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Abstract Background SRSF1, a member of Serine/Arginine-Rich Splicing Factors (SRSFs), has been observed to significantly influence cancer progression. However, the precise role of SRSF1 in osteosarcoma (OS) remains unclear. This study aims to investigate the functions of SRSF1 and its underlying mechanism in OS. Methods SRSF1 expression level in OS was evaluated on the TCGA dataset, TAGET-OS database. qRT-PCR and Western blotting were employed to assess SRSF1 expression in human OS cell lines as well as the interfered ectopic expression states. The effect of SRSF1 on cell migration, invasion, proliferation, and apoptosis of OS cells were measured by transwell assay and flow cytometry. RNA sequence and bioinformatic analyses were conducted to elucidate the targeted genes, relevant biological pathways, and alternative splicing (AS) events regulated by SRSF1. Results SRSF1 expression was consistently upregulated in both OS samples and OS cell lines. Diminishing SRSF1 resulted in reduced proliferation, migration, and invasion and increased apoptosis in OS cells while overexpressing SRSF1 led to enhanced growth, migration, invasion, and decreased apoptosis. Mechanistically, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) revealed that the biological functions of SRSF1 were closely associated with the dysregulation of the protein targeting processes, location of the cytosolic ribosome, extracellular matrix (ECM), and proteinaceous extracellular matrix, along with the PI3K-AKT pathway, Wnt pathway, and HIPPO pathway. Transcriptome analysis identified AS events modulated by SRSF1, especially (Skipped Exon) SE events and (Mutually exclusive Exons) MXE events, revealing potential roles of targeted molecules in mRNA surveillance, RNA degradation, and RNA transport during OS development. qRT-PCR confirmed that SRSF1 knockdown resulted in the occurrence of alternative splicing of SRRM2, DMKN, and SCAT1 in OS. Conclusions Our results highlight the oncogenic role of high SRSF1 expression in promoting OS progression, and further explore the potential mechanisms of action. The significant involvement of SRSF1 in OS development suggests its potential utility as a therapeutic target in OS.

Abstract Accurate intraoperative differentiation of primary central nervous system lymphoma (PCNSL) remains pivotal in guiding neurosurgical decisions. However, distinguishing PCNSL from other lesions, notably glioma, through frozen sections challenges pathologists. Here we sought to develop and validate a deep learning model capable of precisely distinguishing PCNSL from non-PCNSL lesions, especially glioma, using hematoxylin and eosin (H&E)-stained frozen whole-slide images. Also, we compared its performance against pathologists of varying expertise. Additionally, a human-machine fusion approach integrated both model and pathologic diagnostics. In external cohorts, LGNet achieved AUROCs of 0.965 and 0.972 in distinguishing PCNSL from glioma and AUROCs of 0.981 and 0.993 in differentiating PCNSL from non-PCNSL lesions. Outperforming several pathologists, LGNet significantly improved diagnostic performance, further augmented to some extent by fusion approach. LGNet’s proficiency in frozen section analysis and its synergy with pathologists indicate its valuable role in intraoperative diagnosis, particularly in discriminating PCNSL from glioma, alongside other lesions.

Abstract Background Risk stratification and personalized care are crucial in managing osteosarcoma due to its complexity and heterogeneity. However, current prognostic prediction using clinical variables has limited accuracy. Thus, this study aimed to explore potential molecular biomarkers to improve prognostic assessment. Methods High-throughput inhibitor screening of 150 compounds with broad targeting properties was performed and indicated a direction towards super-enhancers (SEs). Bulk RNA-seq, scRNA-seq, and immunohistochemistry (IHC) were used to investigate SE-associated gene expression profiles in osteosarcoma cells and patient tissue specimens. Data of 212 osteosarcoma patients who received standard treatment were collected and randomized into training and validation groups for retrospective analysis. Prognostic signatures and nomograms for overall survival (OS) and lung metastasis-free survival (LMFS) were developed using Cox regression analyses. The discriminatory power, calibration, and clinical value of nomograms were evaluated. Results High-throughput inhibitor screening showed that SEs significantly contribute to the oncogenic transcriptional output in osteosarcoma. Based on this finding, focus was given to 10 SE-associated genes with distinct characteristics and potential oncogenic function. With multi-omics approaches, the hyperexpression of these genes was observed in tumor cell subclusters of patient specimens, which were consistently correlated with poor outcomes and rapid metastasis, and the majority of these identified SE-associated genes were confirmed as independent risk factors for poor outcomes. Two molecular signatures were then developed to predict survival and occurrence of lung metastasis: the SE-derived OS-signature (comprising LACTB, CEP55, SRSF3, TCF7L2, and FOXP1) and the SE-derived LMFS-signature (comprising SRSF3, TCF7L2, FOXP1, and APOLD1). Both signatures significantly improved prognostic accuracy beyond conventional clinical factors. Conclusions Oncogenic transcription driven by SEs exhibit strong associations with osteosarcoma outcomes. The SE-derived signatures developed in this study hold promise as prognostic biomarkers for predicting OS and LMFS in patients undergoing standard treatments. Integrative prognostic models that combine conventional clinical factors with these SE-derived signatures demonstrate substantially improved accuracy, and have the potential to facilitate patient counseling and individualized management.

