DP-MP: a novel cross-subject fatigue detection framework with DANN-based prototypical representation and mix-up pairwise learning.

OBJECTIVE: Electroencephalography (EEG) is widely recognized as an effective method for detecting fatigue. However, practical applications of EEG for fatigue detection in real-world scenarios are often challenging, particularly in cases involving subjects not included in the training datasets, owing to bio-individual differences and noisy labels. This study aims to develop an effective framework for cross-subject fatigue detection by addressing these challenges. APPROACH: In this study, we propose a novel framework, termed DP-MP, for cross-subject fatigue detection, which utilizes a Domain-Adversarial Neural Network (DANN)-based prototypical representation in conjunction with Mix-up pairwise learning. Our proposed DP-MP framework aims to mitigate the impact of bio-individual differences by encoding fatigue-related semantic structures within EEG signals and exploring shared fatigue prototype features across individuals. Notably, to the best of our knowledge, this work is the first to conceptualize fatigue detection as a pairwise learning task, thereby effectively reducing the interference from noisy labels. Furthermore, we propose the Mix-up pairwise learning (MixPa) approach in the field of fatigue detection, which broadens the advantages of pairwise learning by introducing more diverse and informative relationships among samples. RESULTS: Cross-subject experiments were conducted on two benchmark databases, SEED-VIG and FTEF, achieving state-of-the-art performance with average accuracies of 88.14% and 97.41%, respectively. These promising results demonstrate our model's effectiveness and excellent generalization capability. SIGNIFICANCE: This is the first time EEG-based fatigue detection has been conceptualized as a pairwise learning task, offering a novel perspective to this field. Moreover, our proposed DP-MP framework effectively tackles the challenges of bio-individual differences and noisy labels in the fatigue detection field and demonstrates superior performance. Our work provides valuable insights for future research, promoting the application of brain-computer interfaces for fatigue detection in real-world scenarios. .

Regulatory role of exosome-derived miRNAs and other contents in adipogenesis.

Intramuscular fat (IMF) content significantly impacts meat quality. influenced by complex interactions between skeletal muscle cells and adipocytes. Adipogenesis plays a pivotal role in IMF formation. Exosomes, extracellular membranous nanovesicles, facilitate intercellular communication by transporting proteins, nucleic acids (DNA and RNA), and other biomolecules into target cells, thereby modulating cellular behaviors. Recent studies have linked exosome-derived microRNAs (miRNAs) and other cargo to adipogenic processes. Various cell types, including skeletal muscle cells, interact with adipocytes via exosome secretion and uptake. Exosomes entering adipocytes regulate adipogenesis by modulating key signaling pathways, thereby influencing the extent and distribution of IMF deposition.This review comprehensively explores the origin, formation, and mechanisms of exosome action, along with current research and their applications in adipogenesis. Emphasis is placed on exosome-mediated regulation of miRNAs, non-coding RNAs (ncRNAs), proteins, lipids, and other biomolecules during adipogenesis. Leveraging exosomal contents for genetic breeding and treating obesity-related disorders is discussed. Insights gathered contribute to advancing understanding and potential therapeutic applications of exosome-regulated adipogenesis mechanisms.

Tailoring Coherent Microwave Emission from a Solid-State Hybrid System for Room-Temperature Microwave Quantum Electronics.

Quantum electronics operating in the microwave domain are burgeoning and becoming essential building blocks of quantum computers, sensors, and communication devices. However, the field of microwave quantum electronics has long been dominated by the need for cryogenic conditions to maintain delicate quantum characteristics. Here, a solid-state hybrid system, constituted by a photo-excited pentacene triplet spin ensemble coupled to a dielectric resonator, is reported for the first time capable of both coherent microwave quantum amplification and oscillation at X band via the masing process at room temperature. By incorporating external driving and active dissipation control into the hybrid system, efficient tuning of the maser emission characteristics at ≈9.4 GHz is achieved, which is key to optimizing the performance of the maser device. The work not only pushes the boundaries of the operating frequency and functionality of the existing pentacene masers but also demonstrates a universal route for controlling the masing process at room temperature, highlighting opportunities for optimizing emerging solid-state masers for quantum information processing and communication.

