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Although several synthetic hydrogels with defined stiffness have been developed to facilitate the proliferation and maintenance of human pluripotent stem cells (hPSCs), the influence of biochemical cues in lineage-specific differentiation and functional cluster formation has been rarely reported. Here, we present the application of Supragel, a supramolecular hydrogel formed by synthesized biotinylated peptides, for islet-like cluster differentiation. We observed that Supragel, with a peptide concentration of 5 mg/mL promoted spontaneous hPSCs formation into uniform clusters, which is mainly attributable to a supporting stiffness of ∼1.5 kPa as provided by the Supragel matrix. Supragel was also found to interact with the hPSCs and facilitate endodermal and subsequent insulin-secreting cell differentiation, partially through its components: the sequences of RGD and YIGSR that interacts with cell membrane molecules of integrin receptor. Compared to Matrigel and suspension culturing conditions, more efficient differentiation of the hPSCs was also observed at the stages 3 and 4, as well as the final stage toward generation of insulin-secreting cells. This could be explained by 1) suitable average size of the hPSCs clusters cultured on Supragel; 2) appropriate level of cell adhesive sites provided by Supragel during differentiation. It is worth noting that the Supragel culture system was more tolerance in terms of the initial seeding densities and less demanding, since a standard static cell culture condition was sufficient for the entire differentiation process. Our observations demonstrate a positive role of Supragel for hPSCs differentiation into islet-like cells, with additional potential in facilitating germ layer differentiation.

Abstract Background The development of alternative carbon sources is important for reducing the cost of heterotrophic microalgae cultivation. Among cheap feedstocks, galactose is one of the most abundant sugars and can be easily obtained from many natural biomasses. However, it is generally difficult to be utilized by microalgae. In addition, the mechanism of its low utilization efficiency in heterotrophic cultivation is still unknown. Results Among seven tested carbon sources, only glucose and acetate could be efficiently utilized by C. sorokiniana in heterotrophic cultivation while there were no apparent signs of utilization of other carbohydrates, including galactose, in regular heterotrophic cultivation. However, galactose could be utilized in cultures with high inoculation sizes. This confirmed that C. sorokiniana has a complete pathway for transporting and assimilating galactose under dark conditions, but the rate of galactose utilization is quite low. In addition, the galactose utilization was greatly enhanced in mixotrophic cultures, which indicated that galactose utilization could be enhanced by additional pathways that can enhance cell growth. Based on above results, a mixed carbon source culture strategy was proposed to improve the utilization rate of galactose, and a significant synergistic effect on cell growth was achieved in cultures using a mixture of galactose and acetate. Conclusions This study indicated that the galactose metabolism pathway may not be inherently deficient in Chlorophyta. However, its utilization rate was too low to be detected in regular heterotrophic cultivation. Mixed carbon source culture strategy was confirmed effective to improve the utilization rate of galactose. This study contributes to a deeper understanding of the utilization ability of difficultly utilized substrates in the heterotrophic cultivation of microalgae, which is of great significance for reducing the cost of heterotrophic cultivation of microalgae.

Twin-roll strip casting (TRSC) technology has unique advantages in the production of non-oriented electrical steel. However, the hot deformation behavior of high-grade electrical steel produced by TRSC has hardly been reported. This work systematically studied the hot deformation behavior of free-Al 2.43 wt.% Si electrical steel strip produced by twin-roll strip casting. During the simulated hot rolling test, deformation reduction was set as 30%, and the ranges of deformation temperature and strain rate were 750~950 °C and 0.01~5 s−1, respectively. The obtained true stress–strain curves show that the peak true stress decreased with an increase in the deformation temperature and with a decrease in the strain rate. Then, the effect of hot deformation parameters on microstructure and texture was analyzed using optical microstructure observation, X-ray diffraction, and electron backscattered diffraction examination. In addition, based on the obtained true stress–strain curves of the strip cast during hot deformation, the constitutive equation for the studied silicon steel strip was established, from which it can be found that the deformation activation energy of the studied steel strip is 83.367 kJ/mol. Finally, the kinetics model of dynamic recrystallization for predicting the recrystallization volume percent was established and was verified by a hot rolling experiment conducted on a rolling mill.

