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Aiming at the current problems in the safety monitoring of urban manhole covers, this paper proposes a safety monitoring system for manhole covers based on smart light poles. The system uses STM32F103C8T6 as the microcontroller, and processes and controls the movement, loss, tilt, flooding, and positioning data of the manhole cover. Then, the data frame is sent to the LoRa gateway of the nearby smart light pole through the LoRa communication protocol, and the LoRa gateway will transmit the abnormal state of the manhole cover to the large screen display of the smart light pole through the bus. At the same time, a voice broadcast is carried out to remind localized road vehicles and pedestrians. Besides, it is sent to the IoT cloud platform KitLink, and the cloud platform will push the abnormal status data to the subscribed management user, and the user will quickly process it according to the positioning data. Among them, the terminal sensing control device of the manhole cover adopts an integrated package, and at the same time, it is installed at the center point under the manhole cover by using a waterproof material. It can not only carry out reliable and accurate installation without changing the original components but also can effectively monitor the safety. Through the design and implementation test of the system, it can be seen that the system can efficiently and accurately realize all-round and multi-modal safety linkage monitoring of urban manhole covers. [ABSTRACT FROM AUTHOR]

Objective. To explore the role and mechanism of interleukin-8-mediated autophagy regulation of gastric cancer (GC) cells in GC. Methods. After cell culture, the SGC7901 cell line was separated into the control group and IL-8 (20 ng/mL) group, IL-8 (40 ng/mL) group, and IL-8 (60 ng/mL) group, to verify the effects of the PI3K/Akt signal path on the modulation of autophagy in GC cells. Western blot detected autophagy markers, ATG12-ATG5 complexes, autophagy-associated pathways, and apoptosis-associated factors in GC cells. Transwell was utilized to identify invasion capability. Results. Compared with the control group, the expression of LC3II, Atg5, ATG7, Beclin1, Bax, C-cas3, C-cas9, P-PI3K, P-Akt, and ATG12-ATG5 was remarkably elevated in the IL-8 (60 ng/mL) group, IL-8 (20 ng/mL) group, and the IL-8 (40 ng/mL) group. The expression of P62 and Bcl-2 in the IL-8 (60 ng/mL) group was also lower than that of the IL-8 (20 ng/mL) group and IL-8 (40 ng/mL) group, in contrast to the controls. The invasive quantity of GC SGC7901 cells in the IL-8 (60 ng/mL) group was also remarkably higher in contrast to the IL-8 (20 ng/mL) and IL-8 (40 ng/mL) groups. The relative expressions of LC3II, Atg5, ATG7, Beclin1, Bax, C-cas3, C-cas9, P-PI3K, P-Akt, and ATG12-ATG5 complex proteins in LY294002 group were considerably elevated. LC3II, Atg5, ATG7, Beclin1, Bax, C-cas3, C-cas9, P-PI3K, P-Akt, and ATG12-ATG5 were decreased in the IL-8 + LY294002 group. The relative expressions of P62 and Bcl-2 proteins in the IL-8 + LY294002 group were remarkably elevated, and the invasion of SGC7901 cells in the IL-8 group was elevated. In contrast to the IL-8 group, the invasion quantity of gastric cancer SGC7901 cells in the IL-8 + LY294002 group was considerably decreased. Conclusion. IL-8 promotes autophagy and aggression and suppresses apoptosis of GC SGC7901 cells by regulating PI3K/AKT pathway phosphorylation. [ABSTRACT FROM AUTHOR]

Objective. To study the development process of the human retina, we analyzed the development track of main cell types and transitional cell populations, identifying the retinal organoid cell differentiation-related genes (RDRGs). Methods. Single-cell RNA sequencing data (scRNA-Seq) of human retinal organoids were downloaded from Gene Expression Omnibus (GEO) database in this study. Data were processed with quality analysis and analysis of variance. Principal component analysis and t -distributed stochastic neighbor embedding were used to conduct dimension reduction analysis and type annotation for the screened data. Marker genes and RDRGs were identified by differential analysis. Cell differentiation characteristics were determined by trajectory analysis. Enrichment pathways were analyzed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG), and functional modules were obtained by protein-protein interaction (PPI) network analysis. Results. iPSCs were mainly located at the root of differentiation trajectory, while neurons and astrocytes were distributed in different branches, respectively. Meanwhile, 220 RDRGs were obtained. They were involved in the biological functions related to vision and visual development, as well as significantly enriched in signaling pathways associated with retinal vascular development and retinal neuroregulation. Protein-protein interaction network construction and functional subnetwork analysis were conducted on RDRGs, and two functional submodules were obtained. The enrichment analysis presented that the two submodules played a vital role in retinal development, visual perception, and cell respiration. Conclusions. This study identified RDRGs and revealed the biological functions involved in these genes, which are expected to provide evidence for researching retinal development and diseases. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the malignancies with an extremely inferior prognosis in the abdominal cavity, making it essential to develop more effective biomarkers for HCC. Although GNG5 has been linked to increased patient survival in a variety of human malignancies, no evidence has been found for its involvement in the development of HCC yet. Our study first analyzed the expression and prognosis of GNG5 in HCC using The Cancer Genome Atlas database (TCGA database) with the Gene Expression Omnibus database (GEO database) and found that GNG5 has a potential oncogenic role. Based on survival analysis, the clinical importance and prognostic value of the GNG5 gene were studied. Relying on tumor Immune Estimation Resource database (TIMER database), we analyzed the correlation between the GNG5 gene and HCC Immune infiltration cells. GNG5 expression levels were significantly higher in HCC tissues compared to normal liver tissues. HCC patients with high GNG5 expression had significantly reduced overall survival time and affected multiple immune cell infiltrates. Additionally, KEGG functional enrichment analysis indicated the PI3K-Akt signaling pathway as the most promising carcinogenic pathway associated with GNG5. This is the first comprehensive revelation of GNG5 as a possible new biological marker associated with immune infiltration in HCC. Additionally, it holds promise as an emerging target for HCC immunotherapy. [ABSTRACT FROM AUTHOR]

