered as potential therapies for genetic disease as well as infectious disease. However, the sensitivity of LNPs to high shear stress during the nebulization process results in loss of the integrity of the nanostructure and the capability of delivering active pharmaceutical ingredients. Herein we have provided a fast extrusion method to prepare liposomes incorporated with a DNA hydrogel (hydrogel-LNPs) to improve the stability of the LNPs. Taking advantage of the good cellular uptake efficiency, we also demonstrated the potential of hydrogel-LNPs in delivering small molecular doxorubicin (Dox) and nucleic acid drugs. This work provides not only highly biocompatible hydrogel-LNPs for aerosol delivery, but also a strategy to regulate the elasticity of LNPs, which will benefit the potential optimization of drug delivery carriers.

Background: Inetetamab (cipterbin) is an innovative anti-HER2 humanized monoclonal antibody. The efficacy and safety of a combination of inetetamab and vinorelbine in the first-line treatment of human epidermal receptor positive (HER2+) metastatic breast cancer (MBC) have been confirmed. We aimed to investigate real-world data of inetetamab in complex clinical practice., Methods: We retrospectively reviewed the medical records of patients who received inetetamab as a salvage treatment at any line setting from July 2020 to June 2022. The main endpoint was progression-free survival (PFS)., Results: A total of 64 patients were included in this analysis. The median progression-free survival (mPFS) was 5.6 (4.6-6.6) months. Of the patients, 62.5% received two or more lines of therapy before treatment with inetetamab. The most common chemotherapy and anti-HER2 regimens combined with inetetamab were vinorelbine (60.9%) and pyrotinib (62.5%), respectively. Patients treated with inetetamab plus pyrotinib plus vinorelbine benefited the most (p=0.048), with the mPFS of 9.3 (3.1-15.5) months and an objective response rate of 35.5%. For patients with pyrotinib pretreatment, inetetamab plus vinorelbine plus pyrotinib agents resulted in mPFS of 10.3 (5.2-15.4) months. Regimens (inetetamab plus vinorelbine plus pyrotinib vs. other therapeutic agents) and visceral metastases (yes vs. no) were independent predictors of PFS. Patients with visceral metastases treated with inetetamab plus vinorelbine plus pyrotinib had a mPFS of 6.1(5.1-7.1) months. The toxicity of inetetamab was tolerable, with the most common grade 3/4 adverse event being leukopenia (4.7%)., Conclusions: HER2+ MBC patients pretreated with multiple-line therapies still respond to inetetamab-based treatment. Inetetamab combined with vinorelbine and pyrotinib may be the most effective treatment regimen, with a controllable and tolerable safety profile., Competing Interests: XW was employed by REMEGEN, LTD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Zhang, Li, Song, Liu, Shao, Li, Wang and Yu.)

Introduction: To understand the prevalence of avian methicillin-resistant Staphylococcus aureus (MRSA) and the current status of drug resistance in Qingdao, a comprehensive molecular epidemiological investigation and analysis of evolutionary relationships of MRSA isolates from broiler and layer chickens and waterfowl was conducted., Material and Methods: One hundred and two avian MRSA strains were identified by multi-locus sequence typing, staphylococcal protein A ( spa ) and staphylococcal cassette chromosome mec (SCCmec) typing, and whole-genome sequencing., Results: The sequence type (ST) 9-t899-SCC mec IVb type represented the highest proportion of avian-derived MRSA strains (71.57%), with ST398 type strains occasionally observed in broilers and waterfowl. The poultry-derived MRSA strains were all resistant to eight or more antimicrobials. Avian-derived MRSA strains carried 20 resistance genes, 109 virulence genes and 10 plasmids. Strains carrying the cfr oxazolidinone resistance gene were occasionally seen in broiler- and layer-derived MRSA. Single nucleotide polymorphism (SNP) core genome evolution and locus difference analysis showed that the closest strains were all of ST9-t899 type (to which also affiliated the highest number of strains) and this type occurred on all three kinds of poultry farm, but the SNP difference loci between strains of the same type ranged from 0 to 1472., Conclusion: The dominant type of MRSA from different poultry sources in Qingdao is ST9-t899-SCC mec IVb, which is commonly resistant to a variety of antimicrobial drugs and carries a variety of resistance genes and a large number of virulence genes. Sequence type 9-t899 type is widely spread among the three kinds of poultry investigated, but there are differences in affiliations., Competing Interests: Conflict of Interests Statement: The authors declare that there is no conflict of interests regarding the publication of this article., (© 2023 Zhen Xiao et al., published by Sciendo.)

