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Background: Stigma is among the most prevalent and disturbing consequences of being infertile among women, yet it remains unknown whether fertility stigma is affected by irrational parenthood cognitions (IPC). The current study aimed to assess IPC, infertility stigma, and their interrelationship among a group of Chinese women referred to an infertility center in Changsha, Hunan, China. Methods: A cross-sectional study was conducted among 376 women seeking treatment for infertility in Changsha City, China. Pearson correlation test was used to explore the association between IPC and infertility stigma, while multivariate linear regression was used to explore the independent influencing factors of infertility stigma. Results: Participants had a mean score of 42.41 ± 13.03 for IPC and 62.89 ± 24.50 for ISS. IPC was highly correlated with infertility stigma with a large effect size (r = 0.55, p

Transformer oil plays the role of heat dissipation and insulation in power transformers, and its electrical and thermal characteristics are directly related to the stable operation of the transformer. At the same time, it is important to master the electric–thermal characteristics of transformer oil for transformer state evaluation, latent fault prediction, and maintenance planning. Based on this, the gas production rule and electrical characteristics of transformer oil under accelerated aging are studied in this paper. First, the experimental platform for power transformer aging is established to accelerate the aging of power transformers. Second, the accelerated aging transformer oil is taken as the research object, and the power frequency, DC, lightning, and gas chromatography are measured and analyzed. Finally, a transformer oil aging evaluation model is established, which takes into account four factors: carbon and oxygen gas factors in transformers, life loss factors calculated by hotspot temperature, hydrocarbon gas factors dissolved in transformer oil, and oil quality factors, and conducts aging evaluation. The conclusion shows that the T parameter proposed in this paper can effectively evaluate the quality of transformer oil. When T is less than or equal to 0.6, there is no aging of the oil. When T is greater than 0.6 and less than 1, the transformer oil has been aging, but it is not manifested. Those are parameters whose chromatography and breakdown voltage are not far beyond the IEEE standard. When T = 1, the aging of oil with significant changes in gas content and breakdown voltage can be observed. When T is greater than 1, the oil has undergone serious aging.

The converter transformer is an electrical equipment with a symmetrical structure. Due to its symmetry, the ground current should be small when the core is grounded at one point. The research and analysis of grounding currents in the converter transformer can effectively help staff to judge the working state of the converter transformer. Therefore, it is very meaningful to study the calculation problem of the grounding current under the multi-point grounding state. First of all, a homogenization modeling method considering the characteristics material of the core silicon steel sheet is proposed; secondly, on this basis, the finite element simulation model of multi-point grounding of the core of the converter transformer is established and simulated; then a multi-point grounding test was conducted using the shrinkage model of the converter transformer to verify the finite element simulation results; the final consequence show that the homogenization modeling method can effectively calculate the grounding current at multi-grounding.

For the detections of typical faults gases, namely NO2 and O3, in the air insulated switchgears (AIS), we purpose Au- and B-embedded graphene (Au- and B-graphene) as promising sensing material using the first-principles theory. We firstly investigate the Au- and B-embedding behavior on the graphene, and find that both Au and B atoms are chemical stably adsorbed on the vacancy-defected graphene; in the gas adsorbed systems, it is found that NO2 and O3 adsorptions on Au-graphene are identified as chemisorption, while those on B-graphene are physisorption. The electronic properties of Au- and B-graphene in the gas adsorptions indicate the resistance-type sensing potential of Au-graphene upon O3 as well as that of B-graphene upon NO2. Besides, Au-graphene is a promising WF-based gas sensor upon NO2 and O3. The findings in this work uncover the strong potentials of Au- and B-graphene for detections of the NO2 and O3 in AIS, which gives the guidance to explore novel graphene-based gas sensors for applications in the power system.

When the converter transformer core is grounded at multi-points, a fault loop will be formed and a circulation will be generated, leading to local overheating of the magnetic core and decomposition of insulating oil. Therefore, the converter transformer core will be single point grounded. As a rare internal lead of converter transformer, the ground current on the core ground lead can often reflect the running state of converter transformer. In this paper, theoretical analysis, modeling simulation and experimental research are carried out on the ground current of converter transformer at one point. Firstly, according to the structure characteristics of converter transformer, the analytical modeling of ground current is carried out. Secondly, based on the structure characteristics of oil paper insulation, the equivalent capacitance of converter transformer is calculated. Then, the analytical and finite element simulation model of converter transformer is established, and the ground current of converter transformer is calculated. Finally, the correctness of the proposed scheme is verified by measuring the grounding current of converter transformer core.

