The therapeutic effect and targets of herba Sarcandrae on breast cancer and the construction of a prognostic signature consisting of inflammation-related genes.

Background: The prevalence of breast cancer (BRCA), which is common among women, is on the rise. This study applied network pharmacology to explore the potential mechanism of action of herba sarcandrae in BRCA and construct a prognostic signature composed of inflammation-related genes. Methods: The active ingredients of herba sarcandrae were screened using the SymMap, TCMID, and TCMSP platforms, and the molecular targets were determined in the UniProt database. The "drug-active compound-potential target" network was established with Cytoscape 3.7.2. The molecular targets were subjected to disease ontology, gene ontology (GO), and Kyoto Encyclopedia of Genes (KEGG) analyses. AutoDock software was used for molecular docking. Differentially expressed genes (DEGs) related to inflammation were obtained from the BRCA Cancer Genome Atlas (TCGA) database. In the training cohort, the univariate Cox regression model was applied to preliminarily screen prognostic genes. A multigene signature was built by the least absolute shrinkage and selection operator (LASSO) regression model, followed by validation through Kaplan‒Meier, Cox, and receiver operating characteristic (ROC) analyses. Results: Forty-one active compounds were identified, and 265 therapeutic targets for herba sarcandrae were predicted. GO enrichment results revealed significant enrichment of biological processes, such as response to xenobiotic stimuli, response to nutrient levels, and response to lipopolysaccharide. KEGG analysis revealed significant enrichment of pathways such as AGE-RAGE and chemical carcinogenesis receptor activation signaling pathways. In addition, the herbs Marc-Andre and rutin were shown to mediate BRCA cell proliferation and apoptosis via the interferon regulatory factor 1 (IRF1)/signal transducer and activator of transcription 3 (STAT3)/programmed death-ligand 1 (PD-L1) pathway. Sixteen inflammatory signatures, including BST2, GPR132, IL12B, IL18, IL1R1, IL2RB, IRF1, and others, were constructed, and the risk score was found to be a strong independent prognostic factor for overall survival in BRCA patients. The 16-inflammation signature was associated with several clinical features (age, clinical stage, T, and N classifications) and could reflect immune cell infiltration in tumor microenvironments with different immune cells. Conclusions: Herba sarcandrae and rutin were shown to mediate BRCA cell proliferation and apoptosis via the IRF1/STAT3/PD-L1 pathway, and the 16-member inflammatory signature might be a novel biomarker for predicting BRCA patient prognosis, providing more accurate guidance for clinical treatment prognosis evaluation and having important reference value for individualized treatment selection.

Ultrasmall and Highly Dispersed Pt Entities Deposited on Mesoporous N-doped Carbon Nanospheres by Pulsed CVD for Improved HER.

Vapor-based deposition techniques are emerging approaches for the design of carbon-supported metal powder electrocatalysts with tailored catalyst entities, sizes, and dispersions. Herein, a pulsed CVD (Pt-pCVD) approach is employed to deposit different Pt entities on mesoporous N-doped carbon (MPNC) nanospheres to design high-performance hydrogen evolution reaction (HER) electrocatalysts. The influence of consecutive precursor pulse number (50-250) and deposition temperature (225-300 °C) are investigated. The Pt-pCVD process results in highly dispersed ultrasmall Pt clusters (≈1 nm in size) and Pt single atoms, while under certain conditions few larger Pt nanoparticles are formed. The best MPNC-Pt-pCVD electrocatalyst prepared in this work (250 pulses, 250 °C) reveals a Pt HER mass activity of 22.2 ± 1.2 A mg-1 Pt at -50 mV versus the reversible hydrogen electrode (RHE), thereby outperforming a commercially available Pt/C electrocatalyst by 40% as a result of the increased Pt utilization. Remarkably, after optimization of the Pt electrode loading, an ultrahigh Pt mass activity of 56 ± 2 A mg-1 Pt at -50 mV versus RHE is found, which is among the highest Pt mass activities of Pt single atom and cluster-based electrocatalysts reported so far.

