Single-Cell Transcriptional Profile Construction of Rat Pituitary Glands before and after Sexual Maturation and Identification of Novel Marker Spp1 in Gonadotropes.

The mammalian pituitary gland drives highly conserved physiological processes such as somatic cell growth, pubertal transformation, fertility, and metabolism by secreting a variety of hormones. Recently, single-cell transcriptomics techniques have been used in pituitary gland research. However, more studies have focused on adult pituitary gland tissues from different species or different sexes, and no research has yet resolved cellular differences in pituitary gland tissue before and after sexual maturation. Here, we identified a total of 15 cell clusters and constructed single-cell transcriptional profiles of rats before and after sexual maturation. Furthermore, focusing on the gonadotrope cluster, 106 genes were found to be differentially expressed before and after sexual maturation. It was verified that Spp1, which is specifically expressed in gonadotrope cells, could serve as a novel marker for this cell cluster and has a promotional effect on the synthesis and secretion of follicle-stimulating hormone. The results provide a new resource for further resolving the regulatory mechanism of pituitary gland development and pituitary hormone synthesis and secretion.

Risk factors for delayed extubation after pediatric perineal anaplasty in patients less than 1 year of age: a retrospective study.

BACKGROUND: Anorectal malformation is a common congenital problem occurring in 1 in 5,000 births and has a spectrum of anatomical presentations, requiring individualized surgical treatments for normal growth. Delayed extubation or reintubation may result in a longer intensive care unit (ICU) stay and hospital stay, increased mortality, prolonged duration of mechanical ventilation, increased tracheostomy rate, and higher hospital costs. Extensive studies have focused on the role of risk factors in early extubation during major infant surgery such as Cardiac surgery, neurosurgery, and liver surgery. However, no study has mentioned the influencing factors of delayed extubation in neonates and infants undergoing angioplasty surgery. MATERIALS AND METHODS: We performed a retrospective study of neonates and infants who underwent anorectal malformation surgery between June 2018 and June 2022. The principal goal of this study was to observe the incidence of delayed extubation in pediatric anorectal malformation surgery. The secondary goals were to identify the factors associated with delayed extubation in these infants. RESULTS: We collected data describing 123 patients who had anorectal malformations from 2019 to 2022. It shows that 74(60.2%) in the normal intubation group and 49(39.8%) in the longer extubation. In the final model, anesthesia methods were independently associated with delayed extubation (P < 0.05). CONCLUSION: We found that the anesthesia method was independently associated with early extubation in neonates and infants who accepted pediatric anorectal malformation surgery.

Characterization of Bacillus amyloliquefaciens PM415 as a potential bio-preserving probiotic.

Animal feed is vulnerable to fungal infections, and the use of bio-preserving probiotics has received increasing attention. In contrast to Lactobacillus and Bifidobacteria spp., fewer Bacillus spp. have been recognized as antifungal probiotics. Therefore, our objective was to screen antifungal strains and provide more Bacillus candidates to bridge this gap. Here, we screened 56 bacterial strains for cyclic lipopeptide genes and conducted an antifungal assay with Aspergillus niger as a representative fungus. We found that a Bacillus strain Bacillus amyloliquefaciens PM415, isolated from pigeon manure, exhibited the highest fungal inhibition activity as demonstrated by the confrontation assay and morphological observation under scanning electron microscope (SEM). Preliminary safety assessment and probiotic characterization revealed its non-pathogenic feature and stress tolerance capability. Whole genome sequencing of Bacillus amyloliquefaciens PM415 revealed a genome size of 4.16 Mbp and 84 housekeeping genes thereof were used for phylogenetic analysis showing that it is most closely related to Bacillus amyloliquefaciens LFB112. The in silico analysis further supported its non-pathogenic feature at the genomic level and revealed potential biosynthetic gene clusters responsible for its antifungal property. RNA-seq analysis revealed genome-wide changes in transportation, amino acid metabolism, non-ribosomal peptides (NRPs) biosynthesis and glycan degradation during fungal antagonism. Our results suggest that Bacillus amyloliquefaciens PM415 is a safe and effective probiotic strain that can prevent fungal growth in animal feeds.