Abstract Magnetic liquid metal (LM) soft robots attract considerable attentions because of distinctive immiscibility, deformability and maneuverability. However, conventional LM composites relying on alloying between LM and metallic magnetic powders suffer from diminished magnetism over time and potential safety risk upon leakage of metallic components. Herein, we report a strategy to composite inert and biocompatible iron oxide (Fe3O4) magnetic nanoparticles into eutectic gallium indium LM via reactive wetting mechanism. To address the intrinsic interfacial non-wettability between Fe3O4 and LM, a silver intermediate layer was introduced to fuse with indium component into Ag x In y intermetallic compounds, facilitating the anchoring of Fe3O4 nanoparticles inside LM with improved magnetic stability. Subsequently, a miniature soft robot was constructed to perform various controllable deformation and locomotion behaviors under actuation of external magnetic field. Finally, practical feasibility of applying LM soft robot in an ex vivo porcine stomach was validated under in-situ monitoring by endoscope and X-ray imaging.

Summary: Accurate tumor diagnosis by pathologists relies on identifying specific morphological characteristics. However, summarizing these unique morphological features in tumor classifications can be challenging. Although deep learning models have been extensively studied for tumor classification, their indirect and subjective interpretation obstructs pathologists from comprehending the model and discerning the morphological features accountable for classifications. In this study, we introduce a new approach utilizing Style Generative Adversarial Networks, which enables a direct interpretation of deep learning models to detect significant morphological characteristics within datasets representing patients with deficient mismatch repair/microsatellite instability-high gastric cancer. Our approach effectively identifies distinct morphological features crucial for tumor classification, offering valuable insights for pathologists to enhance diagnostic accuracy and foster professional growth.

Failure of any of the drive systems in a Four-Wheel Independent Drive (4WID) electric vehicle may affect the control performance and driving safety of the whole vehicle. Therefore, in this paper, a fault-tolerant controller (FTC) for 4WID electric vehicles considering drive actuator failures is proposed. First, a comprehensive characterization of multiple fault types is achieved by establishing a generalized fault model and designing a comprehensive fault factor. Second, based on the comprehensive fault factor, an LPV model with faults is constructed. Further, a fault-tolerant controller based on LPV/H∞ output feedback is designed by combining the weighting function. Finally, the effectiveness of the FTC in this paper is verified by simulation and hardware-in-the-loop (HIL) experiments. The experimental results show that the FTC designed in this paper can improve the stability of the vehicle traveling while ensuring tracking accuracy when the drive system fails.

Obg-like ATPase 1 (OLA1) is a member of the Obg family of P-loop NTPases and has recently been detected in several human cancer cells. However, its expression type and clinical relevance in gastric cancer remains unclear. In the present study, mRNA level of OLA1 in gastric cancer (GC) was detected in 2 datasets downloaded from the open Gene Expression Omnibus database and 30 cancer tissues. Immunohistochemistry was performed on GC and its association with Snail in 334 GC patients. The results showed that OLA1 mRNA and protein were elevated in GC tissues. High expression of OLA1 was significantly associated with aggressive features, such as tumour size, lymph-node-metastasis and tumour-nodus-metastases stage ( p = 0.0146, p = 0.0037, p < 0.001, respectively). Moreover, high levels of OLA1 predicted worse overall survival. Multivariate Cox regression analysis indicated that high expression of OLA1 was an independent prognostic factor for poor overall survival ( p = 0.009). Additionally, OLA1 expression was positively correlated with Snail, and a combination of them revealed improved prognostic accuracy for GC patients. High expression of OLA1 predicts poor prognosis in GC patients and may be serviced as a novel target for GC.

AbstractSince the outbreak and spread of COVID-19 all over the world, many countries, including China, are taking measures for epidemic prevention and control, and some measures require citizens to provide personal privacy information. In the era of big data, it is worth paying attention to how people view the collection of personal privacy data under the special background that China collects personal information to better fight against the COVID-19 epidemic. In particular, it is of great significance and value to explore the privacy concept of Chinese higher education groups, the most important participants in the era of big data in China. This study focuses on the privacy concept of Chinese higher education groups under the background of COVID-19 epidemic, and higher education groups from 19 provinces, 4 municipalities and 4 autonomous regions are selected as research samples. Through questionnaire survey and statistical analysis, individual privacy sensitivity, individual privacy deliver willingness, individual privacy security and other issues of Chinese higher education groups under the COVID-19 epidemic situation are discussed. And this study tries to explore the influencing factors behind it. It is found that Chinese higher education groups generally have high privacy sensitivity and high perception of privacy risk. However, in the special period of fighting against the COVID-19 epidemic, Chinese higher education groups generally have a high willingness to deliver private information and a high privacy security. In addition, education level, discipline background and parents’ education level are important factors affecting the privacy concept of Chinese higher education groups.

Early-life exposure to maternal obesity predisposes offspring to metabolic-associated fatty liver disease (MAFLD). This study aimed to determine if peripartum weight loss, either through dietary intervention or pharmacological intervention, improved adverse liver health outcomes in the offspring of mothers with obesity. C57Bl/6 dams were fed a chow diet or a high-fat diet (HFD) for 8 weeks. HFD-fed mice either continued HFD, transitioned to a chow diet, or were administered liraglutide for 4 weeks. Pregnancy was induced following a one-week washout of liraglutide during which all animals remained on their respective diets. A proportion of HFD-fed mice transitioned to a chow diet during pregnancy. All offspring were weaned to the HFD. Offspring anthropometric, metabolic, and hepatic outcomes were assessed at postnatal week 12. The offspring of mothers with obesity had phenotypic changes consistent with MAFLD. The offspring of mothers that had weight loss with perinatal dietary intervention had reduced insulin resistance (p < 0.001) and hepatic expression of markers of inflammation (p < 0.001), oxidative stress (p < 0.05), and fibrosis (p < 0.05). A similar phenotype was observed in the offspring of mothers with pre-pregnancy weight loss via liraglutide despite ongoing consumption of the HFD during pregnancy. All methods and timing of maternal weight intervention were effective at ameliorating adverse liver effects in the offspring.

