Feasibility and tolerability of eribulin-based chemotherapy versus other chemotherapy regimens for patients with metastatic triple-negative breast cancer: a single-centre retrospective study.

Background: Patients with Triple-negative breast cancer (TNBC) face a poor prognosis and limited therapeutic options. Current data on eribulin usage to treat TNBC is scarce. Therefore, we sought to compare the feasibility and tolerability of eribulin-based regimens with other chemotherapy regimens in patients with TNBC. Method: This retrospective study was conducted at Fujian Medical University Cancer Hospital and included 159 patients with TNBC enrolled between October 2011 and January 2023. Patients underwent treatment with eribulin-based and other chemotherapy regimens. The study's primary endpoints were progression-free survival (PFS) and overall survival (OS), while its secondary endpoint was objective response rate (ORR), disease control rate (DCR), and safety. Tumour response was assessed using RECIST V.1.1 criteria. Results: Of the 159 participants in the study, 42 individuals (26.4%) received treatment with eribulin, whereas 117 participants (73.6%) were administered alternative chemotherapy regimens, which included nab-paclitaxel-based therapy (n = 45) and platinum-based therapy (n = 51). The follow-up period for all patients ended on 31 December 2022, and the median follow-up time was 18.3 months (range:0.7-27.5). Following propensity score matching (PSM), eribulin-based treatment resulted in longer median progression-free survival compared to platinum-based (hazard ratio (HR) = 0.41, p = 0.006), nab-paclitaxel-based (hazard ratio = 0.36, p = 0.001) and other chemotherapy (HR = 0.39, p < 0.001). Also, eribulin induced a remarkable prolongation of the median overall survival duration in all three comparative groups. The group receiving eribulin treatment showed significantly reduced incidences of any grade of anaemia, peripheral neuropathy, nausea and vomiting, and hair loss compared to other chemotherapy groups. Conclusion: For the salvage treatment of advanced TNBC, treatment with eribulin produced longer median PFS and OS than other chemotherapy regimens, with a well-tolerated safety profile. Therefore, further investigation of eribulin-based treatment in larger randomized trials for patients with advanced TNBC is warranted.

Geographic differences in pharmacotherapy patterns and outcomes of acute ischemic stroke in China.

BACKGROUND: Vast economic and healthcare status discrepancies exist among regions in China, contributing to different treatment patterns. This study was aimed to investigate the current status of pharmacotherapy for acute ischemic stroke (AIS) and outcomes in China and explore the geographic variation in stroke care. METHODS: This study was a multicenter prospective registry study, which collected the data of patients with AIS from 80 hospitals in 46 cities in 2015-2017 across China. Poor functional outcome defined as a modified Rankin Scale score of 3-6 was assessed at 3 and 12 months. Multivariate logistic regression was used. RESULTS: Among 9973 eligible patients, the number of receiving intravenous thrombolysis (IVT), antiplatelet agents, anticoagulants, statin and human urinary kallidinogenase was 429 (4.3%), 9363 (93.9%), 1063 (10.7%), 6828 (74.7%) and 5112 (51.2%), respectively. Multivariable analysis showed IVT use in northeastern was significantly more frequent than in eastern region (OR = 3.17, 95% CI, 2.53-3.99), while the antiplatelets agents use were less frequent (OR = 0.46, 95%CI: 0.38-0.57). The proportions of poor outcomes at 3 and 12 months were 20.7% and 15.8%, respectively. Multivariate analysis showed AIS patients from northeastern and central region had significantly lower risk of poor outcome at month 3 and 12 than those from eastern region (all P < 0.05). CONCLUSIONS: There was a low IVT use and a high antiplatelet agent and statin use for AIS in China. The pharmacotherapy and prognosis of AIS had variation by geographic region. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (NCT02470624).

A real-world study of the effectiveness and safety of apatinib-based regimens in metastatic triple-negative breast cancer.