Granulosa Cell-Layer Stiffening Prevents Escape of Mural Granulosa Cells from the Post-Ovulatory Follicle.

Ovulation is vital for successful reproduction. Following ovulation, cumulus cells and oocyte are released, while mural granulosa cells (mGCs) remain sequestered within the post-ovulatory follicle to form the corpus luteum. However, the mechanism underlying the confinement of mGCs has been a longstanding mystery. Here, in vitro and in vivo evidence is provided demonstrating that the stiffening of mGC-layer serves as an evolutionarily conserved mechanism that prevents mGCs from escaping the post-ovulatory follicles. The results from spatial transcriptome analysis and experiments reveal that focal adhesion assembly, triggered by the LH (hCG)-cAMP-PKA-CREB signaling cascade, is necessary for mGC-layer stiffening. Disrupting focal adhesion assembly through RNA interference results in stiffening failure, mGC escape, and the subsequent development of an abnormal corpus luteum characterized by decreased cell density or cavities. These findings introduce a novel concept of "mGC-layer stiffening", shedding light on the mechanism that prevents mGC escape from the post-ovulatory follicle.

Tuning the magnetic properties of van der Waals Fe3GaTe2 crystals by Co doping.

Tuning the magnetic properties of two-dimensional van der Waals ferromagnets has special importance for their practical applications. Using first-principles calculations, we investigate the magnetic properties of Co-doped Fe3GaTe2 with different Co concentrations and different Co atomic sites. Calculation results show that Fe or Co atoms with relatively lower atomic concentrations preferentially occupy Fe1 sites with interlayer coupling, which is more energetically favorable. As the doping concentration of Co atoms increases, the total magnetic moment of the doped system decreases, while the average atomic magnetic moments of Fe1 and Fe2 increase and decrease, respectively, with Fe1 reaching ∼2.08µB. The spin polarization of the doped model 2Co-2 near the Fermi energy level is significantly reduced, while 4Co-3 exhibits an enhanced trend. At some doping level, a phase change from ferromagnetism to antiferromagnetism appears at high Co concentration. These results provide a theoretical basis for experimental studies and valuable information for the development of Fe3GaTe2-based spintronic devices.

Single-cell sequencing reveals the transcriptional alternations of 17ß-estradiol suppressing primordial follicle formation in neonatal mouse ovaries.

Estrogen has been implicated in multiple biological processes, but the variation underlying estrogen-mediated primordial follicle (PF) formation remains unclear. Here, we show that 17ß-estradiol (E2) treatment of neonatal mice led to the inhibition of PF formation and cell proliferation. Single-cell RNA sequencing (scRNA-seq) revealed that E2 treatment caused significant changes in the transcriptome of oocytes and somatic cells. E2 treatment disrupted the synchronised development of oocytes, pre-granulosa (PG) cells and stromal cells. Mechanistically, E2 treatment disrupted several signalling pathways critical to PF formation, especially down-regulating the Kitl and Smad1/3/4/5/7 expression, reducing the frequency and number of cell communication. In addition, E2 treatment influenced key gene expression, mitochondrial function of oocytes, the recruitment and maintenance of PG cells, the cell proliferation of somatic cells, as well as disordered the ovarian microenvironment. This study not only revealed insights into the regulatory role of estrogen during PF formation, but also filled in knowledge of dramatic changes in perinatal hormones, which are critical for the physiological significance of understanding hormone changes and reproductive protection.

The origin and spread of HIV-1 CRF59_01B epidemic in China: A molecular network and phylogeographic analysis.