Intelligent driving vehicles require more accurate and stable braking control. Electrohydraulic braking (EHB) systems can better adapt to the development of autonomous driving technology. The gear transmission system plays a crucial role in EHB deceleration and torque increase mechanisms. However, its dead-zone nonlinearity poses challenges for EHB control. To address the position-control problem in the EHB gear transmission system, we propose a finite-time adaptive control method for the symmetrical dead zone. This approach combines adaptive control theory with finite-time control theory and designs parameter-updating laws for the unknown parameters in the system. Boundary estimates are introduced into the parameter-update laws and control laws to compensate for unknown disturbances. By adjusting the relevant parameters, the convergence rate can be improved, ensuring that errors converge within a specified range within a limited time. After modifying the parameter-updating laws and control laws, all closed-loop signals remain bounded. Finally, we validate the proposed control strategy through simulation and hardware-in-the-loop (HIL) testing. The results demonstrate that the control strategy developed in this study achieves high tracking accuracy and stability even in the presence of dead zones, unknown parameters, and unknown interferences in the EHB gear-drive servo system.

Epstein–Barr virus-associated gastric cancer shows a robust response to immune checkpoint inhibitors. Here the authors introduce a deep convolutional neural network and its fusion with pathologists for predicting it from histopathology.

Hydrogel, a material with outstanding biocompatibility and shape deformation ability, has recently become a hot topic for researchers studying innovative functional materials due to the growth of new biomedicine. Due to their stimulus responsiveness to external environments, hydrogels have progressively evolved into “smart” responsive (such as to pH, light, electricity, magnetism, temperature, and humidity) materials in recent years. The physical and chemical properties of hydrogels have been used to construct hydrogel micro-nano robots which have demonstrated significant promise for biomedical applications. The different responsive deformation mechanisms in hydrogels are initially discussed in this study; after which, a number of preparation techniques and a variety of structural designs are introduced. This study also highlights the most recent developments in hydrogel micro-nano robots’ biological applications, such as drug delivery, stem cell treatment, and cargo manipulation. On the basis of the hydrogel micro-nano robots’ current state of development, current difficulties and potential future growth paths are identified.

Chronic kidney disease (CKD) is rising in global prevalence and has become a worldwide public health problem, with adverse outcomes of kidney failure, cardiovascular disease, and premature death. However, current treatments are limited to slowing rather than reversing disease progression or restoring functional nephrons. Hence, innovative strategies aimed at kidney tissue recovery hold promise for CKD therapy. Mesenchymal stem cells (MSCs) are commonly used for regenerative therapy due to their potential for proliferation, differentiation, and immunomodulation. Accumulating evidence suggests that the therapeutic effects of MSCs are largely mediated by paracrine secretion of extracellular vesicles (EVs), predominantly exosomes. MSC-derived exosomes (MSC-Exos) replicate the functions of their originator MSCs via delivery of various genetic and protein cargos to target cells. More recently, MSC-Exos have also been utilized as natural carriers for targeted drug delivery. Therapeutics can be effectively incorporated into exosomes and then delivered to diseased tissue. Thus, MSC-Exos have emerged as a promising cell-free therapy in CKD. In this paper, we describe the characteristics of MSC-Exos and summarize their therapeutic efficacy in preclinical animal models of CKD. We also discuss the potential challenges and strategies in the use of MSC-Exos-based therapies for CKD in the future.

The G protein–coupled CXC chemokine receptor 4 (CXCR4) is a candidate therapeutic target for tissue fibrosis. A fully human single-domain antibody-like scaffold i-body AD-114-PA600 (AD-114) with specific high binding affinity to CXCR4 has been developed. To define its renoprotective role, AD-114 was administrated in a mouse model of renal fibrosis induced by folic acid (FA). Increased extracellular matrix (ECM) accumulation, macrophage infiltration, inflammatory response, TGF-β1 expression, and fibroblast activation were observed in kidneys of mice with FA-induced nephropathy. These markers were normalized or partially reversed by AD-114 treatment. In vitro studies demonstrated AD-114 blocked TGF-β1–induced upregulated expression of ECM, matrix metalloproteinase-2, and downstream p38 mitogen-activated protein kinase (p38 MAPK) and PI3K/AKT/mTOR signaling pathways in a renal proximal tubular cell line. Additionally, these renoprotective effects were validated in a second model of unilateral ureteral obstruction using a second generation of AD-114 (Fc-fused AD-114, also named AD-214). Collectively, these results suggest a renoprotective role of AD-114 as it inhibited the chemotactic function of CXCR4 as well as blocked CXCR4 downstream p38 MAPK and PI3K/AKT/mTOR signaling, which establish a therapeutic strategy for AD-114 targeting CXCR4 to limit renal fibrosis.

