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Abstract Heat shock proteins (HSPs) are a kind of molecular chaperone that helps protein folding, which is closely related to cancer. However, the association between HSPs and clear cell renal clear cell carcinoma (ccRCC) is uncertain. We explored the prognostic value of HSP110, HSP90, HSP70 and HSP60 families in ccRCC and their role in tumor immune microenvironment. The data obtained from the Cancer Genome Atlas (TCGA) were applied to determine the differential expression of HSPs in normal tissues and ccRCC. We comprehensively analyzed the prognostic value of HSPs in ccRCC and constructed a prognostic signature. We further explored the differences of tumor immune microenvironment and targeted therapy based on the signature. Cell proliferation, invasion and metastasis were detected by CCK8 assay, wound healing and transwell. Three clusters were identified with differences in overall survival and tumor stage. 6-gene signature (HSPA8, HSP90B1, HSPA7, HSPA12B, HSPA4L, HSPA1L) was identified to predict ccRCC patients’ prognosis. The signature was confirmed in the internal cohort. Survival analysis, receiver operating characteristic (ROC) curve, univariate and multivariate COX regression analysis demonstrated the accuracy and independence of signature. The expression of HSPA7, HSPA8 and HSP90B1 were validated with quantitative real-time PCR. Our signature played a pivotal role in predicting tumor immune microenvironment, immune checkpoint gene expression, drug sensitivity, and tumor mutational burden (TMB) in patients with ccRCC. Our cellular experiments confirmed HSPA7 promotes the proliferation, invasion and metastasis of ccCRC cells. The HSPs signature identified in this study could serve as potential biomarkers for predicting prognosis and treatment response in ccRCC patients. It may provide new ideas for the current research on targeted therapy and immunotherapy strategies for ccRCC patients.

Abstract As for the problems of boundary blurring and information loss in the multi-focus image fusion method based on the generative decision maps, this paper proposes a new gradient-intensity joint proportional constraint generative adversarial network for multi-focus image fusion, with the name of GIPC-GAN. First, a set of labeled multi-focus image datasets using the deep region competition algorithm on a public dataset is constructed. It can train the network and generate fused images in an end-to-end manner, while avoiding boundary errors caused by artificially constructed decision maps. Second, the most meaningful information in the multi-focus image fusion task is defined as the target intensity and detail gradient, and a jointly constrained loss function based on intensity and gradient proportional maintenance is proposed. Constrained by a specific loss function to force the generated image to retain the information of target intensity, global texture and local texture of the source image as much as possible and maintain the structural consistency between the fused image and the source image. Third, we introduce GAN into the network, and establish an adversarial game between the generator and the discriminator, so that the intensity structure and texture gradient retained by the fused image are kept in a balance, and the detailed information of the fused image is further enhanced. Last but not least, experiments are conducted on two multi-focus public datasets and a multi-source multi-focus image sequence dataset and compared with other 7 state-of-the-art algorithms. The experimental results show that the images fused by the GIPC-GAN model are superior to other comparison algorithms in both subjective performance and objective measurement, and basically meet the requirements of real-time image fusion in terms of running efficiency and mode parameters quantity.

Abstract To analyze the expression levels, prognostic value and immune infiltration association of Holliday junction protein (HJURP) as well as its feasibility as a pan-cancer biomarker for different cancers. The Protter online tool was utilized to obtain the localization of HJURP, then the methylation of HJURP in tumors were further explored. Thereafter, the mRNA data and clinical characteristics of 33 tumor types from TCGA database were obtained to investigate the expression and prognostic relationship of HJURP in different tumor types. Finally, the composition pattern and immune infiltration of HJURP in different tumors were detected in Tumor Immune Estimation Resource. HJURP was abnormally expressed in most of the cancer types and subtypes in TCGA database. Also, it was associated with poor prognosis of different cohorts. At the same time, the results also showed that HJURP was related to tumor immune evasion through different mechanisms, including T cell rejection and methylation in different cancer types. Besides, the methylation of HJURP was inversely proportional to mRNA expression levels, which mediated the dysfunctional phenotypes of T cells and poor prognosis of different cancer types. Alternatively, our results indicated that HJURP expression was associated with immune cell infiltration in a variety of cancers. HJURP may serve as an oncogenic molecule, and its expression and immune infiltration characteristics can be used as a biomarker for cancer detection, prognosis, treatment design and follow-up.