Human immunodeficiency virus type 1 CRF59_01B, identified in China in 2013, has been detected nationwide, exhibiting notably high prevalence in Guangzhou and its vicinity. This study aimed to unravel its origin and migration. A data set was established, incorporating all available CRF59_01B pol gene sequences and their metadata from Guangzhou and the public database. Bayesian phylogeographic analysis demonstrated that CRF59_01B originated in Shenzhen, the neighboring city of Guangzhou, around 1998 with posterior probability of 0.937. Molecular network analysis detected 1131 transmission links and showed a remarkably high clustering rate (78.9%). Substantial inter-city transmissions (26.5%, 300/1131) were observed between Shenzhen and Guangzhou while inter-region transmissions linked Guangzhou with South (46) and Southwest (64) China. The centre of Guangzhou was the hub of CRF59_01B transmission, including the inflow from Shenzhen (3.57 events/year) and outflow to the outskirts of Guangzhou (>2 events/year). The large-scale analysis revealed significant migration from Shenzhen to Guangzhou (5.08 events/year) and North China (0.59 events/year), and spread from Guangzhou to Central (0.47 events/year), East (0.42 events/year), South (0.76 events/year), Southwest China (0.76 events/year) and Shenzhen (1.89 events/year). Shenzhen and Guangzhou served as the origin and the hub of CRF59_01B circulation, emphasizing inter-city cooperation and data sharing to confine its nationwide diffusion.

Rejuvenation of young blood on aging organs: Effects, circulating factors, and mechanisms.

Aging causes degenerative changes in organs, leading to a decline in physical function. Over the past two decades, researchers have made significant progress in understanding the rejuvenating effects of young blood on aging organs, benefiting from heterochronic parabiosis models that connect the blood circulation of aged and young rodents. It has been discovered that young blood can partially rejuvenate organs in old animals by regulating important aging-related signaling pathways. Clinical trials have also shown the effectiveness of young blood in treating aging-related diseases. However, the limited availability of young blood poses a challenge to implementing anti-aging therapies on a large scale for older individuals. As a promising alternative, scientists have identified some specific anti-aging circulating factors in young blood that have been shown to promote organ regeneration, reduce inflammation, and alleviate fibrosis associated with aging in animal experiments. While previous reviews have focused primarily on the effects and mechanisms of circulating factors on aging, it is important to acknowledge that studying the rejuvenating effects and mechanisms of young blood has been a significant source of inspiration in this field, and it will continue to be in the future. In recent years, new findings have emerged, further expanding our knowledge in this area. This review aims to summarize the rejuvenating effects and mechanisms of young blood and circulating factors, discussing their similarities and connections, addressing discrepancies in previous studies, outlining future research directions, and highlighting the potential for clinical translation in anti-aging interventions.

Naoxintong capsule for treating cardiovascular and cerebrovascular diseases: from bench to bedside.

Naoxintong Capsule (NXT), a renowned traditional Chinese medicine (TCM) formulation, has been broadly applied in China for more than 30 years. Over decades, accumulating evidences have proven satisfactory efficacy and safety of NXT in treating cardiovascular and cerebrovascular diseases (CCVD). Studies have been conducted unceasingly, while this growing latest knowledge of NXT has not yet been interpreted properly and summarized comprehensively. Hence, we systematically review the advancements in NXT research, from its chemical constituents, quality control, pharmacokinetics, to its profound pharmacological activities as well as its clinical applications in CCVD. Moreover, we further propose specific challenges for its future perspectives: 1) to precisely clarify bioactivities of single compound in complicated mixtures; 2) to evaluate the pharmacokinetic behaviors of NXT feature components in clinical studies, especially drug-drug interactions in CCVD patients; 3) to explore and validate its multi-target mechanisms by integrating multi-omics technologies; 4) to re-evaluate the safety and efficacy of NXT by carrying out large-scale, multicenter randomized controlled trials. In brief, this review aims to straighten out a paradigm for TCM modernization, which help to contribute NXT as a piece of Chinese Wisdom into the advanced intervention strategy for CCVD therapy.

Biodegradable microspheres come into sight: A promising biomaterial for delivering drug to the posterior segment of the eyeball.