Abstract Objectives This study was designed to investigate to test the effect of exosomes from urine-derived mesenchymal stem cells (USCs) on the survival and viability of aging retinal ganglion cells (RGCs), and explored the preliminary related mechanisms. Methods Primary USCs were cultured and identified by immunofluorescence staining. Aging RGCs models were established by D-galactose treatment and identified by β-Galactosidase staining. After treatment with USCs conditioned medium (with USCs removal), flow cytometry was performed to examine the apoptosis and cell cycle of RGCs. Cell viability of RGCs was detected by Cell-counting Kit 8 (CCK8) assay. Moreover, gene sequencing and bioinformatics analysis were applied to analyze the genetic variation after medium treatment in RGCs along with the biological functions of differentially expressed genes (DEGs). Results The number of apoptotic aging RGCs was significantly reduced in USCs medium-treated RGCs. Besides, USCs-derived exosomes exert significant promotion on the cell viability and proliferation of aging RGCs. Further, sequencing data analyzed and identified DEGs expressed in aging RGCs and aging RGCs treated with USCs conditioned medium. The sequencing outcomes demonstrated 117 upregulated genes and 186 downregulated genes in normal RGCs group vs aging RGCs group, 137 upregulated ones and 517 downregulated ones in aging RGCs group vs aging RGCs + USCs medium group. These DEGs involves in numerous positive molecular activities to promote the recovery of RGCs function. Conclusions Collectively, the therapeutic potentials of USCs-derived exosomes include suppression on cell apoptosis, enhancement on cell viability and proliferation of aging RGCs. The underlying mechanism involves multiple genetic variation and changes of transduction signaling pathways.

Intermittent partial discharge has become an essential threat to the safety and stability of high voltage electrical equipment. In order to reduce the sudden insulation breakdown failure due to the intermittent and latent partial discharge of the operating equipment, this paper analyzes the discharge characteristics of the intermittent partial discharge in the constant voltage mode. The UHF partial discharge spectrum of typical intermittent partial discharges is obtained, and the intermittent discharges are divided into low-risk and high-risk categories by adopting PCA and FCM cluster algorithms. Aiming at the characteristics of intermittent partial discharge and the on-line monitoring method of partial discharge, a partial discharge signal collection method based on dynamic frequency is proposed. An intelligent monitoring system of intermittent partial discharge is designed to acquire partial discharge signals initially locate defects. Then the BP neural network method is applied to automatically evaluate and early warn the internal insulation status. The test concluded that the designed monitoring system for intermittent partial discharge could dynamically track and warn the low-risk and high-risk, and evaluate the insulation status of the equipment.

Converter transformer is the key equipment in UHVDC transmission. If a local overheating fault occurs, it will inevitably form a local hot spot on the core, winding or other structural parts. Among these faults, multipoint grounding and interlaminar short circuit faults account for 30–50% of core accidents. The continuous overheating of 150–250 °C will cause ablation on the silicon steel sheet, which will destroy the insulation material and reduce the insulation performance. In severe cases, it will cause thermal expansion, resulting in local deformation or displacement of the core. Considering the scale of size and temperature parameters, the scale model of converter transformer is established based on the principle of constant magnetic flux density. By using the homogenization theory, the scaled model under multipoint grounding and interlaminar short circuit fault is simulated by electromagnetic heat. First, the single-phase four-column model of the core is established according to the scaled principle, and the core is refined. Secondly, taking the refined model as the research object, the magnetic thermal coupling simulation and analysis are carried out under multi-point grounding and interlaminar short circuit fault, and the magnetic density, eddy current loss and temperature distribution on each lamination are obtained. Finally, the correctness of the simulation is verified by the one-dimensional eddy current loss analytical equation, which provides a reference for the local overheating problem of converter transformers.