Carbon sinks in mangrove soils play a critical role in climate change mitigation globally. Soil dissolved organic matter (DOM) is a major form of labile organic matter and influences carbon cycling in wetland ecosystems. However, the factors regulating DOM pools in mangrove soils on a regional scale are not well understood. Here, we used a novel approach to assess soil DOM dynamics and its environmental drivers in mangrove wetlands on a national scale in China. Soil samples were collected from 43 sampling sites and distributed in mangroves across the coastline of China. DOM extracted from mangrove soils was characterized by fluorescence spectroscopy. We estimated that dissolved organic carbon (DOC) content ranged from 0.20 ± 0.02 g/kg to 3.85 ± 0.09 g/kg and nationally averaged 0.73 ± 0.07 g/kg in mangrove soils. Soil DOM was composed of humic-like substances, including humic acid-like (53.46 ± 8.74%) and fulvic acid-like (46.54 ± 8.74%). DOM pools in mangrove soils were identified to be perturbed by terrestrial inputs. Besides, the coupling interactions of environmental controls on the soil DOM pool were validated by establishing the structural equation modeling (SEM). We found that precipitation is the most important driver, which controlled directly the inputs and outputs of DOM pools. It also indirectly influenced DOM pools by regulating soil parameters through the cascade reactions. Cu, salinity, and clay are key mediators among soil parameters for precipitation affecting DOM pools. Precipitation influences soil DOC negatively and CDOM and FDOM positively markedly. The results provide novel insights into the labile carbon pool in mangrove soils and are beneficial for improving the assessment frameworks in the blue carbon ecosystems.

Mangrove ecosystems play a critical role in supporting ecological service values and regulating the global carbon cycle. They have become one of the most highly vulnerable ecosystems in the Anthropocene under the long-term influence of diverse human perturbations. Soil dissolved organic matter (DOM) is an active fraction within the carbon cycle in mangrove ecosystems. However, it remains unclear how human perturbations regulate DOM dynamics. Here, we used the fluorescence method and structural equation modeling to quantify the anthropogenic and environmental influence on soil DOM across the urban development gradient on a national scale in China. Anthropogenic activities (urban construction and sewage discharge) and environmental factors (salinity, metals, pH, and soil organic carbon) were striking forces that shaped DOM quality in mangrove soils. Both indirect and direct effects played critical roles in the soil DOM heterogeneity across the gradient of urbanization. Environmental factors can act as cofactors mediating human impact on DOM pools and as promoters transforming soil DOM in mangroves. Our study provided novel insights into the relationship between coastal developments and mangrove soil DOM heterogeneity and improved knowledge of coastal ecosystems as blue carbon sinks.

For cancer immunotherapy, triggering toll-like receptors (TLRs) in dendritic cells (DCs) can potentiate antigen-based immune responses. Nevertheless, to generate robust and long-lived immune responses, a well-designed nanovaccine should consider different locations of TLRs on DCs and co-deliver both antigens and TLR agonist combinations to synergistically induce optimal antitumor immunity. Herein, we fabricated lipid-polymer hybrid nanoparticles (LPNPs) to spatio-temporally deliver model antigen ovalbumin (OVA) on the surface of the lipid layer, TLR4 agonist monophosphoryl lipid A (MPLA) within the lipid layer, and TLR7 agonist imiquimod (IMQ) in the polymer core to synergistically activate DCs by both extra- and intra-cellular TLRs for enhancing adaptive immune responses. LPNPs-based nanovaccines exhibited a narrow size distribution at the mean diameter of 133.23 nm and zeta potential of −2.36 mV, showed a high OVA loading (around 70.83 μg/mg) and IMQ encapsulation efficiency (88.04%). Our data revealed that LPNPs-based nanovaccines showed great biocompatibility to immune cells and an excellent ability to enhance antigen internalization, thereby promoting DCs maturation and cytokines production. Compared to Free OVA, OVA-LPNPs promoted antigen uptake, lysosome escape, depot effect and migration to secondary lymphatic organs. In vivo immunization showed that IMQ-MPLA-OVA-LPNPs with dual agonists induced more powerful cellular and humoral immune responses. Moreover, prophylactic vaccination by IMQ-MPLA-OVA-LPNPs effectively suppressed tumor growth and increased survival efficacy. Hence, the nanovaccines we fabricated can effectively co-deliver antigens and different TLR agonists and realize coordinated stimulation of DCs in a spatio-temporal manner for enhanced immune responses, which provides a promising strategy for cancer immunotherapy.