Posterior segment disease acts as a major cause of irreversible visual impairments. Successful treatment of posterior segment disease requires the efficient delivery of therapeutic substances to the targeted lesion. However, the complex ocular architecture makes the bioavailability of topically applied drugs extremely low. Invasive delivery approaches like intravitreal injection may cause adverse complications. To enhance the efficiency, several biomedical engineering systems have been developed to increase the penetration efficiency and improve the bioavailability of drugs at the posterior segments. Advantageously, biodegradable microspheres are found to deliver the therapeutic agents in a controlled fashion. The microspheres prepared from novel biomaterials can realize the prolonged release at the posterior segment with minimum side effects. Moreover, it will be degraded automatically into products that are non-toxic to the human body without the necessity of secondary operation to remove the residual polymer matrix. Additionally, biodegradable microspheres have decent thermoplasticity, adjustable hydrophilicity, controlled crystallinity, and high tensile strength, which make them suitable for intraocular delivery. In this review, we introduce the latest advancements in microsphere production technology and elaborate on the biomaterials that are used to prepare microspheres. We discuss systematically the pharmacological characteristics of biodegradable microspheres and compare their potential advantages and limitations in the treatment of posterior segment diseases. These findings would enrich our knowledge of biodegradable microspheres and cast light into the discovery of effective biomaterials for ocular drug delivery.

Triclosan Dioxygenase: A Novel Two-component Rieske Nonheme Iron Ring-hydroxylating Dioxygenase Initiates Triclosan Degradation.

The emerging contaminant triclosan (TCS) is widely distributed both in surface water and in wastewater and poses a threat to aquatic organisms and human health due to its resistance to degradation. The dioxygenase enzyme TcsAB has been speculated to perform the initial degradation of TCS, but its precise catalytic mechanism remains unclear. In this study, the function of TcsAB was elucidated using multiple biochemical and molecular biology methods. Escherichia coli BL21(DE3) heterologously expressing tcsAB from Sphingomonas sp. RD1 converted TCS to 2,4-dichlorophenol. TcsAB belongs to the group IA family of two-component Rieske nonheme iron ring-hydroxylating dioxygenases. The highest amino acid identity of TcsA and the large subunits of other dioxygenases in the same family was only 35.50%, indicating that TcsAB is a novel dioxygenase. Mutagenesis of residues near the substrate binding pocket decreased the TCS-degrading activity and narrowed the substrate spectrum, except for the TcsAF343A mutant. A meta-analysis of 1492 samples from wastewater treatment systems worldwide revealed that tcsA genes are widely distributed. This study is the first to report that the TCS-specific dioxygenase TcsAB is responsible for the initial degradation of TCS. Studying the microbial degradation mechanism of TCS is crucial for removing this pollutant from the environment.

Retarded sodium alloying interface reaction for stable anode-less sodium metal batteries.

Improving the sodiophilicity of the substrate is essential to enhance the reversibility of anode-less sodium metal batteries. Here, we have prepared a sodiophilic nano-Pb coating on aluminum-based collectors by magnetron sputtering. The slow alloying kinetics between Pb and sodium allows prolonged Pb retention in the coating, endowing the coating with a durable sodiophilicity.

Enhanced Hydrogen Peroxide Decomposition in a Continuous-Flow Reactor over Immobilized Catalase with PAES-C.

Due to the specificity, high efficiency, and gentleness of enzyme catalysis, the industrial utilization of enzymes has attracted more and more attention. Immobilized enzymes can be recovered/recycled easily compared to their free forms. The primary benefit of immobilization is protection of the enzymes from harsh environmental conditions (e.g., elevated temperatures, extreme pH values, etc.). In this paper, catalase was successfully immobilized in a poly(aryl ether sulfone) carrier (PAES-C) with tunable pore structure as well as carboxylic acid side chains. Moreover, immobilization factors like temperature, time, and free-enzyme dosage were optimized to maximize the value of the carrier and enzyme. Compared with free enzyme, the immobilized-enzyme exhibited higher enzymatic activity (188.75 U g-1, at 30 °C and pH 7) and better thermal stability (at 60 °C). The adsorption capacity of enzyme protein per unit mass carrier was 4.685 mg. Hydrogen peroxide decomposition carried out in a continuous-flow reactor was selected as a model reaction to investigate the performance of immobilized catalase. Immobilized-enzymes showed a higher conversion rate (90% at 8 mL/min, 1 h and 0.2 g) compared to intermittent operation. In addition, PAES-C has been synthesized using dichlorodiphenyl sulfone and the renewable resource bisphenolic acid, which meets the requirements of green chemistry. These results suggest that PAES-C as a carrier for immobilized catalase could improve the catalytic activity and stability of catalase, simplify the separation of enzymes, and exhibit good stability and reusability.