Abstract Background It remains unclear whether polycystic ovary syndrome (PCOS) is an independent risk factor for pregnancy complications in women undergoing assisted reproductive technology (ART) treatment. For the integrative treatment of PCOS patients, it is still important to investigate the pregnancy outcomes of PCOS patients after adjusting for potential biases, such as body mass index, embryo quality and endometrial preparation method. Methods This retrospective cohort study ultimately included a total of 336 PCOS patients who conceived after single thawed blastocyst transfer in the PCOS group and 2,325 patients in the control group from January 2018 to December 2020. A propensity score matching (PSM) model was used, and 336 PCOS patients were matched with 336 patients in the control group. Results Before PSM, no differences in the miscarriage rate, pregnancy complication rate, preterm birth rate, or live birth rate were found between the PCOS group and the control group. After PSM, the late miscarriage rate of the PCOS group was significantly higher than that of the control group (3.3% vs. 0.6%, P = 0.040), although the early miscarriage rates were similar (14.0% vs. 13.7%). The rates of pregnancy complications, preterm birth and live birth in the PCOS group were comparable to those in the matched control group (P = 0.080, P = 0.105, P = 0.109, respectively). The neonatal weights of male infants and female infants were similar between the two groups (P = 0.219, P = 0.169). Subgroup analysis showed that PCOS patients with homeostasis model assessment of insulin resistance (HOMA-IR) levels ≥ 2.49 had a significantly increased risk of preterm birth compared with those with HOMA-IR levels

BackgroundSOX17 has been identified as a critical factor in specification of human primordial germ cells, but whether SOX17 regulates development of germ cells after sex differentiation is poorly understood. MethodsWe collected specimens of gonadal ridge from an embryo (n=1), and ovaries of foetuses (n=23) and adults (n=3). Germ cells were labelled with SOX17, VASA (classic germ cells marker), phosphohistone H3 (PHH3, mitosis marker) and synaptonemal complex protein 3 (SCP3, meiosis marker). ResultsSOX17 was detected in both cytoplasm and nucleus of oogonia and oocytes of primordial and primary follicles from 15 to 28 gestational weeks (GW). However, it was exclusively expressed in cytoplasm of oogonia at 7 GW, and in nucleus of oocytes in secondary follicles. Co-expression rates of SOX17 in VASA+ germ cells ranged from 81.29% to 97.81% in foetuses. Co-staining rates of SOX17 and PHH3 or SCP3 were 0%-34% and 0%-57%, respectively. Interestingly, we distinguished a subpopulation of SOX17+VASA- germ cells in fetal ovaries. These cells clustered in the cortex and could be co-stained with the mitosis marker PHH3 but not the meiosis marker SCP3.ConclusionsThe dynamic expression of SOX17 was detected in human female germ cells. We discovered a population of SOX17+ VASA- germ cells clustering at the cortex of ovaries. We could not find a relationship between mitosis or meiosis and SOX17 or VASA staining in germ cells. Our findings provide insight into the potential role of SOX17 involving germ cells maturation after specification, although the mechanism is unclear and needs further investigation.

Abstract In order to solve the problems of poor thermal stability and high frequency noise of transformer in traditional DC‐DC converter, the medium frequency transformer in isolated DC‐DC converter is designed and studied, which adopts 0.15 mm ultra‐thin silicon steel sheet. Firstly, the magnetism of ultra‐thin silicon steel is measured by using single‐piece silicon steel sheet measuring device, and the B‐H curves and B‐P curves at different frequencies are given. According to the magnetic measurement results, the electromagnetic scheme of three port medium frequency transformer is designed by AP method and applied the particle swarm algorithm to further design under the constraint of loss minimization. Secondly the three‐winding transformer of DC‐DC converter is optimized and simulated. The magnetic flux density, loss, temperature field distribution, output voltage and current waveform of the transformer under different working conditions are given. Finally, the 20 kW DC‐DC converter was manufactured and the magnetic characteristics of the medium frequency transformer were experimented to verify the correctness of the proposed scheme.

When the transformer is running, the vibration which is generated in the core and winding will spread outward through the medium of metal, oil, and air. The magnetic field of the core changes with the variation of the transformer excitation source and the state of the core, so the corresponding vibration and noise change. Therefore, the vibration and noise of the transformer contain a lot of information. If the information can be associated with the fault characteristics of the transformer, it is significant to evaluate the running state of the transformer through the vibration and noise signal, which improve the intelligence, safety, and stability of the transformer operation. Based on this, modeling and simulation of transformer multi-point grounding, DC bias, and short-circuit between silicon steel sheets fault are first carried out in this paper, and vibration and noise distribution of transformer under different faults are given. Second, a fault diagnosis method based on transformer vibration and noise characteristics is proposed. In the process of implementation, vibration and noise signals under multi-point grounding, DC bias, and short-circuit between silicon steel sheets are taken as the sample data, and the probabilistic neural network algorithm is used to effectively predict the transformer fault. Finally, the effectiveness of the proposed scheme is verified by identifying the simulation faults-the proposed fault diagnosis method based on PNN can be effectively applied to transformer.