PURPOSE: This investigation sought to examine the efficacy and safety of low-dose apatinib used alongside chemotherapy in the clinical management of patients with metastatic triple-negative breast cancer (TNBC) within a real-world setting, whilst comparing the outcomes with those treated solely with chemotherapy. METHODS: This case series study analyzed clinical data and treatment outcomes of 163 patients with metastatic TNBC who underwent rescue treatment at the Medical Oncology Department of Clinical Oncology, Fujian Cancer Hospital, School of Fujian Medical University, China, between October 2011 and January 2023. All the patients underwent rescue treatment with either chemotherapy alone or apatinib (250 mg/day) combined with chemotherapy. The study's primary outcome was progression-free survival (PFS), whereas the secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles. RESULTS: The study was designed to compare two groups [1]. Out of the 163 TNBC patients who participated in the study, 107 individuals (65.6%) received treatment based on chemotherapy, whereas 56 patients (34.4%) were given treatment based on a combination of low-dose apatinib (250 mg/day) and other treatments, including chemotherapy. After propensity score matching (PSM), the objective response rate (ORR) and disease control rate (DCR) of patients with advanced triple-negative breast cancer (TNBC) who received apatinib-based treatment were 50.0 and 90.0%, respectively, while they were 6.7 and 20.0%, respectively, for the chemotherapy-based group (P < 0.001). The group that received apatinib-based treatment showed superior results in both PFS and OS compared to the group that received chemotherapy. The median PFS and OS for the apatinib-based group were 7.8 and 20.3 months, respectively, while they were only 2.2 months and 9.0 months, respectively, for the chemotherapy-based group (P < 0.001) [2]. Patients who were administered combo therapies, including PD-1 inhibitors, were excluded. In total, 97 patients received chemotherapy alone, while 34 patients were treated with apatinib in combination with chemotherapy. After propensity score matching (PSM), the ORR and DCR for the total group who received combo therapies were 44.4 and 81.5%, respectively, while they were 11.1 and 22.2%, respectively, for the chemotherapy alone group (P < 0.001). The group receiving both apatinib and chemotherapy displayed notable advantages over the group solely receiving chemotherapy in regards to PFS and OS for the entirety of the population. The PFS was found to be 7.8 months in comparison to 2.1 months (P < 0.001) and the OS was 21.1 months in contrast to 9.0 months (P < 0.001). Apatinib combined with chemotherapy induced grade 3/4 hematological toxicities, including neutropenia (8.8%) and thrombocytopenia (2.9%). Additionally, non-hematological toxicities were commonly observed, such as Hand-foot syndrome (35.3%), proteinuria (26.5%), hypertension (61.8%), higher alanine aminotransferase levels (26.5%), and fatigue (35.3%). The most frequent non-hematological grade 3/4 toxicities were Hand-foot syndrome (2.9%) and hypertension (5.9%). The study did not report any fatal adverse effects. CONCLUSIONS: The combination of low-dose apatinib with chemotherapy has proven to be more effective than chemotherapy alone in treating metastatic triple-negative breast cancer (TNBC). Additionally, the occurrence of grade 3/4 non-hematologic toxicities was significantly lower compared to the recommended dose of apatinib.

Root-associated bacteria strengthen their community stability against disturbance of antibiotics on structure and functions.

Antibiotics affect bacterial community structure and functions in soil. However, the response and adaptation of root-associated bacterial communities to antibiotic stress remains poorly understood. Here, rhizobox experiments were conducted with maize (Zea mays L.) upon exposure to antibiotics ciprofloxacin or tetracycline. High-throughput sequencing analysis of bacterial community and quantitative PCR analysis of nitrogen cycling genes show that ciprofloxacin and tetracycline significantly shift bacterial community structure in bulk soil, whereas plant host may mitigate the disturbances of antibiotics on bacterial communities in root-associated niches (i.e., rhizosphere and rhizoplane) through the community stabilization. Deterministic assembly, microbial interaction, and keystone species (e.g., Rhizobium and Massilia) of root-associated bacterial communities benefit the community stability compared with those in bulk soil. Meanwhile, the rhizosphere increases antibiotic dissipation, potentially reducing the impacts of antibiotics on root-associated bacterial communities. Furthermore, rhizospheric effects deriving from root exudates alleviate the impacts of antibiotics on the nitrogen cycle (i.e., nitrification, organic nitrogen conversion and denitrification) as confirmed by functional gene quantification, which is largely attributed to the bacterial community stability in rhizosphere. The present study enhances the understanding on the response and adaptation of root-associated bacterial community to antibiotic pollution.

