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Abstract Ischemic stroke represents a significant danger to human beings, especially the elderly. Interventions are only available to remove the clot, and the mechanism of neuronal death during ischemic stroke is still in debate. Ferroptosis is increasingly appreciated as a mechanism of cell death after ischemia in various organs. Here we report that the serine protease, thrombin, instigates ferroptotic signaling by promoting arachidonic acid mobilization and subsequent esterification by the ferroptotic gene, acyl-CoA synthetase long-chain family member 4 (ACSL4). An unbiased multi-omics approach identified thrombin and ACSL4 genes/proteins, and their pro-ferroptotic phosphatidylethanolamine lipid products, as prominently altered upon the middle cerebral artery occlusion in rodents. Genetically or pharmacologically inhibiting multiple points in this pathway attenuated outcomes of models of ischemia in vitro and in vivo. Therefore, the thrombin-ACSL4 axis may be a key therapeutic target to ameliorate ferroptotic neuronal injury during ischemic stroke.

In order to improve the coverage and reliability of the information perception layer of the power Internet of things, a method of constructing a cross layer fusion network of low-voltage power line and micro-power wireless communication (CPW) is proposed. Firstly, a unified medium access control (MAC) layer model of CPW is established to provide basic support for realizing the integration of CPW network layers; then an improved ant colony algorithm combining Brownian motion and local convergence times control is proposed to complete the networking process of CPW; Distribute the sub-service flow of CPW, and propose the bit error rate requirement factor in the service distribution, and accomplish the cross-layer integration of low-voltage power line and micro-power wireless communication network. The simulation results show that the communication link service quality of the cross-layer fusion network is better than that of the power line and wireless dual-mode or cascaded communication networks. The communication efficiency of CPW is improved to 398.20kbits/s. The coverage of the power line and wireless communication fusion network can be expanded by setting corresponding bit error rate demand factors according to different services. It takes into account the balance of communication link quality and network load.

To explore the correlation between earthquakes and the pre-earthquake ionospheric shallow frequency (ELF) electric field perturbations phenomenon, the paper investigated the pre-earthquake ionospheric perturbations phenomenon, and then the Spatio-temporal evolution characteristics of the electromagnetic field before and after the global Ms ≥6.0 strong earthquakes from 2019 to 2021 were statistically analyzed. In this paper, the power spectrum data of the ELF (19.5–250 Hz) band of ionospheric electric field observed by the China Seismo-Electromagnetic Satellite (CSES) electric field detector are preclinically processed by the C-value method. A stable background field observation model was constructed using the data from 75 to 45 days before the earthquake observed by the CSES in the range of 15° above the epicenter. Then, the amplitude of the spatial electric field disturbance over the epicenter relative to the background field is extracted. Finally, the superposition analysis method statistically analyzes the spatial and temporal evolution of the spatial electric field before and after the earthquake with different characteristics. The statistical results show that the anomalies first appear in the fourth period (15–19 days before the earthquake) and the third period (10–14 days before the earthquake) and then reach the most vital and most evident during the pro-earthquake period (4 days before the earthquake and the day of the earthquake); In terms of the intensity of the anomalies caused, the magnitude seven earthquakes are stronger than the magnitude 6.0–7.0 earthquakes, and marine earthquakes are stronger than land earthquakes; in terms of the ease of observing the anomalies, the magnitude 7.0 and above are more accessible to observe than the magnitude 6.0–7.0 earthquakes, and marine earthquakes are more accessible to observe than land earthquakes.

To explore the correlation between earthquakes and spatial ultra-low frequency electric field disturbances and to study the phenomenon of seismic ionospheric disturbances, this study uses 3 years of electric field ULF band data from 2019 to 2021 observed by the electric field detector carried by the CSES to identify anomalous disturbances using the anomaly automatic detection algorithm based on empirical mode decomposition for the 2,329 seismic events of magnitude not less than 5.0 and the electric field ULF disturbances in this period are analyzed by Superposed Epoch Analysis, and the statistical results are compared and analyzed in depth by earthquake location and different magnitudes in terms of both spatial and temporal scales and spatial distribution. The results show that: 1) There is a correlation between earthquakes of magnitude not less than 5.0 and ultra-low frequency disturbances in the electric field. The abnormal disturbance mainly occurred 11 days before the earthquake, 2 days before the earthquake to the day of the earthquake, and the location of the earthquake is within 200 km from the epicenter. 2) Sea earthquakes can observe more pre-seismic anomalous electromagnetic disturbances than land earthquakes. 3) In terms of earthquake magnitude, the larger the magnitude, the earlier the pre-earthquake anomalous disturbances appear and the wider the range of anomalies. This study provides an effective way to explain seismic ionospheric phenomena, and also provides a reference for the application of electromagnetic monitoring satellites in earthquake prediction and early warning as well as disaster prevention and mitigation.

Protists are a trophically diverse and biogeochemically significant component of water environments and are widely reported as hosts of bacteria. However, the potential role of protists in wastewater treatment plants (WWTPs) as reservoirs for human pathogens does not appear to have received adequate attention. Here, a combination of fluorescence-activated cell sorting and Illumina sequencing was applied to characterize the dynamics of the internalized bacterial community of the enriched protists from the influents and effluents of five WWTPs. The results showed that Proteobacteria (mainly Betaproteobacteria) dominate the intracellular bacterial communities of protists in both influents and effluents of WWTPs, accounting for 72.6% of the total intracellular bacterial communities. The most frequently detected genus was Sulfuricurvum in the influent samples, Chryseobacterium and Pseudomonas were most prevalent in the effluent samples. Compared with the influents, a more diverse and abundant intracellular bacterial community was observed in the effluents. Moreover, the potential intracellular bacterial pathogens were 26 times higher in effluents than in influents, with Pseudomonas fluorescens and Pseudomonas putida significantly enriched in effluents. This work provides insights into the dynamics of bacterial communities and potential pathogens harbored by protists in the influents and effluents from WWTPs, contributing to the improved evaluation of biosafety in WWTPs.