BackgroundSuccessful cause-related marketing (CRM) campaigns can help companies stand out from their competitors; however, CRM may not have pleasant outcomes, even if it receives substantial investment. ObjectiveThis research aimed to investigate how gamified CRM projects influence consumers’ favorability. MethodsWe introduced 3 different CRM projects in 3 different studies. Every project had 2 versions according to the level of gamification, and participants were randomly assigned into these 2 groups. Additionally, we used a 2 (gamification: lower, higher) 2 (rules presentation: without visual cues, with visual cues) between-subjects design to test the moderation role of rules presentation in gamified CRM projects. ResultsIn Study 1, we identified that the highly gamified CRM program induces more enjoyment (F1,139=21.11, P

Dissolved gas analysis (DGA) is a common technology used in the on-site maintenance of oil-immersed power transformers in the power industry at present. However, when the content of dissolved gas in the oil reaches the attention value DGA method can effectively diagnose the operating state of the transformer. Due to the lack of gas production data of free gas which was detected when the faults occur, DGA method cannot timely diagnose the transformer status. To solve the above problem, an experimental platform is built for studying the free gas generation law in oil-immersed transformers under discharge faults, and the characteristic free gas information under discharge fault of transformer is obtained through the experiment. It is found that the existing DGA method cannot accurately analyze the types and severity of sudden serious insulation faults. When high-energy partial discharge fault occurred in the equipment, CO, CO2, CH4, and H2 will be collected in large quantities on the oil surface. These four gases can be used as the basis for characterizing high-energy partial discharge faults. When spark discharge occurred in the equipment, C2H6, C2H4, and C2H2 also be collected on the oil surface which can be used as a diagnostic basis for spark discharge. Moreover, it is found that the existing three-ratio method cannot be used for accurate analysis of oil free characteristic gas, so it is necessary to explore new diagnostic methods. The aim of this study is to explore the pattern of free gas production law by experiments when discharge faults occur and to provide data for a new diagnostic method.

In recent years, the calculation of the core grounding current of the converter transformer is difficult, low precision, and time-consuming, especially when the core is grounded by multiple points. This makes it difficult to analyze the core grounding current. To improve the accuracy of the calculation and reduce the complexity of the calculation, this paper carries out analytical calculation, simulation analysis, and experimental research on the grounding current of the converter transformer core. Firstly, a calculation method of core grounding current considering the winding connection of the converter transformer is proposed. In the implementation process, the converter transformer circuit model is established and the influence of saturation characteristics is considered, and the core grounding current is calculated and analyzed. Secondly, the grounding current of the converter transformer core is calculated by the finite element method (FEM). Finally, the proposed scheme is verified by experiments. The results show that the analytical method is close to the FEM and the experimental method, which indicates that the analytical method proposed can meet the accuracy requirements of engineering in this paper, and provides a new scheme for fast and accurate calculation of the grounding current of the converter transformer core.

Abstract The information of dissolved gas in transformer oil can reflect the potential fault in oil immersed power transformer. In order to improve the accuracy of transformer fault diagnosis, a transformer fault diagnosis model based on IFA‐LPboost‐CART is proposed here. First, a LPboost‐CART model is established. The classification and regression tree (CART) are used as the weak classifiers, and the linear programming boosting (LPboost) ensemble learning method is used to adjust the weight of each weak classifier to construct a strong classifier. Then the improved firefly algorithm (IFA) is adopted to optimize the number of CART and the maximum number of splits of CART in LPboost‐CART to obtain the IFA‐LPboost‐CART model. The experimental results show that, compared with the existing methods, such as CART and support vector machine (SVM), the proposed IFA‐LPboost‐CART model has higher fault diagnosis accuracy, which can provide technical support for transformer fault diagnosis.

