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Nanoparticles are characterized by their large surface area per unit and high dispersion, with excellent affinity and adhesion to the tissue, which help them to contact drugs with tissues. However, the relationship between nuclear-targeted nanoparticles and PI3K/Akt/mTOR pathway, as well as their roles in cervical spondylosis of vertebral artery type (CSA) remain unclear. bEnd.3 cells were in this study exposed to nuclear-targeted nanoparticles, followed by determination of cell biological processes. The role of nuclear-targeted nanoparticles in CSA in relation to PI3K/Akt/mTOR pathway was then analyzed through detection of autophagy-related proteins pathway-related proteins. Nuclear-targeted nanoparticles led to reduced bEnd.3 cell proliferation with IC50 at indicated time points shown as (12.8±0.67), (8.8±0.43), and (4.6±0.42) μmol/L, respectively. Nuclear-targeted nanoparticles blocked bEnd.3 cells in G2/M phase, and induced apoptosis. In addition, nuclear-targeted nanoparticles inhibited the PI3K/Akt/mTOR pathway in the bEnd.3 cells, as evidenced by reduced PI3K, Akt and mTOR levels. Nuclear-targeted nanoparticles decreased the expression of Beclin-1, LC3, p62, Cathepsin D, and ATG5, and increased expression of GSK-3 and Bcl-2. Our present study demonstrated that the nucleartargeted nanoparticles could regulate the growth of bEnd.3 cells in CSA and promote autophagy of cells through blockage of the PI3K/Akt/mTOR signaling pathway.

The aim of this study was to investigate the role of BTBD10 in glioma tumorigenesis. The mRNA and protein levels of BTBD10 in 52 glioma tissues and eight normal brain tissues were determined using reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis, respectively. U251 human glioblastoma cells were infected with BTBD10-expressing or control lentiviruses. Cell growth was evaluated using the methyl thiazolyl tetrazolium (MTT) assay. Cell apoptosis and cell cycle distribution were analyzed using flow cytometry. Cyclin D1 and p-Akt levels were determined using western blot analysis. The results showed that BTBD10 mRNA and protein levels were significantly lower in glioma tissues than in normal brain tissues. Additionally, BTBD10 levels were significantly lower in high-grade gliomas than in low-grade tumors. Compared with control cells, U251 cells overexpressing BTBD10 exhibited decreased cell proliferation, increased cell accumulation at the G0/G1 phase, increased cell apoptosis, and decreased levels of cyclin D1 and p-Akt. These findings show that BTBD10 is downregulated in human glioma tissue and that BTBD10 expression negatively correlates with the pathological grade of the tumor. Furthermore, BTBD10 overexpression inhibits proliferation, induces G0/G1 arrest, and promotes apoptosis in human glioblastoma cells by downregulating cyclin D1- and Akt-dependent signaling pathways.

These figures contain extensions of data that would not fit in the primary manuscript but are important for a complete understanding of the work. These include analysis of other data sets, correlations between genomic profiling our stromal subtyping and information on bioinformatics and animal models.

Molecular subtypes at baseline.

Treatment of metastatic gastric cancer typically involves chemotherapy and monoclonal antibodies targeting HER2 (ERBB2) and VEGFR2 (KDR). However, reliable methods to identify patients who would benefit most from a combination of treatment modalities targeting the tumor stroma, including new immunotherapy approaches, are still lacking. Therefore, we integrated a mouse model of stromal activation and gastric cancer genomic information to identify gene expression signatures that may inform treatment strategies. We generated a mouse model in which VEGF-A is expressed via adenovirus, enabling a stromal response marked by immune infiltration and angiogenesis at the injection site, and identified distinct stromal gene expression signatures. With these data, we designed multiplexed IHC assays that were applied to human primary gastric tumors and classified each tumor to a dominant stromal phenotype representative of the vascular and immune diversity found in gastric cancer. We also refined the stromal gene signatures and explored their relation to the dominant patient phenotypes identified by recent large-scale studies of gastric cancer genomics (The Cancer Genome Atlas and Asian Cancer Research Group), revealing four distinct stromal phenotypes. Collectively, these findings suggest that a genomics-based systems approach focused on the tumor stroma can be used to discover putative predictive biomarkers of treatment response, especially to antiangiogenesis agents and immunotherapy, thus offering an opportunity to improve patient stratification. Cancer Res; 76(9); 2573–86. ©2016 AACR.

These figures contain extensions of data that would not fit in the primary manuscript but are important for a complete understanding of the work. These include analysis of other data sets, correlations between genomic profiling our stromal subtyping and information on bioinformatics and animal models.