Abstract Background Fulminant myocarditis is a clinical syndrome associated with threatening dysrhythmia which temporary pacemaker can be used for life-saving support. As a method of physiological pacing, His bundle pacing (HBP) maintain better cardiac synchronization than traditional right ventricular (RV) pacing. Case presentation It’s a severe case of fulminant myocarditis in a 41-year-old patient who presented for recurrent arrhythmias with hemodynamic instability. Temporary His bundle pacing combined with optimal medical therapy and extracorporeal membrane oxygenators (ECMO) supported him through his critical period of hospitalization. Conclusions During 1-year follow up, the cardiac function recovery was obvious without any pacing related complications. Echocardiography showed better atrioventricular and intra-ventricular synchronization during HBP in DDD mode. This is the first reported case of temporary His-purkinje conduction system pacing used for severe fulminant myocarditis.

Abstract N6-methyladenosine (m6A) is one of the most important epigenetic regulation of RNAs, such as lncRNAs. However, the underlying regulatory mechanism of m6A in diabetic cardiomyopathy (DCM) is very limited. In this study, we sought to define the role of METTL14-mediated m6A modification in pyroptosis and DCM progression. DCM rat model was established and qRT-PCR, western blot, and immunohistochemistry (IHC) were used to detect the expression of METTL14 and TINCR. Gain-and-loss functional experiments were performed to define the role of METTL14-TINCR-NLRP3 axis in pyroptosis and DCM. RNA pulldown and RNA immunoprecipitation (RIP) assays were carried out to verify the underlying interaction. Our results showed that pyroptosis was tightly involved in DCM progression. METTL14 was downregulated in cardiomyocytes and hear tissues of DCM rat tissues. Functionally, METTL14 suppressed pyroptosis and DCM via downregulating lncRNA TINCR, which further decreased the expression of key pyroptosis-related protein, NLRP3. Mechanistically, METTL14 increased m6A methylation level of TINCR gene, resulting in its downregulation. Moreover, the m6A reader protein YTHDF2 was essential for m6A methylation and mediated the degradation of TINCR. Finally, TINCR positively regulated NLRP3 by increasing its mRNA stability. To conclude, our work revealed the novel role of METTL14-mediated m6A methylation and lncRNA regulation in pyroptosis and DCM, which could help extend our understanding the epigenetic regulation of pyroptosis in DCM progression.

Arbuscular mycorrhizal fungi (AMF) derived refractory organic matter, mainly in glomalin-related soil protein (GRSP), stores globally significant amounts of carbon, attracting wide attention in response to climatic change. However, there is no synthesis review has been done so far to reveal global research progresses on GRSP, especially its ecological role for climate mitigation. Here,we conducted a bibliometric analysis of the papers on GRSP research from 1998 to 2021, based on the Web of Science (WOS) Core Collection.We collected a total of 634 papers and analyzed the characteristics of publication outputs in various countries and institutions. In addition, keywords analysis was conducted to reveal the main research directions and hot trends in the field of GRSP. We confirmed that 1) the number of papers published per year has gradually increased since 2010, and increased sharply in 2019; 2) the United States was the earliest country to conduct GRSP research, while China currently has the largest number of publications; 3) relevant studies focus on the role from AMF and GRSP in soil health and plant health; 4) the contribution of GRSP to soil carbon and its ecological function in mitigating climate change are the hotspot of research. The benefits of GRSP have become a consensus, however, the nature of glomalin and the mechanisms of GRSP-associated benefits still need to explore. As an important soil recalcitrant organic carbon, further studies are need to elucidate the land-ocean biogeochemical processes of GRSP and its contribution to global blue carbon.

Cerium–lanthanum alloys are the main component of nickel–metal hydride batteries, and they are thus an important material in the green-energy industry. However, these alloys have very strong chemical activity, and their surfaces are easily oxidized, leading to great difficulties in their application. To improve the corrosion resistance of cerium–lanthanum alloys, it is necessary to obtain a nanoscale surface with low roughness. However, these alloys can easily succumb to spontaneous combustion during machining. Currently, to inhibit the occurrence of fire, machining of this alloy in ambient air needs to be conducted at very low cutting speeds while spraying the workpiece with a large amount of cutting fluid. However, this is inefficient, and only a very limited range of parameters can be optimized at low cutting speeds; this restricts the optimization of other cutting parameters. To achieve ultraprecision machining of cerium–lanthanum alloys, in this work, an auxiliary machining device was developed, and its effectiveness was verified. The results show that the developed device can improve the cutting speed and obtain a machined surface with low roughness. The device can also improve the machining efficiency and completely prevent the occurrence of spontaneous combustion. It was found that the formation of a build-up of swarf on the cutting tool is eliminated with high-speed cutting, and the surface roughness (Sa) can reach 5.64 nm within the selected parameters. Finally, the oxidation processes of the cerium–lanthanum alloy and its swarf were studied, and the process of the generation of oxidative products in the swarf was elucidated. The results revealed that most of the intermediate oxidative products in the swarf were Ce3+, there were major oxygen vacancies in the swarf, and the final oxidative product was Ce4+.