We demonstrate a methodology for computationally investigating the mechanical response of a pure molten lead surface system to the lateral mechanical cyclic loads and try to answer the following question: how does the dynamically driven liquid surface system follow the classical physics of the elastic-driven oscillation? The steady-state oscillation of the dynamic surface tension (or excess stress) under cyclic load, including the excitation of high-frequency vibration mode at different driving frequencies and amplitudes, was compared with the classical theory of a single-body driven damped oscillator. Under the highest studied frequency (50 GHz) and amplitude (5%) of the load, the increase of in (mean value) dynamic surface tension could reach ∼5%. The peak and trough values of the instantaneous dynamic surface tension could reach (up to) 40% increase and (up to) 20% decrease compared to the equilibrium surface tension, respectively. The extracted generalized natural frequencies seem to be intimately related to the intrinsic timescales of the atomic temporal-spatial correlation functions of the liquids both in the bulk region and in the outermost surface layers. These insights uncovered could be helpful for quantitative manipulation of the liquid surface using ultrafast shockwaves or laser pulses., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Breast cancer (BC) is the most common malignant cancer. The prognosis of patients differs according to the location of distant metastasis, with pleura being a common metastatic site in BC. Nonetheless, clinical data of patients with pleural metastasis (PM) as the only distant metastatic site at initial diagnosis of metastatic BC (MBC) are limited., Patient Cohort and Methods: The medical records of patients who were hospitalized in Shandong Cancer Hospital between January 1, 2012 and December 31, 2021 were reviewed, and patients eligible for the study were selected. Survival analysis was conducted using Kaplan-Meier (KM) method. Univariate and multivariate Cox proportional-hazards models were used to identify prognostic factors. Finally, based on these selected factors, a nomogram was constructed and validated., Results: In total, 182 patients were included; 58 (group A), 81 (group B), and 43 (group C) patients presented with only PM, only lung metastasis (LM), and PM combined with LM, respectively. The KM curves revealed no significant difference in overall survival (OS) among the three groups. However, in terms of survival after distant metastasis (M-OS), the difference was significant: patients with only PM exhibited the best prognosis, whereas those with PM combined with LM exhibited the worst prognosis (median M-OS: 65.9, 40.5, and 32.4 months, respectively; P = 0.0067). For patients with LM in groups A and C, those with malignant pleural effusion (MPE) exhibited significantly worse M-OS than those without MPE. Univariate and multivariate analyses indicated that primary cancer site, T stage, N stage, location of PM, and MPE were independent prognostic factors for patients with PM without other distant metastasis. A nomogram prediction model incorporating these variables was created. According to the C-index (0.776), the AUC values of the 3-, 5-, and 8-year M-OS (0.86, 0.86, and 0.90, respectively), and calibration curves, the predicted and actual M-OS were in good agreement., Conclusion: BC patients with PM only at the first diagnosis of MBC exhibited a better prognosis than those with LM only or PM combined with LM. We identified five independent prognostic factors associated with M-OS in this subset of patients, and a nomogram model with good predictive efficacy was established., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Li, Shao, Liu, Sun and Yu.)

