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Background: Cuproptosis, a newly defined regulated form of cell death, is mediated by the accumulation of copper ions in cells and related to protein lipoacylation. Seven genes have been reported as key genes of cuproptosis phenotype. Cuproptosis may be developed by subsequent research as a target to treat cancer, such as breast cancer. Long-noncoding RNA (lncRNA) has been proved to play a vital role in regulating the biological process of breast cancer. However, the role of lncRNAs in cuproptosis is poorly studied. Methods: Based on TCGA (The Cancer Genome Atlas) database and integrated several R packages, we screened out 153 cuproptosis-related lncRNAs and constructed a novel cuproptosis-related prognostic 2-lncRNAs signature (BCCuS) in breast cancer and then verified. By using pRRophetic package and machine learning, 72 anticancer drugs, significantly related to the model, were screened out. qPCR was used to detect the differentially expression of two model lncRNAs and seven cuproptosis genes between 10 pairs of breast cancer tissue samples and adjacent samples. Results: We constructed a novel cuproptosis-related prognostic 2-lncRNAs (USP2-AS1, NIFK-AS1) signature (BCCuS) in breast cancer. Univariate COX analysis ( p < .001) and multivariate COX analysis ( p < .001) validated that BCCuS was an independent prognostic factor for breast cancer. Overall survival Kaplan Meier-plotter, ROC curve and Risk Plot validated the prognostic value of BCCuS both in test set and verification set. Nomogram and C-index proved that BCCuS has strong correlation with clinical decision-making. BCCuS still maintain inspection efficiency when patients were splitting into Stage I−II ( p = .024) and Stage III−IV ( p = .003) breast cancer. BCCuS-high group and BCCuS-low group showed significant differences in gene mutation frequency, immune function, TIDE (tumor immune dysfunction and exclusion) score and other phenotypes. TMB (tumor mutation burden)-high along with BCCuS-high group had the lowest Survival probability ( p = .005). 36 anticancer drugs whose sensitivity (IC50) was significantly related to the model were screened out using pRRophetic package. qPCR results showed that two model lncRNAs (USP2-AS1, NIFK-AS1) and three Cuproptosis genes (FDX1, PDHA1, DLAT) expressed differently between 10 pairs of breast cancer tissue samples and adjacent samples. Conclusion: The current study reveals that cuproptosis-related prognostic 2-lncRNAs signature (BCCuS) may be useful in predicting the prognosis, biological characteristics, and appropriate treatment of breast cancer patients.

Background Metastatic tumors pose clinical treatment challenges due to their high adaptability to diverse environments. The cooperation of epigenetic modifications and metabolic adaptations enables tumor cells to dynamically adjust for survival in variable environments, which is crucial for tumor metastasis and worth exploring in depth. Methods RNA immunoprecipitation sequencing, transmission electron microscopy photograph and GFP-mCherry-LC3 fluorescence imaging were employed to reveal the role of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in triple-negative breast cancer (TNBC) cells. Then, in the presence of rapamycin, further experiments showed that IGF2BP3’s role in TNBC metastasis was autophagy-mediated. Methylated RNA immunoprecipitation sequencing, luciferase assays and co-immunoprecipitation mass spectrometry showed that IGF2BP3 promoted mRNA translation initiation in an N6-methyladenosine (m6A)-dependent manner. Results We found that IGF2BP3 could link epigenetic modification and metabolic adaptation to promote autophagy-mediated TNBC metastasis. As an m6A binding protein that is specifically highly expressed in TNBC, IGF2BP3 could bind to the m6A motif of c-Met mRNA, regulating autophagy-mediated epithelial-to-mesenchymal transition via the c-Met/PI3K/AKT/mTOR pathway. Moreover, IGF2BP3 recruited eIF4G2 as a collaborator, promoting c-Met protein expression by facilitating m6A-dependent and cap-independent mRNA translation initiation, rather than affecting mRNA stability. Conclusions Our study expands the understanding of IGF2BP3’s role in TNBC metastasis by establishing its function in regulating autophagy. Notably, IGF2BP3 could bind to the m6A motif on the 5′ and 3′ untranslated regions (UTRs) of c-Met mRNA to facilitate its translation in a cap-independent manner.