BackgroundGastrodia elata Blume (GEB), a traditional Chinese medicine, has been widely used to treat dizziness, numbness of limbs, and infantile convulsion, among other issues. Gastrodin is the main component of GEB. This meta-analysis aimed to evaluate the efficacy and safety of gastrodin in the treatment of migraine.MethodsTen electronic databases, namely the Cochrane Library, Embase, EBSCO, PubMed, Web of Science, CENTRAL, CNKI (China National Knowledge Infrastructure), CBM (Chinese Biomedicine Database), WanFang, and VIP (Chinese Scientific Journals Database), were searched for randomized controlled trials (RCTs) of gastrodin for migraine published before September 2021. The data were analyzed by RevMan 5.3 software and evaluated by GRADEpro.ResultsA total of 1,332 subjects were included in 16 RCTs. The meta-analysis showed that gastrodin was significantly effective in treating migraine (RR = 1.21, 95%CI = [1.17, 1.27]), reducing the pain degree (MD = −1.65, 95% CI = [−2.28, −1.02]), reducing the frequency of migraine attack (SMD = −2.77, 95% CI = [−3.92, −1.62]), shortening the duration of migraine attack (SMD = −1.64, 95% CI = [−2.35, −0.93]), and slowing average arterial cerebral blood flow velocity (SMD = −3.19, 95% CI = [−5.21, −1.17]), as well as being safe.ConclusionsThis systematic review revealed gastrodin is effective and safe in the treatment of migraine.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=197094, identifier: CRD42020197094.

As a new form of online reviews, Q&A reviews have been recently used by many e-commerce platforms to compensate for the weaknesses and problems related to trust and helpfulness found in traditional online reviews. This research documents what motivates people to share products or purchasing knowledge with others through Q&A reviews and why e-commerce platforms should place an emphasis on Q&A reviews. Importantly, our results provide evidence that, when receiving feedback (i.e., comments and likes), people are more likely willing to share knowledge with others and will have a higher level of loyalty. We believe that this study contributes to knowledge sharing and the e-commerce literature, and also has practical implications.

Promoting energy expenditure is known to curb obesity and can be exploited for its treatment. Our previous study has demonstrated that activation of HSF1/PGC-1α axis efficiently induced mitochondrial biogenesis and adaptive oxidation and thus ameliorating lipid accumulation, however, whether it can be a therapeutic approach for metabolic disorders treatment needs explored. Here, a high-efficient and specific HSF1/PGC-1α activator screening system was established and the natural clinical liver-protecting agent matrine was identified as a robust HSF1/PGC-1α activator. Matrine treatment efficiently induced mitogenesis and thermogenic program in primary mouse adipose stem cell derived adipocytes by enriching HSF1 to the promoter of Pgc-1α. Deficiency of PGC-1α in adipocytes diminished the browning induction ability of matrine. Oral administration of matrine to the obese mice induced by high fat and high cholesterol diet increased energy expenditure and corrected the degeneration of thermogenesis in brown adipose tissue (BAT). Also, matrine treatment markedly induced the transformation of brown-like adipocytes in subcutaneous white adipose tissue (sWAT) via a mechanism of HSF1/PGC-1α, thereby attenuating obesity and myriads of metabolic disorders. This led to an improvement in adaptive thermogenesis to cold stimuli. These findings are of great significance in understanding the regulation mechanisms of the HSF1/PGC-1α axis in thermogenesis and providing a novel therapeutic approach for obesity treatment. Matrine may have potential therapeutic implications for the treatment of obesity in clinics.

The audible signal (20 Hz to 20 kHz) generated during the operation of a dry-type reactor is one of the key features to evaluate its operation state. However, at present, the time/frequency domain features of the audible signal under typical insulation defects are not clear, which makes it difficult to effectively carry out the fault diagnosis of the dry-type reactor based on audible signals. Based on this, the audible signal features under typical insulation defect discharge of the dry-type reactor are studied in this paper. Three typical insulation defect discharge models (metal protrusion defect, pollution defect, and metal foreign bodies defect) are simulated; then, the discharge acoustic signals are collected under the voltage of 8 kV. Analysis of acoustic signal features shows that the acoustic signal of metal protrusion defect discharge occurs in the positive half cycle of power frequency with the cycle of 20 ms. Both pollution defect discharge and metal foreign bodies defect discharge show intermittent discharge; during the discharge, the discharge acoustic signal of pollution defect has features similar to that of metal protrusion defect, while the discharge of metal foreign bodies defect shows randomness with a larger amplitude of discharge acoustic signal (up to 110 dB). Based on the frequency domain feature vectors’ extraction, it is found that the odd harmonic component of the metal protrusion defect discharge acoustic signal accounts for more than twice the even-order harmonic, and the high-frequency energy (12.5–25 kHz) is the main component. The discharge acoustic signal of the metal foreign bodies defect is mainly low-frequency energy, and the high-frequency energy proportion of pollution defect discharge acoustic signal is similar to that of low-frequency energy. In addition, the variance of high-frequency energy ratio (Rhf) of the metal foreign bodies defect discharge acoustic signal is 5.25 and 21 times that of the metal protrusion defect and pollution defect. This study provides some technical support for further detection and assessment of the operation state of the dry-type reactor based on audible signals.