Abstract Background Neuromedin U (NMU) is a neuropeptide belonging to the neuromedin family. Recently, significant associations between NMU and several cancers have been reported. However, no studies have examined the association between NMU and hepatocellular carcinoma (HCC). The purpose of this study was to examine the role of NMU in HCC. Methods An enzyme-linked immunosorbent assay was used to measure the level of NMU protein in the sera of patients with hepatic hemangioma and HCC. NMU and cytokine mRNA expression was assessed in HCC samples via RT-qPCR. A tissue microarray consisting of 228 HCC peri- and intra-tumor tissues was used to detect NMU expression via immunohistochemical analysis. The association between NMU expression and overall survival (OS) and disease-free survival (DFS) was analyzed by Kaplan-Meier curves, the log-rank test, and Cox proportional hazard model. Results The level of NMU protein was increased in the sera of HCC patients (p = 0.006). NMU was expressed in intercellular space, rather than in hepatocytes or HCC cells. The prognosis of HCC patients with high NMU expression in peri-tumor tissue was significantly poorer than that of patients with low NMU expression (OS: p = 0.002, DFS: p = 0.033). Peri-tumor NMU expression was also a significant independent prognostic factor for OS (hazard ratio: 1.541, 95% confidence interval: 1.092–2.175, p = 0.014). The level of NMU expression was positively associated with M2 macrophage percentage and the levels of type-2 inflammatory cytokines in HCC tissue. Conclusions NMU may serve as a novel prognostic biomarker for HCC patients, although further validation is needed in the future. The activation of M2 macrophages and a type-2 inflammatory response may involve in the role of NMU in patients with HCC.

In this article, three kinds of cellulose carbonated derivatives are synthesized by modifying cellulose with alkyl halides (namely bromopropane, benzyl bromide and bromomethyl cyclopropane) in DBU/DMSO/CO2 system. The wet spinnability and filament properties of the obtained cellulose carbonated derivatives are investigated. Through rheological analysis, the solutions of various cellulose carbonated derivative in Newtonian fluid state can show good wet spinnability. Filaments with smooth surface and uniform morphology can be obtained from the solution with viscosity over 0.07Pa•s. The cellulose carbonated derivatives in the filament show similar in tight orderly rows. Among them, the cellulose propyl carbonated derivative filament exhibits the highest mechanical properties and heat resistance. By using of DBU/DMSO/CO2 system, the wet spinning and key control condition of cellulose carbonated derivatives are combined to achieve for the formation of filament with uniform morphology.

Pathological MVI diagnosis could help to determine the prognosis and need for adjuvant therapy in hepatocellular carcinoma (HCC). However, narrative reporting (NR) would miss relevant clinical information and non-standardized sampling would underestimate MVI detection. Our objective was to explore the impact of innovative synoptic reporting (SR) and seven-point sampling (SPRING) protocol on microvascular invasion (MVI) rate and patient outcomes. In retrospective cohort, we extracted MVI status from NR in three centers and re-reviewed specimen sections by SR recommended by the College of American Pathologists (CAP) in our center. In prospective cohort, our center implemented the SPRING protocol, and external centers remained traditional pathological examination. MVI rate was compared between our center and external centers in both cohorts. Recurrence-free survival (RFS) before and after implementation was calculated by Kaplan-Meier method and compared by the log-rank test. In retrospective study, we found there was no significant difference in MVI rate between our center and external centers [10.3% (115/1112) vs. 12.4% (35/282), P=0.316]. In our center, SR recommended by CAP improved the MVI detection rate from 10.3 to 38.6% (P

The present work aims to explore the psychological quality and quality of college students' entrepreneurship under higher education and moral education. First, relationships among entrepreneurial traits, entrepreneurial self-efficacy, entrepreneurial alertness, and entrepreneurial attitude are analyzed through questionnaire surveys and statistics. Second, the role of college students' entrepreneurial attitudes in improving entrepreneurial self-efficacy and entrepreneurial alertness is discussed. Eventually, the relationship mechanism of entrepreneurial self-efficacy and entrepreneurial alertness in entrepreneurial traits and entrepreneurial attitude is explored. Results demonstrate: (1) the mediating effect through the entrepreneurial self-efficacy reaches 36.91%; (2) the mediating effect through entrepreneurial alertness accounts for 38.72%; (3) the mediating effect through entrepreneurial self-efficacy and entrepreneurial alertness reaches 9.15%. Therefore, the entrepreneurial traits of college students affect their entrepreneurial attitude through two intermediary paths: entrepreneurial self-efficacy and entrepreneurial alertness. Data comparison suggests that the entrepreneurial traits of college students are significantly positively correlated to entrepreneurial attitudes; the entrepreneurial self-efficacy of college students is significantly positively correlated to entrepreneurial attitude; the entrepreneurial alertness of college students is significantly positively correlated to entrepreneurial attitudes. College students' entrepreneurial self-efficacy plays a mediating role in the relationship between entrepreneurial traits and entrepreneurial attitude, and college students' entrepreneurial alertness plays a mediating role in the relationship between entrepreneurial traits and entrepreneurial attitude.