Aquaporin 4 Mediates the Effect of Iron Overload on Hydrocephalus After Intraventricular Hemorrhage.

BACKGROUND: Iron overload plays an important role in hydrocephalus development following intraventricular hemorrhage (IVH). Aquaporin 4 (AQP4) participates in the balance of cerebrospinal fluid secretion and absorption. The current study investigated the role of AQP4 in the formation of hydrocephalus caused by iron overload after IVH. METHODS: There were three parts to this study. First, Sprague-Dawley rats received an intraventricular injection of 100 µl autologous blood or saline control. Second, rats had IVH and were treated with deferoxamine (DFX), an iron chelator, or vehicle. Third, rats had IVH and were treated with 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020), a specific AQP4 inhibitor, or vehicle. Rats underwent T2-weighted and T2* gradient-echo magnetic resonance imaging to assess lateral ventricular volume and intraventricular iron deposition at 7, 14, and 28 days after intraventricular injection and were then euthanized. Real-time quantitative polymerase chain reaction, western blot analysis, and immunofluorescence analyses were conducted on the rat brains to evaluate the expression of AQP4 at different time points. Hematoxylin and eosin-stained brain sections were obtained to assess the ventricular wall damage on day 28. RESULTS: Intraventricular injection of autologous blood caused a significant ventricular dilatation, iron deposition, and ventricular wall damage. There was increased AQP4 mRNA and protein expression in the periventricular tissue in IVH rats through day 7 to day 28. The DFX treatment group had a lower lateral ventricular volume and less intraventricular iron deposition and ventricular wall damage than the vehicle-treated group after IVH. The expression of AQP4 protein in periventricular tissue was also inhibited by DFX on days 14 and 28 after IVH. The use of TGN-020 attenuated hydrocephalus development after IVH and inhibited the expression of AQP4 protein in the periventricular tissue between day 14 and day 28 without a significant effect on intraventricular iron deposition or ventricular wall damage. CONCLUSIONS: AQP4 located in the periventricular area mediated the effect of iron overload on hydrocephalus after IVH.

Recent Advances in Nanotechnology-Based Targeted Delivery Systems of Active Constituents in Natural Medicines for Cancer Treatment.

Owing to high efficacy and safety, natural medicines have found their way into the field of cancer therapy over the past few decades. However, the effective ingredients of natural medicines have shortcomings of poor solubility and low bioavailability. Nanoparticles can not only solve the problems above but also have outstanding targeting ability. Targeting preparations can be classified into three levels, which are target tissues, cells, and organelles. On the premise of clarifying the therapeutic purpose of drugs, one or more targeting methods can be selected to achieve more accurate drug delivery and consequently to improve the anti-tumor effects of drugs and reduce toxicity and side effects. The aim of this review is to summarize the research status of natural medicines' nano-preparations in tumor-targeting therapies to provide some references for further accurate and effective cancer treatments.

Study on performance of a relay-assisted UWOC system based on adaptive optics.

To improve the performance of underwater wireless optical communication (UWOC) systems, we propose a relay-assisted UWOC system model based on adaptive optics (AO). The closed expressions of the scintillation index, composite channel probability density function, and outage probability of the Gaussian beam before and after AO compensation are derived using the extended Rytov theory and Meijer G-function. The performance variation of an UWOC system with different parameters is analyzed by simulation. The results show that AO correction can compensate for the distorted wavefront and significantly reduce the intensity fluctuation at the receiving end. The proposed system can efficiently alleviate channel fading, improving the outage probability performance of the UWOC system.

The relationship between hematoma morphology and intraventricular hemorrhage in supratentorial deep intracerebral hemorrhage.