Multi-Scale Masked Autoencoders for Cross-Session Emotion Recognition.

Affective brain-computer interfaces (aBCIs) have garnered widespread applications, with remarkable advancements in utilizing electroencephalogram (EEG) technology for emotion recognition. However, the time-consuming process of annotating EEG data, inherent individual differences, non-stationary characteristics of EEG data, and noise artifacts in EEG data collection pose formidable challenges in developing subject-specific cross-session emotion recognition models. To simultaneously address these challenges, we propose a unified pre-training framework based on multi-scale masked autoencoders (MSMAE), which utilizes large-scale unlabeled EEG signals from multiple subjects and sessions to extract noise-robust, subject-invariant, and temporal-invariant features. We subsequently fine-tune the obtained generalized features with only a small amount of labeled data from a specific subject for personalization and enable cross-session emotion recognition. Our framework emphasizes: 1) Multi-scale representation to capture diverse aspects of EEG signals, obtaining comprehensive information; 2) An improved masking mechanism for robust channel-level representation learning, addressing missing channel issues while preserving inter-channel relationships; and 3) Invariance learning for regional correlations in spatial-level representation, minimizing inter-subject and inter-session variances. Under these elaborate designs, the proposed MSMAE exhibits a remarkable ability to decode emotional states from a different session of EEG data during the testing phase. Extensive experiments conducted on the two publicly available datasets, i.e., SEED and SEED-IV, demonstrate that the proposed MSMAE consistently achieves stable results and outperforms competitive baseline methods in cross-session emotion recognition.

Perioperative and Oncological Outcomes of Partial Versus Radical Nephrectomy for Complex Renal Tumors (RENAL Score ≥ 7): Systematic Review and Meta-Analysis.

OBJECTIVE: Which is superior, partial nephrectomy (PN) or radical nephrectomy (RN), for the treatment of complex renal tumours (RENAL or score ≥ 7)? METHODS: This systematic review and meta-analysis was conducted in accordance with the PRISMA statement. A systematic search of the literature published before November 2023 was conducted using Pubmed, Embase, Cochran, and Web of Science libraries. We included studies comparing perioperative and oncologic outcomes of partial nephrectomy and radical nephrectomy for complex renal tumors. RESULTS: A total of 2602 patients from six studies meeting the criteria were included. The PN group had a longer operative time, increased estimated blood loss, and major complications but a smaller reduction in renal function. There were no significant differences in complications, length of hospital stay, and blood transfusion. In terms of oncological outcomes, the PN group had longer OS, CSS, and no significant difference in RFS. CONCLUSIONS: For complex renal tumours, PN requires more operative time and has a higher chance of complications in the short term. However, in long-term follow-up, PN has a small decrease in renal function with longer OS and CSS.

Mayo Adhesion Probability Score Predicts Perioperative Outcome of Partial Nephrectomy: A Systematic Review and Meta-Analysis.

Objective: Assessing whether Mayo adhesive probability (MAP) levels affect perioperative outcomes after partial nephrectomy (PN). Methods: This systematic review and meta-analysis were conducted in accordance with the PRISMA statement. A systematic search of the literature published before February 1, 2023 was conducted using Pubmed, Embase, Cochran, and Web of Science libraries. We included all articles evaluating adherent perirenal fat by MAP during PN. Results: A total of 1807 patients from 7 studies meeting the criteria were included. In the high MAP group, the operation time was longer, and the estimated blood loss and postoperative complications were increased. There was no significant difference in positive surgical margin, warm ischemia time, and hospitalization time. Conclusions: As a simple and easy scoring method, MAP can predict the perioperative outcome of PN patients, especially when ≥3 is the boundary. However, more cohort studies are still needed to determine the optimal cutoff point of MAP.

Comparing the safety and efficacy of single-port versus multi-port robotic-assisted techniques in urological surgeries: a systematic review and meta-analysis.

