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Abstract Background Yiganling (YGL) capsule is a traditional Chinese medicine preparation consisting of eight herbs that has been clinically proven to have a favorable treatment effect on Hepatitis B (HB). However, due to its multiple targets and multi-pharmacological effects, the mechanisms of YGL capsule in the treatment of HB are unknown. Methods First, the chemical constituents of YGL capsules were obtained from the Chinese medicine database, and YGL capsules were constructed. Second, active compounds were screened by the ADME model. The target fishing model was used to screen the corresponding targets of active compounds and to construct a compounds and compound targets network. Using human disease databases and literature mining, we systematically identified genes associated with HB, constructed disease-specific protein-protein interaction networks, and performed clustering and enrichment analyses of these networks. These networks were then merged to obtain a compound-disease target network, and cluster and enrichment analyses were performed on the compound-disease target network to acquire a compounds-disease targets-mechanism network and a clustering network. Results We successfully built eight pharmacological network diagrams, including four primary networks and other network maps. The four dominating network maps included a HB disease-associated protein-protein interaction network, a YGL capsule compounds-target network, a YGL capsule ingredient target-HB disease target network, and a YGL-HB disease mechanism network. Other networks included a pathway of HB disease targets, the HB disease protein-protein interaction cluster analysis network, and the YGL-HB target clustering network. Conclusion This study successfully forecasted, illuminated, and confirmed the synergistic effects of HB disease molecules and discovered the potential of HB relevant targets, clusters, and target-related biological processes and signaling pathways. Our research not only provides theoretical support for the molecular and pharmacological mechanisms of YGL capsule in HB treatment, but also provides new research methods for the study of the other traditional Chinese medicinal compounds.

Nuclear Power Plant (NPP) have increasing demand to improve safety and reliability of air compressors with various fault diagnosis methods. Fault diagnosis methods may provide early fault warning information for air compressors rapidly and give a reference for maintenance, especially for the serious faults affecting security strongly. In this work, a method framework of fault diagnosis system based on the Vibration Observation Window (VOW) for air compressors is proposed. The VOW constructs a dynamic vibration tensor which presents the operating state of air compressors according to the real time vibration data, strengthens the association among the monitoring data in spatial domain and time domain. Thus, dynamic characteristic, which reflects the fault information, can be contained in the dynamic vibration tensor explicitly. For proving the advantage of VOW method, we compare the performance between the fault diagnosis system with VOW and the fault diagnosis system without VOW based on different hardware environments: embedded computer, and high speed Industrial PC. The results show that the VOW method can both improve the performance of the vibration fault diagnosis system of NPPs in different hardware environments.

When antibiotic-resistant pathogenic bacteria pose a high threat to human health, bacterial multidrug efflux pumps become major contributors to the high-level antibiotic resistance in most microorganisms. Since traditional antibiotics are still indispensable currently, we report a dual drug delivery system to maximize the antibacterial efficacy of antibiotics by inhibiting efflux pumps in bacteria before their exposure to antibiotics. In this research, a microsphere/hydrogel composite was constructed from ciprofloxacin (Cip)-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres and ginsenoside Rh2 (G-Rh2) dispersed thermo-sensitive hydrogel to treat skin infections. In vitro drug release studies indicated that while G-Rh2 in hydrogel presented a faster and short-term release manner to rapidly inhibit the NorA efflux pumps, Cip showed a sustained and long-term release behavior to provide a local high concentration gradient for facilitating drug percutaneous penetration. The combination of Cip and G-Rh2 demonstrated a high degree of synergism against both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), hence significantly improving their in vitro antibacterial activity and efficiency. Moreover, the antibacterial performance of the microsphere/hydrogel composite with a sequential release profile is superior to that of other formulations in mouse model of MRSA skin infections, indicating its great potential to treat antibiotic-resistant skin infections.

Mesoporous silica with uniform 2-D hexagonal pores has been newly employed as facile reservoir to impove the dissolution rate of water insoluble drugs. However, rapid drug release from mesoporous silica is usually accompanied by the generation of supersaturated solution, which leads to the drug precipitation and compromised absorption. To address this issue, a supersaturated ternary hybrid system was constructed in this study by utilizing inorganic mesoporous silica and organic precipitation inhibitor. Vinylprrolidone-vinylacetate copolymer (PVP VA64) with similar solubility parameter to model drug fenofibrate (FNB) was expected to well inhibit the precipitation. Mesoporous silica Santa Barbara amorphous-15 (SBA-15) was synthesized in acidic media and hybrid matrix was produced by hot melt extrusion technique. The results of in vitro supersaturation dissolution test obviously revealed that the presence of PVP VA64 could effectively sustain a higher apparent concentration. PVP VA64 was suggested to simultaneously reduce the rate of nucleation and crystal growth and subsequently maintain a metastable supersaturated state. The absorption of FNB delivered by the organic-inorganic hybrid matrix was remarkably enhanced in beagle dogs, and its AUC value was 1.92-fold higher than that of FNB loaded mesoporous silica without PVP VA 64. In conclusion, the supersaturated organic-inorganic hybrid matrix can serve as a modular strategy to enhance the oral availability of water insoluble drugs.

Nuclear energy can make an important contribution to low-carbon energy supply for Industry 4.0, while Industry 4.0 can reform this industry in return. As a typical and complex man-machine-network integration system, various faults, insufficient automation and stressed human operators limit the further popularization of nuclear power plants (NPPs) while these issues can be addressed by the aid of artificial intelligence (AI) technologies. In this work, we try to present a systemic review of how AI can benefit NPPs in a top-to-down fashion. We discuss limitations in current NPPs and introduce the concept of Nuclear Power Plant Human-Cyber-Physical System (NPPHCPS) as the top-level design. Then, we category AI-related nuclear power applications into Physical-Plant-Centered and Human-Operator-Centered technologies and review research works from 7 typical NPP functional scenarios in the recent two decades. In each NPP functional scenario, how researchers integrate AI into NPPs is presented following timeline. We hope this review can be used as the guideline for NPPs’ Design in the future and contribute to green Industry 4.0.

The nuclear receptor Pparg regulates urothelial differentiation in vitro but its role in healthy urothelium is unclear. Here, the authors show that PPAR gamma mediates urothelial development during both homeostasis (via mitochondrial function) and following infection, via an inflammatory response.

