Improving physical and mental health in women with breast cancer undergoing anthracycline-based chemotherapy through wearable device-based aerobic exercise: a randomized controlled trial.

Purpose: Aimed to assess the impact of wearable device-based aerobic exercise on the physical and mental well-being of women with breast cancer (BC) undergoing chemotherapy. Methods: Forty adult women with BC who underwent anthracycline-based chemotherapy were randomly allocated to the exercise group (n = 21) or the control group (n = 19). Both groups received standard health education and oncology care. In addition, the exercise group wore wearable devices to engage in moderate to high-intensity (50-90% HRmax) aerobic exercise during chemotherapy, while the control group did not carry out exercise intervention. Health-related physical fitness level, physical activity energy expenditure (PAEE), anxiety and depression scores, sleep quality, cancer-related fatigue, and overall quality of life (QoL), were assessed both before (prior to the first chemotherapy session) and after (prior to the fifth chemotherapy session) the exercise intervention. Exercise-related adverse events, exercise compliance, number and severity of gastrointestinal reactions and myelosuppression occurred were recorded during the exercise intervention. Results: After the intervention, compared to the control group, the exercise group (1) had significantly higher relative VO2peak (p = 0.003) and handgrip strength (p < 0.001); (2) had significantly higher PAEE (p < 0.001); (3) had a significantly lower scores in anxiety (p = 0.007), depression (p = 0.028), sleep quality in domains of subjective sleep quality (p = 0.010), sleep disturbances (p = 0.004), daytime dysfunction (p = 0.007), cancer-related fatigue in domains of physical (p < 0.001) and affective (p < 0.001); and (4) had a significantly lower scores in QoL in domains of physical well-being (p < 0.001) and emotional well-being (p = 0.019), while a significantly higher scores in functional well-being (p < 0.001). Patients in the exercise group experienced less severe gastrointestinal reactions (p = 0.028) and myelosuppressive symptoms (p < 0.001) than that in the control group. Patients in the exercise group had no serious exercise-related adverse events, with a mean exercise adherence of 81.8%. Conclusion: Wearable device-based aerobic exercise during chemotherapy can be an effective adjunctive therapy to improve physical and mental health in BC patients. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=200247, Identifier: ChiCTR2300073667.

Prognostic Value of IGFBP6 in Breast Cancer: Focus on Glucometabolism.

IGFBP6, a member of the IGF binding protein (IGFBP) family, is a specific inhibitor of insulin-like growth factor II (IGF-II) and can inhibit the growth of malignant tumors overexpressing IGF-II. Type 2 diabetes (T2D) is a basic disorder of glucose metabolism that can be regulated by IGF-related pathways. We performed bioinformatics analysis of the TCGA database to explore the possible mechanism of IGFBP6 in breast cancer (BC) metabolism and prognosis and collected clinical samples from BC patients with and without T2D to compare and verify the prognostic effect of IGFBP6. In our study, the levels of IGFBP1-6 were positively correlated with overall survival (OS) in patients with breast cancer. IGFBP6 was upregulated in estrogen receptor (ER)-positive BC, and ER-positive and progesterone receptor (PR) positive patients had a higher expression level of IGFBP6 than ER-negative and PR-negative patients. IGFBP6 could be used as an independent prognostic factor in BC. The expression of IGFBP6 was decreased in BC tissue, and BC tissue from patients with T2D had lower IGFBP6 expression levels than BC tissue from patients without T2D. IGFBP6 is mainly involved in the PI3K-Akt and TGF-ß signaling pathways and tumor microenvironment regulation. In terms of metabolism, the expression of IGFBP6 was negatively correlated with that of most glucose metabolism-related genes. IGFBP6 expression was mainly correlated with mutations in TP53, PIK3CA, CDH1, and MAP3K1. In addition, the upregulation of IGFBP6 in BC increased the drug sensitivity to docetaxel, paclitaxel and gemcitabine. Overall, these results indicated that high expression of IGFBP6 is associated with a good prognosis in BC patients, especially in those without T2D. It is not only involved in the maintenance of the tumor microenvironment in BC but also inhibits the energy metabolism of cancer cells through glucose metabolism-related pathways. These findings may provide a new perspective on IGFBP6 as a potential prognostic marker for BC.