Avian leukosis virus usurps the cellular SERBP1 protein to enhance its transcription and promote productive infections in avian cells.

Avian leukosis virus subgroup K (ALV-K) is composed of newly emerging isolates, which cluster separately from the well-characterized subgroups A, B, C, D, E, and J in sequence analysis, and exhibits a specific host range and a unique pattern of superinfection interference. Avian leukosis virus subgroup K replicate more slowly in avian cells than other ALV strains, leading to escaped detection during ALV eradication, but the underlying mechanism are largely unknown. In our previous study, we have reported that JS11C1 and most of other suspected ALV-K strains possessed unique mutations in the U3 region. Here, we selected 5 mutations in some important transcriptional regulation elements to explore the possible factor contributing for the lower activity of LTR, including CA-TG mutation in the CAAT box, 21 nt deletion in the CAAT box, A-G and A-T mutations in the CArG boxes, 11 nt insertion in the PRE boxes, and C-T mutation in the TATA box. On the basis of infectious clone of JS11C1, we demonstrated that the 11 nt fragment in the PRE boxes was associated with the transcription activity of LTR, the enhancer ability of U3, and the replication capacity of the virus. Notably, we determined the differential U3-protein interaction profile of ALVs and found that the 11 nt fragment specifically binds to cellular SERPINE1 mRNA binding protein 1 (SERBP1) to increase the LTR activity and enhance virus replication. Collectively, these findings reveal that a 11 nt fragment in the U3 gene contributed to its binding ability to the cellular SERBP1 to enhance its transcription and the infectious virus productions in avian cells. This study highlighted the vital role of host factor in retrovirus replication and thus provides a new perspective to elucidate the interaction between retrovirus and its host and a molecular basis to develop efficient strategies against retroviruses.

Clinical Analysis of Atorvastatin Calcium, Fenofibrate, and Acipimox in the Treatment of Hypertriglyceridemia-induced Acute Pancreatitis.

Background: Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is an increasingly recognized and potentially severe form of acute pancreatitis. The effective management of HTG-AP is critical due to its association with significant morbidity and mortality. HTG-AP poses a considerable burden on affected individuals and healthcare systems. It can result in persistent upper abdominal pain, nausea, vomiting, abdominal distension, fever, and in severe cases, hypotension or shock and multiple organ dysfunction. Standard treatment strategies often involve lipid-lowering agents, but the optimal therapeutic approach remains a subject of ongoing research. This study aims to evaluate the efficacy of atorvastatin calcium, fenofibrate, and acipimox, either individually or in combination, in the treatment of HTG-AP, providing insights into more effective management strategies. Methods: 150 HTG-AP patients admitted to the first hospital of Putian from June 2020 to December 2022 were selected. The age range of the patients included in the study was between 30 and 70 years, with an average age of approximately 48 years. The cohort consisted of 90 males and 60 females, resulting in a male-to-female ratio of 3:2. The patients were grouped: atorvastatin calcium, acipimox, fenofibrate, fenofibrate + Atorvastatin calcium, fenofibrate + acipimox, and no drug. The therapeutic effects and clinical indicators of the six groups were compared. Results: Patients in the fenofibrate + acipimox and fenofibrate groups experienced significantly reduced hospitalization duration compared to the other groups. They also had shorter abdominal pain relief time and gastrointestinal function relief time. Additionally, these groups had lower peak levels of amylase (an enzyme) and cholesterol compared to the other groups. In terms of neutrophil (NEUT) increase, the fenofibrate + acipimox, atorvastatin calcium, and fenofibrate groups had significantly lower peak levels compared to the other groups, indicating a less pronounced increase in NEUT. Furthermore, the fenofibrate and acipimox groups exhibited significantly lower peak levels of C-reactive protein (CRP) compared to the other groups. CRP is an indicator of inflammation. On the other hand, the atorvastatin calcium group had higher levels of procalcitonin (a marker of infection) and a higher peak score on the acute physiology and chronic health evaluation II (APACHE II) scale, which assesses the severity of acute pancreatitis, compared to the other groups (all P < .05). Conclusion: The findings of this study highlight the effectiveness of combining fenofibrate and acipimox in the treatment of HTG-AP, leading to rapid disease recovery and significant improvement in clinical symptoms. These results have important implications for clinical practice, as the combination therapy can be widely adopted as an effective treatment strategy for HTG-AP patients. Moreover, this study provides valuable insights into the management of HTG-AP and suggests that lipid-lowering agents, such as atorvastatin calcium and fenofibrate, play a crucial role in the treatment of this condition. However, further research is needed to explore the optimal dosages, treatment durations, and potential side effects of these medications in HTG-AP patients.