Abstract Background A growing body of evidence supports the use of laparoscopic pancreaticoduodenectomy (LPD) as an efficient and feasible surgical technique. However, few studies have investigated its applicability in pancreatic ductal adenocarcinoma (PDAC), and the long-term efficacy of LPD on PDAC remains unclear. This study aimed to compare the short- and long-term outcomes between LPD and open pancreaticoduodenectomy (OPD) for PDAC. Methods The data of patients who had OPD or LPD for PDAC between January 2013 and September 2017 were retrieved. Their postoperative outcomes and survival were compared after propensity score matching. Results A total of 309 patients were included. After a 2:1 matching, 93 cases in the OPD group and 55 in the LPD group were identified. Delayed gastric emptying (DGE), particularly grade B/C DGE, occurred less frequently in the LPD group than in the OPD group (1.8% vs. 36.6%, P

Background: Human sinoatrial cardiomyocytes are essential building blocks for cell therapies of conduction system disorders. However, current differentiation protocols for deriving nodal cardiomyocytes from human pluripotent stem cells (hPSCs) are very inefficient. Methods: By employing the hPSCs to cardiomyocyte (CM) in vitro differentiation system and generating E2A-knockout hESCs using CRISPR/Cas9 gene editing technology, we analyze the functions of E2A in CM differentiation. Findings: We found that knockout of the transcription factor E2A substantially increased the proportion of nodal-like cells in hESC-derived CMs. The E2A ablated CMs displayed smaller cell size, increased beating rates, weaker contractile force, and other functional characteristics similar to sinoatrial node (SAN) cells. Transcriptomic analyses indicated that ion channel-encoding genes were up-regulated in E2A ablated CMs. E2A directly bounded to the promoters of genes key to SAN development via conserved E-box motif, and promoted their expression. Unexpect enhanced activity of NOTCH pathway after E2A ablation could also facilate to induct ventricle workingtype CMs reprogramming into SAN-like cells. Interpretation: Our study revealed a new role for E2A during directed cardiac differentiation of hESCs and may provide new clues for enhancing induction efficiency of SAN-like cardiomyocytes from hPSCs in the future. Funding: This work was supported by the NSFC (No.82070391, N.S.; No.81870175 and 81922006, P.L.), the National Key R&D Program of China (2018YFC2000202, N.S.; 2017YFA0103700, P.L.), the Haiju program of National Children's Medical Center EK1125180102, and Innovative research team of high-level local universities in Shanghai and a key laboratory program of the Education Commission of Shanghai Municipality (ZDSYS14005).

Background:. Brachial plexus injury is often debilitating because it can severely impair upper extremity function and, thus, quality of life. The surgical treatment of injuries to the brachial plexus is very demanding because it requires a profound understanding of the anatomy and expertise in microsurgery. The aim of this study was to get an overview of the landscape in adult brachial plexus injury surgery, and to understand how this has changed over the years. Methods:. The most frequently cited articles in English relevant to adult brachial plexus injury were identified through the Web of Science online database. Results:. The average number of citations per article was 32.8 (median 24, range 4–158). Authors from 26 countries contributed to our list, and the US was the biggest contributor. Almost half of all nerve transfer cases were described by Asian authors. Amongst nerve transfer, the spinal accessory nerve was the preferred donor overall, except in Asia, where intercostal nerves were preferred. Distal nerve transfers were described more often than plexo-plexal and extra-plexal-to-plexal transfers. The most common grafts were sural nerve grafts and vascularized ulnar nerve grafts, which became popular in the last decade. Conclusions:. Our study sheds light on the regional variations in treatment trends of adult brachial plexus injury, and on the evolution of the field over the last 30 years. The articles included in our analysis are an excellent foundation for those interested in the surgical management of brachial plexus injuries.

ObjectiveAs a result of the inconsistency between reports, a meta-analysis was designed to appraise the clinical implications of long non-coding RNAs (lncRNAs) in exosomes for the diagnosis of bladder cancer.MethodsThe PubMed, EMBASE, and Cochrane library databases were searched to identify the relevant literature on lncRNAs in exosomes for bladder cancer diagnosis from database inception to May 2021. The literature was screened according to the inclusion and exclusion criteria, and the Quality Assessment of Diagnostic Accuracy Studies-2 entry tool was applied to evaluate the quality of the literature, and the sources of heterogeneity were explored using meta-regression and subgroup analysis. Stata 14.0 and RevMan 5.3 software were used for statistical analysis.ResultsA total of 23 studies described in 10 articles were included, with a total of 1883 patients with bladder cancer and 1721 patients in the non-cancerous control group. The exosome-derived lncRNAs performed better in the diagnosis of bladder cancer with a pooled sensitivity of 0.74 (95% CI, 0.69-0.77), specificity of 0.76 (95% CI, 0.72-0.80), and area under the curve of 0.83. The heterogeneity between studies was partly as a result of differences in specimen type, number of lncRNAs, lncRNA expression form, and reference gene type. Subgroup analysis showed that the detection efficacy based on the combination of multiple lncRNAs (0.86, 95% CI, 0.82-0.88) was higher than that based on a single lncRNA (0.81, 95% CI, 0.78-0.85), and exosomal lncRNAs with blood as the detection sample had a high diagnostic efficacy (0.86, 95% CI, 0.82-0.86).ConclusionsExosome-derived lncRNAs hold great promise as non-invasive diagnostic biomarkers of bladder cancer. However, their clinical value needs to be examined in further comprehensive prospective studies.

Non-destructive testing of the cracks on the in-service bolt’s shank with size M18 is a challenging technical problem. Due to the weak echo energy of cracks with large buried depths, the conventional phased array ultrasonic sector scan imaging has a low signal-to-noise ratio, resulting in the effective defect echo submerged in the structural wave of bolts. This work proposes a method of phased array ultrasonic sector scan imaging based on vector coherence factors to detect the microcracks on the surface of the bolt shank. This is achieved by weighting the phased array sector scan imaging with the vector coherence factor to detect the microcracks of the in-service helicopter damper bolt. Experimental work is also carried out to contrast the SNR value of cracks at buried depths of 70 mm and 90 mm with traditional phased array ultrasonic sector scanning images. This demonstrates that the proposed phased array ultrasonic sector scan imaging based on vector coherence factors detected the cracks with a depth of 0.1 mm at the buried depth of 90 mm. The SNR value of the cracks at the buried depth 70 mm in DAS_VCF images is improved by 11.67 dB, compared with the traditional DAS images, in the case of the focus depth at 60 mm.

Carbon dots (CDs) have excellent optical properties, low toxicity and easy preparation, which have led to them being widely used in biomedicine, sensing and optical devices. However, although great progress has been made in the preparation of CDs, the detailed exploration of their photoluminescence (PL) mechanism is still under debate due to their complex structures and surface functionalities. Here, we proposed a single change in the pH of the synthesis condition, which had no effect on the CDs intrinsic core states and avoided the mutual influence of multiple PL origins. The m-phenylenediamine (m–PD) served as a carbon source, whose protonation degree determined the surface state of the resulting CDs and the accompanying fluorescence characteristics. The as-obtained CDs materials can be applied in the chemical sensor and anti-counterfeiting fields in a targeted manner. Therefore, our work not only contributes to the explanation of the CDs PL mechanism, but also obtains a series of CDs materials with controllable PL properties.