In order to grasp the distribution characteristics of the pressure field on the inner wall of the volute casing of an atypical open impeller centrifugal pump, the instantaneous pressure at different operating conditions was experimentally measured under four operating rotational speeds to obtain the distribution characteristics of the average static pressure field in the volute casing of this pump model. The pressure pulsation amplitude and pressure pulsation intensity were also analyzed at different rotational speed cases, and the standard deviation analysis was performed. The results showed that the instantaneous pressure pulsation on the inner wall of the volute casing strongly fluctuates during the pump operating, and the closer to the volute casing outlet, the more intense the pressure pulsation was. After increasing the pump shaft speed, the fluctuation amplitude gradually decreased. The pressure pulsation on the wall of tip clearance is more intense than that on the inner wall of the volute shell. The intensity of the pressure pulsation on the wall of tip clearance decreases with the increase of the rotational speed, and the higher the speed, the less intense the pressure pulsation. [ABSTRACT FROM AUTHOR]

Inspired by the theories of Tate and Zaera, a theoretical analysis model including the erosion of the projectile, the cracking of ceramic composites, and the deformation of metal backplate was established in this study to investigate the bulletproof capability of the ceramic composites under impact by an armor piecing projectile (AP). The analysis results were verified by ballistic tests. As for the ceramic composites, the volume of the cracked ceramic conoid and the change in the compressive strength were included. Regarding the deformation of the metal backplate, the plastic deformation work, the external work, and the conservation of kinetics were considered. Based on the thickness of the target plate, failure modes were separated into the plug type and the petal type. The ordinary differential equation solver of MATLAB, ode45, was adopted to solve relevant ordinary differential equations. In this study, the powder metallurgy was used to produce the Al2O3/ZrO2 multilayered ceramic composites of three layers; each layer was 3 mm in thickness. The ceramic composites were paired with a backplate made of 6061-T6 aluminum alloy with a thickness of either 1 mm or 4 mm. The ballistic tests were executed by using 0.30″ AP projectiles to impact the specimens. The results from theoretical model and ballistic tests were compared and shown consistent in the field of residual velocity, residual bullet mass, and the failure modes of the metal backplate. [ABSTRACT FROM AUTHOR]

Centrifugal pump often operates at different working flow rates to meet engineering requirement. To better reveal the transient behavior of centrifugal pump in the process of decreasing flow rate, the finite volume method (FVM), RNG k-ε turbulence model, sliding mesh technology, and user-defined functions (UDF) were employed to simulate the three-dimensional unsteady viscous incompressible flow in a low-specific-speed centrifugal pump during the abrupt valve-off period. The results show that the differences are very obvious between transient and quasi-steady calculations. The velocity is maximum on the wall of hub and shroud, while the velocity is minimum and uniform distribution at middle positions. The transient flow field lags behind the quasi-steady flow field, which may be related to the reasons; namely, kinetic energy cannot convert pressure energy in time. [ABSTRACT FROM AUTHOR]

In this paper, a sequence decision framework based on the Bayesian search is proposed to solve the problem of using an autonomous system to search for the missing target in an unknown environment. In the task, search cost and search efficiency are two competing requirements because they are closely related to the search task. Especially in the actual search task, the sensor assembled by the searcher is not perfect, so an effective search strategy is needed to guide the search agent to perform the task. Meanwhile, the decision-making method is crucial for the search agent. If the search agent fully trusts the feedback information of the sensor, the search task will end when the target is "detected" for the first time, which means it must take the risk of founding a wrong target. Conversely, if the search agent does not trust the feedback information of the sensor, it will most likely miss the real target, which will waste a lot of search resources and time. Based on the existing work, this paper proposes two search strategies and an improved algorithm. Compared with other search methods, the proposed strategies greatly improve the efficiency of unmanned search. Finally, the numerical simulations are provided to demonstrate the effectiveness of the search strategies. [ABSTRACT FROM AUTHOR]