Background: Reprogrammed metabolic network is a key hallmark of cancer. Profiling cancer metabolic alterations with spatial signatures not only provides clues for understanding cancer biochemical heterogeneity, but also helps to decipher the possible roles of metabolic reprogramming in cancer development., Methods: Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) technique was used to characterize the expressions of fatty acids in breast cancer tissues. Specific immunofluorescence staining was further carried out to investigate the expressions of fatty acid synthesis-related enzymes., Results: The distributions of 23 fatty acids in breast cancer tissues have been mapped, and the levels of most fatty acids in cancer tissues are significantly higher than those in adjacent normal tissues. Two metabolic enzymes, fatty acid synthase (FASN) and acetyl CoA carboxylase (ACC), which being involved in the de novo synthesis of fatty acid were found to be up-regulated in breast cancer. Targeting the up-regulation of FASN and ACC is an effective approach to limiting the growth, proliferation, and metastasis of breast cancer cells., Conclusions: These spatially resolved findings enhance our understanding of cancer metabolic reprogramming and give an insight into the exploration of metabolic vulnerabilities for better cancer treatment., (© 2023. The Author(s).)

This study is aimed to develop and validate a novel nomogram model that can preoperatively predict axillary lymph node pathological complete response (pCR) after NAT and avoid unnecessary axillary lymph node dissection (ALND) for breast cancer patients. A total of 410 patients who underwent NAT and were pathologically confirmed to be axillary lymph node positive after breast cancer surgery were included. They were divided into two groups: patients with axillary lymph node pCR and patients with residual node lesions after NAT. Then the nomogram prediction model was constructed by univariate and multivariate logistic regression. The result of multivariate logistic regression analysis showed that molecular subtypes, molybdenum target (MG) breast, computerized tomography (CT) breast, ultrasound (US) axilla, magnetic resonance imaging (MRI) axilla, and CT axilla (all p < 0.001) had a significant impact on the evaluation of axillary lymph node status after NAT. The nomogram score appeared that AUC was 0.832 (95% CI 0.786-0.878) in the training cohort and 0.947 (95% CI 0.906-0.988) in the validation cohort, respectively. The decision curve represented that the nomogram has a positive predictive ability, indicating its potential as a practical clinical tool., (© 2023. The Author(s).)

The development of high-performance catalysts with high activity, selectivity, and stability are essential for the practical applications of H 2 O 2 electrosynthesis technology, but it is still formidably challenging. It is reported that the low-coordinated structure of Pd sites in amorphous PdSe 2 nanoparticles (a-PdSe 2 NPs) can significantly boost the electrocatalytic synthesis of H 2 O 2 . Detailed investigations and theoretical calculations reveal that the disordered arrangement of Pd atoms in a-PdSe 2 NPs can promote the activity, while the Pd sites with low-coordinated environment can optimize the adsorption toward oxygenated intermediate and suppress the cleavage of O-O bond, leading to a significant enhancement in both the H 2 O 2 selectivity and productivity. Impressively, a-PdSe 2 NPs/C exhibits high H 2 O 2 selectivity over 90% in different pH electrolytes. H 2 O 2 productivities with ≈3245.7, 1725.5, and 2242.1 mmol g Pd -1  h -1 in 0.1 m KOH, 0.1 m HClO 4 , and 0.1 m Na 2 SO 4 can be achieved, respectively, in an H-cell electrolyzer, being a pH-universal catalyst for H 2 O 2 electrochemical synthesis. Furthermore, the produced H 2 O 2 can reach 1081.8 ppm in a three-phase flow cell reactor after 2 h enrichment in 0.1 m Na 2 SO 4 , showing the great potential of a-PdSe 2 NPs/C for practical H 2 O 2 electrosynthesis., (© 2022 Wiley-VCH GmbH.)