Cigarette smoking (CS) leads to several adverse health effects, including diseases, disabilities, and even death. Post-operative and trauma patients who smoke have an increased risk for complications, such as delayed bone or wound healing. In clinical trials, microcurrent (MC) has been shown to be a safe, non-invasive, and effective way to accelerate wound healing. Our study aimed to investigate if MC with the strength of 100 μA may be beneficial in treating CS-related healing impairment, especially in regard to angiogenesis. In this study, we investigated the effect of human keratinocyte cells (HaCaT) on angiogenesis after 72 h of cigarette smoke extract (CSE) exposure in the presence or absence of 100 μA MC. Cell viability and proliferation were evaluated by resazurin conversion, Sulforhodamine B, and Calcein-AM/Hoechst 33342 staining; the pro-angiogenic potential of HaCaT cells was evaluated by tube formation assay and angiogenesis array assay; signaling pathway alterations were investigated using Western blot. Constant exposure for 72 h to a 100 μA MC enhanced the angiogenic ability of HaCaT cells, which was mediated through the PI3K-Akt signaling pathway. In conclusion, the current data indicate that 100 μA MC may support wound healing in smoking patients by enhancing angiogenesis.

Based on the meteorological, ozone (O3), and vertical observation data of 2020, this study sought to evaluate the daily variation in O3, particularly the characteristics of nocturnal ozone pollution. We also discuss the effect of local and mesoscale horizontal transport and vertical mixing on the formation of nocturnal O3 pollution. Distinct seasonal characteristics of the daily O3 variation in Shenzhen were identified. In particular, significant nocturnal peaks were found to regularly occur in the winter and spring (November–December and January–April). The monthly average of daily variation had a clear bimodal distribution. During the period, O3 pollution frequently occurred at night, with the maximum hourly O3 concentration reaching 203.5 μg/m3. Nocturnal O3 pollution was closely associated with horizontal transport and vertical mixing. During the study period, the O3 maximum values were recorded on 68 nights, primarily between 23:00 and 03:00, with occasional observation of two peaks. The impact of horizontal transport and vertical mixing on the nocturnal secondary O3 maximum values was elaborated in two case studies, where vertical mixing was mainly associated with low-level jets, with strong wind shear enhancing turbulent mixing and transporting O3 from the upper layers to the surface.

Upconversion (UC) nanostructures, which can upconvert near-infrared (NIR) light with low energy to visible or UV light with higher energy, are investigated for theranostic applications. The surface of lanthanide (Ln)-doped UC nanostructures can be modified with different functional groups and bioconjugated with biomolecules for therapeutic systems. On the other hand, organic molecular-based UC nanostructures, by using the triplet-triplet annihilation (TTA) UC mechanism, have high UC quantum yields and do not require high excitation power. In this review, the major UC mechanisms in different nanostructures have been introduced, including the Ln-doped UC mechanism and the TTA UC mechanism. The design and fabrication of Ln-doped UC nanostructures and TTA UC-based UC nanostructures for theranostic applications have been reviewed and discussed. In addition, the current progress in the application of UC nanostructures for diagnosis and therapy has been summarized, including tumor-targeted bioimaging and chemotherapy, image-guided diagnosis and phototherapy, NIR-triggered controlled drug releasing and bioimaging. We also provide insight into the development of emerging UC nanostructures in the field of theranostics.

Abstract Background Joubert syndrome (JBTS) is a rare genetic disorder that is characterized by midbrain‐hindbrain malformations. Multiple variants in genes that affect ciliary function contribute to the genetic and clinical heterogeneity of JBTS and its subtypes. However, the correlation between genotype and phenotype has not been elucidated due to the limited number of patients available. Methods In this study, we observed different clinical features in two siblings from the same family. The older sibling was classified as a pure JBTS patient, whereas her younger sibling displayed oral‐facial‐digital defects and was therefore classified as an oral‐facial‐digital syndrome type VI (OFD VI) patient. Next, we performed human genetic tests to identify the potential pathogenic variants in the two siblings. Results Genetic sequencing indicated that both siblings harbored compound heterozygous variants of a missense variant (c.1067C>T, p.S356F) and a frameshift variant (c.8377_8378del, p.E2793Lfs*24) in CPLANE1 (NM_023073.3). Conclusion This study reports that two novel CPLANE1 variants are associated with the occurrence of JBTS and OFD VI. These results help elucidate the intrafamilial phenotypic variability associated with CPLANE1 variants.

Summary: Oncogenic histone lysine-to-methionine mutations block the methylation of their corresponding lysine residues on wild-type histones. One attractive model is that these mutations sequester histone methyltransferases, but genome-wide studies show that mutant histones and histone methyltransferases often do not colocalize. Using chromatin immunoprecipitation sequencing (ChIP-seq), here, we show that, in fission yeast, even though H3K9M-containing nucleosomes are broadly distributed across the genome, the histone H3K9 methyltransferase Clr4 is mainly sequestered at pericentric repeats. This selective sequestration of Clr4 depends not only on H3K9M but also on H3K14 ubiquitylation (H3K14ub), a modification deposited by a Clr4-associated E3 ubiquitin ligase complex. In vitro, H3K14ub synergizes with H3K9M to interact with Clr4 and potentiates the inhibitory effects of H3K9M on Clr4 enzymatic activity. Moreover, binding kinetics show that H3K14ub overcomes the Clr4 aversion to H3K9M and reduces its dissociation. The selective sequestration model reconciles previous discrepancies and demonstrates the importance of protein-interaction kinetics in regulating biological processes.

Epilepsy is a complex brain disorder characterized by repetitive seizure events. Epilepsy patients often suffer from various and severe physical and psychological comorbidities (e.g., anxiety, migraine, and stroke). While general comorbidity prevalences and incidences can be estimated from epidemiological data, such an approach does not take into account that actual patient-specific risks can depend on various individual factors, including medication. This motivates to develop a machine learning approach for predicting risks of future comorbidities for individual epilepsy patients. In this work, we use inpatient and outpatient administrative health claims data of around 19,500 U.S. epilepsy patients. We suggest a dedicated multimodal neural network architecture (Deep personalized LOngitudinal convolutional RIsk model—DeepLORI) to predict the time-dependent risk of six common comorbidities of epilepsy patients. We demonstrate superior performance of DeepLORI in a comparison with several existing methods. Moreover, we show that DeepLORI-based predictions can be interpreted on the level of individual patients. Using a game theoretic approach, we identify relevant features in DeepLORI models and demonstrate that model predictions are explainable in light of existing knowledge about the disease. Finally, we validate the model on independent data from around 97,000 patients, showing good generalization and stable prediction performance over time.

Reactive power is the core problem of voltage stability and economical operation in power systems. Aiming at the problem that multi-objective normalization reactive power optimization function is dependent on weight, an integrated synthesis of adaptive multi-objective particle swarm optimization (ISAMOPSO) is proposed to achieve weight adaptive. Through seven test functions and three algorithm comparison experiments, it is proved that the ISAMOPSO algorithm has stronger global search capability and better convergence. Considering the optimal access position and capacity of distributed generation (DG), the ISAMOPSO algorithm is used for three-objective reactive power optimization. Finally, the results indicate that the ISAMOPSO algorithm can not only provide a variety of optimization schemes to meet different needs, but also realize dynamic reactive power optimization, which further proves that the algorithm can provide effective technical support for solving reactive power optimization problems in practical engineering.