Background: Intraventricular hemorrhage (IVH) after intracerebral hemorrhage (ICH) is a strong independent predictor of poor outcomes. Although the location and volume of ICH are associated with IVH, our knowledge concerning the mechanism of IVH after ICH is still limited. This study aimed to investigate the relationship between hematoma morphology and IVH in patients with supratentorial deep ICH. Methods: We retrospectively analyzed adult patients (aged ≥18 years) with spontaneous supratentorial deep ICH who underwent computed tomography (CT) within 48 h after ICH symptom onset in Peking University First Hospital between January 2017 and August 2022. We collected the clinical and imaging data of the patients and assessed hematoma morphology using several quantitative radiological parameters including hematoma volume, sphericity index, A/B ratio (A: the largest area of hematoma; B: the largest diameter 90° to A on the same slice), and our newly proposed largest diameter-midline angle (LMA). Multivariable logistic regression analysis was used to analyze the relationship between these parameters and the presence of IVH on the initial CT scan. Results: Among 114 patients with spontaneous supratentorial deep ICH, 41 (36.0%) had IVH. In patients with IVH, the sphericity index was lower than that in individuals without IVH, while the LMA was larger. Multivariate logistic regression analysis showed that sphericity index [0.1-unit odds ratio (OR) =0.252; 95% CI: 0.089-0.709; P=0.009] and the LMA (10-unit OR =1.281; 95% CI: 1.007-1.630; P=0.04) were independently associated with the presence of IVH in patients with supratentorial deep ICH. Univariate analyses showed that hematoma volume, A/B ratio, sphericity index, and the LMA were significantly associated with poor outcomes at discharge. Conclusions: Two quantitative parameters of hematoma morphology, sphericity index and the LMA, were significantly associated with the presence of IVH in patients with supratentorial deep ICH. Further prospective studies with larger sample sizes are needed to validate our results.

Epilepsy in a Patient With Brain Herniation Into the Arachnoid Granulation.

This case report describes epilepsy in a 50-year-old patient with brain herniation into the arachnoid granulation.

A linear and circular dual-conformation noncoding RNA involved in oxidative stress tolerance in Bacillus altitudinis.

Circular RNAs have been extensively studied in eukaryotes, but their presence and/or biological functionality in bacteria are unclear. Here, we show that a regulatory noncoding RNA (DucS) exists in both linear and circular conformation in Bacillus altitudinis. The linear forms promote B. altitudinis tolerance to H2O2 stress, partly through increased translation of a stress-responsive gene, htrA. The 3' end sequences of the linear forms are crucial for RNA circularization, and formation of circular forms can decrease the levels of the regulatory linear cognates. Bioinformatic analysis of available RNA-seq datasets from 30 bacterial species revealed multiple circular RNA candidates, distinct from DucS, for all the examined species. Experiments testing for the presence of selected circular RNA candidates in four species successfully validated 7 out of 9 candidates from B. altitudinis and 4 out of 5 candidates from Bacillus paralicheniformis; However, none of the candidates tested for Bacillus subtilis and Escherichia coli were detected. Our work identifies a dual-conformation regulatory RNA in B. altitutidinis, and indicates that circular RNAs exist in diverse bacteria. However, circularization of specific RNAs does not seem to be conserved across species, and the circularization mechanisms and biological functionality of the circular forms remain unclear.

Analysis of spatial and temporal changes in human interference in important ecological function areas in China: the Gansu section of Qilian Mountain National Park as an example.

The disturbance characteristics and driving factors of human activity intensity in national parks are important factors affecting environmental change in ecological function areas. In-depth analysis of these must be the basis of improving the ecological environment in northwest China. This study selected data related to human activities from 2000 to 2020 to analyze the comprehensive impact of human interference on national park development and found that the NDVI (Normalized Difference Vegetation Index) of Qilian Mountain National Park showed an increasing trend and that the NPP (net primary productivity) showed spatial distribution characteristics of decreasing from east to west during the study period. This showed that human interference in and around the national park was changing significantly and that the high value area was gradually shifting southward. In the first decade, economic and social development was slow; related industries such as industry, tourism, and modern agriculture were not introduced on a large scale; and the ecological environment was in relatively good condition, with relatively weak human interference. However, in the second decade, human interference was prominent, with deeper ecological damage, but rapid economic development. Infrastructure development, population urbanization, and traditional production and living practices were the main factors driving changes in human interference. The Chinese government's proposed green building policy will further reduce the ecological impact of human activities while ensuring economic development. Building upon this, the present paper puts forth a "zero-disturbance" framework for national parks, aiming to offer recommendations for the future development of such parks.