Partial discharge (PD) ultrasonic detection is an early sign of the insolation defects of power transformers. The early diagnosis of PD requires the high sensitivity and reliability of ultrasonic sensing systems. For this purpose, a reformative PD ultrasonic sensing system based on phase-shifted FBG (PS-FBG) was demonstrated. By using PS-FBG as the ultrasonic sensing unit, the ultrasonic sensing system improved the response to the ultrasonic signal and overcame the electromagnetic noise. To compensate for the influence of temperature change on the ultrasonic sensing system, an automatic wavelength scanning demodulating method was carried out. The wavelength spanning strategy was optimized based on the principle of cross-correlation, in order to quicken the spanning. A PD detection test in the transformer oil was conducted, and the result shows that PS-FBG was 17.5 times more sensitive than PZT. Because of the better ultrasonic response, the proposed system was able to achieve the early diagnosis of insolation faults in a power transformer.

Research has shown that HMGB1 can activate dendritic cells (DCs), but its molecular mechanisms are not clear. In this study, we reported that the myeloid dendritic cells (mDCs) were activated in the peripheral blood of SLE patients, and the activation of mDCs was associated with the up-regulation of HMGB1 and mTOR. After stimulated by HMGB1, expression of mTOR and its substrates P70S6K and 4EBP1 in dendritic cells increased considerably (P < 0.01). The expression of HLA-DR, CD40, and CD86 on dendritic cells also significantly increased following these stimuli (P < 0.01). In addition, stimulation with HMGB1 enhanced cytokine (IL-1β, IL-6, and TNF-a) production in dendritic cells. In contrast, the HMGB1-mediated expression of HLA-DR, CD40, and CD86 on dendritic cells and production of IL-1β, IL-6, and TNF-α were reduced by rapamycin. Rapamycin can inhibit HMGB1-induced activation of mDCs and secretion of pro-inflammatory cytokines. These findings indicated that HMGB1activates mDCs by up-regulating the mTOR pathway in SLE.

Traumatic brain injury (TBI) contributes to hypocoagulopathy associated with prolonged bleeding and hemorrhagic progression. Bloodletting puncture therapy at hand twelve Jing-well points (BL-HTWP) has been applied as a first aid measure in various emergent neurological diseases, but the detailed mechanisms of the modulation between the central nervous system and systemic circulation after acute TBI in rodents remain unclear. To investigate whether BL-HTWP stimulation modulates hypocoagulable state and exerts neuroprotective effect, experimental TBI model of mice was produced by the controlled cortical impactor (CCI), and treatment with BL-HTWP was immediately made after CCI. Then, the effects of BL-HTWP on the neurological function, cerebral perfusion state, coagulable state, and cerebrovascular histopathology post-acute TBI were determined, respectively. Results showed that BL-HTWP treatment attenuated cerebral hypoperfusion and improve neurological recovery post-acute TBI. Furthermore, BL-HTWP stimulation reversed acute TBI-induced hypocoagulable state, reduced vasogenic edema and cytotoxic edema by regulating multiple hallmarks of coagulopathy in TBI. Therefore, we conclude for the first time that hypocoagulopathic state occurs after acute experimental TBI, and the neuroprotective effect of BL-HTWP relies on, at least in part, the modulation of hypocoagulable state. BL-HTWP therapy may be a promising strategy for acute severe TBI in the future.