Although genetic transformation has opened up a new era for cotton molecular breeding, it still suffers from the limitation problem of long transformation periods, which slows down the generation of new cotton germplasms. In this study, LT gene (SV40 large T antigen), which promotes the transformation efficiency of animal cells, was codon-optimized. Its overexpression vector was transformed into cotton. It was observed that EC (embryogenic callus) formation period was 33% shorter and transformation efficiency was slightly higher in the LT T0 generation than that of control. RNA-seq data of NEC (non-embryonic callus) and EC from LT and control revealed that more DEGs (differential expression genes) in NEC were identified than that of EC, indicating LT mainly functioned in NEC. Further KEGG, GO, and transcription factor analyses showed that DEGs were significantly enriched in brassinosteroid biosynthesis pathways and that bHLH, MYB, and AP2/ERF were the top three gene families, which are involved in EC formation. In addition, the key genes related to the auxin pathway were differentially expressed only in LT overexpression NEC, which caused early response, biosynthesis, and transportation of the hormone, resulting in EC earlier formation. In summary, the results demonstrated that LT can promote somatic embryogenesis in cotton, which provides a new strategy for improving cotton transformation and shortening EC formation time.

Tree height is an essential indicator in forestry research. This indicator is difficult to measure directly, as well as wind disturbance adds to the measurement difficulty. Therefore, tree height measurement has always been an issue that experts and scholars strive to improve. We propose a tree height measurement method based on tree fisheye images to improve the accuracy of tree height measurements. Our aim is to extract tree height extreme points in fisheye images by proposing an improved lightweight target detection network YOLOX-tiny. We added CBAM attention mechanism, transfer learning, and data enhancement methods to improve the recall rate, F1 score, AP, and other indicators of YOLOX-tiny. This study improves the detection performance of YOLOX-tiny. The use of deep learning can improve measurement efficiency while ensuring measurement accuracy and stability. The results showed that the highest relative error of tree measurements was 4.06% and the average relative error was 1.62%. The analysis showed that the method performed better at all stages than in previous studies.

Abstract Background Breast cancer (BC) is one of the most common female malignancies in the world. Chemotherapeutic resistance is the major cause of BC therapy failure, leading to tumor recurrence and metastasis. Studies have illustrated the close relationship between glycolysis and BC progression and drug resistance. The key glycolysis regulator, PFKFB3 makes a difference during BC progression and drug resistance. However, the mechanism remains to be unknown. Methods Mass spectrometry analyses were used to found that PIM2 was a potential new binding protein of PFKFB3. Co‐immunoprecipitated and western blot were used to verify the interaction between PIM2 and PFKFB3 in BC and the molecular mechanism by which PIM2 phosphorylates PFKFB3 in regulating the protein function. PFKFB3 mutant forms were used to demonstrate the need for PFKFB3 in BC drug resistance. Results We identified that PIM2 is a new binding protein of PFKFB3. We used biochemical methods to determine that PIM2 can directly bind and change the phosphorylation of PFKFB3 at Ser478 to enhance PFKFB3 protein stability through the ubiquitin‐proteasome pathway. Importantly, phosphorylation of PFKFB3 at Ser478 promoted glycolysis, BC cell growth, and paclitaxel resistance together with PIM2 in vitro and in vivo. Conclusion Our study demonstrates that PIM2 mediates PFKFB3 phosphorylation thus regulates glycolysis and paclitaxel resistance to promote tumor progression in BC and provides preclinical evidence for targeting PFKFB3 as a new strategy in BC treatment to battle paclitaxel resistance.

Objective To analyze the clinical effect of the Brisson operation modified by a Y-shaped incision in treating adolescent concealed penis. Methods We retrospectively analyzed clinical data of 27 adolescents with a concealed penis treated with the Brisson operation modified by a Y-shaped incision in our hospital from January 2017 to March 2020. Results The operation went smoothly in all 27 patients. Postoperative foreskin edema occurred in 12 patients and spontaneously resolved within 1 month postoperatively. Two patients developed postoperative retropubic infection. After administering antibiotics and symptomatic treatment, both patients’ conditions improved within 1 week. All operations obtained satisfactory results. Postoperatively, when the penis was in a non-erect state, it was clearly exposed without retraction or concealment; thus, demonstrating good surgical results. The prepuce was distributed naturally without obvious accumulation of redundant preputial tissue. The penile scar resembled that after circumcision. The postoperative follow-up period was 6 months, during which no patients developed recurrence. Conclusion The Brisson operation modified by a Y-shaped incision is effective for treating a concealed penis in adolescent patients. This technique may relieve the pathological abnormalities and retain the penile skin's integrity to the greatest extent with minimal scarring and a satisfactory appearance.

Background: miR-301b-3p is reported in various human cancers for its abnormal expression, while the role and molecular mechanisms in lung adenocarcinoma (LUAD) remain unclear, and this is the focus of the present study. Materials and Methods: TCGA database was consulted to know gene expression in LUAD tissue. CCK-8, colony formation assay and Transwell assay were applied to identify the role of target genes in regulating LUAD cell biological properties. Bioinformatics analysis plus dual-luciferase assay were performed to validate the potential connection between genes. Results: miR-301b-3p and DLC1 were the target genes of this study and respectively differentially up-regulated and down-regulated in LUAD. Functional experiments indicated that miR-301b-3p contributed to cancer cell proliferation, migration and invasion, while this effect was reversed with overexpressed DLC1 which was identified as a direct target of and regulated by miR-301b-3p. Conclusions: Collectively, miR-301b-3p was identified to actively function on LUAD malignant progression by suppressing DLC1 expression. This discovery provides a novel therapeutic strategy for LUAD patients, which helps improve the survival of patients.

Symbiosis of marine algae is inevitable in the marine environment, and species may occur interaction on the growth. In this study, the macroalgae Ulva pertusa and marine microalgae Heterosigma akashiwo were selected as target species to study the interaction mechanism between them. After the 8 days of co-cultivation, the inhibition on growth was observed for both of U. pertusa and H. akashiwo. Eight fatty acids in U. pertusa was detected, with the significant decrease in contents of polyunsaturated fatty acids (PUFAs) especially for C18:2, C18:3n-3 and C18:3n-6. Twelve fatty acids in H. akashiwo was detected, with the significant change for PUFAs. PUFA concentrations in the co-culture group were less than those in the mono-culture. Meanwhile the principal component analysis was conducted to insight into the interaction between U. pertusa and H. akashiwo by fatty acids content and carbon stable isotope ratio of fatty acids (δ13CFAs). Fatty acid content could not distinguish mono and co-culture. However, δ13CFAs could distinguish not only the culture time of algae, but also the living environment of algae. In addition, this study combined fatty acids content and δ13CFAs to explore the release of fatty acids by algae into the seawater. The C18:3n-3 was identified as the allelochemical released by U. pertusa to inhibit the growth of H. akashiwo. The ratio of δ13CFAs in seawater decreased. This study provides a theoretical basis for the symbiosis of marine algae, and a new method of compound-specific stable carbon isotopes was used to better explore the metabolism of fatty acids in algae.