OBJECTIVE: Comparing the safety and efficacy of single-port (SP) versus multi-port (MP) robotic-assisted techniques in urological surgeries. METHODS: A systematic review and cumulative meta-analysis was performed using PRISMA criteria for primary outcomes of interest, and quality assessment followed AMSTAR. Four databases were systematically searched: Embase, PubMed, The Cochrane Library, and Web of Science. The search time range is from database creation to December 2022. Stata16 was used for statistical analysis. RESULTS: There were 17 studies involving 5015 patients. In urological surgeries, single-port robotics had shorter length of stay (WMD = - 0.63, 95% Cl [- 1.06, - 0.21], P < 0.05), less estimated blood loss (WMD = - 19.56, 95% Cl [- 32.21, - 6.91], P < 0.05), less lymph node yields (WMD = - 3.35, 95% Cl [- 5.16, - 1.55], P < 0.05), less postoperative opioid use (WMD = - 5.86, 95% Cl [- 8.83, - 2.88], P < 0.05). There were no statistically significant differences in operative time, positive margins rate, overall complications rate, and major complications rate. CONCLUSION: Single-port robotics appears to have similar perioperative outcomes to multi-port robotics in urological surgery. In radical prostatectomy, single-port robotics has shown some advantages, but the specific suitability of single-port robots for urological surgical types needs to be further explored.

Involvement of RFC3 in tamoxifen resistance in ER-positive breast cancer through the cell cycle.

Since the establishment of the molecular subtyping system, ER positive breast cancer was considered to be the most prevalent type of breast cancer, and endocrine therapy was a very important solution. However, numerous studies have shown that the cell cycle plays a key role in the progression and metastasis of breast cancer. The present study showed that RFC3 was involved in the cell cycle through DNA replication. Furthermore, RFC3 expression was significantly higher in breast cancer-resistant cells than in parental cells, which correlated with the cell cycle. We confirmed these results by established drug-resistant cell lines for breast cancer, raw letter analysis and immunohistochemical analysis of primary and recurrent tissues from three ER+ breast cancers. In addition, analysis of the results through an online database revealed that RFC3 expression was significantly associated with poor prognosis in ER+ breast cancer. We also demonstrated that in ER positive breast cancer-resistant cells, knockdown of RFC3 blocked the S-phase of cells and significantly attenuated cell proliferation, migration and invasion. Furthermore, RFC3 overexpression in ER positive breast cancer cells enhanced cell proliferation, migration and invasion. Taking all these findings into account, we could conclude that RFC3 was involved in endocrine resistance in breast cancer through the cell cycle. Thus, RFC3 may be a target to address endocrine therapy resistance in ER positive breast cancer and may be an independent prognostic factor in ER positive breast cancer.

Tamoxifen induces ferroptosis in MCF-7 organoid.

BACKGROUND: Breast cancer is the most common female malignant tumor type globally. The occurrence and development of breast cancer involve ferroptosis, which is closely related to its treatment. The development of breast cancer organoids facilitates the analysis of breast cancer molecular background and tumor biological behavior, including clinical pathological characteristics, drug response, or drug resistance relationship, and promotes the advancement of precision treatment for breast cancer. The three-dimensional (3D) cell culture of breast cancer MCF-7 organoid is more similar to the in vivo environment and thus obtains more realistic results than 2D cell culture. Our study examined the new mechanism of tamoxifen in treating breast cancer through breast cancer MCF-7 organoids. METHODS: We used 3D cells to culture breast cancer MCF-7 organoid, as well as tamoxifen-treated MCF-7 and tamoxifen-resistant MCF-7 (MCF-7 TAMR) cells. We used transcriptome sequencing. We detected GPX4 and SLC7A11 protein levels using Western blotting and the content of ATP, glutathione, and ferrous ions using the Cell Counting Lite 3D Kit. We assessed cell viability using the Cell Counting Kit-8 (CCK-8) assay. RESULTS: Tamoxifen significantly inhibited the growth of MCF-7 organoids and significantly induced ferroptosis in MCF-7 organoids. The ferroptosis inhibitor reversed the significant tamoxifen-induced MCF-7 organoid inhibition activity. Moreover, the ferroptosis activator enhanced the tamoxifen-induced MCF-7 TAMR cell activity inhibition. CONCLUSION: Our study revealed that ferroptosis plays an important role in tamoxifen-induced MCF-7 organoid cell death and provides a new research idea for precise treatment of breast cancer through an organoid model.