A. Subgroup analyses of percent change in Ki67 from baseline to week 2 were performed on KE population based on progesterone receptor status, tumor size, baseline disease stage, tumor grade, baseline lymph node involvement, and baseline Ki67 (index 20%). B. Ki67 changes at baseline, 2 weeks, and end of treatment. C. Geometric mean percentage suppression of Ki67 from baseline to end of treatment by treatment arm. D. Mean percentage rate of response as determined by complete cell cycle arrest (responder: Ki76

Supplementary Figure S1. ER, PR, and HER2 mRNA and protein levels across endocrine-sensitive (parental) and endocrine-resistant BC cell lines. Supplementary Figure S2. Reduced sensitivity to CDK4/6 inhibition is associated with IFN-signaling in ER+ and endocrine-resistant derivative BC cell lines. Supplementary Figure S3. The cyclin D-CDK4/6-Rb axis is altered in ER+ cell lines with acquired resistance to palbociclib. Supplementary Figure S4. Effect of acute IFN-signaling activation on sensitivity to palbociclib in ER+ BC cell lines. Supplementary Figure S5. Proteomic profiles of MCF7 P, MCF7 EDR, and their PalboR derivatives. Supplementary Figure S6. Relationship between IFN-signaling and Rb status in ER+/HER2- BC. Supplementary Figure S7. DNMT1 mRNA levels in palbociclib-sensitive and PalboR MCF7 and T47D cell lines. Supplementary Figure S8. Mutations of DNA damage response genes are not associated with IFN-signaling in ER+ BC. Supplementary Figure S9. Levels of ER and ER signalling in palbociclib-sensitive and PalboR MCF7 and T47D cell lines. Supplementary Figure S10. HALLMARK gene sets significantly up-regulated in ER+/HER2- BC patients stratified by the status (+/-) of RBsig and IRPS. Supplementary Figure S11. Impact of selected IRPS genes on relapse-free survival of ER+ BC patients.

This file contains details too lengthy to put in the primary manuscript file as well as methods for supplemental data

Supplementary Table S1. Details of antibodies used in this study. Supplementary Table S2. Q-PCR primers. Supplementary Table S3. HALLMARK gene-set enrichment analysis (GSEA) of baseline tumor samples from the NeoPalANA trial. Supplementary Table S4. Palbociclib IC50 values in MCF7 P, MCF7 EDR, T47D P-LM, and T47D EDR palbociclib-resistant (PalboR)-LM cell lines. Supplementary Table S5. Top-20 Gene Ontology (GO) terms significantly enriched in PalboR cell lines. Supplementary Table S6. HALLMARK gene sets significantly up-regulated in cell lines with acquired resistance to palbociclib. Supplementary Table S7. RPPA of MCF7 P, MCF7 EDR, and their PalboR derivatives.

Supplemental Materials and Methods and Materials present a complete description of methods, reagents, and statistics required to reproduce the experiments in the paper.

Purpose:neoMONARCH assessed the biological effects of abemaciclib in combination with anastrozole in the neoadjuvant setting.Patients and Methods:Postmenopausal women with stage I–IIIB HR+/HER2− breast cancer were randomized to a 2-week lead-in of abemaciclib, anastrozole, or abemaciclib plus anastrozole followed by 14 weeks of the combination. The primary objective evaluated change in Ki67 from baseline to 2 weeks of treatment. Additional objectives included clinical, radiologic, and pathologic responses, safety, as well as gene expression changes related to cell proliferation and immune response.Results:Abemaciclib, alone or in combination with anastrozole, achieved a significant decrease in Ki67 expression and led to potent cell-cycle arrest after 2 weeks of treatment compared with anastrozole alone. More patients in the abemaciclib-containing arms versus anastrozole alone achieved complete cell-cycle arrest (58%/68% vs. 14%, P < 0.001). At the end of treatment, following 2 weeks lead-in and 14 weeks of combination therapy, 46% of intent-to-treat patients achieved a radiologic response, with pathologic complete response observed in 4%. The most common all-grade adverse events were diarrhea (62%), constipation (44%), and nausea (42%). Abemaciclib, anastrozole, and the combination inhibited cell-cycle processes and estrogen signaling; however, combination therapy resulted in increased cytokine signaling and adaptive immune response indicative of enhanced antigen presentation and activated T-cell phenotypes.Conclusions:Abemaciclib plus anastrozole demonstrated biological and clinical activity with generally manageable toxicities in patients with HR+/HER2− early breast cancer. Abemaciclib led to potent cell-cycle arrest, and in combination with anastrozole, enhanced immune activation.

These are the figure legends for the supplemental figures and tables.

Materials and methods.