Background: The ‘obesity paradox’ in elderly patients suffering from percutaneous coronary intervention (PCI) remains a source of controversy. The present meta-analysis focused on exploring the real existence of ‘obesity paradox’ in these patients. Methods: As of November 2022, PubMed, Cochrane and Embase databases were comprehensively searched to identify articles reporting all-cause mortality according to diverse body mass index (BMI) categories after PCI among the old cases developing coronary artery disease (CAD). Summary estimates of risk ratios (RRs) were assigned four BMI groups, including underweight, normal weight, overweight, and obesity groups. Results: There were altogether nine articles involving 25,798 cases selected for further analysis. Relative to normal weight group, overweight and obesity groups had decreased all-cause mortality (RR 0.86, 95%CI 0.77-0.95 for overweight group; RR 0.57,95%CI 0.40-0.80 for obesity group), while underweight group had elevated all-cause mortality (RR 1.52, 95%CI 1.01-2.29). Conclusions: Our study revealed an ‘obesity paradox’ relation of BMI with all-cause mortality in elderly cases receiving PCI. In comparison with normal weight group, overweight and obesity groups had decreased all-cause mortality, while underweight group had increased all-cause mortality.

Abstract Objective This work focused on investigating the relation of centromeric protein A (CENPA) gene expression with prognosis of papillary renal cell carcinoma (PRCC). Methods We obtained data from PRCC cases in TCGA. Thereafter, CENPA levels between the paired PRCC and matched non-carcinoma samples were analyzed by Wilcoxon rank-sum test, while the relations of clinicopathological characteristics with CENPA level were examined by logistic regression and Wilcoxon rank-sum test. The prognostic value of CENPA was assessed by plotting the receiver operating feature curve (ROC) and calculating the value of area under curve (AUC). In addition, relations between clinicopathological characteristics and PRCC survival were analyzed through Kaplan–Meier (KM) and Cox regression analyses. After dividing the total number of patients into the trial cohort and the validation cohort in a ratio of 7:3, we constructed a nomogram in trial cohort according to multivariate Cox regression results for predicting how CENPA affected patient survival and used the calibration curve to verify its accuracy in both cohorts. We also determined CENPA levels within cancer and matched non-carcinoma samples through immunohistochemistry (IHC). Finally, we utilized functional enrichment for identifying key pathways related to differentially expressed genes (DEGs) between PRCC cases with CENPA up-regulation and down-regulation. Results CENPA expression enhanced in PRCC tissues compared with healthy counterparts (P

Objective: Adrenocortical carcinoma (ACC) is a rare malignant tumor. Chromatin regulators (CRs) can drive epigenetic changes, which have been considered as one of the most vital hallmarks of tumors. This study aimed to explore the CR signature for ACC in order to clarify the molecular basis of ACC’s pathogenic mechanism and provide novel methods to diagnose and treat ACC clinically.Methods: This study obtained transcriptome sequencing datasets of ACC patients and sequencing data on normal adrenal tissues in TCGA and GTEx databases, respectively. Meanwhile, prognostic genes were selected through Lasso and Cox regression analyses. Using the transcriptome sequencing datasets of ACC patients downloaded from the GEO database to finish validation, we performed Kaplan–Meier (KM) analysis for evaluating the differential survival between low- and high-risk groups. Then, this work constructed the risk model for predicting ACC prognosis. TIMER 2.0 was employed to assess the differences in immune infiltration between the two groups. Furthermore, this work adopted the R package “pRRophetic” for exploring and estimating the sensitivity of patients to different chemotherapeutic agents.Results: A 5-CR model was established to predict ACC survival, and the CR signature was confirmed as a factor in order to independently predict ACC patient prognosis. In addition, a nomogram composed of the risk score and clinical T stage performed well in the prediction of patients’ prognosis. Differentially expressed CRs (DECRs) were mostly associated with the cell cycle, base excision repair, colon cancer, gene duplication, homologous recombination, and other signaling pathways for the high-risk group. As for the low-risk group, DECRs were mainly enriched in allograft rejection, drug metabolism of cytochrome P450, metabolism of xenogeneic organisms by cytochrome P450, retinol metabolism, and other signaling pathways. According to TIMER analysis, the immune infiltration degrees of endothelial cells, M2 macrophages, myeloid dendritic cells, CD4+ Th1 cells, NKT cells, and M0 macrophages showed significant statistical differences between the high- and low-risk groups, and high infiltration levels of M0 and M2 macrophages were more pronounced in higher T stage (T3 and T4), N stage (N1), and clinical stages (III and IV). In addition, high-risk cases exhibited higher sensitivity to etoposide and doxorubicin. Additionally, low-risk patients had significantly decreased expression of RRM1 compared with high-risk cases, suggesting the better effect of mitotane treatment.Conclusion: This study identified the DECRs, which might be related to ACC genesis and progression. The pathways enriched by these DECRs were screened, and these DECRs were verified with excellent significance for estimating ACC survival. Drug sensitivity analysis also supported the current clinical treatment plan. Moreover, this study will provide reliable ideas and evidence for diagnosing and treating ACC in the clinic.