The Synergetic Effect of 3D Printing and Electrospinning Techniques in the Fabrication of Bone Scaffolds.

The primary goal of bone tissue engineering is to restore and rejuvenate bone defects by using a suitable three-dimensional scaffold, appropriate cells, and growth hormones. Various scaffolding methods are used to fabricate three-dimensional scaffolds, which provide the necessary environment for cell activity and bone formation. Multiple materials may be used to create scaffolds with hierarchical structures that are optimal for cell growth and specialization. This study examines a notion for creating an optimal framework for bone regeneration using a combination of the robocasting method and the electrospinning approach. Research indicates that the integration of these two procedures enhances the benefits of each method and provides a rationale for addressing their shortcomings via this combination. The hybrid approach is anticipated to provide a manufactured scaffold that can effectively replace bone defects while possessing the necessary qualities for bone regeneration.

Virome characterization of diarrheic red-crowned crane (G. japonensis).

BACKGROUND: The red-crowned crane is one of the vulnerable bird species. Although the captive population has markedly increased over the last decade, infectious diseases can lead to the death of young red-crowned cranes while few virological studies have been conducted. METHODS: Using a viral metagenomics approach, we analyzed the virome of tissues of the dead captive red-crowned crane with diarrhea symptoms in Dongying Biosphere Reserve, Shandong Province, China and feces of individual birds breeding at the corresponding captive breeding center, which were pooled separately. RESULTS: There is much more DNA and RNA viruses in the feces than that of the tissues. RNA virus belonging to the families Picornaviridae, and DNA viruses belonging to the families Parvoviridae, associated with enteric diseases were detected in the tissues and feces. Genomes of the picornavirus, genomovirus, and parvovirus identified in the study were fully characterized, which further suggested that infectious viruses of these families were possibly presented in the diseased red-crowned crane. CONCLUSION: RNA virus belonging to the families Picornaviridae, and DNA viruses belonging to the families Genomoviridae and Parvoviridae were possibly the causative agent for diarrhea of red-crowned crane. This study has expanded our understanding of the virome of red-crowned crane and provides a baseline for elucidating the etiology for diarrhea of the birds.

Mechanisms and therapeutic targets of mitophagy after intracerebral hemorrhage.

Mitochondria are dynamic organelles responsible for cellular energy production. In addition to regulating energy homeostasis, mitochondria are responsible for calcium homeostasis, clearance of damaged organelles, signaling, and cell survival in the context of injury and pathology. In stroke, the mechanisms underlying brain injury secondary to intracerebral hemorrhage are complex and involve cellular hypoxia, oxidative stress, inflammatory responses, and apoptosis. Recent studies have shown that mitochondrial damage and autophagy are essential for neuronal metabolism and functional recovery after intracerebral hemorrhage, and are closely related to inflammatory responses, oxidative stress, apoptosis, and other pathological processes. Because hypoxia and inflammatory responses can cause secondary damage after intracerebral hemorrhage, the restoration of mitochondrial function and timely clearance of damaged mitochondria have neuroprotective effects. Based on studies on mitochondrial autophagy (mitophagy), cellular inflammation, apoptosis, ferroptosis, the BNIP3 autophagy gene, pharmacological and other regulatory approaches, and normobaric oxygen (NBO) therapy, this article further explores the neuroprotective role of mitophagy after intracerebral hemorrhage.