Electrical stimulation to improve meat quality: Factors at interplay, underlying biochemical mechanisms and a second look into the molecular pathways using proteomics.

Ensuring consistent beef eating quality is paramount for meeting consumer demands and sustaining the meat industry. Electrical stimulation (ES) is a post-slaughter intervention used to accelerate post-mortem glycolysis, to avoid cold shortening, to control the tenderization rate of meat through sophisticated physical, chemical and biochemical mechanisms including proteolysis, to improve beef tenderness and to achieve normal pHu that might lead to positive impact on color. This review comprehensively examines the multifaceted effects of ES on beef quality, encompassing factors and settings influencing its efficacy and the underlying biochemical mechanisms revealed using traditional biochemistry methods. It then delves into the molecular pathways modulated by ES, as unveiled by muscle proteomics, aiming to provide a second look and an unprecedented understanding of the underlying biochemical mechanisms through an integrative proteomics analysis of low-voltage ES (LVES) proteomics studies. The proteins changing as a result of ES were gathered in a compendium of 67 proteins, from which 14 were commonly identified across studies. In-depth bioinformatics of this compendium allowed a comprehensive overview of the molecular signatures and interacting biochemical pathways behind electrically stimulated beef muscles. The proteins belong to interconnected molecular pathways including the ATP metabolic process and glycolysis, muscle structure and contraction, heat shock proteins, oxidative stress, proteolysis and apoptosis. Understanding the intricate interplay of molecular pathways behind ES could improve the efficiency of beef production, ensuring consistent meat quality and meeting consumer expectations. The integrative analysis approach performed in this study holds promise for the meat industry's sustainability and competitiveness.

Prognosis and metabolism with a Golgi apparatus-related genes-based formula in breast cancer.

The Golgi apparatus (GA), an organelle that processes, sorts, and transports proteins synthesized by the endoplasmic reticulum, is also involved in many cellular processes associated with cancer, such as angiogenesis, the innate immune response, and tumor invasion and migration. We aimed to construct a breast cancer (BC) prognosis prediction model based on GA-related genetic information to evaluate the prognosis of patients with BC more accurately than existing models and to stratify patients for clinical therapy. In this study, The Cancer Genome Atlas-breast invasive carcinoma was used as the training cohort, and the Molecular Taxonomy of Breast Cancer International Consortium cohort was used as the validation cohort. Using bioinformatics methods, we constructed a GA-related gene risk score (GRS). The GRS was used to divide BC patients into a high-GRS group and a low-GRS group, and functional analysis, survival analysis, mutation analysis, immune landscape analysis, and metabolic analysis were performed to compare the 2 groups. Finally, a nomogram was constructed for clinical application. The genes in the GRS model were mainly related to the glucose metabolism pathway, and the main mutations in the 2 groups of patients were mutations in TP53 and CHD1. The mutation rate in the high-GRS group was greater than that in the low-GRS group. The high GRS group had higher tumor immune activity glycolysis; the pentose phosphate pathway tended to be the dominant metabolic pathways in this group, while fatty acid oxidation and glutamine catabolism tended to be dominant in the low-GRS group. GA-related genes were used to construct a prediction model for BC patients and had high accuracy in predicting prognosis. The mutations associated with the GRS are mainly TP53 and CDH1. Interestingly, the GRS is correlated with glucose metabolism in terms of gene expression and functional enrichment. In summary, the role of GRS-related genes in glucose metabolism is worthy of further study.

Early Diagnostic Markers for Esophageal Squamous Cell Carcinoma: Copy Number Alteration Gene Identification and cfDNA Detection.