Different humidity environments do not affect the subsequent exercise ability of college football players after aerobic high-intensity interval training.

Previous studies have explored the effect of differing heat and relative humidity (RH) environments on the performance of multiple anaerobic high-intensity interval training (HIIT). Still, its impact on physiological responses and performance following aerobic HIIT has not been well studied. This study examined the effects of differing RH environments on physiological responses and performance in college football players following HIIT. Twelve college football completed HIIT under four different environmental conditions: (1) 25 °C/20% RH (Control group); (2) 35 °C/20% RH (H20 group); (3) 35 °C/40% RH (H40 group); (4) 35 °C/80% RH (H80 group). The heart rate (HR), mean arterial pressure (MAP), lactate, tympanic temperature (TT), skin temperature (TS), thermal sensation (TS), and rating of perceived exertion (RPE) were recorded continuously throughout the exercise. The heart rate variability (HRV): including root mean squared differences of the standard deviation (RMSSD)、standard deviation differences of the standard deviation (SDNN)、high frequency (HF), low frequency (LF), squat jump height (SJH), cycling time to exhaustion (TTE), and sweat rate (SR) were monitored pre-exercise and post-exercise. The HR, MAP, lactate, TT, Ts, TS, and RPE in the 4 groups showed a trend of rapid increase, then decreased gradually. There was no significant difference in HR, MAP, TT, or RPE between the 4 groups at the same time point (p > 0.05), in addition to this, when compared to the C group, the lactate, Ts, TS in the other 3 groups significant differences were observed at the corresponding time points (p < 0.05). The RMSSD, SDNN, HF, and LF levels in the 4 groups before exercise were not significantly different. The RMSSD and HF in the H40 and H80 groups were significantly decreased and other HRV indicators showed no significant difference after exercise. In sports performance measurement, the SJH and TTE were significantly decreased, but there was no significant difference in the 4 groups. The SR was no significant difference in the 4 groups after exercise. In conclusion, heat and humidity environments elicited generally greater physiological effects compared with the normal environment but did not affect sports performance in college football players.

Target-Oriented Reference Construction for supervised cell-type identification in scRNA-seq.

Cell-type identification is the most crucial step in single cell RNA-seq (scRNA-seq) data analysis, for which the supervised cell-type identification method is a desired solution due to the accuracy and efficiency. The performance of such methods is highly dependent on the quality of the reference data. Even though there are many supervised cell-type identification tools, there is no method for selecting and constructing reference data. Here we develop Target-Oriented Reference Construction (TORC), a widely applicable strategy for constructing reference given target dataset in scRNA-seq supervised cell-type identification. TORC alleviates the differences in data distribution and cell-type composition between reference and target. Extensive benchmarks on simulated and real data analyses demonstrate consistent improvements in cell-type identification from TORC. TORC is freely available at https://github.com/weix21/TORC.

Single-cell multiomics reveals ENL mutation perturbs kidney developmental trajectory by rewiring gene regulatory landscape.