Acetylation reprograms MITF target selectivity and residence time.

The ability of transcription factors to discriminate between different classes of binding sites associated with specific biological functions underpins effective gene regulation in development and homeostasis. How this is achieved is poorly understood. The microphthalmia-associated transcription factor MITF is a lineage-survival oncogene that plays a crucial role in melanocyte development and melanoma. MITF suppresses invasion, reprograms metabolism and promotes both proliferation and differentiation. How MITF distinguishes between differentiation and proliferation-associated targets is unknown. Here we show that compared to many transcription factors MITF exhibits a very long residence time which is reduced by p300/CBP-mediated MITF acetylation at K206. While K206 acetylation also decreases genome-wide MITF DNA-binding affinity, it preferentially directs DNA binding away from differentiation-associated CATGTG motifs toward CACGTG elements. The results reveal an acetylation-mediated switch that suppresses differentiation and provides a mechanistic explanation of why a human K206Q MITF mutation is associated with Waardenburg syndrome.

SALL1 promotes proliferation and metastasis and activates phosphorylation of p65 and JUN in colorectal cancer cells.

BACKGROUND: Colorectal cancer (CRC) is one of the most usual malignant tumors, and its incidence continues to rise. Our purpose was to explore the function and potential regulatory mechanisms of SALL1, a differentially methylated gene in CRC, in vivo and in vitro. METHODS: Firstly, methylation differential gene SALL1 in CRC was screened and validated. SALL1 overexpression plasmids or SALL1 siRNAs were transfected in HT-29 and SW480 cells. Moreover, 10 µM T-5224 was added in SALL1-overexpressed CRC cells. CCK-8, flow cytometry and transwell assays were utilized to assess cell proliferation, cycle, migration, and invasion, respectively. Then CRC organoids were cultured. Next, HT-29 and SW480 cells transfected with SALL1 overexpression lentivirus were analyzed by transcriptome sequencing. Finally, in vivo tumorigenesis was used to analyze the effect of SALL1 overexpression on subcutaneous tumorigenesis in nude mice. RESULTS: The methylation level of CpG island in SALL1 promoter was increased in CRC tissues and could distinguish tumor tissues. Overexpression of SALL1 accelerated proliferation, migration and invasion of HT-29 and SW480 cells, and silencing of SALL1 attenuated proliferation, migration and invasion of HT-29 and SW480 cells. Through analysis and validation, we found that overexpression of SALL1 also could upregulate p-p65 and p-JUN expressions. Besides, c-Fos/activator protein (AP)- 1 inhibitor (T-5224) could reverse the induction of CRC progression by SALL1 overexpression. In vivo, we also proved that overexpression of SALL1 significantly increased tumor volume, tumor weight, and p-JUN expression. CONCLUSIONS: SALL1 could promote the proliferation, migration, and invasion of CRC cells and activate phosphorylation of p65 and JUN.

In Situ Growth of Nano-MoS2 on Graphite Substrates as Catalysts for Hydrogen Evolution Reaction.

In order to synthesize a high-efficiency catalytic electrode for hydrogen evolution reactions, nano-MoS2 was deposited in situ on the surface of graphite substrates via a one-step hydrothermal method. The effects of the reactant concentration on the microstructure and the electrocatalytic characteristics of the nano-MoS2 catalyst layers were investigated in detail. The study results showed that nano-MoS2 sheets with a thickness of about 10 nm were successfully deposited on the surface of the graphite substrates. The reactant concentration had an important effect on uniform distribution of the catalyst layers. A higher or lower reactant concentration was disadvantageous for the electrochemical performance of the nano-MoS2 catalyst layers. The prepared electrode had the best electrocatalytic activity when the thiourea concentration was 0.10 mol·L-1. The minimum hydrogen evolution reaction overpotential was 196 mV (j = 10 mV·cm-2) and the corresponding Tafel slope was calculated to be 54.1 mV·dec-1. Moreover, the prepared electrode had an excellent cycling stability, and the microstructure and the electrocatalytic properties of the electrode had almost no change after 2000 cycles. The results of the present study are helpful for developing low-cost and efficient electrode material for hydrogen evolution reactions.