Abstract Background Ovarian cancer constitutes one of the most lethal gynecologic malignancies for females. Currently, early detection strategies and therapeutic options for ovarian cancer are far from satisfactory, leading to high diagnosis rates at late stages and disease relapses. New avenues of therapy are needed that target key processes in ovarian cancer progression. While a variety of non-coding RNAs have been proven to regulate ovarian cancer metastatic progression, the functional roles of RNA-binding proteins (RBPs) in this process are less well defined. Results In this study, we identify that the RBP sorbin and SH3 domain containing 2 (SORBS2) is a potent suppressor of ovarian cancer metastatic colonization. Mechanistic studies show that SORBS2 binds the 3′ untranslated regions (UTRs) of WFDC1 (WAP four-disulfide core domain 1) and IL-17D (Interleukin-17D), two secreted molecules that are shown to act as metastasis suppressors. Enhanced expression of either WFDC1 or IL-17D potently represses SORBS2 depletion-mediated cancer metastasis promotion. By enhancing the stability of these gene transcripts, SORBS2 suppresses ovarian cancer invasiveness and affects monocyte to myeloid-derived suppressor cell and M2-like macrophage polarization, eliciting a tumor-suppressive immune microenvironment. Conclusions Our data illustrate a novel post-transcriptional network that links cancer progression and immunomodulation within the tumor microenvironment through SORBS2-mediated transcript stabilization.

To evaluate the clinical value of serum α-L-fucosidase (AFU), 5’-nucleotidase (5’-NT) and alpha fetoprotein (AFP) as biomarkers for primary hepatocellular carcinoma (PHC) diagnosis. Methods: Thirty six primary hepatocellular carcinoma (PHC) patients and 36 healthy controls were recruited in this study from February 2014 to January 2016 in the Second People’s Hospital of Tianjin. The serum level of AFU, 5’-NT and AFP were examined and compared between the two groups. The diagnostic sensitivity, specificity area under the receiver operating characteristic (ROC) curve were calculated by STATA11.0 software. Results: The serum level of AFU, 5’-NT, AFP were 30.87±10.43(U/L), 5.58±3.89(U/L), 233.60±226.60 (μg/L) respectively for primary hepatocellular carcinoma group and 19.96±6.73 (U/L), 1.87±0.84 (U/L), 16.64±14.17 (μg/L) for healthy control groups. The serum level of AFU, 5’-NT and AFP in primary hepatocellular carcinoma group were significant higher than those of healthy control group (P

Albiflorin (AF) is a small molecule (MW 481) isolated from Paeoniae radix, a plant used as a remedy for various conditions with pathogenesis shared by metabolic diseases. Reported here is our characterization of its therapeutic profiles in three mouse models with distinctive pathological features of metabolic syndrome (MetS). Our results firstly showed that AF alleviated high fat (HF) induced obesity and associated glucose intolerance, suggesting its therapeutic efficacy for MetS. In the type 2 diabetes (T2D) model induced by a combination of HF and low doses of streptozotocin, AF lowered hyperglycaemia and improved insulin-stimulated glucose disposal. In the non-alcoholic steatohepatitis-like model resulting from a HF and high cholesterol (HF-HC) diet, AF reversed the increased liver triglyceride and cholesterol, plasma aspartate aminotransferase, and liver TNFα mRNA levels. Consistent with its effect in promoting glucose disposal in HF-fed mice, AF stimulated glucose uptake and GLUT4 translocation to the plasma membrane in L6 myotubes. However, these effects were unlikely to be associated with activation of insulin, AMPK, ER, or cellular stress signalling cascades. Further studies revealed that AF increased the whole-body energy expenditure and physical activity. Taken together, our findings indicate that AF exerts a therapeutic potential for MetS and related diseases possibly by promoting physical activity associated whole-body energy expenditure and glucose uptake in muscle. These effects are possibly mediated by a new mechanism distinct from other therapeutics derived from Chinese medicine.