Acidic fibroblast growth factor (aFGF) is a promising regulator of glucose with no adverse effects of hypoglycemia. Previous researches revealed that aFGF mediated adipose tissue remodeling and insulin sensitivity. These findings supported rh-aFGF135 would be used as a new candidate for the treatment of insulin resistance and type 2 diabetes. In this study, we aimed to investigate the hypoglycemic efficacy of recombinant human acidic fibroblast growth factor 135 (rh-aFGF135) with low mitogenic in type 2 diabetic ZDF rats. ZDF rats were treated with rh-aFGF135 at a daily dosage of 0.25 and 0.50 mg/kg by tail intravenous injection for 5 weeks. The blood glucose levels, oral glucose tolerance test, insulin tolerance test, HOMA-IR for insulin resistance, serum biochemical parameters, and the histopathological changes of adipose tissue, liver and other organs were detected at designed time point. The glucose uptake activity and anti-insulin resistance effect of rh-aFGF135 were also detected in HepG2 cells. Results revealed that rh-aFGF135 exhibited a better hypoglycemic effect compared with vehicle group and without the adverse effect of hypoglycemia in ZDF rats. Compared with vehicle group, rh-aFGF135 significantly improved the situation of hyperglycemia and insulin resistance. Rh-aFGF135 decreased ALT, AST, GSP, and FFA levels noticeably compared with vehicle control group (P < 0.01 or P < 0.001). After 5 weeks of treatment, high-dosage rh-aFGF135 could remodel adipose tissue, and has no influence on other organs. H&E staining showed that rh-aFGF135 reduced the size of adipocytes. In addition, rh-aFGF135 may improve insulin resistance partly by increasing the protein expression of p-IRS-1 (human Ser 307). As a hypoglycemic drug for long-term treatment, rh-aFGF135 would be a potentially safe candidate for the therapy of type 2 diabetes.

BackgroundAdenocarcinoma of the ampulla of Vater (AAV) is standardly treated using a complex operation, a pancreatoduodenectomy (PD), to remove the tumor. However, dicision-making in AAV clinical treatment remains difficult due to the broad range of AAV types, outcomes, and responses to special chemotherapeutics. Thus, this study aimed to explore clinicopathological prognostic factors associated with overall survival, as well as post-chemotherapeutic effects related to curative resection of AAV.MethodsWe retrospectively reviewed data for clinicopathological outcome of 47 patients diagnosed with AAV that had underwent a PD. Overall survival probabilities were obtained using the Kaplan–Meier estimate method and a Cox proportional hazards model.ResultsForty-five patients underwent LPD (laparoscopic pancreatoduodenectomy) and two patients underwent PD. The patient group was composed of 31 males (66%) and 16 females (34%) with a mean age of 65(34–91)years. We selected 45 patients for long-term survival analysis. One- and three-year overall survival rates after resection were 97.6% and 58.9% respectively. The median survival was 37.7 months for the intestinal-type and 26.9 months in pancreatobiliary-type ampullary tumors. Serum carbohydrate antigen (CA) 19-9 greater than 37 U/ml (HR 0.140, P = 0.007), perineural invasion (HR 0.141, P = 0.003), and classification as pancreatobiliary-type (HR 6.633, P = 0.006) were independently associated with poor survival. Serum carcinoembryonic antigen (CEA) greater than 5 µg/ml (P = 0.031), serum CA 19-9 greater than 37 U/ml (P = 0.002), tumor sizes greater than 2.5cm (P=0.002), and positive perineural invasion (P=0.003) were all associated with a poor prognosis in the histopathological subgroup. Serum CA 19-9 greater than 37 U/ml (P=0.002) and positive perineural invasion (P=0.001) were significantly associated with poor survival in of patients with intestinal-type ampullary tumors. Serum CEA greater than 5 µg/ml (P=0.013) and tumor sizes greater than 2.5cm (P=0.002) were significantly associated with poor survival in patients with pancreatobiliary-type ampullary tumors.ConclusionsPancreatobiliary-type ampullary tumors were associated with poor survival. Serum CA 19-9 in the intestinal-type and CEA in the pancreatobiliary-type were significantly associated with poor survival. Ajuvant chemotherapy could not predict the survival of AAV patients.

Summary: Chromatin dysregulation has emerged as an important mechanism of oncogenesis. To develop targeted treatments, it is important to understand the transcriptomic consequences of mutations in chromatin modifier genes. Recently, mutations in the histone methyltransferase gene nuclear receptor binding SET domain protein 1 (NSD1) have been identified in a subset of common and deadly head and neck squamous cell carcinomas (HNSCCs). Here, we use genome-wide approaches and genome editing to dissect the downstream effects of loss of NSD1 in HNSCC. We demonstrate that NSD1 mutations are responsible for loss of intergenic H3K36me2 domains, followed by loss of DNA methylation and gain of H3K27me3 in the affected genomic regions. In addition, those regions are enriched in cis-regulatory elements, and subsequent loss of H3K27ac correlates with reduced expression of their target genes. Our analysis identifies genes and pathways affected by the loss of NSD1 and paves the way to further understanding the interplay among chromatin modifications in cancer.

Morbidity and mortality caused by infectious diseases rank first among all human illnesses. Many pathogenic mechanisms remain unclear, while misuse of antibiotics has led to the emergence of drug-resistant strains. Infectious diseases spread rapidly and pathogens mutate quickly, posing new threats to human health. However, with the increasing use of high-throughput screening of pathogen genomes, research based on big data mining and visualization analysis has gradually become a hot topic for studies of infectious disease prevention and control. In this paper, the framework was performed on four infectious pathogens (Fusobacterium, Streptococcus, Neisseria, and Streptococcus salivarius) through five functions: 1) genome annotation, 2) phylogeny analysis based on core genome, 3) analysis of structure differences between genomes, 4) prediction of virulence genes/factors with their pathogenic mechanisms, and 5) prediction of resistance genes/factors with their signaling pathways. The experiments were carried out from three angles: phylogeny (macro perspective), structure differences of genomes (micro perspective), and virulence and drug-resistance characteristics (prediction perspective). Therefore, the framework can not only provide evidence to support the rapid identification of new or unknown pathogens and thus plays a role in the prevention and control of infectious diseases, but also help to recommend the most appropriate strains for clinical and scientific research. This paper presented a new genome information visualization analysis process framework based on big data mining technology with the accommodation of the depth and breadth of pathogens in molecular level research.