Sweet taste receptors play roles in artificial sweetener-induced enhanced urine output in mice.

Sweet taste receptors found in oral and extra oral tissues play important roles in the regulation of many physiological functions. Studies have shown that urine volume increases during the lifetime exposure to artificial sweeteners. However, the detailed molecular mechanism and the general effects of different artificial sweeteners exposure on urine volume remain unclear. In this study, we investigated the relationship between urinary excretion and the sweet taste receptor expression in mice after three artificial sweeteners exposure in a higher or lower concentration via animal behavioral studies, western blotting, and real-time quantitative PCR experiment in rodent model. Our results showed that high dose of acesulfame potassium and saccharin can significantly enhance the urine output and there was a positive correlation between K+ and urination volume. The acesulfame potassium administration assay of T1R3 knockout mice showed that artificial sweeteners may affect the urine output directly through the sweet taste signaling pathway. The expression of T1R3 encoding gene can be up-regulated specifically in bladder but not in kidney or other organs we tested. Through our study, the sweet taste receptors, distributing in many tissues as bladder, were indicated to function in the enhanced urine output. Different effects of long-term exposure to the three artificial sweeteners were shown and acesulfame potassium increased urine output even at a very low concentration.

Postoperative outcomes of pediatric patients with perioperative COVID-19 infection: a systematic review and meta-analysis of observational studies.

OBJECTIVE: To quantify the risk of adverse postoperative outcomes in pediatric patients with COVID-19 infection. METHODS: We searched PubMed, Embase, Cochrane Library from December 2019 to 21 April 2023. Observational cohort studies that reported postoperative early mortality and pulmonary complications of pediatric patients with confirmed COVID-19-positive compared with COVID-19-negative were eligible for inclusion. We excluded pediatric patients underwent organ transplantation or cardiac surgery. Reviews, case reports, letters, and editorials were also excluded. We used the Newcastle-Ottawa Scale to assess the methodological quality and risk of bias for each included study. The primary outcome was postoperative early mortality, defined as mortality within 30 days after surgery or during hospitalization. The random-effects model was performed to assess the pooled estimates, which were expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). RESULTS: 9 studies involving 23,031 pediatric patients were included, and all studies were rated as high quality. Compared with pediatric patients without COVID-19, pediatric patients with COVID-19 showed a significantly increased risk of postoperative pulmonary complications (PPCs) (RR = 4.24; 95% CI 2.08-8.64). No clear evidence was found for differences in postoperative early mortality (RR = 0.84; 95% CI 0.34-2.06), postoperative intensive care unit (ICU) admission (RR = 0.80; 95% CI 0.39-1.68), and length of hospital stay (MD = 0.35, 95% CI -1.81-2.51) between pediatric patients with and without COVID-19. CONCLUSION: Perioperative COVID-19 infection was strongly associated with increased risk of PPCs, but it did not increase the risk of postoperative early mortality, the rate of postoperative ICU admission, and the length of hospital stay in pediatric patients. Our preplanned sensitivity analyses confirmed the robustness of our study findings.

LM-Net: A light-weight and multi-scale network for medical image segmentation.