How disruptions to normal cell differentiation link to tumorigenesis remains incompletely understood. Wilms tumor, an embryonal tumor associated with disrupted organogenesis, often harbors mutations in epigenetic regulators, but their role in kidney development remains unexplored. Here, we show at single-cell resolution that a Wilms tumor-associated mutation in the histone acetylation reader ENL disrupts kidney differentiation in mice by rewiring the gene regulatory landscape. Mutant ENL promotes nephron progenitor commitment while restricting their differentiation by dysregulating transcription factors such as Hox clusters. It also induces abnormal progenitors that lose kidney-associated chromatin identity. Furthermore, mutant ENL alters the transcriptome and chromatin accessibility of stromal progenitors, resulting in hyperactivation of Wnt signaling. The impacts of mutant ENL on both nephron and stroma lineages lead to profound kidney developmental defects and postnatal mortality in mice. Notably, a small molecule inhibiting mutant ENL's histone acetylation binding activity largely reverses these defects. This study provides insights into how mutations in epigenetic regulators disrupt kidney development and suggests a potential therapeutic approach.

Alterations of the bile microbiome is associated with progression-free survival in pancreatic ductal adenocarcinoma patients.

BACKGROUND: Patients with pancreatic ductal adenocarcinoma (PDAC) display an altered oral, gastrointestinal, and intra-pancreatic microbiome compared to healthy individuals. However, knowledge regarding the bile microbiome and its potential impact on progression-free survival in PDACs remains limited. METHODS: Patients with PDAC (n = 45), including 20 matched pairs before and after surgery, and benign controls (n = 16) were included prospectively. The characteristics of the microbiomes of the total 81 bile were revealed by 16  S-rRNA gene sequencing. PDAC patients were divided into distinct groups based on tumor marker levels, disease staging, before and after surgery, as well as progression free survival (PFS) for further analysis. Disease diagnostic model was formulated utilizing the random forest algorithm. RESULTS: PDAC patients harbor a unique and diverse bile microbiome (PCoA, weighted Unifrac, p = 0.038), and the increasing microbial diversity is correlated with dysbiosis according to key microbes and microbial functions. Aliihoeflea emerged as the genus displaying the most significant alteration among two groups (p < 0.01). Significant differences were found in beta diversity of the bile microbiome between long-term PFS and short-term PFS groups (PCoA, weighted Unifrac, p = 0.005). Bacillota and Actinomycetota were identified as altered phylum between two groups associated with progression-free survival in all PDAC patients. Additionally, we identified three biomarkers as the most suitable set for the random forest model, which indicated a significantly elevated likelihood of disease occurrence in the PDAC group (p < 0.0001). The area under the receiver operating characteristic (ROC) curve reached 80.8% with a 95% confidence interval ranging from 55.0 to 100%. Due to the scarcity of bile samples, we were unable to conduct further external verification. CONCLUSION: PDAC is characterized by an altered microbiome of bile ducts. Biliary dysbiosis is linked with progression-free survival in all PDACs. This study revealed the alteration of the bile microbiome in PDACs and successfully developed a diagnostic model for PDAC.

Prediction of wheat SPAD using integrated multispectral and support vector machines.

Rapidly obtaining the chlorophyll content of crop leaves is of great significance for timely diagnosis of crop health and effective field management. Multispectral imagery obtained from unmanned aerial vehicles (UAV) is being used to remotely sense the SPAD (Soil and Plant Analyzer Development) values of wheat crops. However, existing research has not yet fully considered the impact of different growth stages and crop populations on the accuracy of SPAD estimation. In this study, 300 materials from winter wheat natural populations in Xinjiang, collected between 2020 to 2022, were analyzed. UAV multispectral images were obtained in the experimental area, and vegetation indices were extracted to analyze the correlation between the selected vegetation indices and SPAD values. The input variables for the model were screened, and a support vector machine (SVM) model was constructed to estimate SPAD values during the heading, flowering, and filling stages under different water stresses. The aim was to provide a method for the rapid acquisition of winter wheat SPAD values. The results showed that the SPAD values under normal irrigation were higher than those under water restriction. Multiple vegetation indices were significantly correlated with SPAD values. In the prediction model construction of SPAD, the different models had high estimation accuracy under both normal irrigation and water limitation treatments, with correlation coefficients of predicted and measured values under normal irrigation in different environments the value of r from 0.59 to 0.81 and RMSE from 2.15 to 11.64, compared to RE from 0.10% to 1.00%; and under drought stress in different environments, correlation coefficients of predicted and measured values of r was 0.69-0.79, RMSE was 2.30-12.94, and RE was 0.10%-1.30%. This study demonstrated that the optimal combination of feature selection methods and machine learning algorithms can lead to a more accurate estimation of winter wheat SPAD values. In summary, the SVM model based on UAV multispectral images can rapidly and accurately estimate winter wheat SPAD value.