The high mortality rate of esophageal squamous cell carcinoma (ESCC) is exacerbated by the absence of early diagnostic markers. The pronounced heterogeneity of mutations in ESCC renders copy number alterations (CNAs) more prevalent among patients. The identification of CNA genes within esophageal squamous dysplasia (ESD), a precancerous stage of ESCC, is crucial for advancing early detection efforts. Utilization of liquid biopsies via droplet-based digital PCR (ddPCR) offers a novel strategy for detecting incipient tumor traces. This study undertook a thorough investigation of CNA profiles across ESCC development stages, integrating data from existing databases and prior investigations to pinpoint and confirm CNA markers conducive to early detection of ESCC. Targeted sequencing was employed to select potential early detection genes, followed by the establishment of prediction models for ESCC early detection using ddPCR. Our analysis revealed widespread CNAs during the ESD stage, mirroring the CNA landscape observed in ESCC. A total of 40 CNA genes were identified as highly frequent in both ESCC and ESD lesions, through a comprehensive gene-level CNA analysis encompassing ESD and ESCC tissues, ESCC cell lines, and pan-cancer data sets. Subsequent validation of 5 candidate markers via ddPCR underscored the efficacy of combined predictive models encompassing PIK3CA, SOX2, EGFR, MYC, and CCND1 in early ESCC screening, as evidenced by the area-under-the-curve values exceeding 0.92 (P < .0001) across various detection contexts. The findings highlighted the significant utility of CNA genes in the early screening of ESCC, presenting robust models that could facilitate early detection, broad-scale population screening, and adjunctive diagnosis.

Ultrasensitive Detection of Cancer Biomarkers Using Photonic-Crystal-Enhanced Single-Molecule Imaging.

The rapid and sensitive quantification of low-abundance protein markers holds immense significance in early disease diagnosis and treatment. Single-molecule fluorescence imaging exhibits very high detection sensitivity and thus has great application potential in this area. The single-molecule signal, however, is often susceptible to interference from background noise due to its inherently weak intensity. A variety of signal amplification techniques based on cascading reactions have been developed to improve the signal-to-noise ratio of single-molecule imaging. Nevertheless, the operation of these methods is typically complicated and time-consuming, which limits the clinical application. Herein, we introduce an enzyme-free, photonic-crystal-based single-molecule (PC-SM) biochip for cost-effective, time-efficient, and ultrasensitive detection of disease markers. The PC-SM biochip can enhance the signal-to-noise ratio of single molecules by nearly 3-fold compared with unamplified samples, through coupling of the single-molecule photon energy with the optical band gap of the photonic crystal. We used the PC-SM biochip to detect the low-abundance leukemia inhibitory factor in the blood of pancreatic cancer patients and healthy people and achieved a detection limit of 2.0 pg/L and an AUC of 0.9067. The method exhibits exceptional sensitivity and specificity, showing great application potential in various clinical settings.

Meibography signal intensity as a novel image biomarker for meibomian gland function: evidence from cross-sectional and longitudinal analyses.

Background: Meibomian gland dysfunction (MGD), one of the most common ocular surface diseases, can induce dry eye and reduce patients' quality of life. Methodological limitations have resulted in contradictory interpretations of gland function. This study sought to investigate the correlation between meibography signal intensity (SI) and meibomian gland (MG) function and to validate an MGD classification strategy based on different levels of SI. Methods: A multicenter, cross-sectional analysis was conducted on 817 eyes from 361 patients with MGD and 52 healthy controls. Additionally, 78 eyes from 39 patients with MGD who had undergone LipiFlow treatment were recruited for longitudinal analyses. The SI value was obtained via meibography using an automated analyzer, and all participants underwent ocular surface examinations. A cross-sectional analysis was performed to determine SI distribution and its relationship to clinical characteristics via a generalized estimating equation model. Longitudinal analyses were conducted on the treatment cohort using a mixed-effects model to explore the outcome in different SI levels. Results: Regression analysis revealed significant correlations between SI and lipid layer thickness (ß=0.016), meibum expressibility (ß=-0.676), meibum quality (ß=-0.251), and fluorescein-stained tear-film break-up time (FBUT) (ß=0.064) (all P values <0.001 for the above associations). Low-level SI MGD cases exhibited the most severe clinical signs, including the worst meibum expressibility (16% for level 3) and quality scores (19% for level 3), the shortest FBUT (3.82±0.13 s), and the thinnest lipid layer (65.68±2.58 nm), (all P values <0.05, respectively). Patients with medium SI showed the lowest ocular surface disease index (OSDI) value (26.64±1.06), the longest FBUT (4.56±0.08 s), and the thickest lipid layer (80.20±2.90 nm). After treatment, the high SI values reduced significantly at each follow-up point compared to baseline (all P values <0.05). The medium SI group demonstrated the greatest improvement in symptoms and signs, followed by the high SI group, and the low SI group. Conclusions: Automated measurements of SI can effectively reflect MG secretory activity. The proposed low, medium, and high SI classifications represent different functional subtypes of MGD.