Current medical image segmentation approaches have limitations in deeply exploring multi-scale information and effectively combining local detail textures with global contextual semantic information. This results in over-segmentation, under-segmentation, and blurred segmentation boundaries. To tackle these challenges, we explore multi-scale feature representations from different perspectives, proposing a novel, lightweight, and multi-scale architecture (LM-Net) that integrates advantages of both Convolutional Neural Networks (CNNs) and Vision Transformers (ViTs) to enhance segmentation accuracy. LM-Net employs a lightweight multi-branch module to capture multi-scale features at the same level. Furthermore, we introduce two modules to concurrently capture local detail textures and global semantics with multi-scale features at different levels: the Local Feature Transformer (LFT) and Global Feature Transformer (GFT). The LFT integrates local window self-attention to capture local detail textures, while the GFT leverages global self-attention to capture global contextual semantics. By combining these modules, our model achieves complementarity between local and global representations, alleviating the problem of blurred segmentation boundaries in medical image segmentation. To evaluate the feasibility of LM-Net, extensive experiments have been conducted on three publicly available datasets with different modalities. Our proposed model achieves state-of-the-art results, surpassing previous methods, while only requiring 4.66G FLOPs and 5.4M parameters. These state-of-the-art results on three datasets with different modalities demonstrate the effectiveness and adaptability of our proposed LM-Net for various medical image segmentation tasks.

[Expression and Clinical Significance of Exosome Component 4 in Newly Diagnosed Patients with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To explore the expression of Exosome Component 4（EXOSC4） in the tissues of newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance. METHODS: The expression of EXOSC4 protein in the tissues of 181 newly diagnosed DLBCL patients was analyzed by immunohistochemical staining. Clinical data were collected. The correlation between EXOSC4 protein expression in the tissues of newly diagnosed DLBCL patients and clinical features were analyzed and its prognostic significance. RESULTS: The positive rate of EXOSC4 protein expression was 68.51% in the tissues of 181 newly diagnosed DLBCL patients. These patients were divided into two groups, with 44 cases in high expression group and 137 cases in low expression group. There were no significant differences in age, gender, B symptoms, serum lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group (ECOG) score, Ann Arbor stage, extranodal disease, International Prognostic Index (IPI) score, National Comprehensive Cancer Network IPI (NCCN-IPI) score, and cell origin between the two groups (P>0.05). Cox multivariate regression analysis showed that high EXOSC4 protein expression in tissues was an independent poor prognostic factor for OS and PFS in newly diagnosed DLBCL patients (all P<0.05). K-M survival analysis showed that newly diagnosed DLBCL patients with high EXOSC4 protein expression had significantly shorter overall survival (OS) and progression free survival (PFS) than those patients with low EXOSC4 protein expression (all P<0.05). CONCLUSION: High EXOSC4 protein expression in tissues of newly diagnosed DLBCL patients is an independent poor prognostic factor for survival.

Plasma thrombin-activatable fibrinolysis inhibitor and the 1040C/T polymorphism are risk factors for diabetic kidney disease in Chinese patients with type 2 diabetes.

Background: Inflammatory and hemostatic disorders in diabetic microangiopathy (DMA) can be linked to thrombin-activatable fibrinolysis inhibitor (TAFI) and its own gene polymorphisms. Thus, the study aimed to investigate the associations of plasma TAFI and gene polymorphisms with DMA in Chinese patients with type 2 diabetes (T2D). Methods: Plasma TAFI of 223 patients with T2D was measured, and the genotypes and alleles of the 1040C/T, 438G/A, and 505G/A polymorphisms of the TAFI gene were analyzed. A ROC curve was constructed to evaluate the identifying power of TAFI between patients with T2D and DMA, and logistic regression analysis was used to observe the correlation of plasma TAFI and gene polymorphisms with the risk for DMA. Results: Plasma TAFI was higher in patients with DMA than in patients with only T2D (p < 0.05). TAFI exhibited the largest area under ROC in identifying diabetic kidney disease (DKD) from only T2D (0.763, 95% CI [0.674-0.853], p < 0.01), and adjusted multivariate analysis showed a high odds ratio (OR: 15.72, 95% CI [4.573-53.987], p < 0.001) for DKD. Higher frequencies of the CT genotype and T allele of the 1040C/T polymorphism were found in DKD compared with only T2D (respectively p < 0.05), and the CT genotype exhibited a high OR (1.623, 95% CI [1.173-2.710], p < 0.05) for DKD. DKD patients with the CT genotype had higher plasma TAFI levels, while T2D and DKD patients with CC/TT genotypes had lower plasma TAFI levels. Conclusion: Plasma TAFI and the CT genotype and T allele of the 1040C/T polymorphism are independent risk factors for DKD in Chinese T2D patients.