The role of robotic retroperitoneal lymph node dissection in testicular cancer: a systematic review and meta-analysis.

OBJECTIVE: To compare the safety and efficacy of robotic-assisted retroperitoneal lymph node dissection (RA-RPLND) versus non-robotic retroperitoneal lymph node dissection in testicular cancer. METHODS: The statistical analysis software used Stata 17. The weighted mean difference (WMD) represents the continuous variable, and the dichotomous variable chooses the odds ratio, and calculates the 95% CI. This systematic review and cumulative meta-analysis was performed according to PRISMA criteria, and AMSTAR guidelines (assessing the methodological quality of systematic reviews). The Embase, PubMed, Cochrane Library, Web of Science, and Scopus databases were searched. The upper limit of the search time frame was February 2023, and no lower limit was set. RESULTS: Seven studies involving 862 patients. Compared with open retroperitoneal lymph node dissection, RA-RPLND appears to have a shorter length of stay [WMD=-1.21, 95% CI (-1.66, -0.76), P <0.05], less estimated blood loss [WMD=-0.69, 95% CI (-1.07, -0.32), P <0.05], and lower overall complications [odds ratio=0.45, 95% CI (0.28, 0.73), P <0.05]. RA-RPLND appears to have more lymph node yields than laparoscopic retroperitoneal lymph node dissection [WMD=5.73, 95% CI (1.06, 10.40), P <0.05]. However, robotic versus open/laparoscopic retroperitoneal lymph node dissection had similar results in operation time, lymph node positivity rate, recurrence during follow-up, and postoperative ejaculation disorders. CONCLUSION: RA-RPLND appears to be safe and effective for testicular cancer, but longer follow-up and more studies are needed to confirm this.

The role of laparoscopic adrenalectomy in the treatment of large pheochromocytomas (>6 cm): a meta-analysis and systematic review.

BACKGROUND: The effectiveness and safety of laparoscopic adrenalectomy (LA) under different routes for the treatment of large pheochromocytomas (PCCs) is unknown. MATERIALS AND METHODS: This meta-analysis and systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines. Three databases were systematically searched, including Medline, PubMed, and Web of Science. The time frame of the search was set from the creation of the database to October 2022. Perioperative outcomes were divided into two groups according to tumor size: SMALL group (≤6 cm in diameter), LARGE group (>6 cm in diameter). RESULTS: Eight studies including 600 patients were included. In the LA group, complications was comparable in both groups (SMALL group and LARGE group), and the LARGE group had longer operative time [OT weighted mean difference (WMD)=32.55; 95% CI: 11.17, 53.92; P <0.01], length of stay (LOS WMD=0.82; 95% CI: 0.19, 1.44; P <0.05), more estimated blood loss (EBL WMD=85.26; 95% CI: 20.71, 149.82; P <0.05), hypertension [odds ratio (OR)=3.99; 95% CI: 1.84, 8.65; P <0.01], hypotension (OR=1.84; 95% CI: 1.11, 3.05; P <0.05), and conversion (OR=5.60; 95% CI: 1.56, 20.13; P <0.01). In the transabdominal LA group, OT, LOS, EBL, complications, hypertension, and hypotension were the same in both groups. In the retroperitoneal LA group, complications and hypotension were the same in both groups, while the LARGE group had longer OT (WMD=52.07; 95% CI: 26.95, 77.20; P <0.01), LOS (WMD=0.51; 95% CI: 0.00, 1.01; P <0.05), more EBL (WMD=92.99; 95% CI: 27.70, 158.28; P <0.01) and higher rates of hypertension (OR=6.03; 95% CI: 1.95, 18.61; P <0.01). CONCLUSIONS: LA remains a safe and effective approach for large PCC. Transabdominal LA is superior to retroperitoneal LA.