Mitochondrial serine catabolism safeguards maintenance of the hematopoietic stem cell pool in homeostasis and injury.

Hematopoietic stem cells (HSCs) employ a very unique metabolic pattern to maintain themselves, while the spectrum of their metabolic adaptations remains incompletely understood. Here, we uncover a distinct and heterogeneous serine metabolism within HSCs and identify mouse HSCs as a serine auxotroph whose maintenance relies on exogenous serine and the ensuing mitochondrial serine catabolism driven by the hydroxymethyltransferase 2 (SHMT2)-methylene-tetrahydrofolate dehydrogenase 2 (MTHFD2) axis. Mitochondrial serine catabolism primarily feeds NAD(P)H generation to maintain redox balance and thereby diminishes ferroptosis susceptibility of HSCs. Dietary serine deficiency, or genetic or pharmacological inhibition of the SHMT2-MTHFD2 axis, increases ferroptosis susceptibility of HSCs, leading to impaired maintenance of the HSC pool. Moreover, exogenous serine protects HSCs from irradiation-induced myelosuppressive injury by fueling mitochondrial serine catabolism to mitigate ferroptosis. These findings reframe the canonical view of serine from a nonessential amino acid to an essential niche metabolite for HSC pool maintenance.

Post-marketing safety concern of PI3K inhibitors in the cancer therapies: an 8-year disproportionality analysis from the FDA Adverse Event Reporting System.

BACKGROUND: The Phosphoinositide 3-kinases (PI3Ks) family plays a crucial role in tumorigenesis. Alpelisib (inhibiting PI3Kα), copanlisib (inhibiting PI3Kα andPI3Kδ), duvelisib (inhibiting PI3Kδ and PI3Kγ), and idelalisib (inhibiting PI3Kδ) were developed to target the PI3K pathway. However, the toxicity limits their application to some extent. It's necessary to investigate the adverse effects (AEs) of these inhibitors. RESEARCH DESIGN AND METHODS: We conducted a comparative analysis of the safety signals of AEs in PI3K inhibitors using disproportionality analysis in the FDA Adverse Event Reporting System database(FAERS). RESULTS: Our study identified significant safety signals for metabolic disorders with all PI3K inhibitors. Notable safety signals for gastrointestinal disorders were observed with most PI3K inhibitors, with the exception of copanlisib. Common AEs shared among all PI3K inhibitors included colitis and dehydration. Alpelisib displayed unique AEs associated with metabolic disorders, whereas copanlisib exhibited idiosyncratic AEs linked to cardiac and vascular disorders. Stevens-Johnson syndrome emerged as a common severe adverse event (SAE) among alpelisib, copanlisib, and idelalisib, while febrile neutropenia was prevalent among copanlisib, duvelisib, and idelalisib. Intestinal perforation was solely associated with alpelisib. CONCLUSIONS: The safety profiles of the five PI3K inhibitors vary concerning adverse events. These findings could guide drug selection and inform future prospective research.

Insights into ionizing radiation-induced bone marrow hematopoietic stem cell injury.

With the widespread application of nuclear technology across various fields, ionizing radiation-induced injuries are becoming increasingly common. The bone marrow (BM) hematopoietic tissue is a primary target organ of radiation injury. Recent researches have confirmed that ionizing radiation-induced hematopoietic dysfunction mainly results from BM hematopoietic stem cells (HSCs) injury. Additionally, disrupting and reshaping BM microenvironment is a critical factor impacting both the injury and regeneration of HSCs post radiation. However, the regulatory mechanisms of ionizing radiation injury to BM HSCs and their microenvironment remain poorly understood, and prevention and treatment of radiation injury remain the focus and difficulty in radiation medicine research. In this review, we aim to summarize the effects and mechanisms of ionizing radiation-induced injury to BM HSCs and microenvironment, thereby enhancing our understanding of ionizing radiation-induced hematopoietic injury and providing insights for its prevention and treatment in the future.

Age­integrated breast imaging reporting and data system assessment model to improve the accuracy of breast cancer diagnosis.