This study investigated the ballistic resistance of a composite target plate fabricated by combining SiC ceramic with the Dyneema fiber. To achieve a light-weight target plate that conforms to the US National Institute of Justice level four (NIJ IV) standards, minimal areal density analysis was conducted to obtain the optimal SiC ceramic-Dyneema fiber thickness combination. This study used energy absorption to analyze the ballistic resistance of the target plates. To drastically reduce experimental costs, most of this work employed ANSYS/LS-DYNA software to conduct finite element numerical simulations. First, ballistic experiments that conformed to NIJ IV standards were conducted to verify the simulation parameter configurations. Subsequently, the correlation function of the relationship between the combined thickness of the composite material and its ballistic resistance was determined through the experimental design, which effectively reduced the simulation analysis time. According to simulation experiments and regression analysis, the equation for the relationship between the combined thickness of the composite material and its ballistic resistance was E A h c , h f = − 6276.5 + 500.6 h c + 1512.6 h f + 30.7 h c h f − 8.1 h c 2 − 113.6 h f 2 , though there were limitations to its application. From the numerical analysis results, 8.1940 mm SiC ceramic and 6.9637 mm Dyneema fiber were determined to constitute the optimal thickness combination for a composite that features a minimal areal density and which conforms to NIJ IV standards. The combination was verified to be consistent with the numerical simulation analysis results. [ABSTRACT FROM AUTHOR]

High compliance with methadone maintenance therapy (MMT) is crucial to successful opioid abstinence in addicts. However, MMT has numerous side effects, including reductions in quality of life and quality of sleep. Many studies have demonstrated that electroacupuncture relieves withdrawal symptoms in opioid addicts. The present study was a case-control study. From January 2015 to September 2016, 106 patients undergoing MMT at a medical center in central Taiwan were recruited and separated into an electroacupuncture treatment group and a control group. Electroacupuncture was performed for 15 minutes twice weekly for 4 weeks. The electroacupuncture treatment group was discovered to have improved quality of life, especially in terms of vitality and mental health. Although electroacupuncture did not significantly improve sleep quality, we found that sleep quality was significantly improved once methadone dosage had been reduced. Electroacupuncture can improve quality of life in patients undergoing MMT. If methadone dosage can be reduced and electroacupuncture can be employed, both sleep and life quality can be improved. [ABSTRACT FROM AUTHOR]

Aims. Recent epidemiological studies have indicated that the incidence of epilepsy peaks after 60 years old, and epilepsy has become increasingly prevalent in elderly populations. The aim of this study is to identify the aetiologic characteristics of epilepsy in the elderly. Methods. We retrospectively recruited elderly patients with newly diagnosed epilepsy identified in three epilepsy centres in western China; elderly patients were defined as individuals aged 60 years or older. Demographic characteristics, clinical epilepsy data, and the diagnosis and aetiology of epilepsy were recorded. Results. A total of 760 patients with newly diagnosed epilepsy were enrolled in our study. Of these patients, 25% had experienced one or more episodes of status epilepticus, and 62.4% were confirmed as symptomatic. Among the symptomatic cohort, stroke and traumatic brain injury (TBI) were the two most common causes of epilepsy, followed by cerebral tumour, dementia, hippocampal sclerosis (HS), and central nervous system (CNS) infection. When analysed by residence and age, ischaemic stroke was the most common cause of epilepsy in urban patients, whereas traumatic brain injury was the leading cause of epilepsy in rural patients. Conclusion. More than three-fifths of newly diagnosed epilepsy cases in elderly patients were confirmed as symptomatic, and stroke and traumatic brain injury were the primary aetiologies in elderly epileptic patients. [ABSTRACT FROM AUTHOR]

Dermatophytosis, which is caused mainly by genera of Trichophyton, Epidermophyton, and Microsporum, is a frequent dermatological problem in tropical and subtropical countries. Investigations were carried out in this study to evaluate the antidermatophytic activity of the stems, leaves, and seeds of Croton tiglium, one of the traditional medicine plants indigenous to Asia. Ethanolic extracts of the stems, leaves, and seeds of C. tiglium were prepared by cold soak or heat reflux methods. The antidermatophytic activities of the extracts were evaluated by disc diffusion and microdilution susceptibility assays against Trichophyton mentagrophytes, T. rubrum, and Epidermophyton floccosum. The active components in the extracts were analyzed and identified by GC-MS. All ethanolic extracts of C. tiglium showed some antifungal activities against the three dermatophytes. The ethanolic stem extract had the greatest inhibitory activities against T. mentagrophytes and E. floccosum with MICs at 0.16 mg/mL and had a lower activity against T. rubrum (MIC: 0.31 mg/mL). Oleic acid and hexadecanoic acid were found to be the major constituents in the stem extract that demonstrated strong antidermatophytic activities. The ethanolic extracts of stem or seed of C. tiglium exhibit strong antidermatophytic activities and, thus, could be considered for application on treating skin fungal infections after appropriate processing. [ABSTRACT FROM AUTHOR]