Natural killer cell-related prognosis signature predicts immune response in colon cancer patients.

Background: Natural killer (NK) cells are crucial components of the innate immune system that fight tumors and viral infections. Patients with colorectal cancer (CRC) have a poor prognosis, and immunotherapeutic tools play a key role in the treatment of CRC. Methods: Public data on CRC patients was collected from the TCGA and the GEO databases. Tissue data of CRC patients were collected from Guangxi Medical University Affiliated Cancer Hospital. An NK-related prognostic model was developed by the least absolute shrinkage and selection operator (LASSO) and Cox regression method. Validation data were collected from different clinical subgroups and an external independent validation cohort to verify the model's accuracy. In addition, multiple external independent immunotherapy datasets were collected to further examine the value of NK-related risk scores (NKRS) in the prediction of immunotherapy response. Potential biological functions of key genes were examined by methods of cell proliferation, apoptosis and Western blotting. Results: A novel prognostic model for CRC patients based on NK-related genes was developed and NKRS was generated. There was a significantly poorer prognosis among the high-NKRS group. Based on immune response prediction, patients with low NKRS may be more suitable for immunotherapy and they are more sensitive to immunotherapy. The proliferation rate of CRC cells was significantly reduced and apoptosis of CRC cells was increased after SLC2A3 was knocked down. SLC2A3 was also found to be associated with the TGF-ß signaling pathway. Conclusion: NKRS has potential applications for predicting prognostic status and response to immunotherapy in CRC patients. SLC2A3 has potential as a therapeutic target for CRC.

Impact of gasless vNOTES vs. traditional vNOTES on hemodynamic profiles and outcomes in patients with benign gynecological disease: study protocol of a randomized controlled trial.

BACKGROUND: Literature regarding the advantages of gasless vNOTES is insufficient. The aim of our study is to compare gasless vNOTES vs. traditional vNOTES on hemodynamic profiles and outcomes in patients with benign gynecological disease. We hypothesize that compared with those in the traditional vNOTES group, hemodynamic profiles will be changed less during gasless vNOTES, while safety can be promised. METHODS: This is a single-center, prospective, single-blind, randomized controlled clinical trial, which has been approved by the Institutional Review Board of Chengdu Women's and Children's Hospital on September 27, 2022. One hundred and twenty patients will be recruited and randomly assigned to either the traditional vNOTES group or the gasless vNOTES group in a 1:1 ratio. For patients allocated to the traditional vNOTES group, after insertion of one port through the vagina, CO2 gas is infused with a pressure of 12-14 mmHg; while for those allocated to the gasless vNOTES group, a special device is used as an abdominal wall-lifting device to facilitate gasless surgery. CO2 pneumoperitoneum will not be used during the whole gasless vNOTES procedure. The primary outcome is vital signs at different time points. The secondary outcomes include surgical conversion rate, duration of surgery and anesthesia, anesthetic consumption, intraoperative estimated blood loss, VAS and PONV scores at postoperative 2 h and 24 h, administration of vasopressor drugs from the beginning of general anesthesia induction to 15 min after endotracheal intubation, including times, dosage, and type, intraoperative and postoperative complications, time of first getting out of bed after surgery, and time of first eating after surgery, including light drink. DISCUSSION: This is the first randomized controlled trial to compare the impacts of gasless vNOTES vs. traditional vNOTES on hemodynamic profiles and outcomes in patients with benign gynecological disease. If a favorable effect and safety of gasless vNOTES for hemodynamic profiles and outcomes in patients are shown, gasless vNOTES would be an optimal treatment option for patients with benign gynecological disease. TRIAL REGISTRATION: The trial was registered at https://www.chictr.org.cn/showproj.html?proj=182441 with registration No. ChiCTR2200064779 on Oct 17, 2022.