Nano-clean fracturing fluids have broad application potential in coalbed methane reservoir fracturing owing to their high stability, good temperature resistance, low filtration loss, and strong frictional resistance reduction. However, the sand-carrying regularity of nano-clean fracturing fluids in coalbed methane reservoirs is unclear, especially for complex fractures with variable directions. This study established a sand transport model that considers proppant collision, wall friction blocking, fracture fluid filtration loss, and the fracture branching angle to study the sand-carrying law of nano-clean fracturing fluids and its influencing factors in complex fractures. The degrees of influence on equilibrium height and placement rate from high to low were the proppant particle size, proppant density, fracturing fluid properties, sand ratio, and pumping discharge volume, and the correlation degrees obtained by grey correlation analysis are 0.862, 0.861, 0.855, 0.854, and 0.832, respectively. As the complexity of the fractures deepens and the resistance increases, the flow rate of the fracturing fluid is reduced, making it difficult for the proppant to enter the branching joints. The sand-carrying performance of a nano-clean fracturing fluid is better than that of a common clear-water fracturing fluid. The fluid-structure coupling model of a nano-clean fracturing fluid can accurately characterize the sand-carrying law of nano-clean fracturing fluids, providing a research basis for optimizing high efficiency sand-carrying fracturing fluid parameters in coalbed methane reservoir fracturing construction.

Abstract Aims His–Purkinje conduction system pacing (HPCSP) utilizing His (HBP) or left bundle branch pacing (LBBP) in patients with atrial fibrillation (AF) and wide QRS duration has not been well studied. We assessed the benefit of left bundle branch block (LBBB) correction during HPCSP in AF patients undergoing atrioventricular junction (AVJ) ablation with LBBB, compared with those with narrow QRS duration. Methods and results This is an observational study in consecutive patients with typical LBBB or narrow QRS duration in whom we attempted HPCSP after AVJ ablation for refractory AF with a left ventricular ejection fraction (LVEF) ≤ 50%. Echocardiographic responses and clinical outcomes were assessed at baseline and during 1 year of follow‐up. A total of 178 patients were enrolled, of which 170 achieved AVJ ablation + permanent HPCSP (age 69.3 ± 10.1 years; LVEF 34.3 ± 7.7%), 133 (78.2%) patients had a narrow QRS duration, and 37 (21.2%) had an LBBB. The QRS duration changed from a baseline of 159.7 ± 16.6 ms to a paced QRS duration of 110.4 ± 12.7 ms in the LBBB cohort and from 95.6 ± 10.4 to 100.8 ± 14.5 ms (both P

Abstract Background The third-generation epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have shown significant therapeutic effects on patients with non-small cell lung carcinoma (NSCLC) who carry active EGFR mutations, as well as those who have developed acquired resistance to the first-generation of EGFR-TKIs due to the T790M mutation. However, most patients develop drug resistance after 8–10 months of treatment. Currently, the mechanism has not been well clarified, and new therapeutic strategies are urgently needed. Methods Osimertinib resistant cell lines were established by culturing sensitive cells in chronically increasing doses of osimertinib. The anticancer effect of reagents was examined both in vitro and in vivo using the sulforhodamine B assay and a xenograft mouse model. The molecular signals were detected by western blotting. The combination effect was analyzed using CompuSyn software. Results We found that bromodomain and extra-terminal proteins (BETs) were upregulated in osimertinib resistant (H1975-OR) cells compared with those in the paired parental cells (H1975-P), and that knockdown of BETs significantly inhibited the growth of H1975-OR cells. The BET inhibitor JQ1 also exhibited stronger growth-inhibitory effects on H1975-OR cells and a greater expression of BETs and the downstream effector c-Myc than were observed in H1975-P cells. The histone deacetylase (HDAC) inhibitor trichostatin A (TSA) showed stronger growth suppression in H1975-OR cells than in H1975-P cells, but vorinostat, another HDAC inhibitor, showed equal inhibitory efficacy in both cell types. Consistently, downregulation of BET and c-Myc expression was greater with TSA than with vorinostat. TSA restrained the growth of H1975-OR and H1975-P xenograft tumors. The combination of TSA and JQ1 showed synergistic growth-inhibitory effects in parallel with decreased BET and c-Myc expression in both H1975-OR and H1975-P cells and in xenograft nude mouse models. BETs were not upregulated in osimertinib resistant HCC827 cells compared with parental cells, while TSA and vorinostat exhibited equal inhibitory effects on both cell types. Conclusion Upregulation of BETs contributed to the osimertinib resistance of H1975 cells. TSA downregulated BET expression and enhanced the growth inhibitory effect of JQ1 both in vitro and in vivo. Our findings provided new strategies for the treatment of osimertinib resistance.