Ultrahigh Mass Activity Pt Entities Consisting of Pt Single atoms, Clusters, and Nanoparticles for Improved Hydrogen Evolution Reaction.

Platinum is one of the best-performing catalysts for the hydrogen evolution reaction (HER). However, high cost and scarcity severely hinder the large-scale application of Pt electrocatalysts. Constructing highly dispersed ultrasmall Platinum entities is thereby a very effective strategy to increase Pt utilization and mass activities, and reduce costs. Herein, highly dispersed Pt entities composed of a mixture of Pt single atoms, clusters, and nanoparticles are synthesized on mesoporous N-doped carbon nanospheres. The presence of Pt single atoms, clusters, and nanoparticles is demonstrated by combining among others aberration-corrected annular dark-field scanning transmission electron microscopy, X-ray absorption spectroscopy, and electrochemical CO stripping. The best catalyst exhibits excellent geometric and Pt HER mass activity, respectively ≈4 and 26 times higher than that of a commercial Pt/C reference and a Pt catalyst supported on nonporous N-doped carbon nanofibers with similar Pt loadings. Noteworthily, after optimization of the geometrical Pt electrode loading, the best catalyst exhibits ultrahigh Pt and catalyst mass activities (56 ± 3 A mg-1 Pt and 11.7 ± 0.6 A mg-1 Cat at -50 mV vs. reversible hydrogen electrode), which are respectively ≈1.5 and 58 times higher than the highest Pt and catalyst mass activities for Pt single-atom and cluster-based catalysts reported so far.

Comparison of the perioperative outcomes of laparoscopic and open retroperitoneal lymph node dissection for low-stage (stage I/II) testicular germ cell tumors: a systematic review and meta-analysis.

OBJECTIVE: Comparison of the perioperative outcomes of laparoscopic retroperitoneal lymph node dissection (L-RPLND) and open retroperitoneal lymph node dissection (O-RPLND) for low-stage (stage I/II) testicular germ cell tumors. METHODS: The authors performed a systematic review and cumulative meta-analysis of the primary outcomes of interest according to PRISMA criteria, and the quality assessment of the included studies followed the AMSTAR guidelines. Four databases were searched, including Embase, PubMed, the Cochrane Library, and Web of Science. The search period was from the creation of each database to October 2022. The statistical analysis software uses Stata17. RESULTS: There were nine studies involving 579 patients. Compared with O-RPLND, L-RPLND was associated with shorter length of stay [weighted mean difference (WMD)=-3.99, 95% CI: -4.80 to -3.19, P <0.05], less estimated blood loss (WMD=-0.95, 95% CI: -1.35 to -0.54, P <0.05), shorter time to oral intake after surgery (WMD=-0.77, 95% CI: -1.50 to -0.03, P <0.05), and lower overall complications (odds ratio=0.58, 95% CI: 0.38-0.87, P <0.05). Subgroup analysis found that the complication rate of Clavien-Dindo grade II was lower in L-RPLND (odds ratio=0.24, 95% CI: 0.11-0.55, P <0.05). Interestingly, there was no statistically significant difference between the two groups in terms of operation time, lymph node yields, and recurrence rate during follow-up. CONCLUSION: L-RPLND is superior to O-RPLND and is worthy of clinical promotion.

CSI-based sliding window fingerprinting method tailored for a signal blocking environment in VLP systems.