Early diagnosis is an effective strategy for decreasing breast cancer mortality. Ultrasonography is one of the most predominant imaging modalities for breast cancer owing to its convenience and non-invasiveness. The present study aimed to develop a model that integrates age with Breast Imaging Reporting and Data System (BI-RADS) lexicon to improve diagnostic accuracy of ultrasonography in breast cancer. This retrospective study comprised two cohorts: A training cohort with 975 female patients from Renmin Hospital of Wuhan University (Wuhan, China) and a validation cohort with 500 female patients from Maternal and Child Health Hospital of Hubei Province (Wuhan, China). Logistic regression was used to construct a model combining BI-RADS score with age and to determine the age-based prevalence of breast cancer to predict a cut-off age. The model that integrated age with BI-RADS scores demonstrated the best performance compared with models based solely on age or BI-RADS scores, with an area under the curve (AUC) of 0.872 (95% CI: 0.850-0.894, P<0.001). Furthermore, among participants aged <30 years, the prevalence of breast cancer was lower than the lower limit of the reference range (2%) for BI-RADS subcategory 4A lesions but within the reference range for BI-RADS category 3 lesions, as indicated by linear regression analysis. Therefore, it is recommended that management for this subset of participants are categorized as BI-RADS category 3, meaning that biopsies typically indicated could be replaced with short-term follow-up. In conclusion, the integrated assessment model based on age and BI-RADS may enhance accuracy of ultrasonography in diagnosing breast lesions and young patients with BI-RADS subcategory 4A lesions may be exempted from biopsy.

Understanding the dynamics of TKI-induced changes in the tumor immune microenvironment for improved therapeutic effect.

BACKGROUND: The dynamic interplay between tyrosine kinase inhibitors (TKIs) and the tumor immune microenvironment (TME) plays a crucial role in the therapeutic trajectory of non-small cell lung cancer (NSCLC). Understanding the functional dynamics and resistance mechanisms of TKIs is essential for advancing the treatment of NSCLC. METHODS: This study assessed the effects of short-term and long-term TKI treatments on the TME in NSCLC, particularly targeting epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations. We analyzed changes in immune cell composition, cytokine profiles, and key proteins involved in immune evasion, such as laminin subunit γ-2 (LAMC2). We also explored the use of aspirin as an adjunct therapy to modulate the TME and counteract TKI resistance. RESULTS: Short-term TKI treatment enhanced T cell-mediated tumor clearance, reduced immunosuppressive M2 macrophage infiltration, and downregulated LAMC2 expression. Conversely, long-term TKI treatment fostered an immunosuppressive TME, contributing to drug resistance and promoting immune escape. Differential responses were observed among various oncogenic mutations, with ALK-targeted therapies eliciting a stronger antitumor immune response compared with EGFR-targeted therapies. Notably, we found that aspirin has potential in overcoming TKI resistance by modulating the TME and enhancing T cell-mediated tumor clearance. CONCLUSIONS: These findings offer new insights into the dynamics of TKI-induced changes in the TME, improving our understanding of NSCLC challenges. The study underscores the critical role of the TME in TKI resistance and suggests that adjunct therapies, like aspirin, may provide new strategies to enhance TKI efficacy and overcome resistance.

The role of ferroptosis in DM-induced liver injury.

The liver damage caused by Diabetes Mellitus (DM) has attracted increasing attention in recent years. Liver injury in DM can be caused by ferroptosis, a form of cell death caused by iron overload. However, the role of iron transporters in this context is still not clear. Herein, we attempted to shed light on the pathophysiological mechanism of ferroptosis. DM was induced in 8-week-old male rats by streptozotocin (STZ) before assessment of the degree of liver injury. Together with histopathological changes, variations in glutathione peroxidase 4 (GPX4), glutathione (GSH), superoxide dismutase (SOD), transferrin receptor 1 (TFR1), ferritin heavy chain (FTH), ferritin light chain (FTL), ferroportin and Prussian blue staining, were monitored in rat livers before and after treatment with Fer-1. In the liver of STZ-treated rats, GSH and SOD levels decreased, whereas those of malondialdehyde (MDA) increased. Expression of TFR1, FTH and FTL increased whereas that of glutathione peroxidase 4 (GPX4) and ferroportin did not change significantly. Prussian blue staining showed that iron levels increased. Histopathology showed liver fibrosis and decreased glycogen content. Fer-1 treatment reduced iron and MDA levels but GSH and SOD levels were unchanged. Expression of FTH and FTL was reduced whereas that of ferroportin showed a mild decrease. Fer-1 treatment alleviated liver fibrosis, increased glycogen content and mildly improved liver function. Our study demonstrates that ferroptosis is involved in DM-induced liver injury. Regulating the levels of iron transporters may become a new therapeutic strategy in ferroptosis-induced liver injury.