Background. In childhood and adolescence, the prevailing bone tumor is osteosarcoma associated with frequent recurrence and lung metastasis. This research focused on predicting the survival and immune landscape of osteosarcoma by developing a prognostic signature and establishing aging-related genes (ARGs) subtypes. Methods. The training group comprised of the transcriptomic and associated clinical data of 84 patients with osteosarcoma accessed at the TARGET database and the validation group consisted of 53 patients from GSE21257. The aging-related subtypes were identified using unsupervised consensus clustering analysis. The ARG signature was developed utilizing multivariate Cox analysis and LASSO regression. The prognostic value was assessed using the univariate and multivariate Cox analyses, Kaplan-Meier plotter, time-dependent ROC curve, and nomogram. The functional enrichment analyses were performed by GSEA, GO, and KEGG analysis, while the ssGSEA, ESTIMATE, and CIBERSORT analyses were conducted to reveal the immune landscape in osteosarcoma. Results. The two clusters of osteosarcoma patients formed based on 543 ARGs, depicted a considerable difference in the tumor microenvironment, and the overall survival and immune cell infiltration rate varied as well. Among these, the selected 23 ARGs were utilized for the construction of an efficient predictive prognostic signature for the overall survival prediction. The testing in the validation group of osteosarcoma patients confirmed the status of the high-risk score as an independent indicator for poor prognosis, which was already identified as such using the univariate and multivariate Cox analyses. Furthermore, the ARG signature could distinguish different immune-related functions, infiltration status of immune cells, and tumor microenvironment, as well as predict the immunotherapy response of osteosarcoma patients. Conclusion. The aging-related subtypes were identified and a prognostic signature was developed in this research, which determined different prognoses and allowed for treatment of osteosarcoma patients to be tailored. Additionally, the immunotherapeutic response of individuals with osteosarcoma could also be predicted by the ARG signature. [ABSTRACT FROM AUTHOR]

Nozzle flowmeter is widely used in industry. In this paper, in order to study the influence of different flow rates and inner wall temperatures on the thermal effect and flow field of the nozzle flowmeter, the fluid-solid coupling numerical calculation of the thermal effect and flow field of nozzle flowmeter is carried out under four different flow rates and five different inner wall temperatures. It is found that, with the increase of flow rate, the heat transfer effect of the nozzle flowmeter is weakened under different inner wall temperatures. The pressure distribution in the fluid domain, the dynamic stress, and fluid-induced vibration deformation generated by the fluid of the nozzle flowmeter are less affected by inner wall temperatures. [ABSTRACT FROM AUTHOR]

Intelligent mechanical fault diagnosis has developed very fast in recent years due to the advancement and application of deep learning technologies. Thus, there are many deep learning network models that have been explored in fault classification and diagnosis. However, there are still limitations in research on the relationship between fault location, fault type, and fault severity. In this paper, a novel method for diagnosis of bearing fault using hierarchical multitask convolution neural networks (HMCNNs) is proposed, taking into account the mentioned relationships. The HMCNN model includes a main task and multiple subtasks. In the HMCNN model, a weighted probability is used to reduce the classification error propagation among multitasks to improve the fault diagnosis accuracy. The validity of the proposed method is verified on bearing datasets. Experimental results show that the proposed method is very effective and superior to the existing methods. [ABSTRACT FROM AUTHOR]

Research of healthy exercise has garnered a keen research for the past few years. It is known that participation in a regular exercise program can help improve various aspects of cardiovascular function and reduce the risk of suffering from illness. But some exercise accidents like dehydration, exertional heatstroke, and even sudden death need to be brought to attention. If these exercise accidents can be analyzed and predicted before they happened, it will be beneficial to alleviate or avoid disease or mortality. To achieve this objective, an exercise health simulation approach is proposed, in which an integrated human thermophysiological model consisting of human thermal regulation model and a nonlinear heart rate regulation model is reported. The human thermoregulatory mechanism as well as the heart rate response mechanism during exercise can be simulated. On the basis of the simulated physiological indicators, a fuzzy finite state machine is constructed to obtain the possible health transition sequence and predict the exercise health status. The experiment results show that our integrated exercise thermophysiological model can numerically simulate the thermal and physiological processes of the human body during exercise and the predicted exercise health transition sequence from finite state machine can be used in healthcare. [ABSTRACT FROM AUTHOR]