Abstract Background Gut microbiota and the tumor microenvironment are thought to be critical factors that modulate the processes of liver diseases, including hepatocellular carcinoma (HCC). Interleukin-25 (IL-25) promotes type 2 immunity via alternative activation of macrophages, and is closely associated with inflammation-related diseases, even malignancies. However, it is not clear which role IL-25 plays in the development of HCC, and whether gut microbiota are involved. Methods IL-25 was detected by ELISA, Western blotting (WB), and immunohistochemistry. Chemokines were measured by RT-qPCR and WB. After co-culture with IL-25-stimulated macrophages, the cell growth, migration, invasion and EMT marker of HCC cell lines (MHCC97L and HepG2) were evaluated by Brdu proliferation, Transwell assays and WB. An antibody neutralization assay of chemokine CXCL10 was performed to confirm its role in HCC development. Furthermore, the effects of IL-25 in HCC were investigated in vivo. Dysbiosis of gut microflora was induced by antibiotics (vancomycin, cefoperazone or combination of ampicillin, neomycin, metronidazole, and vancomycin). We used feces suspension to treat colonic epithelial NCM460 cells, and detected IL-25 and tuft cell marker DCLK1 using WB and immunofluorescence staining. Results We found that the level of IL-25 was significantly elevated in HCC patients, and was negatively correlated with survival rate after hepatectomy. However, IL-25 did not directly promote the development of HCC cells. Then, we observed the significant positive correlation between IL-25 level and M2 percentage (CD206/CD68) in HCC tumors. In vitro and in vivo, IL-25 induced alternative activation of macrophages promoted HCC cell migration, invasion and tumorigenesis, increased the expression of vimentin, Snail and phospho-ERK, and decreased the expression of E-cadherin in HCC cells. After IL-25 treatment, chemokine CXCL10 was increased in macrophages. Neutralizing CXCL10 in macrophage-conditioned medium reversed the IL-25-mediated effect on HCC cells. Vancomycin-induced dysbiosis promoted the growth of orthotopic HCC homograft. Surprisedly, we found the hyperplasia of colonic epithelial tuft cells, from which more IL-25 was secreted . Conclusions IL-25 promotes the progression of HCC through inducing alternative activation and CXCL10 secretion of macrophages in tumor microenvironment, and IL-25 secretion may partly result from hyperplastic epithelial tuft cells in colon, induced by gut microbiota dysbiosis.

Abstract Diabetic kidney disease (DKD) is a life‐limiting condition characterized by progressive and irreversible loss of renal function. Currently, the estimated glomerular filtration rate (eGFR) and albuminuria are used as key markers to define DKD. However, they may not accurately indicate the degree of renal dysfunction and injury. Current therapeutic approaches for DKD, including attainment of blood pressure goals, optimal control of blood glucose and lipid levels, and the use of agents to block the renin‐angiotensin‐aldosterone system (RAAS) can only slow the progression of DKD. Hence, early diagnosis and innovative strategies are needed to both prevent and treat DKD. In recent years, a novel class of noncoding RNA, microRNAs (miRNAs) are reported to be involved in all biological processes, including cellular proliferation, apoptosis, and differentiation. miRNAs are small noncoding RNAs that regulate gene expression by posttranscriptional and epigenetic mechanisms. They are found to be in virtually all body fluids and used successfully as biomarkers for various diseases. Urinary miRNAs correlate with clinical and histologic parameters in DKD and differential urinary miRNA expression patterns have been reported. Kidney fibrosis is the common end stage of various CKD including DKD. Transforming growth factor‐β(TGF‐β) is regarded as the master regulator of kidney fibrosis, which is likely at least in part through regulating miRNA expression. miRNA are widely involved in the progression of DKD via many molecular mechanisms. In this review, the involvement of miRNA in fibrosis, inflammation, hypertrophy, autophagy, endoplasmic reticulum (ER) stress, oxidative stress, insulin resistance, and podocyte injury will be discussed, as these mechanisms are believed to offer new therapeutic targets that can be exploited to develop important treatments for DKD over the next decade.

In this paper, an enabling multi-operation branch-line coupler is proposed initially. The proposed design is configured by ±90° and 180° transmission lines, and the main advantage is that the proposed design can be applied in three different system connection schemes as shown in Fig. 1. Corresponding to the three schemes, the coupler can be with three operations (e.g. the operations of balanced input with single-ended outputs, single-ended input with single-ended outputs, and single-ended input with balanced and single-ended outputs). This can increase the flexibility and freedom of the coupler for systems with different connection types. Furthermore, the common-mode suppression can be achieved under the operation. The standard and mixed-mode S-parameters are utilized to deduce the circuit parameters. Two prototypes using 3/4 λg (λg is the guided wavelength at the center frequency) transmission line (design I) and coupled line with two shorts (design II) to realize the -90° transmission line were designed, fabricated, and measured to verify the theoretical prediction. The sizes of the two prototypes are 0.98 λg × 0.2λg and 0.65λg × 0.2λg, respectively. Design I (design II) exhibits the 15-dB operating bandwidths for the three operations of 8% (9%), 7.3% (9%), and 6.7% (7.8%), respectively.

Purpose: To compare the reliability and performance of Supersonic shear wave elastography (S-SWE) and Toshiba shear wave elastography (T-SWE) in the diagnosis of biliary atresia (BA) and assessment of liver fibrosis among jaundiced infants suspected of BA. Material and Methods: A total of 35 patients with suspected BA who underwent both S-SWE and T-SWE examinations were prospectively included. Diagnostic performances of S-SWE and T-SWE in identifying BA were evaluated. The correlation between two types of SWE values and histological liver fibrosis stages by Metavir scores were investigated in 21 patients with pathology results. The intraclass correlation coefficients (ICCs) were calculated in 16 patients for inter- and intra-observer agreement. The area under the receiver operating characteristic curve (AUC) analysis was compared using a DeLong test. Results: There were 22 patients with BA and 13 patients without BA. The diagnostic performance of S-SWE was comparable to that of T-SWE (AUC 0.895 vs. 0.822, p = 0.071) in diagnosing BA. The AUCs of S-SWE in predicting liver fibrosis stages were from 0.676 to 1.000 and showed no statistical differences from that of T-SWE (from 0.704 to 1.000, all p > 0.05). T-SWE provided higher inter-operator agreement (ICC 0.990) and intra-operator agreement (ICCs 0.966–0.993), compared with that of S-SWE in a previous study (ICC 0.980 for inter-operator and 0.930–0.960 for intra-operator). Conclusions: For infants suspected of BA, T-SWE had good performances in the diagnosis of BA and the assessment of liver fibrosis compared with S-SWE. Furthermore, T-SWE showed higher measurement reproducibility than S-SWE.