Since its discovery in Escherichia coli, the emergence and rapid spread of the plasmid-mediated colistin resistance gene mcr-1 have become a public health concern. Livestock manure is a potentially important reservoir of mcr-1 because colistin has been widely used in livestock production. Efforts made to accurately quantify the prevalence of mcr-1 in livestock manure and the dynamic changes therein during thermophilic composting have been few and far between. In this study, mcr-1 in 51 collected samples from four kinds of livestock manures was detected and quantified. In total, 16 manure samples were found to be mcr-1 positive, with a detection frequency of 31% in 51 samples. The numbers of mcr-1 gene copies in 12 positive manure samples with a high prevalence of mcr-1 were 107–109 copies/g dry weight. During composting, >90% of mcr-1 in the manure was eliminated in 15 days at high temperature (44–65 °C), and mcr-1 was completely undetectable after 22 days. The reduction of mcr-1 following manure composting may be ascribed to the decreased number of potential mcr-1–harboring bacteria, Enterobacteriaceae and Pseudomonas. The results indicated that thermophilic composting effectively eliminated mcr-1 and inhibited its spread from livestock manure to the environment. Keywords: Mcr-1, QPCR, Thermophilic composting, Enterobacteriaceae, Pseudomonas

Abstract There is a fundamental limit on the capacity of fibre optical communication system (Shannon Limit). This limit can be potentially overcome via using Nonlinear Frequency Division Multiplexing. Dealing with noises in these systems is one of the most critical parts in implementing a practical system. In this paper, we discover and characterize the correlations among the NFT channels. It is demonstrated that the correlation is universal (i.e., independent of types of system noises) and can be exploited to maximize transmission throughput. We propose and experimentally confirm a noise model showing that end-to-end noise can be modelled as the accumulation of noise associated with each segment of optical communication which can be dealt with independently. Also, each point noise can be further decomposed into different components, some of which are more significant (and even dominating) than others. Hence, one can further approximate and simplify the noise model by focusing on the significant component.

Lysine27-to-methionine mutations in histone H3 genes (H3K27M) occur in a subgroup of gliomas and decrease genome-wide H3K27 trimethylation. Here the authors utilise primary H3K27M tumour lines and isogenic CRISPR-edited controls and show that H3K27M induces defective chromatin spread of PRC2-mediated repressive H3K27me2/me3.

The harmony search (HS) algorithm is one of the most popular meta-heuristic algorithms. The basic idea of HS was inspired by the music improvisation process in which the musicians continuously adjust the pitch of their instruments to generate wonderful harmony. Since its inception in 2001, HS has attracted the attention of many researchers from all over the world, resulting in a lot of improved variants and successful applications. Even for today, the research on improved HS variants design and innovative applications are still hot topics. This paper provides a detailed review of the basic concept of HS and a survey of its latest variants for function optimization. It also provides a survey of the innovative applications of HS in the field of intelligent manufacturing based on about 40 recently published articles. Some potential future research directions for both HS and its applications to intelligent manufacturing are also analyzed and summarized in this paper.

Wellbore drilling parameters optimization is one of the most important issue in drilling engineering. Rate of penetration or mechanical specific energy was usually utilized as the optimization objective. The rate of penetration directly relates to the drilling cycle, while mechanical specific energy reflects the drilling efficiency. In this paper, except for rate of penetration and mechanical specific energy, the drilling life of bit is also summarized as a comprehensive assessment indicator in wellbore drilling parameters optimization problem. The drilling life of bit is taken into consideration for the design and manufacturing cost of bit compose a significant part of the drilling cost and the bit drilling life greatly influences the drilling efficiency. However, those objectives are usually related in a highly nonlinear relationship and in conflict with each other. Thus, a multi-objective cellular particle swarm optimization (MOCPSO) is developed to solve the three-objective drilling parameters optimization problem. Moreover, the radius basis function (RBF) method is employed into the formation parameters identification for rate of penetration model. Performance of MOCPSO is investigated by taken a comparison with multi-objective PSO and non-dominated sorting genetic algorithm-Ⅱ (NSGA-Ⅱ). Effect of the four commonly used neighborhood function is also investigated by making contrasts with each other. It can be inferred that MOCPSO is statistically superior to both multi-objective PSO, NSGA-Ⅱ at the 0.05 level of significance on the wellbore drilling parameters optimization problem. And the four commonly used neighborhood templates perform comparable with each other, and are not statistically different for the drilling parameters optimization problem.

Abstract Objective To investigate the lung cancer-promoting mechanism of mesenchymal stem cell-secreted extracellular vesicles (MSC-EV). Methods EV were isolated from culture media of human bone marrow-derived MSCs that were pre-challenged with or without hypoxia (referred to as H-EV and N-EV, respectively). After treatment with N-EV or H-EV, A549 and H23 cell proliferation, apoptosis, trans-well invasion and epithelial-to-mesenchymal transition (EMT) were examined. Polarization of human primary monocytes-derived macrophages with or without N-EV or H-EV induction were analyzed by flow cytometry and ELISA. PTEN, PDCD4 or RECK gene was overexpressed in A549 cells, while miR-21-5p was knocked down in MSCs, A549 or H23 lung cancer cells or primary monocytes by miR-21-5p inhibitor transfection. Protein level of PTEN, PDCD4, RECK, AKT or STAT3 as well as phosphorylation level of AKT or STAT3 protein were assayed by western blot. Tumorigenicity of A549 and H23 cells with or without MSC-EV co-injection was assayed on immunocompromised mice. The xenograft tumor were examined for cell proliferation, angiogenesis, apoptosis and intra-tumoral M1/M2 macrophage polarization. Results Comparing to N-EV, H-EV treatment significantly increased A549 and H23 cell proliferation, survival, invasiveness and EMT as well as macrophage M2 polarization. MiR-21-5p knocked down significantly abrogated the cancer-promoting and macrophage M2 polarizing effects of H-EV treatment. H-EV treatment downregulated PTEN, PDCD4 and RECK gene expression largely through miR-21-5p. Overexpressing PTEN, PDCD4 and RECK in A549 cells significantly reduced the miR-21-5p-mediated anti-apoptotic and pro-metastatic effect of H-EV, while overexpressing PTEN in monocytes significantly reduced macrophage M2 polarization after induction with the presence of H-EV. H-EV co-injection significantly increased tumor growth, cancer cell proliferation, intra-tumoral angiogenesis and M2 polarization of macrophages in vivo partially through miR-21-5p. Conclusions Increased miR-21-5p delivery by MSC-EV after hypoxia pre-challenge can promote lung cancer development by reducing apoptosis and promoting macrophage M2 polarization.

In this paper, a slip ratio controller based on model predictive control (MPC) considering road roughness is proposed for electric vehicle (EV) to improve the driving/braking performance under low adhesion coefficient road. A half vehicle dynamic model is derived in which pitching, wheel rolling, and tire vertical movement is taking into account. The influence of vertical force variation caused by road unevenness and tire load transfer is analyzed to design slip ratio controller. In order to ensure vehicle safety, wheel slip stable zone is considered as time-domain constraints of the nonlinear-MPC. Besides, the motor output torque is limited by the motor maximum torque, which is considered as system time-varying constraints. The control objectives include vehicle safety, good longitudinal acceleration and braking performance, preservation of driver comfort, and lower power consumption. The proposed slip ratio controller is verified on a 13-degree-of-freedom (13DOF) EV model in MATLAB/Simulink. Simulation results of different maneuver on roughness surfaces show the benefits of the controller.