A non-invasive artificial intelligence model for identifying axillary pathological complete response to neoadjuvant chemotherapy in breast cancer: a secondary analysis to multicenter clinical trial.

BACKGROUND: This study aims to develop a stacking model for accurately predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) using longitudinal MRI in breast cancer. METHODS: We included patients with node-positive breast cancer who received NAC following surgery from January 2012 to June 2022. We collected MRIs before and after NAC, and extracted radiomics features from the tumour, peritumour, and ALN regions. The Mann-Whitney U test, least absolute shrinkage and selection operator, and Boruta algorithm were used to select features. We utilised machine learning techniques to develop three single-modality models and a stacking model for predicting ALN response to NAC. RESULTS: This study consisted of a training cohort (n = 277), three external validation cohorts (n = 313, 164, and 318), and a prospective cohort (n = 81). Among the 1153 patients, 60.62% achieved ypN0. The stacking model achieved excellent AUCs of 0.926, 0.874, and 0.862 in the training, external validation, and prospective cohort, respectively. It also showed lower false-negative rates (FNRs) compared to radiologists, with rates of 14.40%, 20.85%, and 18.18% (radiologists: 40.80%, 50.49%, and 63.64%) in three cohorts. Additionally, there was a significant difference in disease-free survival between high-risk and low-risk groups (p < 0.05). CONCLUSIONS: The stacking model can accurately predict ALN status after NAC in breast cancer, showing a lower false-negative rate than radiologists. TRIAL REGISTRATION NUMBER: The clinical trial numbers were NCT03154749 and NCT04858529.

Crohn's disease-associated IgA nephropathy may prone to better renal outcome.

BACKGROUND AND AIM: Renal involvement in Crohn's Disease (CD) was rare in the population. Little was known between IgA nephropathy and CD. This study aimed to investigate the differences in clinical and outcome features of CD-associated IgA nephropathy (CD-IgAN) and primary IgA nephropathy (PIgAN). METHODS: Clinical data of patients diagnosed with IgAN by kidney biopsy were collected in the Sixth Affiliated Hospital of Sun Yat-sen University from January 1st, 2016 to June 1st, 2023. 17 patients with CD-IgAN and 87 patients with PIgAN were enrolled in this retrospective study. RESULTS: Compared with PIgAN patients, CD-IgAN patients had lower levels of urinary protein excretion (1.57 g per 24 h vs. 0.33 g per 24 h, p < 0.01), but higher levels of estimated glomerular filtration rate (77.63 ± 40.11 ml per min per 1.73m2 vs. 104.53 ± 32.97 ml per min per 1.73m2, p = 0.008). From the point of renal pathology of PIgAN, patients with CD-IgAN had a less incidence of tubular atrophy or interstitial fibrosis (p = 0.001). CD-IgAN patients had a higher incidence of complete remission of proteinuria (45.8% vs. 81.8%, p = 0.031) or hematuria (10.4% vs. 45.4%, p = 0.019) than PIgAN patients after twelve-month treatments. CONCLUSIONS: CD-IgAN manifests a milder progression of renal function than those PIgAN. After the treatment, proteinuria or hematuria are more prone to remit in patients with CD-IgAN.

Megakaryocytic IGF1 coordinates activation and ferroptosis to safeguard hematopoietic stem cell regeneration after radiation injury.