The physiological and biochemical indexes of different salt-tolerant wheat cultivars under salt stress are affected to different degrees. The changes in physiological and biochemical indexes in salt-tolerant wheat varieties are moderate, while salt-sensitive wheat varieties have bigger changes. In this article, through comprehensive utilization of germination and seedling indoor test morphological indexes, physiological and biochemical index, and output index, combined with the evaluation mechanism of wheat's salt resistance, different salt tolerance types in the middle and lower reaches of the Yangtze River in Shandong province were studied; a collection of 100 wheat varieties and 11 wheat varieties planted over a large area were classified into three groups: strong salt resistance, medium salt resistance, and weak salt resistance. Comparative analysis of different wheat varieties' salt resistance evaluation mechanism was performed, as well as the analysis of the germination rate of wheat varieties, coleoptile growth situation, emergence rate, protect wheat seeding rate, tillering rate, seedling height, root length, seedling dry weight, wet weight, number of leaves, plant growth situation, agronomic characters of the Na+/K+ ratio, and other physiological and biochemical indexes such as salt resistance index. The evaluation mechanism of salt tolerance and the relationship of salt tolerance of different wheat varieties were obtained. The results showed that there were significant differences in salt tolerance among the 100 wheat varieties at the germination stage. Among them, three varieties, YM (Yangmai) 25, YM (Yangmai) 24, and EM (Emai) 25, had the strongest salt tolerance at the germination stage, reaching the level of the salt tolerance variety DK 961, and the salt tolerance was in the first level, while NM 17, NM 23, and other 21 varieties reached the level of the salt tolerance. These 24 varieties with strong salt tolerance at the germination stage can be used to screen the salt tolerance of wheat planted in the saline soil of Jiangsu coastal beach. [ABSTRACT FROM AUTHOR]

The ribophorin family (RPN) is an essential regulatory subunit of the proteasome. By influencing the ubiquitin-proteasome system activity, ribophorins (RPNs) are responsible for almost all physiology and pathology processes of mammalian cells. Nevertheless, little is known about the role of RPNs in HCC. In this work, we first evaluated the transcriptional levels and the prognostic and diagnostic value of RPNs based on the public database. Firstly, we found all RPNs were surprisingly consistently upregulated in HCC tissues. Moreover, the RPNs' expression pattern is correlated with HCC tumor grade. The TCGA HCC platforms' data indicated that RPN2, RPN3, RPN6, RPN9, RPN10, RPN11, and RPN12 have robust diagnosis values. Then, survival analysis revealed that the high expression of RPN1, RPN2, RPN4, RPN5, RPN6, RPN9, and RPN11 was correlated with unfavourable HCC overall survival. Then, genetic alteration, immune infiltration feature, gene-genes network, and functional enrichment for RPNs indicated that RPNs have many potential biosynthesis activities expert for UPS functions. Moreover, western blot and qRT-PCR results confirmed these results. The silencing of RPN6 and RPN9 significantly reduced HCC cells' proliferation, migration, and invasion ability in vitro. An in vivo tumor model further validated the oncogene effect of RPN6 on HCC cell growth. Moreover, RPN6 and RPN9 could promote cell migratory and invasive potential by affecting the epithelial-mesenchymal transition (EMT) process. In summary, this study suggests that the RPN family has the potential to be potential biomarkers and targets for HCC. [ABSTRACT FROM AUTHOR]

Objective. To study the optimum entry point and trajectory for anterior transpedicular root screw (ATPRS) placement into the lower cervical spine (LCS), so as to provide a basis for clinical application. Methods. A retrospective analysis of cervical CT images of patients who underwent cervical CT examination in the Spinal Surgery of Ningbo No. 6 Hospital from January 2020 to August 2021 was conducted. The data were obtained and modeled. On the coronal plane, the vertebral body (VB) between the anterior midline of cervical vertebral segments C3-7 and the left P line (by drawing the line parallel to the anterior midline of the VB at the intersection of the anterior edge of the Luschka's joint and the upper endplate) was equally divided into 9 zones (a-i). The ideal entry point and path of cervical ATPRS were designed and recorded. Additionally, 7 cadaveric specimens were selected, and the screw placement parameters were regenerated according to the above methods for screw placement. Results. Zone i of each segment, with the longest screw length, was the best area for screw placement. In all patients, the horizontal angles of vertebrae C3-7 in zones a, d, and g, zones b, e, and h, and zones c, f, and i showed a gradually decreasing trend. The sagittal angle range of C3-7 in all patients showed a gradually increasing trend in zones a-c, d-f, and g-i. The distance from the anterior midline of C3-7 to the P line increased in all patients, and the distance was longer in males than in females, with statistical significance. Pedicle screws were successfully inserted in all the 7 cadaveric specimens. Conclusions. ATPRS placement can be used for LCS internal fixation, and the precise screw placement parameters can be simulated by the software, which provides theoretical basis for its future clinical application. [ABSTRACT FROM AUTHOR]

The association between collagen type I alpha (COL1A) and chemoresistance has been verified in cancers. However, the specific role of COL1A2 in gastric cancer (GC) cell resistance to apatinib, a highly selective small-molecule inhibitor of vascular endothelial growth factor receptor 2, has not been investigated before. The purpose of this study was to explore the potential factors associated with COL1A2 regulation on GC cell apatinib resistance in vitro. With the aid of the Oncomine database and integrated bioinformatics methods, we identified COL1A2 overexpression in GC and its prognostic value. Mechanistically, the COL1A2 promoter has a distinct H3K27ac modification site and that E1A binding protein p300 (EP300) and twist family bHLH transcription factor 1 (TWIST1) can bind to the COL1A2 promoter, which in turn transcriptionally activated COL1A2 expression. In addition, overexpression of COL1A2 significantly promoted resistance to apatinib in GC cells, but knockdown of EP300 or TWIST1 remarkably inhibited COL1A2 expression and promoted sensitivity of GC cells to apatinib. Our findings demonstrated that the combination of EP300 and TWIST1 has a synergistically regulatory effect on COL1A2 expression, thus contributing to apatinib resistance in GC cells. [ABSTRACT FROM AUTHOR]