Breast cancer has become the most prevalent cancer, globally. Adriamycin is a first-line chemotherapeutic agent, however, cancer cells acquire resistance to it, which is one of the most common causes of treatment failure. ROS and NRF2 are essential oxidative stress factors that play a key role in the oxidative stress process and are associated with cancer. Our goal is to create novel therapeutic drugs or chemical sensitizers that will improve chemotherapy sensitivity. The optimal concentration and duration for MCF-7 and MCF-7/ADR cells in ADR and CYT were determined using the CCK-8 assay. We found that ADR + CYT inhibited the activity of MCF-7 and MCF-7/ADR cells in breast cancer, as well as causing apoptosis in MCF-7 and MCF-7/ADR cells and blocking the cell cycle in the G0/G1 phase. ADR + CYT induces apoptosis in MCF-7 and MCF-7/ADR cells through ROS generation and the P62/NRF2/HO-1 signaling pathway. In breast cancer-bearing nude mice, ADR + CYT effectively suppressed tumor development in vivo. Overall, our findings showed that CYT in combination with ADR has potent anti-breast cancer cell activity both in vivo and in vitro, suggesting CYT as the main drug used to improve chemosensitivity., (© 2023. The Author(s).)

Introduction: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with low 5-year survival rate. Cellular senescence, characterized by permanent and irreversible cell proliferation arrest, plays an important role in tumorigenesis and development. This study aims to develop a cellular senescence-based stratified model, and a multivariable-based nomogram for guiding clinical therapy for HCC. Materials and methods: The mRNAs expression data of HCC patients and cellular senescence-related genes were obtained from TCGA and CellAge database, respectively. Through multiple analysis, a four cellular senescence-related genes-based prognostic stratified model was constructed and its predictive performance was validated through various methods. Then, a nomogram based on the model was constructed and HCC patients stratified by the model were analyzed for tumor mutation burden, tumor microenvironment, immune infiltration, drug sensitivity and immune checkpoint. Functional enrichment analysis was performed to explore potential biological pathways. Finally, we verified this model by siRNA transfection, scratch assay and Transwell Assay. Results: We established an cellular senescence-related genes-based stratified model, and a multivariable-based nomogram, which could accurately predict the prognosis of HCC patients in the ICGC database. The low and high risk score HCC patients stratified by the model showed different tumor mutation burden, tumor microenvironment, immune infiltration, drug sensitivity and immune checkpoint expressions. Functional enrichment analysis suggested several biological pathways related to the process and prognosis of HCC. Scratch assay and transwell assay indicated the promotion effects of the four cellular senescence-related genes (EZH2, G6PD, CBX8, and NDRG1) on the migraiton and invasion of HCC. Conclusion: We established a cellular senescence-based stratified model, and a multivariable-based nomogram, which could predict the survival of HCC patients and guide clinical treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Tan, Wu, Guo, Wang, You, Zhang, Yu, Geng, Zan and Su.)

As an efficient photocatalyst, graphitic carbon nitride (g-C 3 N 4 ) has been widely used in the field of photocatalytic hydrogen production. However, how to prepare hydrogen efficiently and stably has become a challenge. Herein, we successfully realize metal-free edge modification with phenyl groups by one-step thermal polymerization of urea with 4-phenyl-3-thiosemicarbazide. Consequently, the optimal photocatalytic hydrogen production rate for the modified graphitic carbon nitride is increased by three times to a value of 2390.6 μmol h -1 g -1 , while the apparent quantum efficiency (AQE) reaches 8.3 % at a wavelength of 420 nm. We also provide a theoretical explanation for the experiments using density functional theory (DFT) calculations, which suggest that energy level changes and electron redistribution for the modified carbon nitride materials contribute to the observed changes in catalytic performance. This work provides an effective solution for improving the photocatalytic activity of carbon nitride materials and provides theoretical support for the edge modification of carbon nitride materials to promote their photocatalytic hydrogen production efficiency., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This work studies the first-order coherence of noisy multi-agent networks with multi-layered structures. The coherence, which is a sort of performance index of networks, can be seen as a sort of measurement for a system's robustness. Graph operations are applied to design the novel multi-layered networks, and a graph spectrum approach, along with analysis methods, is applied to derive the mathematical expression of the coherence, and the corresponding asymptotic results on the performance index have been obtained. In addition, the coherence of these non-isomorphic multi-layered networks with three different graph parameters are compared and analyzed. We find that, when the cardinalities of the vertex sets of corresponding counterpart layers are the same, the multi-layered topology class with a balanced, complete, multi-partite structure has the best robustness of all the considered networks, if the sufficient conditions for the node-related parameters hold. Finally, simulations are given to verify the asymptotic results.