Unsupervised Local Discrimination for Medical Images.

Contrastive learning, which aims to capture general representation from unlabeled images to initialize the medical analysis models, has been proven effective in alleviating the high demand for expensive annotations. Current methods mainly focus on instance-wise comparisons to learn the global discriminative features, however, pretermitting the local details to distinguish tiny anatomical structures, lesions, and tissues. To address this challenge, in this paper, we propose a general unsupervised representation learning framework, named local discrimination (LD), to learn local discriminative features for medical images by closely embedding semantically similar pixels and identifying regions of similar structures across different images. Specifically, this model is equipped with an embedding module for pixel-wise embedding and a clustering module for generating segmentation. And these two modules are unified by optimizing our novel region discrimination loss function in a mutually beneficial mechanism, which enables our model to reflect structure information as well as measure pixel-wise and region-wise similarity. Furthermore, based on LD, we propose a center-sensitive one-shot landmark localization algorithm and a shape-guided cross-modality segmentation model to foster the generalizability of our model. When transferred to downstream tasks, the learned representation by our method shows a better generalization, outperforming representation from 18 state-of-the-art (SOTA) methods and winning 9 out of all 12 downstream tasks. Especially for the challenging lesion segmentation tasks, the proposed method achieves significantly better performance.

A Heterogeneous Graph to Abstract Syntax Tree Framework for Text-to-SQL.

Text-to-SQL is the task of converting a natural language utterance plus the corresponding database schema into a SQL program. The inputs naturally form a heterogeneous graph while the output SQL can be transduced into an abstract syntax tree (AST). Traditional encoder-decoder models ignore higher-order semantics in heterogeneous graph encoding and introduce permutation biases during AST construction, thus incapable of exploiting the refined structure knowledge precisely. In this work, we propose a generic heterogeneous graph to abstract syntax tree (HG2AST) framework to integrate dedicated structure knowledge into statistics-based models. On the encoder side, we leverage a line graph enhanced encoder (LGESQL) to iteratively update both node and edge features through dual graph message passing and aggregation. On the decoder side, a grammar-based decoder first constructs the equivalent SQL AST and then transforms it into the desired SQL via post-processing. To avoid over-fitting permutation biases, we propose a golden tree-oriented learning (GTL) algorithm to adaptively control the expanding order of AST nodes. The graph encoder and tree decoder are combined into a unified framework through two auxiliary modules. Extensive experiments on various text-to-SQL datasets, including single/multi-table, single/cross-domain, and multilingual settings, demonstrate the superiority and broad applicability.

Isolation and characterization of a novel goose ovaritis-associated cluster 3 Tembusu virus.

Tembusu virus (TMUV) is a member of the genus Flavivirus in the family Flaviviridae. Currently, TMUV was classified into 4 distinct clusters, with cluster 2 strains widely distributed in duck and goose populations in Asia, causing significant economic losses to the producing industries. In this study, a novel TMUV strain TMUV/goose/CHN/2019/HNU-NX2 (HNU-NX2-2019) was isolated and characterized from geese with ovaritis from Hunan province, China. Phylogenetic analyses of genome and the E gene indicated the present TMUV could be grouped into the newly defined TMUV cluster 3. The genome of HNU-NX2-2019 showed the highest identities of 98.1% to 98.2% to the cluster 3 TMUVs newly identified in 2020 and 2021 from chickens with a severe egg-drop syndrome from Guangdong, Guangxi and Shandong provinces of China, which were all showing a close relation to a mosquito-origin TMUV (KT607936) identified in 2012. Further experiments confirmed HNU-NX2-2019 could grow well in chicken fibroblast cell line DF-1 and in SPF chicken embryos, with titers varied from 107.3 to 108.8 viral genomic copies per mL in the culture solutions. A pilot virus challenge study in 3-day-old chicks demonstrated that this virus could efficiently infect chicks with virus distributed in the brains, small intestines and other visceral organs, with titers varied from 105.4 to 106.7viral genomic copies per gram of the tissues. Furthermore, HNU-NX2-2019 can induce specific antibody in ducklings but with no obvious disease and virus shedding, and on necropsy no TMUV was detected in the tissues in the present study. This is the first report to identify a novel cluster 3 TUMV from goose, and further demonstrated this goose TMUV strain could infect chicken efficiently but not in ducklings under the present experimental conditions, which highlighted intensive attentions may be paid to this novel mosquito-origin cluster 3 TMUV.