Abstract Gelsemium is a small genus of flowering plants from the family Loganiaceae comprising five species, three of which, Gelsemium sempervirens (L.) J. St.‐Hil., G. elegans Benth and G. rankinii Small, are particularly popular. Compared with other alkaloids from G. elegans, gelsemine, gelsevirine and koumine exhibit equally potent anxiolytic effects and low toxicity. Although the pharmacological activities and metabolism of koumine and gelsemine have been reported in previous studies, the species differences of gelsevirine metabolism have not been well studied. In this study, the metabolism of gelsevirine was investigated by using liver microsomes of humans, pigs, goats and rats by means of HPLC‐QqTOF/MS. The results indicated that the metabolism of gelsevirine in liver microsomes had qualitative and quantitative species differences. Based on the results, the possible metabolic pathways of gelsevirine in liver microsomes were proposed. Investigation of the metabolism of gelsevirine will provide a basis for further studies of the in vivo metabolism of this drug.

Grasshoppers are common pests, and their intestinal microbes have coevolved with them. These microorganisms have varied community structures, and they participate in the nutritional absorption and metabolism of grasshoppers. Here, we describe the gut microbiota diversity of four species of grasshoppers, Oxya chinensis, Pararcyptera microptera meridionalis, Gastrimargus marmoratus, and Calliptamus abbreviatus. We constructed a 16S rDNA gene library and analyzed the digestibility of cellulose and hemicellulose in grasshoppers using moss black phenol and anthrone colorimetry. The grasshopper with the highest microbial diversity in the gut among the four species was Oxya chinensis, and there were no significant differences in gut microbial diversity between the two geographic collections of Oxya chinensis. The most dominant phyla of the four grasshopper gut microorganisms were Proteobacteria, Bacteroidetes, and Firmicutes, and the most dominant genus was Enterobacter. The gut microbiota features of the four grasshoppers were correlated with their cellulose and hemicellulose digestibility. There was a significant positive correlation with cellulose digestibility for Pantoea. A significant negative correlation was found with cellulose digestibility for Acinetobacter, Enterococcus, Citrobacter, Serratia. A significant negative correlation was found with hemicellulose digestibility for Pantoea. This study contributes to the understanding of the structural composition of different species of grasshoppers gut microbiota, which may be useful for developing grasshopper digestive tracts as bioreactors for cellulose decomposition, improving the decomposition and utilization of agricultural straw, producing clean biomass energy, and processing biologically derived products.

Ambroxol is a commonly used mucolytic agent principally used to treat respiratory diseases, which may have a role as adjunctive therapy for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but there is lack of evidence about its effectiveness on coronavirus disease-2019 (COVID-19) patients. To study the association between ambroxol use and clinical outcomes among hospitalized patients of COVID-19 infection. We conducted a multicenter retrospective cohort study involving 3,111 patients with confirmed SARS-CoV-2 infection from three hospitals in Wuhan from 19 December 2019 to 15 April 2020, and the primary outcome was in-hospital mortality. COVID-19 patients were classified into ambroxol and non-ambroxol groups based on the administration of ambroxol during hospitalization. Two analyses including propensity score matching (PSM) to obtain a 1:1 balanced cohort and logistic regression were used to control for confounding factors. The average age of 3,111 patients was 57.55 ± 14.93 years old, 127 of them died during hospitalization, and 924 of them used ambroxol. Treatment with ambroxol did not have a significant effect on in-hospital mortality of COVID-19 patients when compared with non-ambroxol in PSM model after adjusting for confounders (8.0% vs. 3.5%, adjusted OR, 1.03 [95% CI, 0.54–1.97], p = 0.936). Adverse events such as nausea/vomiting, headache, and rash were comparable between the two groups. Our results suggest that the use of ambroxol is not significantly associated with in-hospital mortality in COVID-19 patients, which provides evidence for evaluating the effects of ambroxol on COVID-19 patient outcomes and may be helpful for physicians considering medication alternatives for COVID-19 patients.

The effects of grafting on the morphology, physiology, and aerenchyma of balsam pear aboveground under waterlogging stress were studied using a two-factor randomized block design. At 8 and 16 days, the degree of reduction of grafted balsam pear was lower than those of self-rooted balsam pear, although the height and leaf number of self-rooted and grafted balsam pears were remarkably reduced under waterlogging stress. Compared with self-rooted balsam pear, grafting considerably decreased the malondialdehyde content of balsam pear leaves but substantially increased the activities of antioxidant enzymes (superoxide dismutase, peroxidase, and catalase) and the contents of osmosis-regulating substances (soluble sugar, soluble protein, and proline) in the leaves of balsam pear under waterlogging stress at 4, 8, and 16 days. The stem of grafted balsam pear formed aerenchyma (pith cavity) at 0 days, whereas the stem of self-rooted balsam pear formed aerenchyma at 4 days. The aerenchyma of the stem formed by grafted balsam pear was more developed than that formed by the self-rooted balsam pear under waterlogging stress. The petiole of self-rooted and grafted balsam pears formed aerenchyma at 16 days, and the aerenchyma of grafted balsam pear was more developed than that of self-rooted balsam pear. These results indicated that grafting improved the antioxidant and osmotic regulation ability of balsam pear and enhanced the tolerance of balsam pear to waterlogging stress by enlarging the pith cavity of the stem and petiole of balsam pear.

AIM:To evaluate the effect of the vault on corneal endothelial cells after implantation of central hole implantable lens(ICL)V4c without viscoelastic microincision.METHODS: Prospective non-randomized controlled study. A total of 70 patients(137 eyes)with myopia who underwent ICL V4c implantation in our hospital from November 2017 to February 2018 were divided into low vault group(100μm

Abstract. Background:. Single-nucleotide polymorphisms (SNPs)-associated genes and long non-coding RNAs (lncRNAs) can contribute to human disease. To comprehensively investigate the contribution of lncRNAs to breast cancer, we performed the first genome-wide lncRNA association study on Han Chinese women. Methods:. We designed an lncRNA array containing >800,000 SNPs, which was incorporated into a 96-array plate by Affymetrix (CapitalBio Technology, China). Subsequently, we performed a two-stage genome-wide lncRNA association study on Han Chinese women covering 11,942 individuals (5634 breast cancer patients and 6308 healthy controls). Additionally, in vitro gain or loss of function strategies were performed to clarify the function of a novel SNP-associated gene. Results:. We identified a novel breast cancer-associated susceptibility SNP, rs11066150 (Pmeta = 2.34 × 10−8), and a previously reported SNP, rs9397435 (Pmeta = 4.32 × 10−38), in Han Chinese women. rs11066150 is located in NONHSAT164009.1 (lncHSAT164), which is highly expressed in breast cancer tissues and cell lines. lncHSAT164 overexpression promoted colony formation, whereas lncHSAT164 knockdown promoted cell apoptosis and reduced colony formation by regulating the cell cycle. Conclusions:. Based on our lncRNA array, we identified a novel breast cancer-associated lncRNA and found that lncHSAT164 may contribute to breast cancer by regulating the cell cycle. These findings suggest a potential therapeutic target in breast cancer.