It is well-known that all progressive chronic kidney disease (CKD) is pathologically characterized by tubulointerstitial fibrosis process. Multiple studies have shown the critical role of inflammation and fibrosis in the development of CKD. Hence strategies that target inflammatory and fibrotic signaling pathways may provide promising opportunities to protect against renal fibrosis. Metformin has been used as the first-line glucose-lowering agent to treat patients with type 2 diabetes mellitus (T2DM) for over 50 years. Accumulating evidence suggests the potential for additional therapeutic applications of metformin, including mitigation of renal fibrosis. In this study, the anti-fibrotic effects of metformin independent of its glucose-lowering mechanism were examined in an adenine -induced mouse model of CKD. Expressions of inflammatory markers MCP-1, F4/80 and ICAM, fibrotic markers type IV collagen and fibronectin, and the cytokine TGF-β1 were increased in adenine-induced CKD when compared to control groups and significantly attenuated by metformin treatment. Moreover, treatment with metformin inhibited the phosphorylation of Smad3, ERK1/2, and P38 and was associated with activation of the AMP-activated protein kinase (AMPK) in the kidneys of adenine-treated mice. These results indicate that metformin attenuates adenine-induced renal fibrosis through inhibition of TGF-β1 signaling pathways and activation of AMPK, independent of its glucose-lowering action.

Mitochondrial dysfunction is implicated in the pathogenesis of diabetic kidney disease. Mitochondrial quality control is primarily mediated by mitochondrial turnover and repair through mitochondrial fission/fusion and mitophagy. We have previously shown that blockade of the calcium-activated potassium channel KCa3.1 ameliorates diabetic renal fibrosis. However, the mechanistic link between KCa3.1 and mitochondrial quality control in diabetic kidney disease is not yet known. Transforming growth factor β1 (TGF-β1) plays a central role in diabetic kidney disease. Recent studies indicate an emerging role of TGF-β1 in the regulation of mitochondrial function. However, the molecular mechanism mediating mitochondrial quality control in response to TGF-β1 remains limited. In this study, mitochondrial function was assessed in TGF-β1-exposed renal proximal tubular epithelial cells (HK2 cells) transfected with scrambled siRNA or KCa3.1 siRNA. In vivo, diabetes was induced in KCa3.1+/+ and KCa3.1−/− mice by low-dose streptozotocin (STZ) injection. Mitochondrial fission/fusion-related proteins and mitophagy markers, as well as BCL2 interacting protein 3 (BNIP3) (a mitophagy regulator) were examined in HK2 cells and diabetic mice kidneys. The in vitro results showed that TGF-β1 significantly inhibited mitochondrial ATP production rate and increased mitochondrial ROS (mtROS) production when compared to control, which was normalized by KCa3.1 gene silencing. Increased fission and suppressed fusion were found in both TGF-β1-treated HK2 cells and diabetic mice, which were reversed by KCa3.1 deficiency. Furthermore, our results showed that mitophagy was inhibited in both in vitro and in vivo models of diabetic kidney disease. KCa3.1 deficiency restored abnormal mitophagy by inhibiting BNIP3 expression in TGF-β1-induced HK2 cells as well as in the diabetic mice. Collectively, these results indicate that KCa3.1 mediates the dysregulation of mitochondrial quality control in diabetic kidney disease.

When a working face is crossing the abandoned roadways, problems such as roof subsidence, rock fracture, and instability will occur, resulting in widespread roof fall and rib spalling, which seriously affect safe and efficient mining on the working face. In this paper, the no. 23 coal pillar working face of Juji coal mine is taken as the engineering background, a mechanical model of crossing the abandoned roadways is constructed aimed at the problem of the working face crossing the abandoned roadway group, the collapse of the abandoned roadway roof is analyzed, a scheme of crossing the abandoned roadways is designed, and the development law of the stress and plastic zone after the reinforcement scheme is stimulated and analyzed. The results show that when the working face advances to the abandoned roadway, key block B crosses the abandoned roadway and the solid coal to form a “cross-roadway long key block.” It is calculated that the minimum support resistance required for the abandoned roadway is 6700 kN. Based on the results of numerical comparison, it is concluded that filling wood pile when the working face passes through the roof abandoned roadway and adding anchor cables for reinforcement support when the working face crosses the coal seam abandoned roadway effectively reduce the stress concentration of surrounding rocks, decrease the development of the plastic zone, and achieve safe and efficient mining when the working face crosses the abandoned roadways.