A prognostic model related to necrotizing apoptosis of breast cancer based on biorthogonal constrained depth semi-supervised nonnegative matrix decomposition and single-cell sequencing analysis.

Breast cancer (BC) is one of the most common malignant tumours in women, and its prognosis is poor. The prognosis of BC patients can be improved by immunotherapy. However, due to the heterogeneity of BC, the identification of new biomarkers is urgently needed to improve the prognosis of BC patients. Necrotic apoptosis has been shown to play an essential role in many cancers. First, this study proposed a novel clustering algorithm called biorthogonal constrained depth semisupervised nonnegative matrix factorization (DO-DSNMF). The DO-DSNMF algorithm added multilayer nonlinear transformation to the coefficient matrix obtained after decomposition, which was used to mine the nonlinear relationship between samples. In addition, we also added orthogonal constraints on the basis matrix and coefficient matrix to reduce the influence of redundant features and samples on the results. We applied the DO-DSNMF algorithm and analysed the differences in survival and immunity between the subtypes. Then, we used prognosis analysis to construct the prognosis model. Finally, we analysed single cells using single-cell sequencing (scRNA-seq) data from the GSE75688 dataset in the GEO database. We identified two BC subtypes based on the BC transcriptome data in the TCGA database. Immune infiltration analysis showed that the necrotizing apoptosis-related genes of BC were related to various immune cells and immune functions. Necrotizing apoptosis was found to play a role in BC progression and immunity. The role of prognosis-related NRGs in BC was also verified by cell experiments. This study proposed a novel clustering algorithm to analyse BC subtypes and constructed an NRG prognostic model for BC. The prognosis and immune landscape of BC patients were evaluated by this model. The cell experiment supported its role in BC, which provides a potential therapeutic target for the treatment of BC.

Pseudo-Label Guided Structural Discriminative Subspace Learning for Unsupervised Feature Selection.

In this article, we propose a new unsupervised feature selection method named pseudo-label guided structural discriminative subspace learning (PSDSL). Unlike the previous methods that perform the two stages independently, it introduces the construction of probability graph into the feature selection learning process as a unified general framework, and therefore the probability graph can be learned adaptively. Moreover, we design a pseudo-label guided learning mechanism, and combine the graph-based method and the idea of maximizing the between-class scatter matrix with the trace ratio to construct an objective function that can improve the discrimination of the selected features. Besides, the main existing strategies of selecting features are to employ l2,1 -norm for feature selection, but this faces the challenges of sparsity limitations and parameter tuning. For addressing this issue, we employ the l2,0 -norm constraint on the learned subspace to ensure the row sparsity of the model and make the selected feature more stable. Effective optimization strategy is given to solve such NP-hard problem with the determination of parameters and complexity analysis in theory. Ultimately, extensive experiments conducted on nine real-world datasets and three biological ScRNA-seq genes datasets verify the effectiveness of the proposed method on the data clustering downstream task.

Naples score: a novel prognostic biomarker for breast cancer patients undergoing neoadjuvant chemotherapy.