The application of horizontal well drilling and large-scale sand fracturing can secure an increased production in shale gas reservoirs despite of frequent gas wellbore blockage. It is vital to remove the residual bridge plug debris and sand in wellbore cleaning operation and to ensure an unblocked downhole production channel of shale gas well for a safe and smooth production process. In this paper, the current situations of the wellbore cleaning technology for horizontal wells were analyzed, and the technical challenges in wellbore cleaning treatment of shale gas horizontal wells were summarized. Based on global development of wellbore cleaning technologies for horizontal wells, technical researches were carried out on cleaning tools & technologies and working fluid performance, and cleaning treatment tools were studied and developed. Besides, technical measures of cleaning treatment were put forward and their field application effects were analyzed. Results reveal that the milling–fishing integrated tool, developed to treat large bore bridge plug, is capable of washing-over and fishing out large bore bridge plug in one trip after running in the hole; for long horizontal sections where reverse cyclone sand-washing tool is applied, the tool can prevent sand from settling so as to flush sand out of the wellbore; for normal-pressure and high-pressure wells, gas well backflow fluid, KCl and CaCl2 solution may serve as working fluid, while for low pressure wells, foam fluid can be used; for low-pressure wells, the negative pressure fishing tool is designed and optimized to drive debris or sediment into the tool through forming local negative pressure adsorption, thus complete the fishing operation. In conclusion, the new wellbore cleaning technology, which suits shale-gas horizontal wells, has laid the groundwork for large-scale wellbore cleaning treatment of shale gas wells. Keywords: Shale gas, Horizontal well, Bridge plug debris and sand, Wellbore plugging, Wellbore cleaning, Challenges, Milling–fishing integrated tool

Diabetes mellitus (DM) is one of the severe metabolic diseases found in all types of people’s lives in lower, middle and high income countries. It is suggested that the prevalence of diabetes is increasing in many countries and most of the cases are type 2 DM, clinical treatments are changing now to manage type 2 DM, however, up-to-date, there is no diagnostic, prognostic, and therapeutic target for type 2 DM. MicroRNAs (miRNAs) is one of a non-protein coding RNAs that have been regulating a wide range cellular processes and induce the development of many diseases. Most of the researchers concluded that miRNAs involvement is an important process in a broad range of signaling pathways such as cell proliferation, stem cell maintenance, migration, apoptosis and gene or protein expressions. Expressed sequence tags (ESTs) are the best source of coding and non-coding sequences for the identification of miRNAs. Although DNA methylation is an important mechanism for miRNAs up-regulation, this has not been highly explored in type 2 DM. The present study is useful to elucidate the molecular mechanism of MiR-1285-5p in type 2 DM and its role in disease progression and we discovered miR-1285 as a novel prognostic, diagnostic and therapeutic target for type 2 DM.