Despite dramatic responses to immune checkpoint inhibitors (ICIs) in patients with colon cancer (CC) harboring deficient mismatch repair (dMMR), more than half of these patients ultimately progress and experience primary or secondary drug resistance. There is no useful biomarker that is currently validated to accurately predict this resistance or stratify patients who may benefit from ICI-based immunotherapy. As hypoxic and acidic tumor microenvironment would greatly impair tumor-suppressing functions of tumor-infiltrating lymphocytes (TILs), we sought to explore distinct immunological phenotypes by analysis of the intratumoral hypoxia state using a well-established gene signature. Based on the Gene Expression Omnibus (GEO) (n = 88) and The Cancer Genome Atlas (TCGA) (n = 49) databases of patients with CC, we found that dMMR CC patients could be separated into normoxia subgroup (NS) and hypoxia subgroup (HS) with different levels of expression of hypoxia-related genes (lower in NS group and higher in HS group) using NMF package. Tumoral parenchyma in the HS group had a relatively lower level of immune cell infiltration, particularly CD8+ T cells and M1 macrophages than the NS group, and coincided with higher expression of immune checkpoint molecules and C-X-C motif chemokines, which might be associated with ICI resistance and prognosis. Furthermore, three genes, namely, MT1E, MT2A, and MAFF, were identified to be differentially expressed between NS and HS groups in both GEO and TCGA cohorts. Based on these genes, a prognostic model with stable and valuable predicting ability has been built for clinical application. In conclusion, the varying tumor-immune microenvironment (TIME) classified by hypoxia-related genes might be closely associated with different therapeutic responses of ICIs and prognosis of dMMR CC patients. [ABSTRACT FROM AUTHOR]

Aims. Although several studies have indicated that valproate (VPA) and oxcarbazepine (OXC) cause reproductive endocrine disorders and sexual dysfunction, there remains some controversy regarding these issues in males with epilepsy. This study is aimed at evaluating the effects of VPA and OXC on sexual function, sperm quality, and sex hormones in young males with epilepsy. Methods. Males with newly diagnosed epilepsy treated with VPA and OXC were recruited, and sexual function questionnaires (International Index of Erectile Function-5 (IIEF-5)), sperm quality, and sex hormone levels were assessed before treatment and at 6 months after treatment with VPA or OXC monotherapy. Results. Forty-four young males with epilepsy (23 treated with VPA, 21 treated with OXC) and 30 age-matched healthy individuals were recruited for our study. The sexual function, sperm quality, marriage rate, and fertility rate of these young males with epilepsy were lower than those of healthy controls. Sperm quality were significantly reduced in young male patients after 6 months of VPA administration. The level of follicle stimulating hormone (FSH) was increased in patients after OXC treatment. Meanwhile, sexual function and sperm quality were not affected. Conclusion. Sexual function and sperm quality were reduced in young males with epilepsy. VPA may exert a negative effect on sperm quality, whereas OXC has no harmful effect on sexual function and sperm quality in young males with epilepsy. [ABSTRACT FROM AUTHOR]

A superconducting quadrupole magnet based on the Canted-Cosine-Theta (CCT) type coil with a gradient field of 40 T/m and a bore diameter of 60 mm has been designed for the preresearch of two projects of high intensity accelerator facility (HIAF) and accelerator driven subcritical system (ADS). The magnet is comprised of two-layer coils embedded in the formers and the end plates for locating. The coil formers made of aluminum alloy are machined with grooves according to the drive equations of CCT for placing the wires. The existence of ribs between two adjacent wires can avoid accumulation of the electromagnetic force. It is important to take the mechanical design for the complex structure to avoid tensile stresses on the conductor and confine the stresses within a reasonable value. The stress analysis for the quadrupole magnet has been carried out considering the thermal shrinking due to cool down as well as the electromagnetic force on the coil. This paper reports the detailed stress analysis for the CCT quadrupole magnet structure, discusses the calculating results, and gives a reasonable mechanical design. [ABSTRACT FROM AUTHOR]