BACKGROUND: Hematopoietic stem cell (HSC) regeneration underlies hematopoietic recovery from myelosuppression, which is a life-threatening side effect of cytotoxicity. HSC niche is profoundly disrupted after myelosuppressive injury, while if and how the niche is reshaped and regulates HSC regeneration are poorly understood. METHODS: A mouse model of radiation injury-induced myelosuppression was built by exposing mice to a sublethal dose of ionizing radiation. The dynamic changes in the number, distribution and functionality of HSCs and megakaryocytes were determined by flow cytometry, immunofluorescence, colony assay and bone marrow transplantation, in combination with transcriptomic analysis. The communication between HSCs and megakaryocytes was determined using a coculture system and adoptive transfer. The signaling mechanism was investigated both in vivo and in vitro, and was consolidated using megakaryocyte-specific knockout mice and transgenic mice. RESULTS: Megakaryocytes become a predominant component of HSC niche and localize closer to HSCs after radiation injury. Meanwhile, transient insulin-like growth factor 1 (IGF1) hypersecretion is predominantly provoked in megakaryocytes after radiation injury, whereas HSCs regenerate paralleling megakaryocytic IGF1 hypersecretion. Mechanistically, HSCs are particularly susceptible to megakaryocytic IGF1 hypersecretion, and mTOR downstream of IGF1 signaling not only promotes activation including proliferation and mitochondrial oxidative metabolism of HSCs, but also inhibits ferritinophagy to restrict HSC ferroptosis. Consequently, the delicate coordination between proliferation, mitochondrial oxidative metabolism and ferroptosis ensures functional HSC expansion after radiation injury. Importantly, punctual IGF1 administration simultaneously promotes HSC regeneration and hematopoietic recovery after radiation injury, representing a superior therapeutic approach for myelosuppression. CONCLUSIONS: Our study identifies megakaryocytes as a last line of defense against myelosuppressive injury and megakaryocytic IGF1 as a novel niche signal safeguarding HSC regeneration.

Noninvasive Artificial Intelligence System for Early Predicting Residual Cancer Burden during Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: To develop an artificial intelligence (AI) system for the early prediction of residual cancer burden (RCB) scores during neoadjuvant chemotherapy (NAC) in breast cancer. SUMMARY BACKGROUND DATA: RCB III indicates drug resistance in breast cancer, and early detection methods are lacking. METHODS: This study enrolled 1048 patients with breast cancer from four institutions, who were all receiving NAC. Magnetic resonance images were collected at the pre- and mid-NAC stages, and radiomics and deep learning features were extracted. A multitask AI system was developed to classify patients into three groups (RCB 0-I, II, and III ) in the primary cohort (PC, n=335). Feature selection was conducted using the Mann-Whitney U- test, Spearman analysis, least absolute shrinkage and selection operator regression, and the Boruta algorithm. Single-modality models were developed followed by model integration. The AI system was validated in three external validation cohorts. (EVCs, n=713). RESULTS: Among the patients, 442 (42.18%) were RCB 0-I, 462 (44.08%) were RCB II and 144 (13.74%) were RCB III. Model-I achieved an area under the curve (AUC) of 0.975 in the PC and 0.923 in the EVCs for differentiating RCB III from RCB 0-II. Model-II distinguished RCB 0-I from RCB II-III, with an AUC of 0.976 in the PC and 0.910 in the EVCs. Subgroup analysis confirmed that the AI system was consistent across different clinical T stages and molecular subtypes. CONCLUSIONS: The multitask AI system offers a noninvasive tool for the early prediction of RCB scores in breast cancer, supporting clinical decision-making during NAC.

Monitoring response to neoadjuvant therapy for breast cancer in all treatment phases using an ultrasound deep learning model.

Purpose: The aim of this study was to investigate the value of a deep learning model (DLM) based on breast tumor ultrasound image segmentation in predicting pathological response to neoadjuvant chemotherapy (NAC) in breast cancer. Methods: The dataset contains a total of 1393 ultrasound images of 913 patients from Renmin Hospital of Wuhan University, of which 956 ultrasound images of 856 patients were used as the training set, and 437 ultrasound images of 57 patients underwent NAC were used as the test set. A U-Net-based end-to-end DLM was developed for automatically tumor segmentation and area calculation. The predictive abilities of the DLM, manual segmentation model (MSM), and two traditional ultrasound measurement methods (longest axis model [LAM] and dual-axis model [DAM]) for pathological complete response (pCR) were compared using changes in tumor size ratios to develop receiver operating characteristic curves. Results: The average intersection over union value of the DLM was 0.856. The early-stage ultrasound-predicted area under curve (AUC) values of pCR were not significantly different from those of the intermediate and late stages (p< 0.05). The AUCs for MSM, DLM, LAM and DAM were 0.840, 0.756, 0.778 and 0.796, respectively. There was no significant difference in AUC values of the predictive ability of the four models. Conclusion: Ultrasonography was predictive of pCR in the early stages of NAC. DLM have a similar predictive value to conventional ultrasound for pCR, with an add benefit in effectively improving workflow.