Background: Long non-coding RNAs (lncRNAs) play a key regulatory role in tumor metabolism. Although hepatocellular carcinoma (HCC) is a metabolic disease, there have been few systematic reports on the association between lncRNA expression and metabolism in HCC.Results: In this study, we screened 557 metabolism-related lncRNAs in HCC. A risk score model based on 13 metabolism-related lncRNA pairs was constructed to predict the outcome and drug response in HCC. The risk score model presented a better prediction of the outcomes than that with common clinicopathological characteristics, such as tumor stage, grade, and status and aneuploidy score in both training and testing cohorts. In addition, patients in the high-risk group exhibited higher responses to gemcitabine and epothilone, whereas those in the low-risk group were more sensitive to metformin and nilotinib.Conclusion: The metabolism-related lncRNAs-based risk score model and the other findings of this study may be helpful for HCC prognosis and personalized treatment prediction.

Reverberation characteristics must be considered in the design of sonar. The research on reverberation characteristics is based on a large number of actual reverberation data. Due to the cost of trials, it is not easy to obtain actual lake and sea trial reverberation data, which leads to a lack of actual reverberation data. Traditionally, reverberation data are obtained by modeling the generation mechanism of seafloor reverberation. The usability of the models requires a large amount of actual seafloor reverberation data to verify. In terms of the reverberation modeling theory, scattering models are mostly empirical, computationally intensive and inefficient. In order to solve the above obstacles, we propose a shallow seafloor reverberation data simulation method based on the generative adversarial network (GAN), which uses a small amount of actual reverberation data as reference samples to train the GAN to generate more reverberation data. The reverberation data generated by the GAN are compared with that simulated by traditional methods, and it is found that the reverberation data generated by the GAN meet the reverberation characteristics. Once the network is trained, the reverberation data are generated with very little computation. In addition, the method is universal and can be applied to any sea area. Compared with the traditional method, this method has a simple modeling idea, less computation and strong universality. It can be used as an alternative method for sea trials to provide data support for the study of seafloor reverberation characteristics, and it has broad application prospects in antireverberation technology research and active sonar design.

Background: Left bundle branch pacing (LBBP) is a novel physiological pacing and previous studies have confirmed the feasibility and safety of it. The incidence of complications in LBBP is relatively low as reported. Here we present a case of interventricular septal hematoma complicating LBBP lead implantation.Case summary: LBBP was achieved for treatment of high-grade atrioventricular block in a 67-year-old female. Chest pain began 1 h after implantation when the electrocardiogram showed ST-T changes. Then bedside echocardiography confirmed the formation of interventricular septal hematoma. Urgent coronary angiography showed the contrast agent retention and overflow in the interventricular septum. The symptom was relieved half an hour later. Echocardiogram performed 2 h later revealed the size of the hematoma was the same as before. The electrocardiography, coronary angiography and CTA confirmed the resolution of the hematoma at 1-month follow-up. Pacing parameters and cardiac function remained stable during 6-month follow-up.Conclusion: This is the first reported case describing the clinic features and management of interventricular septum hematoma complicating LBBP. The importance of routine echocardiograms after implantation for identifying the hematoma should be highlighted.