For problem of complex fault types and uncertain diagnostic features of the ZPW-2000K track circuit, traditional fault diagnosis mainly adopts manual diagnosis methods, which leads to low automatic diagnosis. This paper proposes a fault diagnosis method based on Rough Sets (RS) reduction model and Bayesian Network (BN) structure learning fusion. Firstly, data mining and feature extraction are performed on the fault data table, and expert knowledge is built into the prior knowledge base. Secondly, the K2 algorithm is used to train the fault feature quantity, and the BN model is built by combining the prior knowledge base. Then, a diagnostic decision table is established through the fault instance, and RS is used for attribute reduction, dimensionality reduction, and simplified model. The MLE algorithm is used again to learn the parameters to obtain the conditional probability table of the model, and the complete BN structure is established based on the RS-BN algorithm. Finally, the comparative analysis of the simplified model and the non-simplified model is carried out. Through the experimental simulation of the ZPW-2000K track circuit fault of a high-speed railway station, the accuracy and effectiveness of the diagnostic method are verified.

Cement is one of the essential engineering materials in the construction industry. It has always been the focus of attention to improve the related performance of cement. In view of the effects of chemical admixtures on the strength of Portland cement, this paper has conducted a quantity of experiments, respectively studied the effects of retarder, alcohol amine admixture and inorganic salt admixture on the physical and mechanical properties of cement, obtained the effects of various admixtures on improving the related performance of cement, and provided reference values for the improvement of the performance of cement binding materials.

Background The school–vacation cycle may have impacts on the psychological states of adolescents. However, little evidence illustrates how transition from school to vacation impacts students’ psychological states (e.g. depression and anxiety). Aims To explore the changing patterns of depression and anxiety symptoms among adolescent students within a school–vacation transition and to provide insights for prevention or intervention targets. Method Social demographic data and depression and anxiety symptoms were measured from 1380 adolescent students during the school year (age: 13.8 ± 0.88) and 1100 students during the summer vacation (age: 14.2 ± 0.93) in China. Multilevel mixed-effect models were used to examine the changes in depression and anxiety levels and the associated influencing factors. Network analysis was used to explore the symptom network structures of depression and anxiety during school and vacation. Results Depression and anxiety symptoms significantly decreased during the vacation compared to the school period. Being female, higher age and with lower mother's educational level were identified as longitudinal risk factors. Interaction effects were found between group (school versus vacation) and the father's educational level as well as grade. Network analyses demonstrated that the anxiety symptoms, including ‘Nervous’, ‘Control worry’ and ‘Relax’ were the most central symptoms at both times. Psychomotor disturbance, including ‘Restless’, ‘Nervous’ and ‘Motor’, bridged depression and anxiety symptoms. The central and bridge symptoms showed variation across the school vacation. Conclusions The school–vacation transition had an impact on students’ depression and anxiety symptoms. Prevention and intervention strategies for adolescents’ depression and anxiety during school and vacation periods should be differentially developed.

Micro-expressions refer to brief, subtle facial movements often concealing genuine human emotions. However, the advancement of Micro-Expression Recognition (MER) is hindered by the low frame rates of frame-based cameras. Although the successor event camera has a high frame rate, there are currently difficulties in obtaining and unstable performance issues. Drawing inspiration from the operational principles of event camera, we introduces two event features. Beyond spatial information, these features encode temporal and polarity information of event. Following local normalization, we employ the temporal polar pixel-wise interaction module to extract local feature. Additionally, we construct a temporal polar dynamic network, merging local feature with dense global optical flow to map deeper features. Experimental results demonstrate the superiority of the proposed method across multiple datasets compared to state-of-the-art approaches. This work enriches the encoding of event features, enhancing their performance in micro-expression recognition tasks and contributing to the future proliferation of event camera technology.

Abstract Electrochemical chlorine evolution reaction is of central importance in the chlor-alkali industry, but the chlorine evolution anode is largely limited by water oxidation side reaction and corrosion-induced performance decay in strong acids. Here we present an amorphous CoOxCly catalyst that has been deposited in situ in an acidic saline electrolyte containing Co2+ and Cl- ions to adapt to the given electrochemical condition and exhibits ~100% chlorine evolution selectivity with an overpotential of ~0.1 V at 10 mA cm−2 and high stability over 500 h. In situ spectroscopic studies and theoretical calculations reveal that the electrochemical introduction of Cl- prevents the Co sites from charging to a higher oxidation state thus suppressing the O-O bond formation for oxygen evolution. Consequently, the chlorine evolution selectivity has been enhanced on the Cl-constrained Co-O* sites via the Volmer-Heyrovsky pathway. This study provides fundamental insights into how the reactant Cl- itself can work as a promoter toward enhancing chlorine evolution in acidic brine.