Efficient and eco-friendly cadmium ion recycling: Ultrasonic enhancement of aluminum powder replacement for low-temperature industrial applications.

Replacing cadmium ions in cadmium-containing solutions with aluminum powder is beneficial for cadmium resource recycling and environmental protection. However, the conventional aluminum powder replacement method requires harsh temperatures and prolonged conditions. In this study, the effect and mechanism of ultrasound on the replacement of cadmium with aluminum powder were investigated at low temperatures. Ultrasound has been proven to promote the etching of alumina films through the use of TEM and XPS, providing mechanistic support for the superiority of the new process. A degree of Cd replacement as high as 95.08 % is achieved at a low temperature (60 ℃) and in a short time (20 min) when using ultrasonicated aluminum powder replacement, which is 42.17 % higher than that of conventional aluminum powder. Compared with conventional aluminum powder replacement conditions with the same effect, the introduction of ultrasound can reduce the temperature by 30℃ and shorten the replacement time by 2/3, which has significant advantages in reaction efficiency and safety. The strengthening mechanism of ultrasound on the replacement effect of aluminum powder at low temperatures is revealed through detailed discussions on the corrosion of alumina films, agglomeration of aluminum powder, and adhesion of replacement products to the surface of aluminum powder, dissolved oxygen in the solution, and redissolution of cadmium. Therefore, a new approach for replacing aluminum powder in solutions with high Cd2+ concentrations at low temperatures is proposed in this work, which is expected to solve the existing harsh and dangerous problems of industrial aluminum powder replacement.

Comprehensive study of clinicopathological and immune cell infiltration and lactate dehydrogenase expression in patients with thymic epithelial tumours.

BACKGROUND: Lactate dehydrogenase (LDH) has emerged as a promising biomarker for cancer. However, the current understanding of LDH and circulating LDH expression in thymic epithelial tumour (TET) is lacking. METHODS: A comprehensive literature review and meta-analysis were performed to evaluate the clinical significance of circulating LDH levels in patients with TET. Circulating LDH levels were measured using a laboratory analyser (Cobas8000, Roche, Basel, Switzerland). The maximum standardised uptake value (SUVmax) was determined in patients who underwent whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Multiplex immunohistochemistry (IHC) was performed using a commercially available kit (Opal 6-plex Detection Kit, Akoya Biosciences, Marlborough, MA, USA) and slide scanner (Slideview VS200, Olympus, Tokyo, Japan). All statistical analyses were performed using SPSS (IBM Corp., Armonk, NY, USA) and Prism version 9.0 (GraphPad Inc., San Diego, CA, USA). Differences with p < 0.05 were considered to be statistically significant. RESULTS: Meta-analysis revealed that elevated circulating serum levels of LDH predicted poor prognosis in patients with TET. Circulating levels of LDH were analysed in the serum of 313 patients with TET and 87 with benign mediastinal mass. The mean circulating LDH level in patients with thymic carcinoma (TC) was significantly higher than that in those with thymoma (TM) and the benign group (p < 0.001). Expression levels of circulating LDH were significantly reduced in postoperative samples compared with that in preoperative samples (p < 0.05). Receiver operating characteristic (ROC) curve analysis for diagnosing TC yielded an area under the curve of 0.74, with a sensitivity of 54 % and specificity of 86 %. Furthermore, patients with TC exhibited higher 18F-FDG PET/CT SUVmax values compared to those with TM. Correlation analysis demonstrated a positive association between SUVmax values and circulating LDH levels. In addition, the percentages of LDH-positive cells in TC and type B1 TM tissues were higher than those in other subtypes of TM, and a significant positive correlation between the percentages of LDH-positive and CD20-positive cells was detected in patients with TET (p < 0.05). CONCLUSION: Circulating serum LDH level may serve as a non-invasive biomarker for the diagnosis and prognosis of TET. The relationship between LDH expression and immune cell infiltration merits further regarding its application in companion diagnosis for immunotherapy.