His bundle pacing (HBP) can reverse left ventricular (LV) remodeling in patients with right ventricular (RV) pacing-induced cardimyopathy (PICM) but may be unable to correct infranodal atrioventricular block (AVB). Left bundle branch pacing (LBBP) results in rapid LV activation and may be able to reliably pace beyond the site of AVB. Our study was conducted to assess the feasibility, safety, and outcomes of permanent LBBP in infranodal AVB and PICM patients. Patients with infranodal AVB and PICM who underwent LBBP for cardiac resynchronization therapy (CRT) were included. Clinical evaluation and echocardiographic and electrocardiographic assessments were recorded at baseline and follow-up. Permanent LBBP upgrade was successful in 19 of 20 patients with a median follow-up duration of 12 months. QRS duration (QRSd) increased from 139.3 ± 28.0 ms at baseline to 176.2 ± 21.4 ms (P < 0.001) with right ventricular pacing (RVP) and was shortened to 120.9 ± 15.2 ms after LBBP (P < 0.001). The mean LBBP threshold was 0.7 ± 0.3 V at 0.4 ms at implant and remained stable during follow-up. The left ventricular ejection fraction (LVEF) increased from 36.3% ± 6.5% to 51.9% ± 13.0% (P < 0.001) with left ventricular end-systolic volume (LVESV) reduced from 180.1 ± 43.5 to 136.8 ± 36.7 ml (P < 0.001) during last follow-up. LBBP paced beyond the site of block, which results in a low pacing threshold with a high success rate in infranodal AVB patients. LBBP improved LV function with stable parameters over the 12 months, making it a reasonable alternative to cardiac resynchronization pacing via a coronary sinus lead in infranodal AVB and PICM patients.

Background and PurposeThe profibrotic and proinflammatory effects induced by doxorubicin (DOX) are key processes in the development of serious heart damage. Lack of effective drugs and the unclear mechanisms of its side effects limit the clinical treatment of DOX-induced cardiac injury. This study aimed to explore the protective role of LCZ696 and the potential mechanism of Toll-like receptor 2 (TLR2) in doxorubicin-induced cardiac failure.Experimental ApproachDOX (5 mg/kg/week, three times) was used to establish a chronic cardiomyopathy mouse model. Heart function tests, pathology examinations and molecular biology analyses were used to explore the effects of LCZ696 and TLR2 deficiency in vivo and in vitro. Computational docking was applied to predict the key residues for protein-ligand interaction.Key ResultsThe EF% declined, and the LVIDd, pro-fibrosis marker levels and NF-κB related inflammatory response increased in the chronic cardiomyopathy group induced by DOX. LCZ696 treatment and TLR2 deficiency reversed these heart damage in vivo. In H9C2 cells, pre-treatment with LCZ696 and TLR2 knockdown suppressed the DOX-induced high expression of profibrotic and proinflammatory markers. Moreover, DOX notably increased the TLR2-MyD88 interaction in vivo and in vitro, which was inhibited by LCZ696. Finally, we demonstrated the direct interaction between DOX and TLR2 via hydrogen bonds on Pro-681 and Glu-727 and Pro-681 and Ser-704 may be the key residues by which LCZ696 affects the interaction between DOX and TLR2.Conclusion and ImplicationsLCZ696 prevents DOX-induced cardiac dilation failure, fibrosis and inflammation by reducing the formation of TLR2-MyD88 complexes. LZC696 may be a potential effective drug to treat DOX-induced heart failure.

Background: Higher serum gamma-glutamyltransferase (GGT) is associated with high risk of hypertension. We aimed to examine the association between sex-specific serum GGT levels and incident of hypertension in a Chinese population without metabolic syndrome.Methods: Participants who were free of hypertension and metabolic syndrome from the First Affiliated Hospital of Wenzhou Medical University between 2009 and 2014 were included. Participants were grouped into sex-specific quartiles of GGT levels (Q1–Q4) defined as: ≤19, 20–26, 27–38, and ≥39 U/L for male; ≤12, 13–15, 16–19, and ≥20 U/L for female. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence of hypertension according to sex-specific quartiles of GGT levels. Kaplan–Meier analysis and interaction analysis were conducted.Results: Among 38,806 participants included (average age 36.0 years, 54.0% men), 4,505 of them developed hypertension. In the overall study population, using Q1 as the reference group, participants in Q2, Q3, and Q4 showed a higher risk of developing hypertension, with HRs (95% CIs) of 1.126 (1.029–1.232), 1.187 (1.083–1.302), and 1.300 (1.182–1.431), respectively (P < 0.001), after adjusting for known confounders. Sex-specific analysis showed that the adjusted HRs for participants in Q4 (reference: Q1) were greater in females [1.321 (1.100–1.586, P < 0.001)] than in males [1.268 (1.133–1.420, P < 0.001)] (P for interaction = 0.047). Moreover, interaction analysis showed that this association was consistently observed when the participants were stratified by age, body mass index, and fatty liver status.Conclusion: Among Chinese adults without metabolic syndrome, serum GGT level was positively associated with incidence of hypertension, and the association was stronger in females than in males.