The comprehensive study of the spatial-cellular anatomy of the human liver is critical to addressing the cellular origins of liver disease. Here we conducted spatial transcriptomics on normal human liver tissue sections, providing detailed information of liver zonation at the transcriptional level. We present 6581 high-quality spots from normal livers of two human donors. In this dataset, cells were mainly hepatocytes, and we classified them into four sub-groups. Collectively, these data provide a reliable reference for studies on spatial heterogeneity of liver lobules., (© 2022. The Author(s).)

The equilibrium silica liquid-liquid interface between the high-density liquid (HDL) phase and the low-density liquid (LDL) phase is examined using molecular-dynamics simulation. The structure, thermodynamics, and dynamics within the interfacial region are characterized in detail and compared with previous studies on the liquid-liquid phase transition (LLPT) in bulk silica, as well as traditional crystal-melt interfaces. We find that the silica HDL-LDL interface exhibits a spatial fragile-to-strong transition across the interface. Calculations of dynamics properties reveal three types of dynamical heterogeneity hybridizing within the silica HDL-LDL interface. We also observe that as the interface is traversed from HDL to LDL, the Si/O coordination number ratio jumps to an unexpectedly large value, defining a thin region of the interface where HDL and LDL exhibit significant mixing. In addition, the LLPT phase coexistence is interpreted in the framework of the traditional thermodynamics of alloys and phase equilibria.

Background: Currently, due to synergy enhancement of anti-tumor effects and potent stimulation of abscopal effects, combination therapy with irradiation and programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint inhibition (immuno-radiotherapy, iRT) has revolutionized the therapeutic guidelines. It has been demonstrated that tumor-draining lymph nodes (TDLN) are essential for effective antitumor immunity induced by radiotherapy, immunotherapy, or iRT. Given that the function of TDLN in iRT remains unclear, this study aimed to investigate the function and mechanism of TDLN in iRT-induced abscopal effects., Methods: The function of TDLN was evaluated using unilateral or bilateral MC38 and B16F10 subcutaneous tumor models with or without indicated TDLN. The flow cytometry, multiple immunofluorescence analysis, and NanoString analysis were utilized to detect the composition and function of the immune cells in the primary and abscopal tumor microenvironment. Additionally, we tempted to interrogate the possible mechanisms via RNA-sequencing of tumor-infiltrating lymphocytes and TDLN., Results: TDLN deficiency impaired the control of tumor growth by monotherapy. Bilateral TDLN removal rather than unilateral TDLN removal substantially curtailed iRT-stimulated anti-tumor and abscopal effects. Furthermore, in the absence of TDLN, the infiltration of CD45 + and CD8 + T cells was substantially reduced in both primary and abscopal tumors, and the anti-tumor function of CD8 + T cells was attenuated as well. Additionally, the polarization of tumor-associated macrophages in primary and abscopal tumors were found to be dependent on intact bilateral TDLN. RNA-sequencing data indicated that impaired infiltration and anti-tumor effects of immune cells partially attributed to the altered secretion of components from the tumor microenvironment., Conclusions: TDLN play a critical role in iRT by promoting the infiltration of CD8 + T cells and maintaining the M1/M2 macrophage ratio., (© 2022 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

