Deep Location Soft-Embedding-Based Network with Regional Scoring for Mammogram Classification.

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.

Biomass ash as soil fertilizers: Supercharging biomass accumulation by shifting auxin distribution.

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 2nd and 3rd 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 [3H]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.

Efficacy and safety of disitamab vedotin after trastuzumab for HER2 positive breast cancer: a real-world data of retrospective study.

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.

Prescribed-time cluster practical consensus for nonlinear multi-agent systems based on event-triggered mechanism.

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.

Research on collaborative edge network service migration strategy based on crowd clustering.

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.

Risk Factors of Hidden Blood Loss in Unilateral Biportal Endoscopic Surgery for Patients with Lumbar Spinal Stenosis.

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.

Human Parathyroid Hormone (1-34) accelerates skin wound healing through inducing cell migration via up-regulating the expression of Rac1.

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.

RNF20 contributes to epigenetic immunosuppression through CDK9-dependent LSD1 stabilization.

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.

Distributed consensus of discrete time-varying linear multi-agent systems with event-triggered intermittent control.

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.

The residual cancer burden index as a valid prognostic indicator in breast cancer after neoadjuvant chemotherapy.

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.

Amorphization Activated Multimetallic Pd Alloys for Boosting Oxygen Reduction Catalysis.

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 mgPd-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 mgPd-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.

SRSF1 inhibits ferroptosis and reduces cisplatin chemosensitivity of triple-negative breast cancer cells through the circSEPT9/GCH1 axis.

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 (IC50) 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 IC50 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.

Construction of a risk stratification model integrating ctDNA to predict response and survival in neoadjuvant-treated breast cancer.

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 1st NAC and before the 2nd 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.

Molecular epidemiological characteristics and genetic evolutionary relationships of methicillin-resistant Staphylococcus aureus of different avian origins in Qingdao, China, using whole-genome sequencing.

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-SCCmec 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-SCCmec 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.

Lipid Tales: Optimizing Arylomycin Membrane Anchors.

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.

Integrative proteomic and metabonomic profiling elucidates amino acid and lipid metabolism disorder in CA-MRSA-infected breast abscesses.

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.

Synotisjinpingensis (Asteraceae, Senecioneae), a new species with white ray florets from southeastern Yunnan, China.

Synotisjinpingensis (Asteraceae, Senecioneae), a new species from Jinping county in southeastern Yunnan province, China, is described and illustrated. This species is distinguished by having white ray florets in the genus Synotis, in which only species with yellow ray florets have been hitherto known. In habit and leaf shape S.jinpingensis is most closely similar to S.duclouxii, a species occurring in southwestern Guizhou, southern Sichuan and northeastern Yunnan, China, but differs, in addition to the color of ray florets, by having fewer lateral veins of leaves, obviously longer bracts of calyculus, and larger phyllaries. The membership of the new species within Synotis is strongly corroborated by evidence from floral micromorphology and phylogenetic analyses based on ITS sequence data. Color photographs of living plants, a distribution map, and provisional IUCN status of S.jinpingensis are provided.

PR status is a more decisive factor in efficacy of adding pertuzumab into neoadjuvant therapy for HER2-positive and lymph node-positive breast cancer than ER status: a real-world retrospective study in China.

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.

The HDAC inhibitor HFY-4A improves TUSC2 transcription to induce immunogenic cell death in breast cancer.

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.

FBXO24 Suppresses Breast Cancer Tumorigenesis by Targeting LSD1 for Ubiquitination.

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.