Hybrid redox flow batteries (RFBs) are a special type of RFBs that involve depositing reactions on negative electrodes. The available volume in negative electrodes for cell stacks limits the totally energy-storing capability of these batteries. This paper introduces the first fully flowable Ce–metal flow battery operated with a semisolid, flowable anolyte. Using the semisolid fuel cell concept, we incorporate the sustainable and deposit-abundant features of non-Li-based batteries into the structure of RFBs to develop a fully flowable RFB system. Solid suspension electrodes of hydrophilic carbon particles deposited by earth-abundant metals with redox activity are investigated as alternatives to the redox-active molecules employed in typical RFBs to decouple the power delivery capability from the energy storage capacity in fully flowable RFBs. While being charged, earth-abundant redox-active metal (Cu, Pb or Zn) is electrodeposited on the carbon particle suspension, which is dissolved in the sequent discharging process. On the basis of the proposed contact-charge-transfer mechanism, the electrical contact to the solid suspension electrode is fed by the redox-inert hydrophobic current collector that restrains direct metal deposition on their surfaces due to the hydrophobicity.

Laccase has huge potential application in all aspects of biotechnology due to the ability of laccase to oxidize a wide range of phenolic and nonphenolic compounds. The future success of such applications requires large amounts of laccase with low costs. White-rot fungi are important groups of laccase production. In this study, three white-rot fungi, Phlebia acerina Han 618, Trametes hirsuta Han 726, and Coriolopsis trogii Han 751, isolated from a native North China habitat, were identified by the method of molecular biology and preliminary screening of the ability of laccase-production by guaiacol selection medium. Then they were fermented on different lignocellulosic biomass. Three species showed consistency in preference of lignocellulosic biomass, and the presence of stalk of Sorghum bicolor was more suitable for secreting laccase. The capacity of laccase secretion from different species was significantly different. The capacity of secreting laccase of C. trogii Han 751 was superior to that of P. acerina Han 618 and T. hirsuta Han 726. The discovery of a new strain with superior capacity of secreting laccase and suitable lignocellulosic biomass were helpful for laying a foundation for the optimization of the fermentation conditions for the highest laccase production, the isolation and purification of laccase, and the industrial application of laccase. [ABSTRACT FROM AUTHOR]

AIM: To observe the changes of anterior chamber angle after posterior chamber intraocular lens(ICL)V4c implantation for high myopia.METHODS: Prospective study. ICL V4c implantation was performed on 150 cases(300 eyes)with high myopia, and the changes of visual acuity, intraocular pressure,vault and anterior chamber angle were recorded before and 1d, 1mo, 3mo, 6mo and 1a after operation. Repeated measurement analysis of variance and LSD-t test were used to analyze the data.RESULTS: After 1d, 1mo, 3mo, 6mo, 1a operation, the recovery of UCVA was significantly higher than that before operation(F=98.2, PF=108.256, 112.342, 164.856, 316.549, 115.338, PF=102.68, 548.47, 93.37, 316.549, 117.698, all PPP>0.05).CONCLUSION: After ICL V4c implantation, the anterior chamber angle parameters in the horizontal direction of 1d, 1mo, 3mo, 6mo and 1a were smaller than those before operation, and tended to be stable after 3mo.

The optimum strategy for heart failure (HF) treatment has yet to be elucidated. This study intended to test the benefit of a combination of valsartan (VAL) and perifosine (PER), a specific AKT inhibitor, in protecting against pressure overload induced mouse HF. Mouse were subjected to aortic banding (AB) surgery to establish HF models and then were given vehicle (HF), VAL (50 mg/kg/d), PER (30 mg/kg/d) or combination of VAL and PER for 4 weeks. Mouse with sham surgery treated with VEH were used for control (VEH). VAL or PER treatment could significantly alleviate mouse heart weight, attenuate cardiac fibrosis and improve cardiac function. The combination treatment of VAL and PER presented much better benefit compared with VAL or PER group respectively. PER treatment significantly inhibited AKT/GSK3β/mTORC1 signaling. Besides the classic AT1 inhibition, VAL treatment significantly inhibited MAPK (ERK1/2) signaling. Furthermore, VAL and PER treatment could markedly prevent neonatal rat cardiomyocyte hypertrophy and the activation of neonatal rat cardiac fibroblast. Combination of VAL and PER also presented superior beneficial effects than single treatment of VAL or PER in vitro experiments respectively. This study presented that the combination of valsartan and PER may be a potential treatment for HF prevention.

Abstract Background Postoperative gastrointestinal (GI) dysfunction (PGD) is a common problem after abdominal surgery. PGD can increase the length of hospital stay and may lead to serious complications. Acupuncture and moxibustion are alternative therapies for PGD that have been used in some settings. However, the effect of preventive application of acupuncture or transcutaneous electrical acupuncture stimulation (TEAS) is still uncertain. The purpose of this study is to investigate the efficacy of the continuous application of TEAS on GI function recovery in adults undergoing abdominal surgery. At the same time, we will try to confirm the mechanism of TEAS through the brain–gut axis. Methods/design This study is a prospective, single-center, two-arm, randomized controlled trial that will be performed in a general hospital. In total, 280 patients undergoing abdominal surgery were stratified by type of surgery (i.e. gastric or colorectal procedure) and randomized into two treatment groups. The experimental group will receive TEAS stimulation at L14 and PC6, ST36 and ST37. The sham group will receive pseudo-TEAS at sham acupoints. The primary outcome will be the time to the first bowel motion by auscultation. The recovery time of flatus, defecation, the changes in perioperative brain–intestinal peptides, postoperative pain, perioperative complications, and hospitalization duration will be the secondary outcomes. Discussion The results of this study will demonstrate that continuous preventive application of TEAS can improve the GI function recovery in patients undergoing abdominal surgery and that this effect may act through brain–gut peptides. Trial registration Chinese Clinical Trial Registry, ChiCTR1900023263 . Registered on 11 May 2019.