Plantaginis Semen (PS) has been used to promote diuresis and clear away dampness. Recent reports have shown that PS can be used to treat gouty nephropathy (GN). However, the action and mechanism of PS have not been well defined in treating GN. The present study aimed to define the molecular mechanisms of PS as a potential therapeutic approach to treat GN. A combination of network pharmacology and validation experiments in GN is used to understand the potential mechanism. Information on pharmaceutically active compounds in PS and gene information related to GN was obtained from public databases. The compound target network and protein-protein interaction network were constructed to study the mechanism of action of PS in the treatment of GN. The mechanism of action of PS in the treatment of GN was analyzed via Gene Ontology (GO) biological process annotation and Kyoto Gene and Genomics Encyclopedia (KEGG) pathway enrichment. Validation experiments were performed to verify the core targets. The GN rat model was prepared by the method of combining yeast and adenine. Hematoxylin-eosin (HE) staining was used to observe the morphology of renal tissue in rats. ELISA was applied to detect TGF-β1, TNF-α, and IL-1β levels in renal tissue. The expressions of TGF-β1, TNF-α, and IL-1β were determined using immunohistochemistry. Through the results of network pharmacology, we obtained 9 active components, 118 predicted targets, and 149 GN targets from the public database. Based on the protein-protein interaction (PPI), 26 hub genes for interaction with PS treating for GN were screened, including MMP9, TNF, IL1β, and IL6. The enrichment analysis results showed that the treatment of GN with PS was mainly involved in the TGF-β1 signaling pathway, MAPK signaling pathway, TNF signaling pathway, NF-κB signaling pathway, and PI3K Akt signaling pathway. Validation experiment results showed that PS could reduce the content of urinary protein and UA and deregulate the expression of TGF-β1, TNF-α, and IL-1β in the treatment of GN. The molecular mechanism of PS in the treatment of GN indicated the synergistic features of multicomponent, multitarget, and multipathway of traditional Chinese medicine, which provided an essential scientific basis for further elucidating the mechanism of PS in the treatment of GN. [ABSTRACT FROM AUTHOR]

Epileptic seizures are considered to be a brain network dysfunction, and chronic recurrent seizures can cause severe brain damage. However, the functional brain network underlying recurrent epileptic seizures is still left unveiled. This study is aimed at exploring the differences in a related brain activity before and after chronic repetitive seizures by investigating the power spectral density (PSD), fuzzy entropy, and functional connectivity in epileptic patients. The PSD analysis revealed differences between the two states at local area, showing postseizure energy accumulation. Besides, the fuzzy entropies of preseizure in the frontal, central, and temporal regions are higher than that of postseizure. Additionally, attenuated long-range connectivity and enhanced local connectivity were also found. Moreover, significant correlations were found between network metrics (i.e., characteristic path length and clustering coefficient) and individual seizure number. The PSD, fuzzy entropy, and network analysis may indicate that the brain is gradually impaired along with the occurrence of epilepsy, and the accumulated effect of brain impairment is observed in individuals with consecutive epileptic bursts. The findings of this study may provide helpful insights into understanding the network mechanism underlying chronic recurrent epilepsy. [ABSTRACT FROM AUTHOR]

Objective. Coronary heart disease (CHD) has been regarded as a serious and common disease in the modern society. This study aims to investigate the effect of Granule of BU-XIN RUAN-MAI (BXRM) on angina pectoris of coronary heart disease and to explore the molecular mechanisms underlying Granule of BU-XIN RUAN-MAI-mediated protective activity against this disease. Methods. The effects of Granule of BU-XIN RUAN-MAI on clinical symptoms of patients' angina were indicated by hemorheology indicators including high shear of blood viscosity, low shear of blood viscosity, plasma viscosity, erythrocyte rigidity index, D-D dimer, fibrinogen content, and lipid content. The effects of Granule of BU-XIN RUAN-MAI on isoprenaline-induced myocardial cell injury were determined by conducting H&E staining and by performing ELISA to examine the serum content of MDA, SOD, Na+/K+-ATPase, cAMP, and the content of inflammatory factors in isoprenaline-induced rats. Meanwhile, western blot and real time PCR were used to determine the expression of genes involved in oxidation and energy metabolism, and real time PCR was also used for determination of miR-542-3p expression. Luciferase reporter assay was conducted to test the binding sites of miR-542-3p on GABARAP 3′UTR. The chemical compositions of Granule of BU-XIN RUAN-MAI were determined by liquid LC-QTOF-MS. Results. Granule of BU-XIN RUAN-MAI significantly attenuated the clinical symptoms of patients' angina by improving the patients' heart rate and by decreasing the level of hemorheology indicators and also by reducing the serum content of TC, TG, LDL, and elevated HDL content. H&E staining demonstrated that Granule of BU-XIN RUAN-MAI ameliorated the myocardial ischemia in a dose-dependent manner. Besides, Granule of BU-XIN RUAN-MAI downregulated serum MDA content and upregulated the content of SOD, Na+/K+-ATPase, and cAMP in isoprenaline-induced rats. Granule of BU-XIN RUAN-MAI significantly improved oxidation stress by increasing PPARα expression, and it inhibited inflammation by downregulating expression and contents of IL-6, IL-1β, and TNF-α. Then, Granule of BU-XIN RUAN-MAI-containing serum increased the SOD content, and reduced the MDA content in angiotensin II-stimulated HUVEC cells. The granule of BU-XIN RUAN-MAI-containing serum obviously downregulated protein expressions of P40phox, P47phox, and P67phox in plasma membrane, and it significantly increased protein levels of P40phox, P47phox, and P67phox in the cytoplasm of HUVEC cells. Furthermore, GABARAP was reduced in heart tissues of ISO-induced rats and in angiotensin II-stimulated cell lines, and GABARAP was required for the inhibitory activity of Granule of BU-XIN RUAN-MAI on oxidation and inflammation in vivo and in vivo. GABARAP could be upregulated by Granule of BU-XIN RUAN-MAI by inhibiting the expression of miR-542-3p, which may significantly enhance oxidation and inflammation by targeting GABARAP in cardiomyocytes. Moreover, the silencing of GABARAP could obviously reverse the granule of BU-XIN RUAN-MAI-mediated protective activity against coronary heart disease, and interfering GABARAP expression also could partly block the anti-miR-542-3p-controlled oxidation and inflammation in cardiomyocytes. Besides, salidroside, loganin, and polydatin were the main compounds of granules of BU-XIN RUAN-MAI. Conclusion. Granule of BU-XIN RUAN-MAI is an excellent prescription for treatment of coronary heart disease by suppressing inflammation and NAPDH-mediated oxidative stress. The miR-542-3p/GABARAP axis is required for Granule of BU-XIN RUAN-MAI, exhibiting its protective activity against the pectoris of coronary heart disease. [ABSTRACT FROM AUTHOR]