Purpose:Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (CDK4/6i) are highly effective against estrogen receptor–positive (ER+)/HER2− breast cancer; however, intrinsic and acquired resistance is common. Elucidating the molecular features of sensitivity and resistance to CDK4/6i may lead to identification of predictive biomarkers and novel therapeutic targets, paving the way toward improving patient outcomes.Experimental Design:Parental breast cancer cells and their endocrine-resistant derivatives (EndoR) were used. Derivatives with acquired resistance to palbociclib (PalboR) were generated from parental and estrogen deprivation–resistant MCF7 and T47D cells. Transcriptomic and proteomic analyses were performed in palbociclib-sensitive and PalboR lines. Gene expression data from CDK4/6i neoadjuvant trials and publicly available datasets were interrogated for correlations of gene signatures and patient outcomes.Results:Parental and EndoR breast cancer lines showed varying degrees of sensitivity to palbociclib. Transcriptomic analysis of these cell lines identified an association between high IFN signaling and reduced CDK4/6i sensitivity; thus an “IFN-related palbociclib-resistance Signature” (IRPS) was derived. In two neoadjuvant trials of CDK4/6i plus endocrine therapy, IRPS and other IFN-related signatures were highly enriched in patients with tumors exhibiting intrinsic resistance to CDK4/6i. PalboR derivatives displayed dramatic activation of IFN/STAT1 signaling compared with their short-term treated or untreated counterparts. In primary ER+/HER2− tumors, the IRPS score was significantly higher in lumB than lumA subtype and correlated with increased gene expression of immune checkpoints, endocrine resistance, and poor prognosis.Conclusions:Aberrant IFN signaling is associated with intrinsic resistance to CDK4/6i. Experimentally, acquired resistance to palbociclib is associated with activation of the IFN pathway, warranting additional studies to clarify its involvement in resistance to CDK4/6i.

ObjectiveHeart failure with preserved ejection fraction (HFpEF), an increasing public health concern, is increasing in prevalence and is associated with an elevated risk of hospitalization and mortality. Currently, data on the clinical application value of left ventricular global longitudinal strain (LV GLS) in HFpEF are contradictory. Therefore, we performed the following meta-analysis to appraise the diagnostic and prognostic value of LV GLS in HFpEF.MethodsPubMed, Medline, Scopus, and Web of Science were retrieved exhaustively from their inception until December 20, 2022, to obtain literature assessing the diagnostic and prognostic value of LV GLS in HFpEF.ResultsForty-one studies (including 14,543 patients) published from 2008 to 2022 were included. The results of the meta-analysis were as follows: First, the LV GLS values in HFpEF patients were significantly lower than in healthy individuals (SMD:1.21; 95% CI (0.94, 1.47), p2=85%; P2=92%; P2=84%; P = 0.031) in HFpEF patients.ConclusionsLV GLS is impaired in HFpEF patients despite a normal left ventricular ejection fraction, indicating the existence of mild LV contractile dysfunction. Moreover, LV GLS might be an auxiliary indicator for diagnosing HFpEF and predicting all-cause death in HFpEF patients.

Lin Mei,1,&ast; Xiaodan Li,1,&ast; Shengcai Wang,1,&ast; Run Si,2 Tingting Ji,1 Zhifei Xu,3 Yun Peng,4 Yue Liu,4 Hongbin Li,1 Jie Zhang,1 Yongli Guo,5 Jinghong Tian,6 Guifei Zhou,2 Huifang Huang,2 Jun Tai,1,7,&ast; Jiangang Liu,8,9 Xin Ni1 1Department of Otolaryngology, Head and Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 2School of Computer and Information Technology, Beijing Jiaotong University, Beijing, People’s Republic of China; 3Department of Respiration, Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, Beijing, People’s Republic of China; 4Department of Radiology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 5Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, People’s Republic of China; 6Department of Neurorehabilitation, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 7Department of Otorhinolaryngology, Children’s Hospital, Capital Institute of Pediatrics, Beijing, People’s Republic of China; 8Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, People’s Republic of China; 9Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology of the People’s Republic of China, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiangang LiuBeijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Beijing, 100191, People’s Republic of ChinaEmail jgliu@buaa.edu.cnXin NiDepartment of Otolaryngology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, No. 56 Nanlishilu, Beijing, People’s Republic of ChinaTel +86-139-1011-1999Email nixin@bch.com.cnObjective: To investigate the impacts of obstructive sleep apnea (OSA) on white matter (WM) integrity and cognitive functions of pediatric patients with different levels of OSA severity.Methods: Fifty-eight children with OSA and thirty-four healthy controls (HC) were recruited. All participants underwent diffusion tensor imaging (DTI) examination, polysomnography (PSG), and neurocognitive assessments. Patients were divided into mild OSA (MG) and moderate-severe OSA (SG) groups. WM integrity, PSG data, and neurocognitive assessment scores were compared among those groups.Results: For apnea hypopnea index (AHI), obstructive apnea hypopnea index (OAHI), arousal index, SpO2 nadir, and attention, SG was worse than both MG and HC with MG worse than HC. For baseline SpO2 and intelligence, SG was worse than both MG and HC with no significant difference between MG and HC. Impaired WM integrity was observed in bilateral anterior thalamic radiation, bilateral inferior fronto-occipital fasciculus, bilateral inferior longitudinal fasciculus, right superior longitudinal fasciculus, right hippocampus, left cingulate gyrus, right uncinate fasciculus, callosum forceps major, and callosum forceps minor only for SG than for HC. WM integrity was significantly correlated with OSA severity and neurocognitive assessment scores only for SG, but not for MG.Conclusion: Decreased baseline SpO2, WM impairment, and intelligence decline were all observed only for SG, but not for MG, implying an associated relationship among decreased SpO2, WM impairment and WM impairment. Thus, for SG, additional assessments of brain damage and cognitive function decline are needed for prognostic evaluation of OSA.Keywords: diffusion tensor imaging, obstructive sleep apnoea, children, tract-based spatial statistics, white matter