Abstract Background Obese patients undergoing general anesthesia and mechanical ventilation during laparoscopic abdominal surgery commonly have a higher incidence of postoperative pulmonary complications (PPCs), due to factors such as decreasing oxygen reserve, declining functional residual capacity, and reducing lung compliance. Pulmonary atelectasis caused by pneumoperitoneum and mechanical ventilation is further aggravated in obese patients. Recent studies demonstrated that individualized positive end-expiratory pressure (iPEEP) was one of effective lung-protective ventilation strategies. However, there is still no exact method to determine the best iPEEP, especially for obese patients. Here, we will use the best static lung compliance (Cstat) method to determine iPEEP, compared with regular PEEP, by observing the atelectasis area measured by electrical impedance tomography (EIT), and try to prove a better iPEEP setting method for obese patients. Methods This study is a single-center, two-arm, prospective, randomized control trial. A total number of 80 obese patients with body mass index ≥ 32.5 kg/m2 scheduled for laparoscopic gastric volume reduction and at medium to high risk for PPCs will be enrolled. They will be randomly assigned to control group (PEEP5 group) and iPEEP group. A PEEP of 5 cmH2O will be used in PEEP5 group, whereas an individualized PEEP value determined by a Cstat-directed PEEP titration procedure will be applied in the iPEEP group. Standard lung-protective ventilation methods such as low tidal volumes (7 ml/kg, predicted body weight, PBW), a fraction of inspired oxygen ≥ 0.5, and recruitment maneuvers (RM) will be applied during and after operation in both groups. Primary endpoints will be postoperative atelectasis measured by chest electrical impedance tomography (EIT) and intraoperative oxygen index. Secondary endpoints will be serum IL-6, TNF-α, procalcitonin (PCT) kinetics during and after surgery, incidence of PPCs, organ dysfunction, length of in-hospital stay, and hospital expense. Discussion Although there are several studies about the effect of iPEEP titration on perioperative PPCs in obese patients recently, the iPEEP setting method they used was complex and was not always feasible in routine clinical practice. This trial will assess a possible simple method to determine individualized optimal PEEP in obese patients and try to demonstrate that individualized PEEP with lung-protective ventilation methods is necessary for obese patients undergoing general surgery. The results of this trial will support anesthesiologist a feasible Cstat-directed PEEP titration method during anesthesia for obese patients in attempt to prevent PPCs. Trial registration www.chictr.org.cn ChiCTR1900026466. Registered on 11 October 2019

C13H16O6, monoclinic, P21/c (no. 14), a = 12.180(3) Å, b = 13.813(4) Å, c = 7.842(2) Å, β = 93.917(4)°, V = 1316.2(6) Å3, Z = 4, Rgt(F) = 0.0442, wRref(F2) = 0.1375, T = 296(2) K. [ABSTRACT FROM AUTHOR]

Objectives: Sestrin2 (Sesn2) has been demonstrated to be a cysteine sulfinyl reductase and protects cells from multiple stress insults, including hypoxia, endoplasmic reticulum stress, and oxidative stress. However, the roles and mechanisms of Sesn2 in pressure overload-induced mouse cardiac hypertrophy have not been clearly clarified. This study intended to investigate whether sestrin2 (Sesn2) overexpression could prevent pressure overload-induced cardiac hypertrophy via an AMPKα2 dependent pathway through conditional knockout of AMPKα2.Methods and results: Sesn2 expression was significantly increased in mice hearts at 2 and 4 weeks after aortic banding (AB) surgery, but decreased to 60–70% of the baseline at 8 weeks. Sesn2 overexpression (at 3, 6, and 9 folds) showed little cardiac genetic toxicity in transgenic mice. Cardiac dysfunctions induced by pressure overload were attenuated by cardiomyocyte-specific Sesn2 overexpression when measured by echocardiography and hemodynamic analysis. Results of HE and PSR staining showed that Sesn2 overexpression significantly alleviated cardiac hypertrophy and fibrosis in mice hearts induced by pressure overload. Meanwhile, adenovirus-mediated-Sesn2 overexpression markedly suppressed angiotensin II-induced neonatal rat cardiomyocyte hypertrophy in vitro. Mechanistically, Sesn2 overexpression increased AMPKα2 phosphorylation but inhibited mTORC1 phosphorylation. The cardiac protections of Sesn2 overexpression were also via regulating oxidative stress by enhancing Nrf2/HO-1 signaling, restoring SOD activity, and suppressing NADPH activity. Particularly, we first proved the vital role of AMPKα2 in the regulation of Sesn2 with AMPKα2 knockout (AMPKα2-/-) mice and Sesn2 transgenic mice crossed with AMPKα2-/-, since Sesn2 overexpression failed to improve cardiac function, inhibit cardiac hypertrophy and fibrosis, and attenuate oxidative stress after AMPKα2 knockout.Conclusion: This study uniquely revealed that Sesn2 overexpression showed little genetic toxicity in mice hearts and inhibited mTORC1 activation and oxidative stress to protect against pressure overload-induced cardiac hypertrophy in an AMPKα2 dependent pathway. Thus, interventions through promoting Sesn2 expression might be a potential strategy for treating pathological cardiac hypertrophy and heart failure.