Metasurfaces with local phase tuning by subwavelength elements promise unprecedented possibilities for ultrathin and multifunctional optical devices in which geometric phase design is widely used due to its resonant‐free and large tolerance in fabrications. By arranging the orientations of anisotropic nanoantennas, the geometric phase‐based metasurfaces can convert the incident spin light to its orthogonal state, and enable flexible wave front engineering together with the function of a half‐wave plate. Herein, by incorporating the propagation phase, another important optical device of quarter‐wave plate together with the wave front engineering as well, which is implemented by controlling both the cross‐ and copolarized light simultaneously with a singlet metasurface, is realized. Highly efficient conversion of the spin light to a variety of linearly polarized light is obtained for meta‐holograms, metalens focusing and imaging in the blue light region. This work provides a new strategy for efficient metasurfaces with both phase and polarization control, and enriches the functionalities of metasurface devices for wider application scenarios.

BackgroundDiabetes and cancer are both multifactorial diseases, and epidemiologic evidence indicates that diabetes may be associated with the incidence of certain types of cancer. In diabetes the risk of pancreatic cancer is increased significantly. However, whether certain diabetes treatment being related with the risk of pancreatic cancer remains unclear. In this report, we presented a case of pancreatic ductal adenocarcinoma in a diabetic patient in China after being treated with liraglutide, a novel glucagon-like peptide-1 (GLP-1) analog.Case reportA 71-year-old Han Chinese man who had had a type 2 diabetes for 25 years presented at the endocrinology department with discomfort in the left upper quadrant of abdomen for 10 days. The patient’s vital signs and laboratory findings were unremarkable except for the elevated level of carbohydrate antigen (CA19-9). The upper abdomen routine enhanced computed tomography (CT) scan showed low density of the pancreatic body and tail, and the histopathological result of the pancreatic biopsy samples was pancreatic ductal adenocarcinoma with regional lymph node metastasis. We reviewed his former medical records and found that liraglutide was added to his hypoglycemic treatment regimen 20 months ago. At that time, the level of tumor biomarkers and upper abdomen routine CT were unremarkable. We estimated the causality between liraglutide and pancreatic cancer by the Naranjo Adverse Drug Reaction Probability scale and WHO-Uppsala Monitoring Centre (WHO-UMC) system, and the causality turned out to be possible.ConclusionOur report suggests that liraglutide may be related with the genesis and development of pancreatic cancer and also highlights the importance of regular checkups in diabetic patients treated with liraglutide. However, our report has some notable limitations, and further longer-term follow-up trials with larger sample should be conducted in future to assess the causality between liraglutide and pancreatic cancer.

Introduction: Antiarrhythmic drug therapy can affect pacemaker parameters in both the atrial and ventricular myocardium. It is not known whether antiarrhythmic drugs impact His bundle pacing/sensing parameters and His to ventricle (H-V) intervals following permanent His bundle pacing (HBP). The aims of the study were to prospectively determine the influence of rhythm and rate-controlling drugs on pacing parameters and H-V conduction after His bundle lead implantation and to assess the impact of rhythm and rate-controlling drugs on the safety of HBP.Materials and Methods: Patients (N = 140) with QRS duration < 120 ms who met permanent pacing indications were prospectively enrolled. Propafenone, lidocaine, and adenosine were injected intravenously after implantation of 3,830 lead during the procedure. Metoprolol succinate, amiodarone, and digoxin were taken orally for 1 month. Pacing parameters before and after drug intervention was measured, including His capture threshold, sensing and impedance, H-V interval, and conduction.Results: There were no statistically significant differences in His bundle pacing thresholds, impedance, and sensing after drug intervention at implantation or during a 2-month follow-up (P > 0.05). The HV interval was not affected except in the large-dose propafenone group where HV interval prolonged (P = 0.001). All patients maintained 1:1 H-V conduction following drug administration.Conclusion: There was no adverse impact on the HBP parameters or H-V conduction after the administration of commonly used dosage of rhythm and rate-controlling drugs. The drugs were safe in patients with permanent His bundle pacing.