Localized fine-tuning and clinical evaluation of deep-learning based auto-segmentation (DLAS) model for clinical target volume (CTV) and organs-at-risk (OAR) in rectal cancer radiotherapy.

BACKGROUND AND PURPOSE: Various deep learning auto-segmentation (DLAS) models have been proposed, some of which have been commercialized. However, the issue of performance degradation is notable when pretrained models are deployed in the clinic. This study aims to enhance precision of a popular commercial DLAS product in rectal cancer radiotherapy by localized fine-tuning, addressing challenges in practicality and generalizability in real-world clinical settings. MATERIALS AND METHODS: A total of 120 Stage II/III mid-low rectal cancer patients were retrospectively enrolled and divided into three datasets: training (n = 60), external validation (ExVal, n = 30), and generalizability evaluation (GenEva, n = 30) datasets respectively. The patients in the training and ExVal dataset were acquired on the same CT simulator, while those in GenEva were on a different CT simulator. The commercial DLAS software was first localized fine-tuned (LFT) for clinical target volume (CTV) and organs-at-risk (OAR) using the training data, and then validated on ExVal and GenEva respectively. Performance evaluation involved comparing the LFT model with the vendor-provided pretrained model (VPM) against ground truth contours, using metrics like Dice similarity coefficient (DSC), 95th Hausdorff distance (95HD), sensitivity and specificity. RESULTS: LFT significantly improved CTV delineation accuracy (p < 0.05) with LFT outperforming VPM in target volume, DSC, 95HD and specificity. Both models exhibited adequate accuracy for bladder and femoral heads, and LFT demonstrated significant enhancement in segmenting the more complex small intestine. We did not identify performance degradation when LFT and VPM models were applied in the GenEva dataset. CONCLUSIONS: The necessity and potential benefits of LFT DLAS towards institution-specific model adaption is underscored. The commercial DLAS software exhibits superior accuracy once localized fine-tuned, and is highly robust to imaging equipment changes.

RNA modification gene WDR4 facilitates tumor progression and immunotherapy resistance in breast cancer.

INTRODUCTION: Growing interest toward RNA modification in cancer has inspired the exploration of gene sets related to multiple RNA modifications. However, a comprehensive elucidation of the clinical value of various RNA modifications in breast cancer is still lacking. OBJECTIVES: This study aimed to provide a strategy based on RNA modification-related genes for predicting therapy response and survival outcomes in breast cancer patients. METHODS: Genes related to thirteen RNA modification patterns were integrated for establishing a nine-gene-containing signature-RMscore. Alterations of tumor immune microenvironment and therapy response featured by different RMscore levels were assessed by bulk transcriptome, single-cell transcriptome and genomics analyses. The biological function of key RMscore-related molecules was investigated by cellular experiments in vitro and in vivo, using flow cytometry, immunohistochemistry and immunofluorescence staining. RESULTS: This study has raised an effective therapy strategy for breast cancer patients after a well-rounded investigation of RNA modification-related genes. With a great performance of predicting patient prognosis, high levels of the RMscore proposed in this study represented suppressive immune microenvironment and therapy resistance, including adjuvant chemotherapy and PD-L1 blockade treatment. As the key contributor of the RMscore, inhibition of WDR4 impaired breast cancer progression significantly in vitro and in vivo, as well as participated in regulating cell cycle and mTORC1 signaling pathway via m7G modification. CONCLUSION: Briefly, this study has developed promising and effective tactics to achieve the prediction of survival probabilities and treatment response in breast cancer patients.