This study aimed to investigate the role and mechanisms of Receptor interacting protein kinase 2 (RIP2) in pressure overload-induced cardiac remodeling. Human failing or healthy donor hearts were collected for detecting RIP2 expression. RIP2 cardiomyocyte-specific overexpression, RIP2 global knockout, or wild-type mice were subjected to sham or aortic banding (AB) surgery to establish pressure overload-induced cardiac remodeling in vivo. Phenylephrine (PE)-treated neonatal rat cardiomyocytes (NRCMs) were used for further investigation in vitro. The expression of RIP2 was significantly upregulated in failing human heart, mouse remodeling heart, and Ang II-treated NRCMs. RIP2 overexpression obviously aggravated pressure overload-induced cardiac remodeling. Mechanistically, RIP2 overexpression significantly increased the phosphorylation of TAK1, P38, and JNK1/2 and enhanced IκBα/p65 signaling pathway. Inhibiting TAK1 activity by specific inhibitor completely prevented cardiac remodeling induced by RIP2 overexpression. This study further confirmed that RIP2 overexpression in NRCM could exacerbate PE-induced NRCM hypertrophy and TAK1 silence by specific siRNA could completely rescue RIP2 overexpression-mediated cardiomyocyte hypertrophy. Moreover, this study showed that RIP2 could bind to TAK1 in HEK293 cells, and PE could promote their interaction in NRCM. Surprisingly, we found that RIP2 overexpression caused spontaneous cardiac remodeling at the age of 12 and 18 months, which confirmed the powerful deterioration of RIP2 overexpression. Finally, we indicated that RIP2 global knockout attenuated pressure overload-induced cardiac remodeling via reducing TAK1/JNK1/2/P38 and IκBα/p65 signaling pathways. Taken together, RIP2-mediated activation of TAK1/P38/JNK1/2 and IκBα/p65 signaling pathways played a pivotal role in pressure overload-induced cardiac remodeling and spontaneous cardiac remodeling induced by RIP2 overexpression, and RIP2 inhibition might be a potential strategy for preventing cardiac remodeling.

AIM: To compare the visual quality between implantable collamer lens(ICL)implantation and FS-LASIK for correcting moderate and high myopia.METHODS: Prospective study. Choose in June 2018 to December 2018 for ICL implantation of 58 patients(116 eyes)and 48 patients(96 eyes)underwent FS-LASIK. The diopter, visual acuity and visual quality of the two groups before and after surgery were analyzed and compared.RESULTS: After 3mo operation, the degree of spherical mirror in the ICL group was higher than that in the FS-LASIK group(0.19±0.22D vs 0.09±0.29D, PP>0.05). The modulation transfer function cut off frequency(MTF cut off), objective scatter index(OSI)and OV9% were significantly better in the ICL group than in the FS-LASIK group, while the SR was lower than the FS-LASIK group. Compared with the former, the MTF cut off was significantly increased in the ICL group, the SR and OSI values were decreased, and the SR value was decreased in the FS-LASIK group(all PCONCLUSION: Both ICL implantation and FS-LASIK can effectively improve the visual acuity and diopter of patients, ICL implantation for patients with moderate and high myopia provides relatively good visual quality.

AIM: To investigate the related factors influencing the myopia control effect in adolescents with orthokeratology.METHODS: This study selected 102 adolescents who wearing ortho-k lens in the First Affiliation Hospital of Xi'an Jiaotong University during July 2014-October 2017.Their axial elongation, refraction, wearing time were observed.RESULTS: After 3a treatment, the axial elongation of 102 adolescents increased 0.42±0.37mm. Among the low myopia, the middle and high myopia groups, the axial elongation increased 0.65±0.35mm, 0.32±0.37mm and 0.30±0.29mm, respectively. The axial elongation in the high myopia groups was the most slowest(the combination of orthokeratology and spectacles); There was an interaction between the wearing time and the initial refraction, the wearing time and the initial age(all PF=0.292, P=0.695). The axial elongation has no difference between male and female.CONCLUSION: The initial refraction and the initial age of myopic adolescents were important factors influencing axial elongation. The combination of orthokeratology and spectacles has effection in controlling axial elongation.

Background: Liquiritin (LIQ) is a traditional Chinese medicine that has been reported to regulate inflammation, oxidative stress and cell apoptosis. However, the beneficial effects of LIQ in lipopolysaccharides (LPS)-induced septic cardiomyopathy (SCM) has not been reported. The primary goal of this study was to investigate the effects of LIQ in LPS-induced SCM model.Methods: Mice were pre-treated with LIQ for 7 days before they were injected with LPS (10 mg/kg) for inducing SCM model. Echocardiographic analysis was used to evaluate cardiac function after 12 h of LPS injection. Thereafter, mice were sacrificed to collect hearts for molecular and histopathologic assays by RT-PCR, western-blots, immunohistochemical and terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining analysis respectively. AMPKα2 knockout (AMPKα2−/−) mice were used to elucidate the mechanism of LIQ Neonatal rat cardiomyocytes (NRCMs) treated with or without LPS were used to further investigate the roles and mechanisms of LIQ in vitro experiments.Results: LIQ administration attenuated LPS-induced mouse cardiac dysfunction and reduced mortality, based upon the restoration of EF, FS, LVEDs, heart rate, dp/dt max and dp/dt min deteriorated by LPS treatment. LIQ treatment also reduced mRNA expression of TNFα, IL-6 and IL-1β, inhibited inflammatory cell migration, suppressed cardiac oxidative stress and apoptosis, and improved metabolism. Mechanistically, LIQ enhanced the phosphorylation of AMP-activated protein kinase α2 (AMPKα2) and decreased the phosphorylation of mTORC1, IκBα and NFκB/p65. Importantly, the beneficial roles of LIQ were not observed in AMPKα2 knockout model, nor were they observed in vitro model after inhibiting AMPK activity with an AMPK inhibitor.Conclusion: We have demonstrated that LIQ exerts its protective effects in an SCM model induced by LPS administration. LIQ reduced inflammation, oxidative stress, apoptosis and metabolic alterations via regulating AMPKα2 dependent signaling pathway. Thus, LIQ might be a potential treatment or adjuvant for SCM treatment.

Grasshoppers (Insecta, Orthoptera, Acridoidea) are a large group of agricultural and animal husbandry pests. They have a large food intake with high utilization of plants fibers. However, the composition of the grasshopper gut microbial community, especially the relationship between gut microbial community and cellulose digestibility, remains unclear. In this research, 16S rRNA gene sequences were used to determine the intestinal microbial diversity of Acrida cinerea, Trilophidia annulata, Atractomorpha sinensis and Sphingonotus mongolicus, and Spearman correlation analysis was performed between the intestinal microbes of grasshoppers and the digestibility of cellulose and hemicellulose. The results showed that Proteobacteria was the dominant phylum and Klebsiella was the dominant genus in the guts of the four species of grasshoppers; there was no significant difference in the species composition of the gut microbes of the four species of grasshoppers. Spearman correlation analysis showed that Brevibacterium and Stenotrophomonas were significantly correlated with cellulose digestibility. Brevibacterium, Clavibacter, Microbacterium and Stenotrophomonas were significantly associated with hemicellulose digestibility. Our results confirmed that the gut microbes of grasshoppers were correlated with the digestibility of cellulose and hemicellulose, and indicated that grasshoppers may have the potential to develop into bioreactors, which can be applied to improve straw utilization efficiency in the future.