Distributed optical fiber sensing that enables simultaneous vibration and temperature monitoring is demonstrated in this work, which is achieved by implementing polarization optical time-domain reflectometry (P-OTDR) and Raman optical time-domain reflectometry (ROTDR) respectively through space-division multiplexed (SDM) configuration in different cores of a multicore fiber (MCF). Optimized system setup is obtained in the proposed hybrid system, where only one laser source is used, and the generated pulse is shared by the two reflectometers. Owing to the reason that separate interrogation fiber cores are used by the two reflectometers, the proposed hybrid system allows for simultaneous measurements of spontaneous Raman and Rayleigh scattering signals, thus it no longer suffers from the incompatible pump power levels issue, which results from different pump power demands, and hinders the implementation of the hybrid system in single mode fiber due to the fiber nonlinear effects imposed restriction. In addition, in order to extend the sensing range, we also explore the employment of wavelet transform denoising technique in the improvement of signal-to-noise ratio of ROTDR measurement. Eventually, simultaneous distributed vibration and temperature sensing in 5.76 km sensing range with 3 m spatial resolution and 0.57 °C temperature uncertainty has been demonstrated. The proposed hybrid sensing system has the outstanding advantage of high reliability, since the cross-sensitivity issue is effectively mitigated, which shows great potential for pipeline monitoring in oil and gas industry.

Concrete pile foundations are the main load-carrying and aseismic structures for many large-scale building structures. Their structural quality will have a great impact on the safety of building structures. However, the imaging results still cannot easily meet practical demands in current ultrasonic Computerized Tomography (CT) imaging tests of concrete structures. In view of the current difficulties, a combinatorial optimization tomographic imaging method is proposed. First, a quadric broadening objective function with a clear physical meaning is established according to the characteristics of ultrasonic propagation in concrete. Then, a new CT imaging method of concrete pile foundation is formed by combining fast adaptive optimization search ability of Genetic Algorithm (GA) with the global search control ability of Simulated Annealing Algorithm (SAA). The numerical simulation experiments have shown that the usage of the correct priori information and the excellent characteristic of the Simulated Annealing Genetic Algorithm (SAGA) in searching for the global minimum value of the function have produced accurate and effective results with stable numerical values. Finally, the imaging method is verified by experiment, where results show that SAGA requires fewer iterations, has faster computation speed and gives more accurate imaging results compared with the single GA.

Recently, high-speed optical transmission using single-side-band (SSB) modulation with Kramers-Kronig (KK) scheme has gained great attention due to its high spectral efficiency (SE) and capability of electronic chromatic dispersion compensation (CDC), which can be widely employed in optical metro networks as a promising transmission scheme. To our knowledge, the carrier-signal power ratio (CSPR) is the key parameter to SSB-based systems and the optimum CSPRs can vary distinctly in different SSB modulation schemes. In this paper, the SSB-based KK systems with four kinds of SSB signal generation schemes are investigated, i.e. optical carrier-assisted SSB (OCA-SSB), virtual carrier-assisted SSB (VCA-SSB), SSB subcarrier modulation (SSB SCM) with IQ modulator (IQM) and with dual-drive Mach-Zehnder modulator (DDMZM) respectively. Here, the detailed theoretical derivations of these modulation processing are given and the theoretical relationship between device parameters and the CSPR has been further studied for the different SSB schemes. In order to verify those theoretical analyses, a 224-Gb/s direct detection (DD) transmission with SSB 16-ary quadrature amplitude modulation (16-QAM) signal has been demonstrated based on four SSB generation methods. The results show that theoretical derivations are closely consist with numerical analysis, such as $V_{bias}$ in the scheme of SSB SCM with IQM and optical modulation index (OMI) in SSB SCM with DDMZM. Therefore, our research can provide a theoretical guidance of appropriate device parameter configuration so as to achieve the optimum performance for SSB systems.

In the last 30 years, a flexible job shop scheduling problem (FJSP) has been extensively explored. Production efficiency is a widely utilized objective. With the rise in environmental awareness, green objectives (e.g., energy consumption) have received a lot of attention. Nevertheless, energy consumption has received little attention. Furthermore, controllable processing times (CPT) should be considered in the field of scheduling, because they are closer to some real production. Therefore, this work investigates a FJSP with CPT (i.e., FJSP-CPT) where asymmetrical conditions and symmetrical constraints increase the difficulty of problem solving. The objectives of FJSP-CPT are to minimize simultaneously the maximum completion time (i.e., makespan) and total energy consumption (TEC). First of all, a mathematical model of this multi-objective FJSP-CPT was formulated. To optimize this problem, a novel multi-objective cellular memetic optimization algorithm (MOCMOA) was presented. The proposed MOMOA combined the advantages of cellular structure for global exploration and variable neighborhood search (VNS) for local exploitation. At last, MOCMOA was compared against other multi-objective optimization approaches by performing experiments. Numerical experiments reveal that the presented MOCMOA is superior to its competitors in 15 instances regarding three commonly used performance metrics.

Green manufacturing, which takes environmental effect and production benefit into consideration, has attracted increasing concern with the target of carbon peaking and carbon neutrality proposed. As a critical process in the manufacturing system, shop scheduling is also an important method for enterprises to achieve green manufacturing. Therefore, it is necessary to consider both production benefits and environmental objectives in shop scheduling, which are symmetrical and equally important. In addition, noise pollution has become an important environmental issue that cannot be ignored in the manufacturing processes, but which has been paid less attention in previous studies. Thus, the MODABC algorithm, with the optimization objectives of simultaneously minimizing lead-time/tardiness cost and job-shop noise pollution emission is proposed in this paper. We designed a discrete permutation-based two-layer encoding mechanism to generate the initial population. Then, three crossover methods were used to perform nectar update operations in the employed bee search phase, and three neighbourhood structures were used to improve the onlooker bee search operations. Finally, the MODABC algorithm was compared with other classical MOEAs. The results demonstrate that MODABC can provide non-dominated solution set with good convergence and distribution, and show significant superiority in solving green single-machine multi-objective scheduling problems.

Temperature distribution in concrete is significant to the concrete structure’s macro properties and different factors affect the heat transfer in concrete, and therefore influence the temperature distribution. This work established a three-dimensional transient heat transfer model coupled with various environmental factors, using the finite element method for calculating the results and real-measured data for testing accuracy. In addition, a sensitivity evaluation of various factors was conducted. Due to various environmental factors, the results revealed that the prediction of temperature distribution in concrete by the three-dimensional model had great accuracy with an error of less than 4%. A particular hysteresis effect of temperature response in the concrete existed. Considering heat transfer in different spatial directions, the model can predict the temperature change of each spatial point instead of the spatial surface in different depths, proving the shortcomings of a one-dimensional heat transfer model. A greater solar radiation intensity caused a more significant temperature difference on the concrete surface: the surface temperature difference in July was twice as significant as that in December. Wind speed had a cooling effect on the concrete surface, and stronger wind speed accompanied with a stronger cooling effect made the surface temperature closer to the ambient temperature. Material properties had different effects on the temperature distribution of the surface part and internal part: the specific heat capacity determined the speed of the outer layer temperature change while the thermal conductivity determined the speed of the inner layer temperature change.