The grade groups (GGs) of Gleason scores (Gs) is the most critical indicator in the clinical diagnosis and treatment system of prostate cancer. End-to-end method for stratifying the patient-level pathological appearance of prostate cancer (PCa) in magnetic resonance (MRI) are of high demand for clinical decision. Existing methods typically employ a statistical method for integrating slice-level results to a patient-level result, which ignores the asymmetric use of ground truth (GT) and overall optimization. Therefore, more domain knowledge (e.g., diagnostic logic of radiologists) needs to be incorporated into the design of the framework. The patient-level GT is necessary to be logically assigned to each slice of a MRI to achieve joint optimization between slice-level analysis and patient-level decision-making. In this paper, we propose a framework (PCa-GGNet-v2) that learns from radiologists to capture signs in a separate two-dimensional (2-D) space of MRI and further associate them for the overall decision, where all steps are optimized jointly in an end-to-end trainable way. In the training phase, patient-level prediction is transferred from weak supervision to supervision with GT. An association route records the attentional slice for reweighting loss of MRI slices and interpretability. We evaluate our method in an in-house multi-center dataset ( N = 570) and PROSTATEx ( N = 204), which yields five-classification accuracy over 80% and AUC of 0.804 at patient-level respectively. Our method reveals the state-of-the-art performance for patient-level multi-classification task to personalized medicine.

The accurate phenotyping of the external quality attributes of potato tubers is important in potato breeding. Currently, the assessment of potato tuber shape, together with eye density and depth, are based on subjective naked eye visual evaluation. However, such a manual visual assessment makes it very difficult to reliably phenotype these and other important, more complicated, geometrical traits, such as shape uniformity. In this study, a 3D image analysis method has been developed for counting potato eyes and estimating eye depth based on an evaluation of the curvature of an acquired 3D point cloud. Six shape uniformity-related traits, together with their shape indices (SI), were measured for six potato varieties. These were collected from three field experiments designed initially to study the effects of variation in nitrogen (N), potassium (K) and compound fertilisers along with tuber mass, on all investigated external traits. We demonstrate that a 3D image analysis technique can estimate the number of potato eyes and their depth with a high degree of accuracy. In addition, three shape uniformity traits were identified as offering a better power discrimination between varieties. The preliminary experiment found potato tuber mass to significantly affect both the shape uniformity and eye count, while fertiliser treatments showed no effect on all traits except SI. However, further investigation with a larger sample size is required for confirmation.

Objective: The surgical management of paravebous sinus meningiomas that invade major venous sinuses remains controversial. The need for complete resection of all tumors and the need for venous sinus reconstruction after resection remains a point of debate. In this article, we attempt to illustrate the results of complete resection of the lesion (including the invading venous sinus portion) and the consequences of restoring or not restoring venous circulation in terms of tumor recurrence, mortality, and post-operative complications. Methods: The authors collected 68 patients with paravebous sinus meningiomas. 60 patients belonged to the parasagittal meningiomas: 23 were located in the anterior third, in close relationship with the anterior central vein, 30 in the middle third, in close relationship with the posterior central vein, and 7 in the posterior third. 3 remaining lesions were located in the sinus confluence area, and 5 in the transverse sinus. All patients underwent surgery. We use the following classifications depending on the degree of venous sinus involvement: type I, where the lesion was attached to the outer surface of the sinus wall; type II, where the tumor invaded the sinus wall but did not break through it; type III, where it invaded the ipsilateral wall; type IV, where it invaded the lateral wall and the roof of the sinus; type V: complete occlusion of the sinus without the involvement of the contralateral wall; and type VI: total occlusion of the sinus with the participation of the contralateral fence as well. For type I meningiomas, we treat them by stripping off the outer layer of the sinus wall. In cases of type II to VI invasion of venous sinuses, we employ two strategies: one is non-constitutional, i.e., we remove the tumor together with the affected venous sinuses but do not repair the venous sinuses. The other is reconstructive: after completely removing the tumor, suturing or repairing the venous sinuses. Results: Complete tumor resection was achieved in 97.1% (66/68) of cases, and sinus reconstruction was attempted in 38 of 45 cases (84.4%) with sinus wall and sinus cavity invasion. The recurrence rate of patients in this study group was 5.9%(4/68), with a follow-up period of 33 to 57 months. The recurrence rate was significantly higher in patients with incomplete resection than in patients with complete resection (P=0.0026, Fisher test). The overall mortality rate was 4.4%, and all cases were due to malignant brain swelling caused by the failure to perform venous reconstruction after resectioning the whole meningioma type VI. 7 patients had worsening symptoms of neurological deficits or complete loss of neurological function (10.3%), with a significantly higher incidence in patients without venous reconstruction than in the venous reconstruction group (PConclusion: The relatively low recurrence rate (5.9%) in this study suggests the importance of complete resection of the tumor (including the invasive venous sinus portion). Patients who did not undergo venous reconstruction exhibited significant clinical deterioration postoperatively compared with other subgroups, suggesting that venous sinus reconstruction is necessary.