Cardiac remodeling is a common pathological process in various heart diseases, such as cardiac hypertrophy, diabetes-associated cardiomyopathy and ischemic heart diseases. The inhibition of cardiac remodeling has been suggested to be a potential strategy for preventing heart failure. However, the mechanisms involved in cardiac remodeling are quite complicated. Recent studies have reported a close correlation between autophagy and energy homeostasis in cardiac remodeling associated with various heart diseases. In this review, we summarize the roles of autophagy and energy homeostasis in cardiac remodeling and discuss the relationship between these two processes in different conditions to identify potential targets and strategies for treating cardiac remodeling by regulating autophagy.

Fear extinction remains an unresolved challenge for behavioral exposure therapy in patients with post-traumatic stress disorder (PTSD). Previous reports have suggested that social support from either familiar or unfamiliar same-sex partners is beneficial to attenuating fear responses during fear extinction and renewal. Despite that, few studies have examined the effects of social support in advance on fear extinction and/or retrieval. It is also not clear whether social company by a receptive mating partner in advance facilitates fear extinction. In the present study, we address these questions by introducing a co-housing method, where fear-conditioned male mice are co-housed with or without a receptive mating partner prior to fear extinction. We found that while co-housing with an ovariectomized female mouse showed little effect on fear extinction or retrieval, social company by a receptive mating partner in advance dramatically facilitates fear extinction. In addition, the number of cFos-positive neurons in the basolateral amygdala (BLA) were also found to be reduced in male mice accompanied with receptive mating partner in response to fear extinction and retrieval, indicating diminished neuronal activation. Electrophysiological studies further showed that the excitability of excitatory neurons in BLA was decreased, which is probably due to the attenuated basal level of excitatory synaptic transmission. Together, our observations demonstrate an effect of social company by a receptive mating partner can facilitate fear extinction and afford a possible cellular mechanism.

Icariside II (ICA II), a flavonoid derived from Epimediumbrevicormum Maxin in, has multiple biological activities in Chinese traditional medicine. Our study aimed to investigate the potential activity of ICA II against cardiac remodeling and the underlying mechanism. Mice received aorta banding (AB) or sham surgery, and then were randomly divided into ICA II or vehicle (veh) group for 6 weeks. After echocardiography and pressure-volume loop examination, hearts were harvested for histopathological analysis and molecular mechanism investigation. Additionally, neonatal rat cardiomyocytes (NRCM) were used for in vitro experiments. ICA II attenuated the systolic and diastolic cardiac dysfunction, and protected mouse heart from hypertrophy and fibrosis. The underlying mechanism might involve in the regulation of Akt, AMPKα and mTORC. In in vitro experiment, ICA II prevented phenylephrine (PE) induced NRCM hypertrophy by regulating AMPKα/mTORC pathway. This protective effect was disappeared after treatment with Compound C (CpC), an AMPKα inhibitor. Moreover, ICA II activated AMPK at baseline. ICAII was superior to resveratrol in activating AMPKα and similar to AICAR. ICA II protected against cardiac remodeling and NRCM hypertrophy by regulating AMPK/mTORC pathway. ICA II may be a candidate for the treatment of malignant cardiac remodeling. Keywords: Icariside II, Cardiac remodeling, AMPK/mTORC, Cardiomyocyte

To solve the problem that subnetwork output cannot be optimally integrated in a modular neural network (MNN), this paper proposes an adaptive particle swarm optimization algorithm for dynamic MNN (APSO-DMNN). First, the method identifies the distribution of samples and updates the training parameters based on data potential. Second, the MNN activates the corresponding subnetworks according to the input data. Calculate the weights based on an APSO algorithm, which can dynamically optimize the contribution of the output. Then, the inertia weights in the APSO algorithm are adjusted by a nonlinear function in order to avoid being trapped into local optimal values. Finally, the proposed APSO-DMNN can be obtained based on the optimal integration and dynamic adjustment. Comparisons with other algorithms indicate that the proposed method is more effective in modeling and predicting.

AIM: To investigate and analyze the changes of corneal biomechanics of normal eyes, forme frusta keratoconus eyes, subclinical keratoconus eyes and clinical keratoconus eyes by Corneal visualization Scheimpflug technology(Corvis ST), and provide clinical basis for early diagnosis of keratoconus. METHODS: Case-control study. We randomly selected 40 normal eyes as normal group, 15 forme frusta keratoconus eyes as forme frusta keratoconus group, 23 subclinical keratoconus eyes as subclinical keratoconus group, and 40 clinical keratoconus eyes as keratoconus group. The biomechanical parameters of each group were measured by Corvis ST. The receiver operating characteristic(ROC)curves was plotted to distinguish keratoconus from the normal cornea. RESULTS: There was no significant difference in the parameters of biomechanics between normal group and forme frusta keratoconus group (P>0.05). Compared to normal group and subclinical keratoconus group, the parameters second applanation length(AL2), first velocity of applanation(AV1), central curvature radius at highest concavity(HC-radius), deformation amplitude(DA)were revealed statistically significant differences(PCONCLUSION: The corneal biomechanical parameters of forme frusta keratoconus group are not changed compared with normal group. The changes between normal group and subclinical keratoconus group should combine with other technology to further improve subclinical keratoconic screening. Compared with normal corneas, keratoconus has a great change in biomechanics, which DA diagnosis of the highest efficiency.

AIM: To explore the possibility of human umbilical cord mesenchymal stem cells (hUCMSCs), human umbilical vein endothelial cells (hUVECs), human dental pulp stem cells (hDPSCs) and human periodontal ligament stem cells (hPDLSCs) serving as feeder cells in co-culture systems for the cultivation of limbal stem cells. METHODS: Different feeder layers were cultured in Dulbecco’s modified Eagle’s medium (DMEM)/F12 and were treated with mitomycin C. Rabbits limbal stem cells (LSCs) were co-cultured on hUCMSCs, hUVECs, hDPSCs, hPDLSCs and NIH-3T3, and then comparative analysis were made between each group to see their respective colony-forming efficiency (CFE) assay and immunofluorescence (IPO13,CK3/12). RESULTS: The efficiency of the four type cells in supporting the LSCs morphology and its cellular differentiation was similar to that of NIH-3T3 fibroblasts as demonstrated by the immunostaining properties analysis, with each group exhibiting a similar strong expression pattern of IPO13, but lacking CK3 and CK12 expression in terms of immunostaining. But hUCMSCs, hDPSCs and hPDLSCs feeder layers were superior in promoting colony formation potential of cells when compared to hUVECs and feeder-cell-free culture. CONCLUSION: hUCMSCs, hDPSCs and hPDLSCs can be a suitable alternative to conventional mouse NIH-3T3 feeder cells, so that risk of zoonotic infection can be diminished.