AimsHuman epidermal growth factor receptor 2 (HER2)-positive patients with breast cancer may have different HER2/CEP17 ratios and HER2 copy numbers, with inconsistent responses to anti-HER2 neoadjuvant chemotherapy (NACT). Our study aimed to explore the relationship between different HER2 fluorescence in situ hybridisation (FISH) patterns in HER2-positive patients with breast cancer and responses to anti-HER2 NACT.Methods527 patients with HER2-positive invasive breast cancer who received anti-HER2 NACT from 2015 to 2022 were included and divided into three groups by FISH results, namely group A: HER2/CEP17<2.0 and HER2 copy numbers ≥6.0, HER2 immunohistochemistry 2/3+; group B: HER2/CEP17≥2.0 and HER2 copy numbers ≥4.0 and <6.0; group C: HER2/CEP17≥2.0 and HER2 copy numbers ≥6.0. We compared clinicopathological characteristics and pathological complete response (pCR) rates of different groups.ResultsAccording to HER2 FISH results, 12 patients (2.3%, 12/527) were in group A, 40 (7.6%, 40/527) were in group B and 475 (90.1%, 475/527) were in group C. The pCR rate was the lowest in group B (5.0%), while the pCR rates in group A and group C were 33.3% and 44.4%, respectively (p (group A vs. B) =0.021, p (group C vs. B) < 0.001). Both univariate and multivariate analyses revealed that HER2 FISH pattern was correlated with pCR rate (p (group C vs. B) < 0.001, p (group C vs. B) = 0.025).ConclusionsPatients with HER2/CEP17≥2.0 and HER2 copy numbers ≥4.0 and <6.0 do not benefit to the same extent from current anti-HER2 therapies as FISH-positive patients with other patterns.

This study aimed to evaluate the representativeness of HER2-low and ultralow status in core needle biopsies (CNB) with AI assistance and investigate the clinicopathological and molecular characteristics of HER2-ultralow, HER2-null, and HER2-low breast cancer patients in the Chinese population. CNB-surgical excision biopsy (SEB) concordance was high between HER2-null and ultralow/low groups but limited in the ultralow subgroup. Univariate analyses showed that TNBC subtype, HR negative expression, high Ki-67 index, and AR negative expression were potential indicative factors for the discordance of HER2 status between CNB and SEB. Clinicopathological features showed no significant differences between low and ultralow groups. Genomic analysis revealed subtle mutation pattern differences. The HER2 copy number level did not show additional value in distinguishing subgroups. Conclusions highlight the need to address CNB-SEB diagnostic discordance, particularly in ultralow cases, emphasizing the necessity of HER2 retesting in surgical specimens.

部署于云平台的医疗诊断服务不仅推进了医疗资源的整合, 还提高了病情诊断的精准性和高效性, 但是该场景用户失去了对个人信息的掌控, 对高度敏感的病理数据来说安全与隐私保护是实现基于云平台决断的前提. 云端医疗数据的隐私保护可以通过差分隐私、安全多方计算和同态加密等密码学技术实现, 避免泄露用户医疗大数据中的隐私信息. 差分隐私中引入随机噪声会降低计算精度, 安全多方计算技术面临昂贵的通信成本, 同态加密需要花费较大的时间加密深度学习模型. 本文基于内积加密技术提出一种实现双向隐私保护的医疗诊断云服务方案, 不仅保护用户医疗大数据中的个人隐私, 而且帮助模型开发方避免云端部署造成的模型信息泄漏风险, 甚至能降低隐私保护技术对医疗诊断效率和准确率造成的影响. 为了保障用户个人隐私, 方案中用户上传密文形态的个人医疗数据到云端服务器, 云服务器通过密文数据预测疾病的结果. 该方案的疾病诊断服务由云服务器提供并维护, 而疾病诊断服务的实现依赖于模型开发方部署到云端的模型. 模型开发方使用自行的深度学习算法训练明文形式的数据集, 并获得预训练模型, 使之可以处理密文形式的数据. 实验分析表明, 所述模型能完成 CRC-VAL-HE-7K 数据集上的结直肠癌诊断, 与传统云端 EfficientNet 相比, 本文方案仅损失少量的性能和响应效率.

Proper development of plant roots is critical for primary physiological functions,including water and nutrient absorption and uptake,physical support,and carbohydrate storage（Zhang et al.,2010）.Crop root systems act as the key organ for sensing and response to abiotic and biotic stresses.