Aims Water and nitrogen are essential for potato growth and development. To understand how potato adapts to changes in soil water and nitrogen content. Methods Potato plant adaptations to changes in soil moisture and nitrogen levels were analyzed at the physiological and transcriptomic levels in four treatment groups: adequate nitrogen under drought, adequate nitrogen under sufficient irrigation, limited nitrogen under drought, and limited nitrogen under sufficient irrigation. Results Many light-capture pigment complex genes and oxygen release complex genes were differentially expressed in leaves when nitrogen levels were increased under drought conditions, and several genes encoding rate-limiting enzymes in the Calvin–Benson–Bassham cycle were up-regulated; furthermore, leaf stomatal conductance decreased, whereas the saturated vapor pressure difference and relative chlorophyll content in the chloroplasts increased. StSP6A, a key gene in potato tuber formation, was down-regulated in response to increased nitrogen application, and the stolon growth time was prolonged. Genes related to root nitrogen metabolism were highly expressed, and protein content in the tuber increased. Weighted gene co-expression network analysis (WGCNA) revealed 32 gene expression modules and 34 key candidate genes that responded to changes in water and nitrogen levels. Conclusions High nitrogen levels prolonged the stolon growing period. Under drought conditions, increasing nitrogen levels increased light energy conversion efficiency and tuber protein content. A total of 34 key candidate genes were identified and a preliminary molecular model of potato responses to alterations in soil water and nitrogen content was constructed.

It’s complex to model and solve spherical 2R mechanism on the strength of given positions and attitude angles of endpoints. In this paper, the spherical 2R mechanism is synthetically studied by using conformal geometry algebra, and applied to the design of a seedling pick-up mechanism. Starting from the given key points, the range of the spherical radius where the mechanism moves was studied. The scope was narrowed down as the structural parameters of the mechanism and the interference conditions between the end-effector and the seedling tray. Then, the mathematical model of 2R were established according to the given data. The data of fixed point and rod length were calculated. Furthermore, genetic algorithm was used to select the better fuzzy point with large attitude angle in seedling pushing stage. Finally, a three-dimensional model was established through the parameters of the mechanism and verified by simulation.

Colorectal cancer (CRC) is one of the most common malignant tumors with high morbidity and mortality. The early symptoms are latent, and most patients are in the middle or late stage when they are diagnosed. The best opportunity for surgery has been lost, and surgical resection has failed to achieve good results. In clinical practice, targeted therapy or chemotherapy is usually the main treatment. The mFOLFOX6 regimen is a standardized regimen for the treatment of advanced CRC. The main drugs in this regimen are oxaliplatin and 5-fluorouracil (5-FU). Patients with advanced CRC combined with standard chemotherapy regimens can achieve a higher resection rate of liver metastases in unresectable patients, which can achieve significant survival improvement. Therefore, in this study, oxaliplatin + calcium folinate + 5-Fu + mFOLFOX6 regimen was combined with cetuximab and simvastatin to treat CRC patients, and the clinical efficacy and prognosis were analyzed, as well as the prognostic factors. The results showed that the addition of simvastatin on the basis of conventional mFOLFOX6 regimen combined with cetuximab chemotherapy could effectively improve the efficacy, reduce the total incidence of adverse reactions, improve the overall survival rate, and prolong the overall survival time of patients. Pathological grade and peritoneal metastasis were the factors affecting the mean survival time of CRC patients.

Background This study evaluated the predictive value of gene signatures for biochemical recurrence (BCR) in primary prostate cancer (PCa) patients. Methods Clinical features and gene expression profiles of PCa patients were attained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets, which were further classified into a training set (n = 419), a validation set (n = 403). The least absolute shrinkage and selection operator Cox (LASSO‐Cox) method was used to select discriminative gene signatures in training set for biochemical recurrence‐free survival (BCRFS). Selected gene signatures established a risk score system. Univariate and multivariate analyses of prognostic factors about BCRFS were performed using the Cox proportional hazards regression models. A nomogram based on multivariate analysis was plotted to facilitate clinical application. Kyoto Encyclopedia of Gene and Genomes (KEGG) and Gene Ontology (GO) analyses were then executed for differentially expressed genes (DEGs). Results Notably, the risk score could significantly identify BCRFS by time‐dependent receiver operating characteristic (t‐ROC) curves in the training set (3‐year area under the curve (AUC) = 0.820, 5‐year AUC = 0.809) and the validation set (3‐year AUC = 0.723, 5‐year AUC = 0.733). Conclusions Clinically, the nomogram model, which incorporates Gleason score and the risk score, could effectively predict BCRFS and potentially be utilized as a useful tool for the screening of BCRFS in PCa., In this work, we established the risk score consisting of six gene signatures, which can predict biochemical recurrence in primary prostate cancer. Clinically, the nomogram model, which incorporates the Gleason score and the risk score, could effectively predict BCRFS and potentially be utilized as a useful tool for the screening of BCRFS in PCa.