Background: Zymomonas mobilis is a Gram-negative microaerophilic bacterium with excellent ethanol-producing capabilities. The RecET recombination system provides an efficient tool for direct targeting of genes in the bacterial chromosome by PCR fragments. Results: The plasmids pSUZM2a-RecET and pSUZM2a-RecE588T were first developed to co-express RecE or RecE588 and RecT for homologous recombination. Thereafter, the PCR fragments of the tetracycline resistance marker gene flanked by 60 bp of adhA (alcohol dehydrogenase I) or adhB (alcohol dehydrogenase II) homologous sequences were electroporated directly into ZM4 cells harboring pSUZM2a-RecET or pSUZM2a-RecE588T. Both adhA and adhB were replaced by the tetracycline resistance gene in ZM4, yielding two mutant strains, Z. mobilis ZM4 ΔadhA and Z. mobilis ZM4 ΔadhB. These two mutants showed varying extent of reduction in ethanol production, biomass generation, and glucose metabolism. Furthermore, enzyme activity of alcohol dehydrogenase II in Z. mobilis ZM4 ΔadhB exhibited a significant reduction compared to that of wild-type ZM4. Conclusion: This approach provided a simple and useful method for introducing mutations and heterologous genes in the Z. mobilis genome. Keywords: Dehydrogenase gene, Electroporation, Ethanol, Genetic manipulation, Gram negative, Industrial applications, Knock-out, Primer, Production, Recombination, Vector

In this study, we investigated the utility of native T1 mapping in differentiating between various grades of fibrosis and compared its diagnostic accuracy to magnetization transfer imaging (MTI) in a rat model of CD. Bowel specimens (64) from 46 CD model rats undergoing native T1 mapping and MTI were enrolled. The longitudinal relaxation time (T1 value) and normalized magnetization transfer ratio (MTR) were compared between none-to-mild and moderate-to-severe fibrotic bowel walls confirmed by pathological assessments. The results showed that the correlation between the T1 value and fibrosis (r = 0.438, p < 0.001) was lower than that between the normalized MTR and fibrosis (r = 0.623, p < 0.001). Overall, the T1 values (t = −3.066, p = 0.004) and normalized MTRs (z = 0.081, p < 0.001) in none-to-mild fibrotic bowel walls were lower than those in moderate-to-severe fibrotic bowel walls. The area under the curve (AUC) of the T1 value (AUC = 0.716, p = 0.004) was significantly lower than that of the normalized MTR (AUC = 0.881, p < 0.001) in differentiating moderate-to-severe fibrosis from none-to-mild fibrosis (z = −2.037, p = 0.042). Our results support the view that the T1 value could be a promising imaging biomarker in grading the fibrosis severity of CD. However, the diagnostic performance of native T1 mapping was not superior to MTI.

Mitochondria are critical organelles that play a key role in cellular metabolism, survival, and homeostasis. Mitochondrial dysfunction has been implicated in the pathogenesis of diabetic kidney disease. The function of mitochondria is critically regulated by several mitochondrial protein kinases, including the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1). The focus of PINK1 research has been centered on neuronal diseases. Recent studies have revealed a close link between PINK1 and many other diseases including kidney diseases. This review will provide a concise summary of PINK1 and its regulation of mitochondrial function in health and disease. The physiological role of PINK1 in the major cells involved in diabetic kidney disease including proximal tubular cells and podocytes will also be summarized. Collectively, these studies suggested that targeting PINK1 may offer a promising alternative for the treatment of diabetic kidney disease.

Background: Zymomonas mobilis, as a novel platform for bio-ethanol production, has been attracted more attention and it is very important to construct vectors for the efficient expression of foreign genes in this bacterium. Results: Three shuttle vectors (pSUZM1, pSUZM2 and pSUZM3) were first constructed with the origins of replication from the chromosome and two native plasmids (pZZM401 and pZZM402) of Z. mobilis ZM4, respectively. The three shuttle vectors were stable in Z. mobilis ZM4 and have 3, 32 and 27 copies, respectively. The promoter Ppdc (a), from the pyruvate decarboxylase gene, was cloned into the shuttle vectors, generating the expression vectors pSUZM1(2, 3)a. The codon-optimized glucoamylase gene from Aspergillus awamori combined with the signal peptide sequence from the alkaline phosphatase gene of Z. mobilis was cloned into pSUZM1(2, 3)a, resulting in the plasmids pSUZM1a-GA, pSUZM2a-GA and pSUZM3a-GA, respectively. After transforming these plasmids into Z. mobilis ZM4, the host was endowed with glucoamylase activity for starch hydrolysis. Both pSUZM2a-GA and pSUZM3a-GA were more efficient at producing glucoamylase than pSUZM1a-GA. Conclusions: These results indicated that these expression vectors are useful tools for gene expression in Z. mobilis and this could provide a solid foundation for further studies of heterologous gene expression in Z. mobilis.

A magnetostrictive bioinspired whisker sensor based on a galfenol/beryllium-bronze/galfenol composite cantilever beam was developed in this work. According to the new design concept, the proposed whisker can output positive and negative voltages under different bending directions. Besides, the proposed whisker sensor can realize the bidirectional distance and microforce perception. Using the classical beam theory, a theoretical model was used to predict the output performance of the whisker. An experimental system was established to test the whisker’s output performance. In the experiment, the designed whisker, compared with a traditional unimorph whisker, displayed an output voltage range of −240 to 240 mV. The parameters were as follows: the distance was 0–22 mm, with the microforce sensing range of 9.8–2744 mN, the average distance was 10.90 mm/mV, and the force sensitivity was 11.4 mN/mV. At last, obstacle perception was applied. The experiment showed that the proposed whisker sensor can realize the bidirection tactile perception in one-dimensional space. The work expands the function of the magnetostrictive bioinspired whisker, acquiring the multi-information for single-sensor system.