This article mainly studies first-order coherence related to the robustness of the triplex MASs consensus models with partial complete graph structures; the performance index is studied through algebraic graph theory. The topologies of the novel triplex networks are generated by graph operations and the approach of graph spectra is applied to calculate the first-order network coherence. The coherence asymptotic behaviours of the three cases of the partial complete structures are analysed and compared. We find that under the condition that the number of nodes in partial complete substructures n tends to infinity, the coherence asymptotic behaviour of the two sorts of non-isomorphic three-layered networks will be increased by r-12(r+1), which is irrelevant to the peripheral vertices number p ; when p tends to infinity, adding star copies to the original triplex topologies will reverse the original size relationship of the coherence under consideration of the triplex networks. Finally, the coherence of the three-layered networks with the same sorts of parameters, but non-isomorphic graphs, are simulated to verify the results.

Competing Interests: Conflict of Interest None declared.

Objectives: The aim of this study was to identify the factors for local-regional recurrence (LRR) after breast-conserving therapy (BCT). We established a practical nomogram to predict the likelihood of LRR after BCT based on hematological parameters and clinicopathological features., Methods: A retrospective analysis was performed on 2,085 consecutive breast cancer patients who received BCT in Shandong Cancer Hospital from 2006 to 2016, including 1,460 patients in the training cohort and 625 patients in the validation cohort. Univariate and multivariate analyses were performed based on hematological parameters (fibrinogen, platelets, mean platelet volume, neutrophils, monocytes, and lymphocytes) and clinicopathological characteristics to identify the independent factors for LRR. Subsequently, a nomogram for predicting LRR was established by logistic regression analysis. The nomogram was validated in 625 patients in the validation cohort., Results: During the median follow-up period of 66 months, 44 (3.01%) patients in the training cohort and 19 (3.04%) patients in the validation cohort suffered from LRR. Multivariate analysis showed six independent factors related to LRR, including molecular subtype, pathological N stage, re-resection, radiotherapy or not, platelet count*MPV*fibrinogen (PMF), and neutrophil count/lymphocyte count ratio (NLR). Six variables were entered into logistic regression to establish the nomogram for predicting LRR. The nomogram of LRR showed excellent discrimination and prediction accuracy. The area under the receiver operating characteristic curve (AUC) was 0.89 ( p < 0.001, 95% CI = 0.83, 0.95) in the training cohort and 0.88 ( p < 0.001, 95% CI = 0.8, 0.96) in the validation cohort. Calibration curves for the prediction model in the training and validation cohorts both demonstrated satisfactory consistency between the nomogram-predicted and actual LRR., Conclusion: The combination of hematological parameters and clinicopathological characteristics can predict LRR after BCT. The predictive nomogram based on preoperative and postoperative indicators of BCT might serve as a practical tool for individualized prognostication. More prospective studies should be performed to verify the model., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sun, Zhao, Wang, Song, Wang, Li and Yu.)

Early B cell factor 1 (EBF1) is a transcriptional factor with a variety of roles in cell differentiation and metabolism. However, the functional roles of EBF1 in tumorigenesis remain elusive. Here, we demonstrate that EBF1 is highly expressed in triple-negative breast cancer (TNBC). Furthermore, EBF1 has a pivotal role in the tumorigenicity and progression of TNBC. Moreover, we found that depletion of EBF1 induces extensive cell mitophagy and inhibits tumor growth. Genome-wide mapping of the EBF1 transcriptional regulatory network revealed that EBF1 drives TNBC tumorigenicity by assembling a transcriptional complex with HIF1α that fine-tunes the expression of HIF1α targets via suppression of p300 activity. EBF1 therefore holds HIF1α activity in check to avert extensive mitophagy-induced cell death. Our findings reveal a key function for EBF1 as a master regulator of mitochondria homeostasis in TNBC and indicate that targeting this pathway may offer alternative treatment strategies for this aggressive subtype of breast cancer.