The interoperability of wireless charging for electric vehicles refers to the radio energy transmission that meets the performance and function requirements of different manufacturers and different models of electric vehicles on the premise of meeting the relevant requirements. If it fails to meet the requirements, the wireless charging system of electric vehicles has difficulty to realize interconnection and low charging efficiency, Therefore, how to evaluate the interoperability is a key issue in the promotion of electric vehicle wireless charging. In this paper, an interoperability evaluation method based on two parameters is proposed. The interoperability impedance plane is constructed by the system detuning coefficient A. The comprehensive evaluation of different compensation networks and coupling coils is realized; the power characteristic impedance ε is obtained by analyzing and calculating the relationship between the transmission power of the system while the system impedance, and the transmission power evaluation of the wireless power transmission system is realized. At the same time, according to simulation and experiment, it was verified that A meets the interoperability requirements when A is in the range of (−0.62, 0.62) in the aligned position and (−0.75, 0.75) in the offset position. When the input voltage is 200 V, when ε satisfies 0.1925 ≥ ε > 0.0925, the system WPT2 power level transmission interoperability requirements are met. The method in this paper can guide the interoperability evaluation of electric vehicle wireless charging.

Objectives To investigate alterations in neurocognitive, attention, paediatric sleep questionnaire (PSQ) scores and whole brain white matter (WM) integrity between children with mild and severe obstructive sleep apnoea (OSA) according to sex and whether these changes are associated with OSA severity. Methods Fifty-seven children (36 males and 21 females) diagnosed with OSA were recruited for this study. Children of both sexes were divided into mild (male-MG, female-MG) and severe (male-SG, female-SG) groups according to OSA severity. Polysomnography (PSG), neurocognitive, attention and PSQ tests were compared between groups by one-way samples analysis of variance (ANOVA) F test. Diffusion tensor imaging (DTI) was scanned using a 3T GE MRI scanner and analysed by Tract-based Spatial Statistics (TBSS). Spearman correlation was calculated between DTI Eigenvalues and clinical characteristics. Results Compared to mild OSA patients, severe OSA patients presented greater severity of obstructive apnoea hypopnea index (OAHI), neurocognition, PSQ and attention tests in both male and female patients. Brain WM integrity in the male-SG, compared to the male-MG, demonstrated significantly reduced fractional anisotropy (FA) values in the right middle frontal gyrus and the right frontal sub-gyral regions and increased axial diffusivity (AD) values in the right inferior frontal gyrus, left parietal angular gyrus and sub-gyral regions, while no differences were found between the female-MG and female-SG. Alterations in male-SG brain regions were observably correlated with severity in male OSA patients. Conclusions The integrity of WM, which regulates autonomic, cognitive, and attention functions, is impaired in male, but not female, children with severe OSA.

Chengcheng Sun,1 Meixia Liu,1 Jiangang Liu,2 Tingting Zhang,3 Lei Zhang,4 Hao Li,1 Zenggang Luo5 1Department of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, People’s Republic of China; 2Department of Cardiovascular, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, People’s Republic of China; 3Department of Geriatrics, College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, ShanDong Province, People’s Republic of China; 4Department of Emergency, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, People’s Republic of China; 5Medical Administration Office, Beijing Administration of Traditional Chinese Medicine, Beijing, 100053, People’s Republic of ChinaCorrespondence: Meixia Liu; Jiangang Liu Email liumeixia2004@126.com; liujiangang2002@sina.comBackground: ShenmaYizhi decoction (SMYZD) is an effective prescription of traditional Chinese medicine used to treat vascular dementia (VD). Modern research methods have identified its active ingredients clearly as gastrodin, ferulic acid, ginsenosides, and β-sitosterol. Chronic cerebral hypoperfusion is a driving factor or risk factor for VD, which leads to the disturbance of mitochondrial structure and function.Purpose: To observe whether SMYZD improves cognitive impairment by improving mitochondrial structure and function.Methods: Forty adult rats with vascular cognitive impairment (VCI) caused by the bilateral ligation of common carotid arteries were divided into four groups randomly, including the model group, donepezil group, and low-dose and high-dose SMYZD groups, with 10 rats in each group. Additionally, a sham group was established with 10 rats as the control group. The treatment groups were administered donepezil and two different dosages of SMYZD. The donepezil group was administered 0.45 mg/kg/d donepezil, and the SMYZ-L group was administered 2.97 g/kg/d SMYZ, which were equivalent to the clinical dosage. The SMYZ-H group was administered 11.88 g/kg/d SMYZ, which is 4 times higher than the clinically equivalent dosage. A sham-operated group was used as the control group and administered an equal volume of distilled water. The rats were treated by gavage for 8 consecutive weeks. Morris water maze (MWM) test was performed to evaluate the learning and memory ability. The mitochondria of brain tissue were extracted from brain for further test. Mitochondrial morphology and the signal path of AMPK/PPARα/PGC-1α/UCP2 in mitochondria were detected.Results: With the SMYZD intervention, behavioral performance of rats and pathological changes of mitochondria of brain tissue were significantly improved. In the serum, SOD, GSH-Px, and GSH activities were increased, and the MDA content was decreased. Moreover, the AMPK, PPARα, PGC-1α, UCP2, and ATP5A mRNA and protein expression levels were also reversed by SMYZD.Conclusion: SMYZD may provide a potential therapeutic strategy via activating the AMPK/PPARα/PGC-1α/UCP2 signal pathway to improve mitochondrial structure and energy metabolism thereby alleviate vascular cognitive impairment.Keywords: vascular cognitive impairment, ShenmaYizhi decoction, mitochondria energy metabolism, bilateral common carotid artery occlusion

