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Background Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified. Methods In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed. Results In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation. Conclusion Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.

Abstract Higher-order Weyl semimetals are a family of recently predicted topological phases simultaneously showcasing unconventional properties derived from Weyl points, such as chiral anomaly, and multidimensional topological phenomena originating from higher-order topology. The higher-order Weyl semimetal phases, with their higher-order topology arising from quantized dipole or quadrupole bulk polarizations, have been demonstrated in phononics and circuits. Here, we experimentally discover a class of higher-order Weyl semimetal phase in a three-dimensional photonic crystal (PhC), exhibiting the concurrence of the surface and hinge Fermi arcs from the nonzero Chern number and the nontrivial generalized real Chern number, respectively, coined a real higher-order Weyl PhC. Notably, the projected two-dimensional subsystem with k z = 0 is a real Chern insulator, belonging to the Stiefel-Whitney class with real Bloch wavefunctions, which is distinguished fundamentally from the Chern class with complex Bloch wavefunctions. Our work offers an ideal photonic platform for exploring potential applications and material properties associated with the higher-order Weyl points and the Stiefel-Whitney class of topological phases.

Here the authors experimentally demonstrate a maximally charged Weyl point in a three dimensional photonic crystal, with topological charge of four — the maximal charge number that a two-fold Weyl point can host, which supports quadruple-helicoid Fermi arcs

RNAs play important roles in regulating biological growth and development. Advancements in RNA-imaging techniques are expanding our understanding of their function. Several common RNA-labeling methods in plants have pros and cons. Simultaneously, plants’ spontaneously fluorescent substances interfere with the effectiveness of RNA bioimaging. New technologies need to be introduced into plant RNA luminescence. Aggregation-induced emission luminogens (AIEgens), due to their luminescent properties, tunable molecular size, high fluorescence intensity, good photostability, and low cell toxicity, have been widely applied in the animal and medical fields. The application of this technology in plants is still at an early stage. The development of AIEgens provides more options for RNA labeling. Click chemistry provides ideas for modifying AIEgens into RNA molecules. The CRISPR/Cas13a-mediated targeting system provides a guarantee of precise RNA modification. The liquid–liquid phase separation in plant cells creates conditions for the enrichment and luminescence of AIEgens. The only thing that needs to be looked for is a specific enzyme that uses AIEgens as a substrate and modifies AIEgens onto target RNA via a click chemical reaction. With the development and progress of artificial intelligence and synthetic biology, it may soon be possible to artificially synthesize or discover such an enzyme.

Background: The incidence of silent cerebral embolisms (SCEs) has been documented after pulmonary vein isolation using different ablation technologies; however, it is unreported in patients undergoing with atrial fibrillation (AF) ablation using Robotic Magnetic Navigation (RMN). The purpose of this prospective study was to investigate the incidence, risk predictors and probable mechanisms of SCEs in patients with AF ablation and the potential impact of RMN on SCE rates.Methods and Results: We performed a prospective study of 166 patients with paroxysmal or persistent AF who underwent pulmonary vein isolation. Patients were divided into RMN group (n = 104) and manual control (MC) group (n = 62), and analyzed for their demographic, medical, echocardiographic, and risk predictors of SCEs. All patients underwent cerebral magnetic resonance imaging within 48 h before and after the ablation procedure to assess cerebral embolism. The incidence and potential risk factors of SCEs were compared between the two groups. There were 26 total cases of SCEs in this study, including 6 cases in the RMN group and 20 cases in the MC group. The incidences of SCEs in the RMN group and the MC group were 5.77 and 32.26%, respectively (X2 = 20.63 P < 0.05). Univariate logistic regression analysis demonstrated that ablation technology, CHA2DS2-VASc score, history of cerebrovascular accident/transient ischemic attack, and low ejection fraction were significantly associated with SCEs, and multivariate logistic regression analysis showed that MC ablation was the only independent risk factor of SCEs after an AF ablation procedure.Conclusions: Ablation technology, CHA2DS2-VASc score, history of cerebrovascular accident/transient ischemic attack, and low ejection fraction are associated with SCEs. However, ablation technology is the only independent risk factor of SCEs and RMN can significantly reduce the incidence of SCEs resulting from AF ablation.Clinical Trial Registration: ChiCTR2100046505.