Background The co-occurrence of depression and anxiety among adolescents is typically associated with suicide ideation.Aims The study aimed to investigate the symptom-level relationship between suicide ideation and the comorbidity of depression and anxiety.Methods 1501 adolescents aged 12–19 years were assessed using the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder Scale, and 716 adolescents who scored ≥5 on both scales were selected as participants. Network analysis was used to identify the network structure of depressive symptoms and anxiety symptoms. Participants were categorised into either the suicide ideation or non-suicide ideation groups based on their scoring on the suicide-related item in PHQ-9. A comparison was made between the depression–anxiety symptom networks of the two groups.Results ‘Restlessness’, ‘sad mood’ and ‘trouble relaxing’ were the most prominent central symptoms in the depression–anxiety symptom network, and ‘restlessness’, ‘nervousness’ and ‘reduced movement’ were the bridge symptoms in this network. ‘Sad mood’ was found to be directly related to ‘suicide ideation’ with the highest variance. The network structure was significantly different in properties between the suicide ideation group and the non-suicide ideation group, with ‘restlessness’ and ‘sad mood’ exhibiting significantly higher influence in the network of the suicide ideation group than that in the non-suicide ideation group.Conclusion Restlessness and sad mood could be targeted for the intervention of depression–anxiety symptoms among adolescents with suicide ideation.

If and how non-bonding ligands mediate the electronic states of metal sites is interesting yet remains to be explored. Here the authors show that a non-covalent phenanthroline can promote the population of Co4+ and induce polaron-like Co sites for improved water oxidation.

Abstract Background Mitochondrial disease (MD) is genetically a heterogeneous group of disorders with impairment in respiratory chain complexes or pathways associated with the mitochondrial function. Nowadays, it is still a challenge for the genetic screening of MD due to heteroplasmy of mitochondrial genome and the complex model of inheritance. This study was designed to investigate the feasibility of whole exome sequencing (WES)‐based testing as an alternative option for the diagnosis of MD. Methods A Chinese Han cohort of 48 patients with suspect MD features was tested using nanoWES, which was a self‐designed WES technique that covered the complete mtDNA genome and 21,019 nuclear genes. Fourteen patients were identified with a single genetic variant and three with single deletion in mtDNA. Results The heteroplasmy levels of variants in mitochondrial genome range from 11% to 100%. NanoWES failed to identify multiple deletions in mtDNA compared with long range PCR and massively parallel sequencing (LR‐PCR/MPS). However, our testing showed obvious advantages in identifying variations in nuclear DNA. Based on nanoWES, we identified two patients with nuclear DNA variation. One of them showed Xp22.33‐q28 duplication, which indicated a possibility of Klinefelter syndrome. Conclusion NanoWES yielded a diagnostic rate of 35.4% for MD. With the rapid advances of next generation sequencing technique and decrease in cost, we recommend the usage of nanoWES as a first‐line method in clinical diagnosis.