Cichoric acid aerosol for inhalation therapy in respiratory syncytial virus.

Cichoric acid (CA) is a caffeic acid derivative, which has significant anti respiratory syncytial virus (RSV) effect and low toxicity. However, due to the low oral bioavailability and poor intestinal absorption of CA, it is not suitable to be made into oral preparations. In this study, CA was made into metered dose inhaler (MDI), allowing the drug to target the site of action, thus achieving more effective treatment. Through preliminary experiments, the drug content and prescription composition of the preparation were determined. Clarity and stability of solution were used as indexes to screen the composition of latent solvent. Single factor and orthogonal test were used to optimize the amount of latent solvent in CA-MDI, and the optimal prescription was verified. The aerosol prepared according to the optimal formula was characterized and preliminary stability was studied. The final formula of CA-MDI was: CA 15 mg, absolute ethanol 1 g, propylene glycol 0.4 g and 1,1,1,2-tetrafluoroethane 10 g. CA-MDI was prepared with the best prescription, with the specification of 150 actuation per bottle and 75 µg per actuation. After quality inspection, three batches of inhaled aerosols showed that the main drug content per bottle was 77.91 ± 1.63 µg (n = 3), and the total number of bottles was 185 ± 3 (n = 3), all of which met the standards of China Pharmacopoeia and the proposed specifications. The preliminary stability study showed that the quality of inhaled aerosols in CA was stable and reliable.

Estimating normal metabolic activity for disease quantification via PET/CT images.

In this paper, we propose a novel pipeline for conducting disease quantification in positron emission tomography/computed tomography (PET/CT) images on anatomically pre-defined objects. The pipeline is composed of standardized uptake value (SUV) standardization, object segmentation, and disease quantification (DQ). DQ is conducted on non-linearly standardized PET images and masks of target objects derived from CT images. Total lesion burden (TLB) is quantified by estimating normal metabolic activity (TMAn) in the object and subtracting this entity from total metabolic activity (TMA) of the object, thereby measuring the overall disease quantity of the region of interest without the necessity of explicitly segmenting individual lesions. TMAn is calculated with object-specific SUV distribution models. In the modeling stage, SUV models are constructed from a set of PET/CT images obtained from normal subjects with manually delineated masks of target objects. Two ways of SUV modeling are explored, where the mean of mean values of the modeling samples is utilized as a consistent normality value in the hard strategy, and the likelihood representing normal tissue is determined from the SUV distribution (histogram) for each SUV value in the fuzzy strategy. The evaluation experiments are conducted on a separate clinical dataset of normal subjects and a phantom dataset with lesions. The ratio of absolute TLB to TMA is taken as the metric, alleviating the individual difference of volume sizes and uptake levels. The results show that the ratios in normal objects are close to 0 and the ratios for lesions approach 1, demonstrating that contributions on TLB are minimal from the normal tissue and mainly from the lesion tissue.

Altered HLA-A2-restricted TP53 epitope induces specific CTL cytotoxicity against hepatocellular carcinoma.