In visible light indoor positioning systems, the localization performance of the received signal strength (RSS)-based fingerprinting algorithm would drop dramatically due to the occlusion of the line-of-sight (LOS) signal caused by randomly moving people or objects. A sliding window fingerprinting (SWF) algorithm based on channel state information (CSI) is put forward to enhance the accuracy and robustness of indoor positioning in this work. The core idea behind SWF is to combine CSI with sliding matching. The sliding window is used to match the received CSI and the fingerprints in the database twice to obtain the optimal matching value and reduce the interference caused by the lack of the LOS signal. On this premise, in order to reflect the different contributions of various paths in CSI to the calculation of match values, a weighted sliding window fingerprinting (W-SWF) is also proposed for the purpose of further improving the accuracy of fingerprint matching. A 4 m × 4 m × 3 m indoor multipath scene with four LEDs is established to evaluate the positioning performance. The simulation results reveal that the mean errors of the proposed method are 0.20 cm and 1.43 cm respectively when the LOS signal of 1 or 2 LEDs is blocked. Compared with the traditional RSS algorithm, the weighted k-nearest neighbor (WKNN) algorithm, and the adaptive residual weighted k-nearest neighbor (ARWKNN) algorithm, the SWF algorithm achieves over 90% improvement in terms of mean error and root mean square error (RMSE).

PTPN11 Mosaicism Causes a Spectrum of Pigmentary and Vascular Neurocutaneous Disorders and Predisposes to Melanoma.

Phakomatosis pigmentovascularis is a diagnosis that denotes the coexistence of pigmentary and vascular birthmarks of specific types, accompanied by variable multisystem involvement, including CNS disease, asymmetrical growth, and a predisposition to malignancy. Using a tight phenotypic group and high-depth next-generation sequencing of affected tissues, we discover here clonal mosaic variants in gene PTPN11 encoding SHP2 phosphatase as a cause of phakomatosis pigmentovascularis type III or spilorosea. Within an individual, the same variant is found in distinct pigmentary and vascular birthmarks and is undetectable in blood. We go on to show that the same variants can cause either the pigmentary or vascular phenotypes alone, and drive melanoma development within pigmentary lesions. Protein structure modeling highlights that although variants lead to loss of function at the level of the phosphatase domain, resultant conformational changes promote longer ligand binding. In vitro modeling of the missense variants confirms downstream MAPK pathway overactivation and widespread disruption of human endothelial cell angiogenesis. Importantly, patients with PTPN11 mosaicism theoretically risk passing on the variant to their children as the germline RASopathy Noonan syndrome with lentigines. These findings improve our understanding of the pathogenesis and biology of nevus spilus and capillary malformation syndromes, paving the way for better clinical management.

Research on Remaining Useful Life Prediction Method of Rolling Bearing Based on Digital Twin.

Bearing is a key part of rotating machinery. Accurate prediction of bearing life can avoid serious failures. To address the current problem of low accuracy and poor predictability of bearing life prediction, a bearing life prediction method based on digital twins is proposed. Firstly, the vibration signals of rolling bearings are collected, and the time-domain and frequency-domain features of the actual data set are extracted to construct the feature matrix. Then unsupervised classification and feature selection are carried out by improving the self-organizing feature mapping method. Using sensitive features to construct a twin dataset framework and using the integrated learning CatBoost method to supplement the missing data sets, a complete digital twin dataset is formed. Secondly, important information is extracted through macro and micro attention mechanisms to achieve weight amplification. The life prediction of rolling bearing is realized by using fusion features. Finally, the proposed method is verified by experiments. The experimental results show that this method can predict the bearing life with a limited amount of measured data, which is superior to other prediction methods and can provide a new idea for the health prediction and management of mechanical components.

A robust defect detection method for syringe scale without positive samples.

With the worldwide spread of the COVID-19 pandemic, the demand for medical syringes has increased dramatically. Scale defect, one of the most common defects on syringes, has become a major barrier to boosting syringe production. Existing methods for scale defect detection suffer from large volumes of data requirements and the inability to handle diverse and uncertain defects. In this paper, we propose a robust scale defects detection method with only negative samples and favorable detection performance to solve this problem. Different from conventional methods that work in a batch-mode defects detection manner, we propose to locate the defects on syringes with a two-stage framework, which consists of two components, that is, the scale extraction network and the scale defect discriminator. Concretely, the SeNet is first built to utilize the convolutional neural network to extract the main structure of the scale. After that, the scale defect discriminator is designed to detect and label the scale defects. To evaluate the performance of our method, we conduct experiments on one real-world syringe dataset. The competitive results, that is, 99.7% on F1, prove the effectiveness of our method.