Abstract Background The objective of this study was to evaluate whether apolipoprotein gene polymorphisms confer susceptibility to osteonecrosis of the femoral head (ONFH). Methods The relevant literature was screened from databases of Pubmed, Embase, Wanfang, Weipu and China National Knowledge Internet (CNKI) until May, 2017. In addition, odds ratio (OR) and its corresponding 95% confidence interval (CI) were used as a measure of effect size for calculating effect size. Results Totally, six case-control studies were included in this meta-analysis. It revealed that ApoB-C7623T polymorphism frequency was increased in ONFH group than in control group under three genetic models, including allele model (T vs. C, OR = 4.5149, 95% CI: 1.6968–12.0134); additive model (TC vs. CC, OR = 6.2515, 95% CI: 2.0939–18.6640); and dominant model (TT + TC vs. CC, OR = 5.4998, 95% CI: 1.9246–15.7163). In addition, the increased risk of ONFH were related to ApoA1-rs1799837 polymorphism under additive model (AA vs. GG, OR = 1.4175, 95% CI: 1.0522–1.9096) and recessive model (AA vs. GG + AG, OR = 1.7727, 95% CI: 1.3399–2.3452). However, four ApoB rs1042031, rs693, 3’-VNTR and G12619A polymorphisms under the all genetic models were not associated with susceptibility to ONFH. Conclusion The T allele and TC genotype of ApoB-C7623T and AA genotype of ApoA1-rs1799837 may contribute to increase the risk of ONFH.

The dysregulation of circular RNAs (circRNAs) is implicated in the pathogenesis of prostate cancer (PCa). However, the underlying mechanisms by which hsa_circ_0003768 (circPDHX) contributes to PCa remain elusive. The differentially expressed circRNAs between PCa and normal tissues were identified by Gene Expression Omnibus dataset. The association of circPDHX and miR-378a-3p expression with the clinicopathological parameters and prognosis in patients with PCa was analyzed by fluorescence in situ hybridization and The Cancer Genome Atlas dataset. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assays as well as a xenograft tumor model were used to assess the role of circPDHX in PCa cells. circPDHX-specific binding with miR-378a-3p was validated by bioinformatic analysis, luciferase gene reporter, and RNA immunoprecipitation assays. As a result, we found that increased expression of circPDHX was associated with Gleason score (P = 0.001) and pathogenic T stage (P = 0.01) and acted as an independent prognostic factor of poor survival (P = 0.036) in patients with PCa. Knockdown of circPDHX inhibited cell proliferation and invasion in vitro and in vivo, but ectopic expression of circPDHX reversed these effects. Furthermore, circPDHX could sponge miR-378a-3p to promote cell proliferation, but miR-378a-3p counteracted circPDHX-induced cell proliferation and insulin-like growth factor 1 receptor (IGF1R) expression in PCa cells. In conclusion, our findings demonstrated that circPDHX facilitated the proliferation and invasion of PCa cells by sponging miR-378a-3p.

Importance. The last decade has witnessed the advances of cognitive computing technologies that learn at scale and reason with purpose in medicine studies. From the diagnosis of diseases till the generation of treatment plans, cognitive computing encompasses both data-driven and knowledge-driven machine intelligence to assist health care roles in clinical decision-making. This review provides a comprehensive perspective from both research and industrial efforts on cognitive computing-based CDSS over the last decade. Highlights. (1) A holistic review of both research papers and industrial practice about cognitive computing-based CDSS is conducted to identify the necessity and the characteristics as well as the general framework of constructing the system. (2) Several of the typical applications of cognitive computing-based CDSS as well as the existing systems in real medical practice are introduced in detail under the general framework. (3) The limitations of the current cognitive computing-based CDSS is discussed that sheds light on the future work in this direction. Conclusion. Different from medical content providers, cognitive computing-based CDSS provides probabilistic clinical decision support by automatically learning and inferencing from medical big data. The characteristics of managing multimodal data and computerizing medical knowledge distinguish cognitive computing-based CDSS from other categories. Given the current status of primary health care like high diagnostic error rate and shortage of medical resources, it is time to introduce cognitive computing-based CDSS to the medical community which is supposed to be more open-minded and embrace the convenience and low cost but high efficiency brought by cognitive computing-based CDSS.

Power level control is one of the critical functions in the instrument and control system of nuclear power plants (NPPs). In most power level control systems of NPPs, the power level or average neutron flux in reactor cores provided by out-of-core neutron sensors are usually measured as feedback of power control systems, while, as critical measuring devices, there is a risk of damage to out-of-core neutron sensors. For improving the operation reliability of NPPs under the neutron sensors’ failure, a power control system based on power observer is developed in this work. The simulation based on NPP simulator shows the power control system based on the observer is effective when neutron sensors fail.

Endoplasmic reticulum (ER) stress is associated with acute kidney injury (AKI) caused by various mechanisms, including antibiotics, non-steroidal anti-inflammatory drugs, cisplatin, and radiocontrast. Tunicamycin (TM) is a nucleoside antibiotic that induces ER stress and is a commonly used model of AKI. 4-phenylbutyrate (4-PBA) is a chemical chaperone and histone deacetylase (HDAC) inhibitor and has been shown to protect the kidney from ER stress, apoptosis, and structural damage in a tunicamycin model of AKI. The renal protection provided by 4-PBA is attributed to its ability to prevent misfolded protein aggregation and inhibit ER stress; however, the HDAC inhibitor effects of 4-PBA have not been examined in the TM-induced model of AKI. As such, the main objective of this study was to determine if histone hyperacetylation provides any protective effects against TM-mediated AKI. The FDA-approved HDAC inhibitor vorinostat was used, as it has no ER stress inhibitory effects and therefore the histone hyperacetylation properties alone could be investigated. In vitro work demonstrated that vorinostat inhibited histone deacetylation in cultured proximal tubular cells but did not prevent ER stress or protein aggregation induced by TM. Vorinostat induced a significant increase in cell death, and exacerbated TM-mediated total cell death and apoptotic cell death. Wild type male mice were treated with TM (0.5 mg/kg, intraperitoneal injection), with or without vorinostat (50 mg/kg/day) or 4-PBA (1 g/kg/day). Mice treated with 4-PBA or vorinostat exhibited similar levels of histone hyperacetylation. Expression of the pro-apoptotic protein CHOP was induced with TM, and not inhibited by vorinostat. Further, vorinostat did not prevent any renal damage or decline in renal function caused by tunicamycin. These data suggest that the protective mechanisms found by 4-PBA are primarily due to its molecular chaperone properties, and the HDAC inhibitors used did not provide any protection against renal injury caused by ER stress.