The present study investigated the effects of matrine on non-alcoholic steatohepatitis (NASH) in mice induced by a methionine choline-deficient (MCD) diet and the mechanism involved. The study was performed in C57B/6J mice fed a MCD diet for 6 weeks to induce NASH with or without the treatment of matrine (100 mg/kg/day in diet). Metformin was used (250 mg/kg/day in diet) as a comparator for mechanistic investigation. Administration of matrine significantly reduced MCD-induced elevations in plasma ALT and AST but without changing body or liver fat content. Along with alleviating liver injury, matrine suppressed MCD-induced hepatic inflammation (indicated by TNFα, CD68, MCP-1, and NLRP3) and fibrosis (indicated by collagen 1, TGFβ, Smad3, and sirius-red staining). In comparison, metformin treatment did not show any clear sign of effects on these parameters indicative of NASH. Further examination of the liver showed that matrine treatment rescued the suppressed HSP72 (a chaperon protein against cytotoxicity) and blocked the induction of mTOR (a key protein in a stress pathway). In keeping with the lack of the improvement of the NASH features, metformin did not show any significant effect against MCD-induced changes in HSP72 and mTOR. Matrine protects against MCD-induced development of NASH which is refractory to metformin treatment. Its anti-NASH effects involve enhancing HSP72 and downregulating mTOR but do not rely on amelioration of hepatosteatosis.

Our recent study (referred as Study 1) showed that the triterpenoid oleanolic acid (OA) was able to produce a sustained correction of hyperglycemia beyond treatment period in type 2 diabetes (T2D) mice with liver as a responsible site. To follow up the previous observations, the present study (referred as Study 2) investigated the possible role of acetylation of FoxO1 and associated events in this therapeutic memory by characterizing the pathways regulating the acetylation status during and post-OA treatments. OA treatment (100 mg/kg/day for 4 weeks, during OA treatment) reduced hyperglycemia in T2D mice by ∼87% and this effect was largely (∼70%) maintained even 4 weeks after the cessation of OA administration (post-OA treatment). During OA treatment, the acetylation and phosphorylation of FoxO1 were markedly increased (1.5 to 2.5-fold) while G6Pase expression was suppressed by ∼80%. Consistent with this, OA treatment reversed pyruvate intolerance in high-fat fed mice. Histone acetyltransferase 1 (HAT1) content was increased (>50%) and histone deacetylases (HDACs) 4 and 5 (not HDAC1) were reduced by 30-50%. The OA-induced changes in FoxO1, G6Pase, HAT1 and HDACs persisted during the post-OA treatment period when the increased phosphorylation of AMPK, SIRT1 content and reduced liver triglyceride had subsided. These results confirmed the ability of OA to control hyperglycemia far beyond treatment period in T2D mice. Most importantly, in the present study we demonstrated acetylation of FoxO1 in the liver is involved in OA-induced memory for the control of hyperglycemia. Our novel findings suggest that acetylation of the key regulatory proteins of hepatic gluconeogenesis is a plausible mechanism by the triterpenoid to achieve a sustained glycemic control for T2D.

The charged components of cosmic ray secondary particles are deflected by thunderstorm electric fields as they pass through kilometer-scale thunderclouds. As a result, the information on location of secondary particles reaching the observation level will be affected, and the lateral distribution will also be changed. In this paper, the Monte Carlo method is used to simulate the effects of near-earth thunderstorm electric field on the lateral distribution of secondary particles at LHAASO. A vertical and uniform atmospheric electric field model is used in our simulations. The results show that during thunderstorm the lateral distribution of secondary particles widens, and the variation amplitude is not only associated with the strength of electric field, but also dependent upon the primary energy and zenith angle of cosmic rays. In an electric field of - 1000 V · cm − 1 (below the threshold of the Relatively Runaway Electron Avalanche, RREA), the variation amplitude of the lateral distribution of secondary particles is about 0.7% for θ = 0 ∘ , and the variation amplitude reaches 4.7% for θ = 50 ∘. The primary energy of cosmic rays is about 180 GeV, the increasing amplitude is about 0.6%. When the primary energy is about 560 TeV, the variation can be up to 20.1%. In an electric field of - 1700 V · cm − 1 (above the threshold of the RREA process), the increasing amplitude of the lateral distribution is greater than that in an electric field of - 1000 V · cm − 1. And the variation amplitude is 3.8% for θ = 0 ∘ and 34% for θ = 50 ∘ , respectively. For the primary energy of about 180 GeV, the increasing amplitude of secondary particles is 9.9%. For the primary energy of about 560 TeV, the variation can be as high as 119%. Our simulation results are helpful to understand the deflection mechanisms of cosmic ray secondary particles generated by the near-earth thunderstorm electric field, as well as the variation of LHAASO data during thunderstorms. [ABSTRACT FROM AUTHOR]