Purpose: Cardiomyocyte senescence is associated with a progressive decline in cardiac physiological function and the risk of cardiovascular events. lncRNA H19 (H19), a well-known long noncoding RNA (lncRNA), is involved in the pathophysiological process of multiple cardiovascular disease such as heart failure, cardiac ischemia and fibrosis. However, the role of H19 in cardiomyocyte senescence remains to be further explored.Methods: Senescence-associated β-galactosidases (SA-β-gal) staining was used to detect cardiomyocyte senescence. Western blot, qRT-PCR and luciferase reporter assay were employed to evaluate the role of H19 in cardiomyocyte senescence and its underling molecular mechanism.Results: H19 level was significantly increased in high glucose-induced senescence cardiomyocytes and aged mouse hearts. Overexpression of H19 enhanced the number of SA-β-gal-positive cells, and the expression of senescence-related proteins p53 and p21, whereas H19 knockdown exerted the opposite effects. Mechanistically, H19 was demonstrated as a competing endogenous RNA (ceRNA) for microRNA-19a (miR-19a): H19 overexpression downregulated miR-19a level, while H19 knockdown upregulated miR-19a. The expression of SOSC1 was dramatically increased in senescence cardiomyocytes and aged mouse hearts. Further experiments identified SOCS1 as a downstream target of miR-19a. H19 upregulated SOCS1 expression and activated the p53/p21 pathway by targeting miR-19a, thus promoting the cardiomyocytes senescence.Conclusion: Our results show that H19 is a pro-senescence lncRNA in cardiomyocytes acting as a ceRNA to target the miR-19a/SOCS1/p53/p21 pathway. Our research reveals a molecular mechanism of cardiomyocyte senescence regulation and provides a novel target of the therapy for senescence-associated cardiac diseases.

Copper fiber reinforced needle-coke/carbon (CF-NC/C) composites with different copper fiber contents have been successfully developed for urban rail pantograph slide block. The mechanical properties of needle coke samples containing 0 wt%, 4 wt%, 8 wt%, 12 wt% and 16 wt% were examined separately. It is found that the presence of needle coke with high aspect ratio, strength and electrical conductivity can greatly improves the physical properties of the pure carbon matrix. Therefore, we have obtained a novel carbon matrix composite. It is also revealed that the optimized CF-NC/C with 5 wt% copper fibers (CF-NC/C-5) composite has outstanding mechanical properties, current-carrying friction wear properties. The density, resistivity, and impact strength of the CF-NC/C-5 composite are 1.8788 g cm ^−3 , 35.18 μ Ω·m, 0.16 J cm ^−2 , respectively. In current-carrying friction wear tests (0 A, 5 A, 10 A and 15 A), the CF-NC/C-5 shows an optimum friction wear performance. To avoid agglomeration of copper fibers, the copper fibers are added innovatively during the rolling process and uniformly distributed in the carbon matrix under the tangential force of rolling, which exhibits an improved effect on reinforcing the NC/C composites. Our results greatly advance the development of the needle-coke/carbon composite, which makes the new CF-NC/C composite an ideal candidate for sliding plate material with excellent properties.

High-performance copper-based pantograph slide materials play a crucial role in the rapid development of modern urban rail transit urgently. Herein, a full density graphite/copper-alloy matrix composite for pantograph slide has been successfully obtained by the hot powder forging process. The composite exhibits the full density when forging energy density is 307.6 J cm ^−3 . In addition, the influence of different aging treatments on microstructure and mechanical performances of the composite has been studied in detail. The hardness and resistivity of the forged materials are greatly improved after an optimum aging treatment. Simultaneously, the friction and wear performances with or without currency current have been investigated, which demonstrates the friction coefficient can reach the minimum of 0.109 under 35 N. In current-carrying friction, the wear rate of the composite is an extremely small value of 5.5 × 10 ^–5 mg m ^−1 after the aging treatment, indicating the outstanding anti-friction and self-lubricating performance. All the comprehensive analyses illustrate the full density graphite/copper-alloy matrix composite with excellent mechanical shows an enormous potential for pantograph slide.

In this work, chromium-containing copper matrix com0posites with different flake graphite content (1.8 wt%, 2 wt%, 2.5 wt%) were fabricated by inexpensive powder metallurgy method, and the mechanical properties, friction properties and microstructure of graphite/copper matrix composites were studied. Friction experiments were conducted with copper-based composite materials and copper rings to examine the effect of graphite on the wear of the bow-net structure. During mechanical wear, the wear rate of the copper ring corresponding to the sample increased with the increase of the graphite content in the sample, while the wear rate of the copper ring corresponding to the 1.8 wt% sample was the smallest. In the current-carrying wear process, the wear rate of the 2 wt% sample corresponding to the copper ring is the lowest. Through elemental analysis, it was found that material transfer occurred on the worn surface during wear. In the process of mechanical wear without current-carrying wear is caused primarily by adhesion, abrasion, and oxidation. In the process of current-carrying wear, wear is mainly caused by adhesion, electrical, and oxidative abrasion.