Lactobacillus plantarum, a probiotic, has a high survival rate and high colonization ability in the gastrointestinal tract. Tolerance to the gastrointestinal environment and adhesion to intestinal epithelial cells by some Lactobacillus species (excluding L. plantarum) are related to luxS/AI-2. Here, the role of luxS in tolerance to simulated digestive juice (SDJ) and adhesion to Caco-2 cells by L. plantarum KLDS1.0391 (hereafter, KLDS1.0391) was investigated. The KLDS1.0391 luxS mutant strain was constructed by homologous recombination. When luxS was deleted, acid and bile salt tolerance and survival rates in SDJ significantly decreased (𝑝 < 0.05 for all). The ability of the luxS deletion strain to adhere to Caco-2 cells was markedly lower than that of the wild-type strain (𝑝 < 0.05). The ability of the luxS mutant strain to adhere (competition, exclusion, and displacement) to Escherichia coli ATCC 25922 was significantly lower than that of the wild-type strain (𝑝 < 0.05 for all). A significant decrease was noted only in the exclusion adhesion inhibition of the luxS mutant strain to Salmonella typhimurium ATCC 14028 (𝑝 < 0.05). These results indicate that the luxS gene plays an important role in the gastrointestinal environment tolerance and adhesion ability of KLDS1.0391. [ABSTRACT FROM AUTHOR]

The resistant dextrin was added to rice, red, and white wine, and then the mechanism behind the improvement in appearance, aroma, taste, and flavor were analyzed. Sensory evaluation showed that the organoleptic quality of the rice wine and red wine were improved by adding 5% (wt/vol) resistant dextrin, whereas no significant improvement was noted in the white wine. There were significant negative correlations between viscosity and surface tension in the rice wine and red wine when different concentrations of resistant dextrin (1, 5, 10, 15, and 20% wt/vol) were added but not in the white wine ( p < .05). After analyzing the level of polyphenols in wines, resistant dextrin combined with polyphenols was produced and verified. These results indicated that the cause of the decrease in surface tension and increase in viscosity obtained by adding resistant dextrin to rice wine and red wine could be the combination of resistant dextrin with polyphenols, which resulted in an increase in the organoleptic quality of the wines. Practical applications Adding 5% (wt/vol) resistant dextrin to rice wine and red wine might combine with polyphenols in these wines to increase the viscosity and decrease the surface tension and thus ultimately improve the organoleptic quality of the wines. Our results provided basic information for the application of resistant dextrin in food industry. [ABSTRACT FROM AUTHOR]

Background. Patients suffering from stroke exhibit different levels of capability in retroflex tongues, in our clinical observation. This study aims to derive the association of tongue retroflexibility with the degree of severity for stroke patients. Methods. All ischemic stroke patients were collected from August 2010 to July 2013 in the Stroke Center, Changhua Christian Hospital, Taiwan. All participants underwent medical history collection and clinical examination, including tongue images captured by ATDS. Statistical analysis was performed to compare the differences of ischemic stroke patients with and without retroflex tongue. Result. Among the total of 308 cases collected, 123 patients cannot retroflex their tongues, that is, the non-RT group. The length of stay in the non-RT group, 32.0 ± 21.5, was longer than those of the RT counterparts, 25.9 ± 14.4 (p value: 0.007). The NIHSS on admission, 14.1 ± 7.8 versus 8.9 ± 5.2, was higher and the Barthel Index upon admission, 18.6 ± 20.7 and 35.0 ± 24.2, was lower for the non-RT patients than that of the RT counterparts. Also, the non-RT patients account for 60.2% and 75.6% for Barthel Index ≤ 17 and NIHSS ≥ 9, respectively. Conclusion. The stroke patients in non-RT group showed significantly poor prognosis and were more serious in the degree of severity and level of autonomy than RT group, indicating that the ability to maneuver tongue retroflex can serve as a simple, reliable, and noninvasive means for the prognosis of ischemic stroke patients. [ABSTRACT FROM AUTHOR]