BACKGROUND AND PURPOSE: The Naples Score (NPS) is a novel prognostic indicator that has been used in various cancers, but its potential in breast malignant tumor patients receiving neoadjuvant chemotherapy (NAC) has not been discovered. This study aimed to investigate the relationship between NPS and overall survival (OS) and disease-free survival (DFS) in breast cancer patients. METHODS: A total of 217 breast cancer patients undergoing NAC were incorporated into this retrospectively research. K-M survival curves and log-rank tests are used to determine OS and DFS. Cox regression model was used to evaluate the relationship between NPS and OS and DFS. Nomogram was developed based on the results of multivariate Cox regression analysis. Prognostic models were internally validated using bootstrapping and the consistency index (C-index). RESULTS: Age group was correlated with NPS (p < 0.05). Low and moderate Naples risk patients had higher 5-year OS and DFS rates than high risk Naples patients (93.8% vs. 75.4% vs. 60.0%; X2 = 9.2, P = 0.01; 82.4% vs 64.5% vs 43.7%; X2 = 7.4, P = 0.024; respectively). The nomogram based on demonstrated good performance in predicting OS and DFS (AUC = 0.728, 0.630; respectively). CONCLUSIONS: In breast cancer patients who have undergone NAC, NPS is a novel prognostic indicator. NPS combined with clinicopathological features showed good predictive ability, and its performance was better than that of traditional pathological TNM staging.

PDE-5-Inhibited BMSCs Alleviate High Glucose-Induced Myocardial Fibrosis and Cardiomyocyte Apoptosis by Activating the cGMP/PKG Pathway.

BACKGROUND: Phosphodiesterase-5 (PDE-5) inhibitors have been found to play an important cardio-protective role. This study aimed to clarify the inhibitory effects of PDE-5-silenced bone marrow mesenchymal stem cells (BMSCs) on high glucose-induced myocardial fibrosis and cardiomyocyte apoptosis. METHODS: Cardiomyocytes and fibroblasts of neonatal rats were treated with high glucose (HG), and co-cultured with PDE-5-overexpressed or -knocked down BMSCs. The viability and apoptosis as well as the levels of cytokines, Cardiac troponin I and Vimentin of cardiomyocytes and fibroblasts were studied. The expressions of PDE-5, cyclic guanosine monophosphate (cGMP) and protein kinase G (PKG), in both cells were evaluated. RESULTS: BMSCs that silenced PDE-5 facilitated the viability of cardiomyocytes, decreased the viability of fibroblasts, and inhibited the apoptosis of cardiomyocytes and fibroblasts. The contents of collagen-I, collagen-III, tissue inhibitor of metalloproteinase (TIMP)-1 and Dermin in fibroblasts were decreased by the PDE-5 inhibitor, but the levels of matrix metalloproteinase (MMP)-1 in fibroblasts and troponin-I in cardiomyocytes were increased by the PDE-5 inhibitor. PDE-5 inhibitor also suppressed the expression of PDE-5 but up-regulated cGMP and PKG expression in cardiomyocytes and fibroblasts. CONCLUSIONS: PDE-5-inhibited BMSCs can decrease HG-induced myocardial fibrosis and cardiomyocyte apoptosis by activating the cGMP/PKG pathway, and may play a role in the prevention and treatment of diabetic cardiomyopathy.

Three-Dimensional Digital Technology: A Powerful Assistant for the Reconstruction of Complex Craniofacial Deformities.

Three-dimensional digital technology has been widely applied in craniofacial surgeries, particularly in conventional procedures such as facial contouring and orthognathic surgery. To some extent, the process has already been standardized. As to reconstruction surgeries of complex craniofacial deformity, however, surgical plans need to be patient-specific. Traditionally, individualized surgical treatment largely relies on the surgeon's clinical experience. The application of digital technology mainly focuses on preoperative planning and postoperative evaluation of surgical outcomes rather than intraoperative patient-specific implants or osteotomy guides. For patients with complex craniofacial deformities, requirements for accurate 3-dimensional digital technology can be much higher. This study presents a favorable surgical reconstruction of the severe craniofacial deformity using 3-dimensional digital technology, providing references for craniofacial surgeons, which could be beneficial to clinical practice and treatment efficacy.