Diabetic coronary arterial disease is a leading cause of morbidity and mortality in diabetic patients. The impaired function of large-conductance calcium-activated potassium channels (BK channels) is involved in diabetic coronary arterial disease. Many studies have indicated that the reduced BK channel expression in diabetic coronary artery is attributed to ubiquitin-mediated protein degradation by the ubiquitin–proteasome system. This review focuses on the influence and the mechanisms of BK channel regulation by E3 ubiquitin ligases in diabetic coronary arterial disease. Thus, BK channels regulated by E3 ubiquitin ligase may play a pivotal role in the coronary pathogenesis of diabetic mellitus and, as such, is a potentially attractive target for therapeutic intervention.

Exotic transport properties of type-II Weyl semimetals have been predicted but are yet to be experimentally evidenced. Here, Li et al. report evidences of an anisotropy of negative magnetoresistance and a quantum oscillation arising from the predicted Weyl orbit in the type-II Weyl semimetal WTe2.

Exotic topological particles are reported to arise from special types of symmetry protection. Here, Wang et al. predict an hourglass Dirac chain metal protected by nonsymmorphic symmetries and its possible realization in ReO2.

Whether carbon allotropes may host emergent topological fermions is unknown. Here, Zhonget al. predict a three-dimensional carbon allotrope entirely composed of pentagon rings, showing a plethora of topological fermions under strain.

Condensed matter: Creating black holes in materials A material that mimics the behavior of a black hole is developed by researchers in China and Singapore. Yugui Yao from the Beijing Institute of Technology and colleagues show that mechanical strain in a material known as Dirac semimetal can imitate the warping of space–time predicted by general relativity. Simulations of the Universe predict a wide range of counter-intuitive phenomenon. But many of these are beyond state-of-the-art technology to detect. Instead, scientists can engineer materials that are governed by equations similar to those that define astrophysical phenomena. Yao et al. investigate Dirac semimetals whose electronic bandstructure gives rise to massless quasiparticles that resemble relativistic particles. They show that altering the uniaxial strain enables control over these quasiparticles so that they emulate the behavior associated with black and white holes, event horizons and gravitational lensing.

Abstract Topological metals and semimetals (TMs) have recently drawn significant interest. These materials give rise to condensed matter realizations of many important concepts in high-energy physics, leading to wide-ranging protected properties in transport and spectroscopic experiments. It has been well-established that the known TMs can be classified by the dimensionality of the topologically protected band degeneracies. While Weyl and Dirac semimetals feature zero-dimensional points, the band crossing of nodal-line semimetals forms a one-dimensional closed loop. In this paper, we identify a TM that goes beyond the above paradigms. It shows an exotic configuration of degeneracies without a well-defined dimensionality. Specifically, it consists of 0D nexus with triple-degeneracy that interconnects 1D lines with double-degeneracy. We show that, because of the novel form of band crossing, the new TM cannot be described by the established results that characterize the topology of the Dirac and Weyl nodes. Moreover, triply-degenerate nodes realize emergent fermionic quasiparticles not present in relativistic quantum field theory. We present materials candidates. Our results open the door for realizing new topological phenomena and fermions including transport anomalies and spectroscopic responses in metallic crystals with nontrivial topology beyond the Weyl/Dirac paradigm.