Zymomonas mobilis has the special Entner-Doudoroff (ED) pathway and it has excellent industrial characteristics, including low cell mass formation, high-specific productivity,ethanol yield, notable ethanol tolerance and wide pH range, a relatively small genome size. In this study, the genome sequences of NRRL B-14023 and NRRL B-12526 were sequenced and compared with other strains to explore their evolutionary relationships and the genetic basis of Z. mobilis. The comparative genomic analyses revealed that the 8 strains share a conserved core chromosomal backbone. ZM4, NRRL B-12526, NRRL B-14023, NCIMB 11163 and NRRL B-1960 share 98% sequence identity across the whole genome sequences. Highly similar plasmids and CRISPR repeats were detected in these strains. A whole-genome phylogenetic tree of the 8 strains indicated that NRRL B-12526, NRRL B-14023 and ATCC 10988 had a close evolutionary relationship with the strain ZM4. Furthermore, strains ATCC29191 and ATCC29192 had distinctive CRISPR with a far distant relationship. The size of the pan-genome was 1945 genes, including 1428 core genes and 517 accessory genes. The genomes of Z. mobilis were highly conserved; particularly strains ZM4, NRRL B-12526, NRRL B-14023, NCIMB 11163 and NRRL B-1960 had a close genomic relationship. This comparative study of Z. mobilis presents a foundation for future functional analyses and applications.

A magnetostrictive cantilever beam model is established by combining an energy-based constitutive magnetostrictive model with the classical Euler-Bernoulli beam theory constitutive relations that describe the material behavior are based on energy minimization techniques. We use the saturation magnetization, the magnetostrictive constant and the 4th and 6th order anisotropy constants to calculate the Zeeman, stress-induced anisotropy and magnetocrystalline anisotropy energies per unit volume. The stress of the magnetostrictive cantilever beam is solved by classical beam theory. Experiments and simulations are conducted to study performance of the cantilever. The results demonstrated the sensing is primarily due to the dominating effect of compression over tension. A critical bias magnetic field is required below which the magnetostrictive sensing cannot be observed under bending.

A nonlinear modeling of magnetostrictive cantilever beam actuators is proposed by integrating an energy-based constitutive magnetostrictive model with the classical laminated beam theory in this article. The composite stiffness and the magnetic field are identified as the critical parameters which significantly influence the performance of the cantilever beam. Detailed experimental studies are carried out with different applied magnetic fields and various cantilever beam thicknesses. The experimental results verified the nonlinearity of the magnetomechanical response of the structure.

Purpose. To investigate the expression of TSP50 protein in human gastric cancers and its correlation with clinical/prognostic significance. Methods. Immunohistochemistry (IHC) analysis of TSP50 was performed on a tissue microarray (TMA) containing 334 primary gastric cancers. Western blot was carried out to confirm the expression of TSP50 in gastric cancers. Results. IHC analysis revealed high expression of TSP50 in 57.2% human gastric cancer samples (191 out of 334). However, it was poorly expressed in all of the 20 adjacent nontumor tissues. This was confirmed by western blot, which showed significantly higher levels of TSP50 expression in gastric cancer tissues than adjacent nontumor tissues. A significant association was found between high levels of TSP50 and clinicopathological characteristics including junior age at surgery (P=0.001), later TNM stage (P=0.000), and present lymph node metastases (P=0.003). The survival of gastric cancer patients with high expression of TSP50 was significantly shorter than that of the patients with low levels of TSP50 (P=0.021). Multivariate Cox regression analysis indicated that TSP50 overexpression was an independent prognostic factor for gastric cancer patients (P=0.017). Conclusions. Our data demonstrate that elevated TSP50 protein expression could be a potential predictor of poor prognosis in gastric cancer patients.

Objective: Circular RNAs (circRNAs) have been shown to involve in pathological processes of ischemic stroke (IS), including autophagy. This study was designed to explore the effect of circR-ZC3HC1 on neuronal autophagy in IS and the related mechanisms. Methods: Expression of circR-ZC3HC1 in blood samples of IS patients and healthy controls was detected. Hippocampal neurons were treated with oxygen and glucose deprivation (OGD) to establish IS in vitro model. The expression of LC3 and p62 and the number of autophagosomes were examined to evaluate the autophagy level of OGD induced neurons using western blotting and transmission electron microscope. Cell apoptosis rate and the expression of cleaved caspase-3, Bax, and Bcl-2 were assessed by flow cytometry and western blotting. The binding relationships among circR-ZC3HC1, miR-384-5p, and SIRT1 were predicted and verified. Results: Low expression of circR-ZC3HC1 was found in blood samples of IS patients and OGD-treated neurons. Overexpressed circR-ZC3HC1 or inhibited miR-384-5p expression promoted autophagy and inhibited apoptosis of OGD-treated neurons, which could be reversed by further 3-MA treatment. Mechanistically, circR-ZC3HC1 targeted miR-384-5p to mediate SIRT1 expression. miR-384-5p overexpression or SIRT1 knockdown in the presence of circR-ZC3HC1 overexpression in OGD-treated neurons lead to reduced autophagy and enhanced apoptosis. Conclusion: Collectively, circR-ZC3HC1 promoted neuronal autophagy to attenuate IS via miR-384-5p/SIRT1 axis. [ABSTRACT FROM AUTHOR]