High-frequency mutation of the TP53 tumor suppressor gene is observed in multiple human cancers, which promotes cancer progression. However, the mutated gene-encoded protein may serve as a tumor antigen to elicit tumor-specific immune responses. In this study, we detected widespread expression of shared TP53-Y220C neoantigen in hepatocellular carcinoma with low affinity and low stability of binding to HLA-A0201 molecules. We substituted the amino acid sequences VVPCEPPEV with VLPCEPPEV in the TP53-Y220C neoantigen to yield a TP53-Y220C (L2) neoantigen. This altered neoantigen was found to increase affinity and stability and induce more cytotoxic T lymphocytes (CTLs), indicating improvements in immunogenicity. In vitro assays showed the cytotoxicity of CTLs stimulated by both TP53-Y220C and TP53-Y220C (L2) neoantigens against multiple HLA-A0201-positive cancer cells expressing TP53-Y220C neoantigens; however, the TP53-Y220C (L2) neoantigen showed higher cytotoxicity than the TP53-Y220C neoantigen against cancer cells. More importantly, in vivo assays demonstrated greater inhibition of hepatocellular carcinoma cell proliferation by TP53-Y220C (L2) neoantigen-specific CTLs relative to TP53-Y220C neoantigen in zebrafish and nonobese diabetic/severe combined immune deficiency mouse models. The results of this study demonstrate enhanced immunogenicity of the shared TP53-Y220C (L2) neoantigen, which has the potential as dendritic cells or peptide vaccines for multiple cancers.

SENP6-Mediated deSUMOylation of VEGFR2 Enhances Its Cell Membrane Transport in Angiogenesis.

Angiogenesis is a significant pathogenic characteristic of diabetic microangiopathy. Advanced glycation end products (AGEs) are considerably elevated in diabetic tissues and can affect vascular endothelial cell shape and function. Regulation of the vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2) signaling pathway is a critical mechanism in the regulation of angiogenesis, and VEGFR2 activity can be modified by post-translational changes. However, little research has been conducted on the control of small ubiquitin-related modifier (SUMO)-mediated VEGFR2 alterations. The current study investigated this using human umbilical vein endothelial cells (HUVECs) in conjunction with immunoblotting and immunofluorescence. AGEs increased Nrf2 translocation to the nucleus and promoted VEGFR2 expression. They also increased the expression of sentrin/SUMO-specific protease 6 (SENP6), which de-SUMOylated VEGFR2, and immunofluorescence indicated a reduction in VEGFR2 accumulation in the Golgi and increased VEGFR2 transport from the Golgi to the cell membrane surface via the coatomer protein complex subunit beta 2. VEGFR2 on the cell membrane was linked to VEGF generated by pericytes, triggering the VEGF signaling cascade. In conclusion, this study demonstrates that SENP6 regulates VEGFR2 trafficking from the Golgi to the endothelial cell surface. The SENP6-VEGFR2 pathway plays a critical role in pathological angiogenesis.

Anatomical attention-based prediction of postoperative pulmonary venous obstruction via CTA images.

Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart disease, with which some patients suffer from postoperative pulmonary venous obstruction (PPVO), requiring particular follow-up strategies and treatments. PPVO prediction has important clinical significance, while building a PPVO prediction model is challenging due to limited data and class imbalance distribution. Inspired by the anatomical evidence of PPVO, which is related to the structure of the left atrium (LA) and pulmonary vein (PV), we design an effective multi-task network for PPVO classification. The proposed method incorporates clinical priors and merits of the segmentation-based network into the classification task. The features learned from segmenting LA and PV are concatenated into the PPVO classification branch to constrain the learning of discriminative features. Anatomical-guided attention is applied in the aggregation of these features to restrict them focusing on TAPVC-related regions. To deal with the imbalance classification problem of PPVO, a novel classification loss derived by masked class activation map (MCAM) is designed to improve the classification performance. Computed tomography angiography (CTA) images of 146 patients diagnosed with supracardiac TAPVC in Shanghai Children's Medical Center and Guangdong Provincial People's Hospital were enrolled in this work. The comprehensive experiments demonstrate the effectiveness and generalization of our proposed method. The automatic PPVO prediction model shows the potential application in helping clinicians develop follow-up strategies, thereby improving the survival rate of TAPVC patients.