This study presents an effective high-speed countercurrent chromatography method of two-phase solvent system combined with ionic liquids for the isolation and purification of four major compounds of γ-oryzanol from rice bran oil. The conditions of high-speed countercurrent chromatography, including solvent systems and the content of ionic liquids, were optimized to improve separation efficiency. The optimal solvent system was n-hexane–dichloromethane–acetonitrile–[C4mim][PF6] at a volume ratio of (10:1:10:0.15, v/v). Adding a small amount of ionic liquids significantly improved the separation efficiency. Four compounds of γ-oryzanol, cycloartenyl ferulate, 24-methylene cycloartanyl ferulate, campesteryl ferulate, and sitosteryl ferulate were successfully purified in one run from rice bran oil with the purities of 95.25%, 92.48%, 92.47%, and 93.43%, respectively. The result of bioassay showed that rice bran oil and separated individual cycloartenyl ferulate could significantly inhibit mycelium growth of crop diseases Rhizoctonia solani and Fusarium graminerum, the bioactivity of cycloartenyl was higher than that of the rice bran oil. The cellular antioxidant activity experimental result indicted that cycloartenyl ferulate could alleviate H2O2-induced oxidative stress.

The volatile oil of Mentha haplocalyx is widely used in medicine, food, and cosmetics. However, a large amount of its residue after steam extraction of volatile oil is abandoned, resulting in a waste of resources. The method of aqueous two-phase flotation coupled with preparative high-performance liquid chromatography was established for the separation and purification of nonvolatile active compounds from Mentha haplocalyx for the first time. The parameters of the two-phase aqueous flotation were optimized. Under the optimal conditions including flotation solvent PEG 1000 aqueous solution (1:1, w/w), pH 5, (NH4 )2 SO4 concentration of 350 g/L in aqueous phase, N2 flow rate of 20 mL/min, and flotation time of 20 min, the flotation efficiency of linarin, hesperidin, and didymin was 82.24, 76.38, and 89.33%, respectively. The linarin and hesperidin with the high purities of 95.8 and 97.2%, respectively, were obtained by using preparative high performance liquid chromatography. The neuroprotective effect of linarin against H2 O2 -induced oxidative stress in rat hippocampal neurons was investigated. The experimental result indicated that linarin could alleviate H2 O2 -induced oxidative stress. The work indicated that the combination of aqueous two-phase flotation and preparative high performance liquid chromatography is a feasible and practical method for the purification of nonvolatile active substances from Mentha haplocalyx, which would provide a reference process for the comprehensive utilization of M. haplocalyx. Especially, linarin might be used as a good source of natural neuroprotectants.

In crystalline/crystalline polymer blend systems, complex competition and coupling of crystallization and morphology usually happen due to the different crystal nucleation and growth processes of polymers, making the morphology and crystallization behavior difficult to control. Herein, we probe the crystallization sequence during the film formation process (crystallize simultaneously, component A crystallizes prior to B or inverse) to illustrate the micro-morphology evolution process in poly(3-hexylthiophene) (P3HT) and poly[[N,N-bis(2-octyldodecyl)-napthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]- alt-5, 5'-(2,2'-bithiophene)] (N2200) blend using in situ UV-vis absorption spectra and in situ two-dimensional grazing incidence X-ray diffraction (2D GIXRD). When P3HT and N2200 crystallize simultaneously, a large-sized morphology structure is formed. When strengthening the solution aggregation of P3HT by increasing the solvent-polymer interaction, P3HT crystallizes prior to N2200. A P3HT-based micro-morphology structure is obtained. As the molecular weight of N2200 increases to a critical value (72.0 kDa), the crystallization of N2200 dominates the film formation process. A N2200-based micro-morphology is formed guided by N2200 domains. The results confirm that the crystallization sequence is one of the most important factors to determine the micro-morphology structure in all-crystalline polymer blends.