Abstract Tectal glioma (TG) is a rare low-grade tumor occurring predominantly in the pediatric population. There has been no detailed analysis of molecular alterations in TG. Risk factors associated with inferior outcome and long-term sequelae of TG have not been well-documented. We retrospectively studied TGs treated or referred for review at St. Jude Children’s Research Hospital (SJCRH) between 1986 and 2013. Longitudinal clinical data were summarized, imaging and pathology specimen centrally reviewed, and tumor material analyzed with targeted molecular testing and genome-wide DNA methylation profiling. Forty-five patients with TG were included. Twenty-six (57.8%) were male. Median age at diagnosis was 9.9 years (range, 0.01–20.5). Median follow-up was 7.6 years (range, 0.5–17.0). The most common presenting symptoms were related to increased intracranial pressure. Of the 22 patients treated at SJCRH, 19 (86%) required cerebrospinal fluid diversion and seven (32%) underwent tumor-directed surgery. Five patients (23%) received radiation therapy and four (18%) systemic therapy. Ten-year overall and progression-free survival were 83.9 ± 10.4% and 48.7 ± 14.2%, respectively. Long-term morbidities included chronic headaches, visual symptoms and neurocognitive impairment. Lesion ≥3cm2, contrast enhancement and cystic changes at presentation were risk factors for progression. Among those with tumor tissue available, 83% showed growth patterns similar to pilocytic astrocytoma and 17% aligned best with diffuse astrocytoma. BRAF duplication (a marker of KIAA1549-BRAF fusion) and BRAF V600E mutation were detected in 25% and 7.7%, respectively. No case had histone H3 K27M mutation. DNA methylation profile of TG was distinct from other brain tumors. In summary, TG is an indolent, chronic disease with unique clinical and molecular profiles and associated with long term morbidities. Large size, contrast enhancement and cystic changes are risk factors for progression.

Background Persistent atrial fibrillation may lead to a higher probability of inappropriate shocks in heart failure patients with an implantable cardioverter‐defibrillator (ICD). The aim of this study was to evaluate the impact of His‐Purkinje conduction system pacing combined with atrioventricular node ablation in improving heart function and preventing inappropriate shock therapy in these patients. Methods and Results A total of 86 consecutive patients with persistent atrial fibrillation and heart failure who had indications for ICD implantation were enrolled from January 2010 to March 2018. His‐Purkinje conduction system pacing with ICD and atrioventricular node ablation was attempted in 55 patients, and the remaining patients underwent ICD implantation only. Left ventricular (LV) ejection fraction, LV end‐systolic volume, New York Heart Association (NYHA) classification, shock therapies, and drug therapy were assessed during follow‐up. Overall, 31 patients received ICD implantation with optimal drug therapy (group 1). atrioventricular node ablation combined with His‐Purkinje conduction system pacing was successfully achieved in 52 patients (group 2). During follow‐up, patients in group 2 had lower incidence of inappropriate shock (15.6% versus 0%, P

Floquet topological systems exhibit rich physics associated with quasienergy band structures and new topological states; nevertheless, they are usually explored in Hermitian systems. Recent studies have shown the capability of non-Hermiticity in engineering topological states, while the interplay of Floquet topological phases and non-Hermiticity remains unclear. Here, we reveal that the non-Hermitian modulation can induce the phase transitions between trivial and nontrivial topological Floquet states. Our study theoretically predicts that the non-Hermitian modulation can create a Floquet π mode in an originally topological trivial system according to the reopening of quasienergy band gap (i.e., the π gap), which is well confirmed experimentally in the silicon waveguide platform. Our approach shows the powerful capability of non-Hermitian modulation in engineering topological modes in Floquet photonics systems and would inspire different possibilities in optical field manipulation in open systems.

Objective This study was performed to investigate the association of the admission hemoglobin level with the incidence of in-hospital cardiac arrest (IHCA) in patients with acute coronary syndrome (ACS) complicated by cardiogenic shock (CS). Methods In this retrospective study, we reviewed the medical records of consecutive patients with ACS complicated by CS admitted to the coronary care unit from January 2014 to October 2017. Logistic regression models were carried out to evaluate the association between hemoglobin and the incidence of IHCA. Interaction and subgroup analyses were also performed. Results In total, 211 patients were included in the study, and 61 (28.9%) patients developed IHCA. In the multivariable analysis, hemoglobin was a strong independent predictor of IHCA (odds ratio, 0.971; 95% confidence interval, 0.954–0.989). In the fully adjusted model, patients in the higher hemoglobin tertile were less likely to develop IHCA than patients in the lowest hemoglobin tertile (odds ratio, 0.194; 95% confidence interval, 0.071–0.530). The relationship remained stable in most subgroups except patients aged ≥70 years. Conclusion In patients with ACS complicated by CS, the incidence of IHCA is related to the hemoglobin concentration, and a high hemoglobin concentration is a protective factor against the development of IHCA.