Streptomyces rubrogriseus HDZ-9-47, isolated from eggs of Meloidogyne spp., was evaluated as a potential biocontrol agent of Meloidogyne incognita under in vitro and protective field. Microscopic observations showed that HDZ-9-47 parasitized eggs of M. incognita within 7 days. In vitro, the culture filtrate of HDZ-9-47 caused 97.0% mortality of second-stage juveniles (J2s) of M. incognita and inhibited more than 50% egg hatching. In the field, compared with the control, the root-knot index and J2s density in the treatment of drench the broth contained 1012 HDZ-9-47 spores were respectively reduced by 51.1 and 80.7% at 90 days post transplantation, which were better than that in other application doses and methods. In addition, reduction rates of root-knot index and J2s density of the treatment of combined application of HDZ-9-47 with biofumigation was 87.1 and 91.0%, respectively, better than either of HDZ-9-47 or biofumigation used alone or fosthiazate treatment. And tomato yield also increased by 16.1%. Together, our results suggest that HDZ-9-47 could be an effective biocontrol agent of M. incognita, and that application of HDZ-9-47 combined with cabbage residue biofumigation was a promising and sustainable option for M. incognita control.

To dissect the genetic control of the sensory and textural quality traits of Chinese white noodles, a population of recombinant inbred lines (RILs), derived from the cross of waxy wheat Nuomai 1 (NM1) and Gaocheng 8901 (Gc8901), was used. The RILs were tested in three different environments to determine the role of environmental effects on quantitative trait loci (QTL) analysis. A total of 45 QTLs with additive effects for 17 noodle sensory and textural properties under three environments were mapped on 15 chromosomes. These QTLs showed 4.23–42.68% of the phenotypic variance explained (PVE). Nineteen major QTLs were distributed on chromosomes 1B, 1D, 2A, 3B, 3D, 4A, and 6A, explaining more than 10% of the phenotypic variance (PV). Clusters were detected on chromosomes 2B (3 QTLs), 3B (11 QTLs) and 4A (5 QTLs). The cluster detected on chromosome 4A was close to the Wx-B1 marker. Five co-located QTLs with additive effects were identified on chromosomes 2B, 3D, 4A, 6A, and 7B. The two major QTLs, Qadh.sdau-3B.1 and Qspr.sdau-3B.1, in cluster wPt666008–wPt5870 on chromosome 3B were detected in three different environments, which perhaps can be directly applied to improve the textural properties of noodles. These findings could offer evidence for the selection or development of new wheat varieties with noodle quality using molecular marker-assisted selection (MAS).

AIM: To demonstrate the changes in ultrastructure and histopathology of the cornea in acute corneal alkaline burns after femtosecond laser-assisted deep lamellar keratoplasty. METHODS: The New Zealand white rabbits treated with alkaline corneal burn were randomized into two groups, Group A (16 eyes) with femtosecond laser-assisted deep lamellar keratoplasty 24h after burn and Group B (16 eyes) without keratoplasty as controls. All eyes were evaluated with transmission electron microscopy (TEM) at 1, 2, 3, and 4wk follow-up, then all corneas were tested by hematoxylin and eosin staining histology. RESULTS: The corneal grafts in Group A were transparent, while those in Group B showed corneal stromal edema and loosely arranged collagen fibers. One week after treatment, TEM revealed the intercellular desmosomes in the epithelial layers and intact non-dissolving nuclei in Group A. At week 4, the center of the corneas in Group A was transparent with regularly arranged collagen fibers and fibroblasts in the stroma. In Group B, squamous cells were observed on the corneal surface and some epithelial cells were detached. CONCLUSION: Femtosecond laser-assisted deep lamellar keratoplasty can suppress inflammatory responses, prevent toxic substance-induced injury to the corneal endothelium and inner tissues with quicker recovery and better visual outcomes.

Objective. To characterize the genotype and phenotype of Chinese patients with congenital hyperinsulinism (CHI) caused by activating mutations in GLUD1, the gene that encodes mitochondrial enzyme glutamate dehydrogenase (GDH). Methods. The clinical data of glutamate dehydrogenase hyperinsulinism (GDH-HI) patients were reviewed, and gene mutations were confirmed by whole exome sequencing (WES) and Sanger DNA sequencing. Results. Twenty-six patients with GDH-HI heterozygous missense mutations were identified from 240 patients diagnosed as congenital hyperinsulinism over past 15 years. The median age at onset was 8 months (range: 1 day of life to 3 years). Seizure disorder was common in our cohort of patients (23/26). Four patients had normal serum ammonia levels; the median serum concentration was 101 μmol/L (range: 37–190 μmol/L). Hypoglycemic symptoms could be triggered by fasting or protein meals in all patients while blood glucose could be well controlled in all patients with diazoxide. Dosage of diazoxide could be reduced by protein restriction. Attempts to lower ammonia levels failed with different therapies such as protein restriction, benzoate, or N-carbamoyl glutamate. In follow-up, 15 of 26 patients had normal intelligence. Eleven patients developed epilepsy at the age of 6 months to 11 years. De novo mutations in GLUD1 were found in 24 cases, and dominant inheritance was observed in the other two; all were heterozygous. A total of 35% (9/26) patients carried c.1493C>T (p.S445L) mutation. Conclusions. Phenotypic heterogeneity of GDH-HI patients was observed within the Chinese cohort in the present study. The fact that most patients had a GLUD1 p. S445L mutation implies that this site could be a hotspot in Chinese patients. A high frequency of GDH-HI with normal ammonia has been reported in this study. Hence, GLUD1 mutational analysis may be an important method to differential diagnosis of GDH-HI from other diazoxide-responsive CHI in Chinese patients.