This study is concerned with path planning in a structured greenhouse, in contrast to much of the previous research addressing applications in outdoor fields. The prototype mainly comprises an independently driven Mecanum wheel, a lidar measuring module, a single-chip microcomputer control board, and a laptop computer. Environmental information collection and mapping were completed on the basis of lidar and laptop computer connection. The path planning algorithm used in this paper expanded the 8-search-neighborhood of the traditional A* algorithm to a 48-search-neighborhood, increasing the search direction and improving the efficiency of path planning. The Floyd algorithm was integrated to smooth the planned path and reduced the turning points in the path. In this way, the problems of the traditional A* algorithm could be solved (i.e., slow the path planning speed and high numbers of redundant points). Tests showed that the turning points, planning path time, and distance of the improved algorithm were the lowest. Compared with the traditional 8-search-neighborhood A* algorithm, the turning point was reduced by 50%, the planning time was reduced by 13.53%, and the planning distance was reduced by 13.96%. Therefore, the improved method of the A* algorithm proposed in this paper improves the precision of the planning path and reduces the planning time, providing a theoretical basis for the navigation, inspection, and standardization construction of greenhouses in the future.

Purpose: Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (CDK4/6i) are highly effective against estrogen receptor–positive (ER+)/HER2− breast cancer; however, intrinsic and acquired resistance is common. Elucidating the molecular features of sensitivity and resistance to CDK4/6i may lead to identification of predictive biomarkers and novel therapeutic targets, paving the way toward improving patient outcomes. Experimental Design: Parental breast cancer cells and their endocrine-resistant derivatives (EndoR) were used. Derivatives with acquired resistance to palbociclib (PalboR) were generated from parental and estrogen deprivation–resistant MCF7 and T47D cells. Transcriptomic and proteomic analyses were performed in palbociclib-sensitive and PalboR lines. Gene expression data from CDK4/6i neoadjuvant trials and publicly available datasets were interrogated for correlations of gene signatures and patient outcomes. Results: Parental and EndoR breast cancer lines showed varying degrees of sensitivity to palbociclib. Transcriptomic analysis of these cell lines identified an association between high IFN signaling and reduced CDK4/6i sensitivity; thus an “IFN-related palbociclib-resistance Signature” (IRPS) was derived. In two neoadjuvant trials of CDK4/6i plus endocrine therapy, IRPS and other IFN-related signatures were highly enriched in patients with tumors exhibiting intrinsic resistance to CDK4/6i. PalboR derivatives displayed dramatic activation of IFN/STAT1 signaling compared with their short-term treated or untreated counterparts. In primary ER+/HER2− tumors, the IRPS score was significantly higher in lumB than lumA subtype and correlated with increased gene expression of immune checkpoints, endocrine resistance, and poor prognosis. Conclusions: Aberrant IFN signaling is associated with intrinsic resistance to CDK4/6i. Experimentally, acquired resistance to palbociclib is associated with activation of the IFN pathway, warranting additional studies to clarify its involvement in resistance to CDK4/6i.

High-performance polymer donors are highly demanded to fulfil the potential of layer-by-layer (LBL) processed organic solar cells (OSCs). In this study, we present an effective method to develop high-performance polymer donors for LBL-OSCs by manipulating their solubility properties. The solubility of naphthalenothiophene imide (NTI)-based polymers could be easily manipulated by employing linear or branched alkyl chains in NTI. The polymer PNTB6-Cl with linear alkyl chains insoluble in chloroform could tolerate the chloroform processing by washing away the polymers only in the amorphous region, resulting in an LBL film with a much smoother surface and more efficient photoluminescence quenching, while chloroform-soluble polymer PNTB-Cl did not. PNTB6-Cl:N3 based LBL devices exhibited an efficiency of 17.59%, much higher than 15.24% for PNTB-Cl:N3 based devices and 16.20% for control devices based on PM6:N3. Importantly, the excellent batch-to-batch reproducibility of PNTB6-Cl overcomes the notorious batch-dependent issue in polymer donors, indicating that PNTB6-Cl is a promising polymer donor for LBL-OSCs. Our studies demonstrate that the solubility property of a polymer could significantly impact electron acceptor penetration, phase separation and photovoltaic performance of LBL-OSCs, which provide the guidelines for high-performance polymer donor design.

BACKGROUND: : In the present study, we tried to understand the crosstalk between prostaglandins-COX-mediated rectal tumors and toll-like receptors in rats. METHODS: : The tumor was induced using nicotine (100 μL/mL). Following the induction, the serum and rectal tissue were analyzed for Lipo-polysaccharides (LPS) and prostaglandin E2 in serum, and tissue expression of inflammatory mediators like TLR2,4, NFkB; cancer markers like Matrix metalloproteases 2 (MMP2), 9 and Cyclo-oxygenases 2 (COX-2) were estimated. The gut microflora analysis was carried out using the fresh fecal samples of both the study groups. RESULTS: : In nicotine-induced group, there was a significant alteration in the gut microflora toward high Gram-negative strains and a decline in Gram-positive populations. All the inflammatory as well as cancer prognostic markers were significantly increased in the tumor-induced animals. CONCLUSION: : From the present study, it could be concluded that nicotine significantly induced rectal cancer in the mice model by modulating gut microflora and increasing COX-2 and prostaglandin E2 levels.