Recently, deeply-buried shale (depth > 3500 m) has become an attractive target for shale gas exploration and development in China. Gas-in-place (GIP) is critical to shale gas evaluation, but the GIP content of deep shale and its controlling factors have rarely been investigated. To clarify this issue, an integrated investigation of deep gas shale (3740–3820 m depth) of the Lower Paleozoic Wufeng–Longmaxi Formations (WF–LMX) in the Dingshan area, Sichuan Basin had been carried out. Our results show that the GIP content of the studied WF–LMX shale in the Dingshan area ranges from 0.85 to 12.7 m 3/t, with an average of 3.5 m 3/t. Various types of pores, including organic matter (OM) pore and inorganic pore, are widely developed in the deep shale, with total porosity of 2.2 to 7.3% (average = 4.5%). The OM pore and clay-hosted pore are the dominant pore types of siliceous shale and clay-rich shale, respectively. Authigenic quartz plays a critical role in the protection of organic pores in organic-rich shales from compaction. The TOC content controls the porosity of shale samples, which is the major factor controlling the GIP content of the deep shale. Clay minerals generally play a negative role in the GIP content. In the Sichuan Basin, the deep and ultra-deep WF–LMX shales display the relatively high porosity and GIP contents probably due to the widespread of organic pores and better preservation, revealing great potentials of deep and ultra-deep shale gas. From the perspective of rock mechanical properties, deep shale is the favorable exploration target in the Sichuan Basin at present. However, ultra-deep shale is also a potential exploration target although there remain great challenges.

Objective： To assess the clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma （EOC）. Methods： A retrospective study of young EOC inpatients （≤40 years old） was performed during January 1994 and December 2010 in eight institutions. Results： Data were analyzed from 94 patients treated with fertility-sparing surgery with a median follow-up time of 58.7 months. As histologic grade increased, overall survival （OS） and disease-free survival （DFS） of patients receiving fertility-sparing surgery declined. Neither staging surgery nor laparoscopy of early stage EOC with conservative surgery had a significant effect on OS or DFS. Normal menstruation recommenced after chemotherapy in 89% of the fertility-sparing group. Seventeen pregnancies among twelve patients were achieved by the end of the follow-ups. Conclusions： Fertility-sparing treatment for patients with EOC Stage I Grade 1 could be cautiously considered for young patients. The surgical procedure and surgical route might not significantly influence the prognosis. Standard chemotherapy is not likely to have an evident impact on ovarian function or fertility in young patients.

<正>Dear Editor,Proper development of plant roots is critical for primary physiological functions,including water and nutrient absorption and uptake,physical support,and carbohydrate storage(Zhang et al.,2010).Crop root systems act as the key organ for sensing and response to abiotic and biotic stresses.Previous studies of crop root system development suggest that increased lateral root formation(LRF)could stimulate

Diabetes mellitus (DM) is a common chronic metabolic disease caused by significant accumulation of advanced glycation end products (AGEs). Atrial fibrillation (AF) is a common cardiovascular complication of DM. Here, we aim to clarify the role and mechanism of atrial myocyte senescence in the susceptibility of AF in diabetes. Rapid transesophageal atrial pacing was used to monitor the susceptibility of mice to AF. Whole‐cell patch‐clamp was employed to record the action potential (AP) and ion channels in single HL‐1 cell and mouse atrial myocytes. More importantly, anti‐RAGE antibody and RAGE‐siRNA AAV9 were used to investigate the relationship among diabetes, aging, and AF. The results showed that elevated levels of p16 and retinoblastoma (Rb) protein in the atrium were associated with increased susceptibility to AF in diabetic mice. Mechanistically, AGEs increased p16/Rb protein expression and the number of SA‐β‐gal‐positive cells, prolonged the action potential duration (APD), reduced protein levels of Cav1.2, Kv1.5, and current density of ICa,L, IKur in HL‐1 cells. Anti‐RAGE antibody or RAGE‐siRNA AAV9 reversed these effects in vitro and in vivo, respectively. Furthermore, downregulating p16 or Rb by siRNA prevented AGEs‐mediated reduction of Cav1.2 and Kv1.5 proteins expression. In conclusion, AGEs accelerated atrial electrical remodeling and cellular senescence, contributing to increased AF susceptibility by activating the p16/Rb pathway. Inhibition of RAGE or the p16/Rb pathway may be a potential therapeutic target for AF in diabetes. Diabetes mellitus (DM) is a common chronic metabolic disease and an independent risk factor for atrial fibrillation (AF). However, the regulatory mechanisms underlying atrial electrical remodeling in diabetes are not fully understood. This study presents new insights into the role and mechanism of atrial myocyte senescence in diabetic‐induced AF. Inhibition of RAGE or the p16/Rb pathway may be a potential therapeutic target for AF in diabetes.