Background: In central precocious puberty (CPP), the pulse secretion and release of gonadotropin-releasing hormone (GnRH) are increased due to early activation of the hypothalamic-pituitary-gonadal axis, resulting in developmental abnormalities with gonadal development and appearance of secondary sexual characteristics. The CPP without organic disease is known as idiopathic CPP (ICPP). The objective of the study was to evaluate the clinical efficacy and safety of domestic leuprorelin (GnRH analog) in girls with ICPP. Methods: A total of 236 girls with ICPP diagnosed from April 2012 to January 2014 were selected and were randomized into two groups. One hundred fifty-seven girls in the test group were treated with domestic leuprorelin acetate, 79 girls in the control group were treated with imported leuprorelin acetate. They all were treated and observed for 6 months. After 6-month treatment, the percentage of children with peak luteinizing hormone (LH) ≤3.3 U/L, the percentage of children with peak LH/peak follicle stimulating hormone (FSH) ratio 0.05). Conclusions: Domestic leuprorelin is effective and safe in the treatment of Chinese girls with ICPP. Its effectiveness and safety are comparable with imported leuprorelin.

AIM: To evaluate the visual quality between femtosecond laser small incision lenticule extraction(SMILE)and femtosecond laser in situ keratomileusis(LASIK)in the treatment of myopia. METHODS: This study comprised 22 eyes(11 patients)underwent SMILE and 43 eyes(23 patients)received LASIK with femtosecond laser to correct myopia and myopic astigmatism. The two groups were recorded bydouble-pass optical quality analysis system(OQAS)at preoperative and postoperative 1mo. The two groups were compared: modulation transfer function cutoff frequency(MTF cutoff), strehl ratio(SR), objective scattering index(OSI). The early visual quality after operation between two groups were analyzed and evaluated.RESULTS: The MTF cutoff after operation one month were 34.835±10.113c/deg(SMILE group)and 38.362±10.623c/deg(LASIK group)(t=0.925, P=0.362). The SR after operation one month were 0.204±0.077(SMILE group)and 0.218±0.072(LASIK group)(t=0.557, P=0.582). The OSI after operation one month were 0.608±0.291(SMILE group)and 0.545±0.405(LASIK group)(t=-0.473, P=0.640). CONCLUSION: The double-pass OQAS tell us that there was not statistically significant between femtosecond laser SMILE and femtosecond LASIK in the treatment of myopia.

AIM: To study the role of immature dendritic cells (imDCs) on immune tolerance in rat penetrating keratoplasty (PKP) in high-risk eyes and to investigate the mechanism of immune hyporesponsiveness induced by donor-derived imDCs. METHODS: Seventy-five SD rats (recipient) and 39 Wistar rats (donor) were randomly divided into 3 groups: control, imDC and mature dendritic cell (mDC) group respectively. Using a model of orthotopic corneal transplantation in which allografts were placed in neovascularized high-risk eyes of recipient rat. Corneal neovascularization was induced by alkaline burn in the central cornea of recipient rat. Recipients in imDC group or mDC group were injected donor bone marrow-derived imDCs or mDCs of 1×106 respectively 1 week before corneal transplantation via tail vein. Control rat received the same volume of PBS. In each group, 16 recipients were kept for determination of survival time and other 9 recipients were executed on day 3, 7 and 14 after transplantation. Cornea was harvested for hematoxylin-eosin staining and acute rejection evaluation, Western blot was used to detect the expression level of Foxp3. RESULTS: The mean survival time of imDC group was significantly longer than that of control and mDC groups (all P

The traditional method of gas chromatography-mass spectrometry for monosaccharide component analysis with pretreatment of acetylation is described with slight modifications and verified in detail in this paper. It was then successfully applied to the quantitative analysis of component monosaccharides in polysaccharides extracted from the pine cones. The results demonstrated that the three pine cone polysaccharides all consisted of ribose, rhamnose, arabinose, xylose, mannose, glucose and galactose in different molar ratios. According to the recovery experiment, the described method was proved accurate and practical for the analysis of pine cone polysaccharides, meeting the need in the field of chemical analysis of Pinus plants. Furthermore; the chemical characteristics, such as neutral sugar, uronic acids, amino acids, molecular weights, and antioxidant activities of the polysaccharides were investigated by chemical and instrumental methods. The results showed that the chemical compositions of the polysaccharides differed from each other, especially in the content of neutral sugar and uronic acid. In the antioxidant assays, the polysaccharide fractions exhibited effective scavenging activities on ABTS radical and hydroxyl radical, with their antioxidant capabilities decreasing in the order of PKP > PAP > PSP. Therefore, although the polysaccharide fractions had little effect on superoxide radical scavenging, they still have potential to be developed as natural antioxidant agents in functional foods or medicine.

Genetic variation plays a significant role in maintaining the evolutionary potential of a species. Comparing the patterns of adaptive and neutral diversity in extant populations is useful for understanding the local adaptations of a species. In this study, we determined the fine-scale genetic structure of 6 extant populations of the giant panda (Ailuropoda melanoleuca) using mtDNA and DNA fingerprints, and then overlaid adaptive variations in 6 functional Aime-MHC class II genes (DRA, DRB3, DQA1, DQA2, DQB1, and DQB2) on this framework. We found that: (1) analysis of the mtDNA and DNA fingerprint-based networks of the 6 populations identified the independent evolutionary histories of the 2 panda subspecies; (2) the basal (ancestral) branches of the fingerprint-based Sichuan-derived network all originated from the smallest Xiaoxiangling (XXL) population, suggesting the status of a glacial refuge in XXL; (3) the MHC variations among the tested populations showed that the XXL population exhibited extraordinary high levels of MHC diversity in allelic richness, which is consistent with the diversity characteristics of a glacial refuge; (4) the phylogenetic tree showed that the basal clades of giant panda DQB sequences were all occupied by XXL-specific sequences, providing evidence for the ancestor-resembling traits of XXL. Finally, we found that the giant panda had many more DQ alleles than DR alleles (33∶13), contrary to other mammals, and that the XXL refuge showed special characteristics in the DQB loci, with 7 DQB members of 9 XXL-unique alleles. Thus, this study identified XXL as a glacial refuge, specifically harboring the most number of primitive DQB alleles.