Objective. The objective of this study was to investigate the impact of left atrial (LA) size for the ablation of atrial fibrillation (AF) using remote magnetic navigation (RMN). Methods. A total of 165 patients with AF who underwent catheter ablation using RMN were included. The patients were divided into two groups based on LA diameter. Eighty-three patients had small LA (diameter

Hinged multi-body systems are gaining popularity in the field of ocean engineering. Their performance is commonly evaluated using numerical simulations, but comparisons with experimental data are required to ensure the accuracy of the computational tools. However, there is a dearth of experimental studies on the motion performance of hinged multi-body systems, particularly those involving more than two hinged floating bodies. This study aims to fill this gap in experimental data for hinged multi-body systems beyond two bodies. The rectangular box was chosen as the test model due to its stable hydrodynamic properties and ease of numerical modelling. Five identical boxes were prefabricated and subsequently tested in the pool in a sequence ranging from one to five boxes to capture the motion performance. Additionally, a numerical programme based on potential flow theory was developed for mutual validation with the experimental data. Firstly, the physical properties of each box were determined through equations calculation and a free decay test, enabling the acquisition of all parameters for conducting numerical simulations. Then, the response amplitude operator (RAO) curves for the heave and pitch motion of a single box were depicted, and the results indicated that the resonant frequency in pitch direction obtained from the regular wave test was consistent with that obtained from the free decay test. Finally, the motion RAO curves of hinged multi-body systems were presented and analysed. The agreement between the measured and computed results confirms the suitability of the experimental data presented in this study as benchmark data for validating numerical simulations.

Ebola virus (EBOV) is classified as a category A pathogen as it causes viral hemorrhagic fever, one of the most-deadly virus-related diseases. Since its discovery in 1976, EBOV has caused a number of global public health incidents, which have posed a serious threat to both humans and non-human primates. Thus, numerous preventive vaccine studies are underway, including research on inactivated vaccines, DNA vaccines, subunit vaccines, virus-like particles, Venezuelan equine encephalitis virus replicon particles, and several viral vector vaccines. The vesicular stomatitis virus-based vaccine Ervebo was recently approved by the Food and Drug Administration and the European Union, and several other vaccines have also been proven to confer potent protection in non-human primates against EBOV lethal challenge. This review provides a brief background of EBOV, with a focus on the epidemiology, available animal models, and advances in preventive approaches for EBOV infection.

Abstract The genus Flavivirus comprises numerous emerging and re‐emerging arboviruses causing human illness. Vaccines are the best approach to prevent flavivirus diseases. But pathogen diversities are always one of the major hindrances for timely development of new vaccines when confronting unpredicted flavivirus outbreaks. We used West Nile virus (WNV) as a model to develop a new live‐attenuated vaccine (LAV), WNV‐poly(A), by replacing 5ʹ portion (corresponding to SL and DB domains in WNV) of 3ʹ‐UTR with internal poly(A) tract. WNV‐poly(A) not only propagated efficiently in Vero cells, but also was highly attenuated in mouse model. A single‐dose vaccination elicited robust and long‐lasting immune responses, conferring full protection against WNV challenge. Such “poly(A)” vaccine strategy may be promising for wide application in the development of flavivirus LAVs because of its general target regions in flaviviruses.

Floating structures have become a major part of offshore structure communities as offshore engineering moves from shallow waters to deeper ones. Floating installation ships or platforms are widely used in these engineering operations. Unexpected wave-induced motions affect floating structures, especially in harsh sea conditions. Horizontal motions on the sea surface can be offset by a dynamic positioning system, and heave motions can be controlled by a heave compensation system. Active heave compensation (AHC) systems are applied to control vertical heave motions and improve safety and efficiency. Predictive control based on machine learning prediction algorithms further improves the performance of active heave compensation control systems. This study proposes a predictive control strategy for an active heave compensation system with a machine learning prediction algorithm to minimise the heave motion of crane payload. A predictive active compensation model is presented to verify the proposed predictive control strategy, and proportion–integration–differentiation control with predictive control is adopted. The reliability of back propagation neural network (BPNN) and long short-term memory recurrent neural network (LSTM RNN) prediction algorithms is proven. The influence of the predictive error on compensation performance is analysed by comparing predictive feedforward cases with actual-data feedforward cases. Predictive feedforward control with regular and irregular wave conditions is discussed, and the possible strategies are examined. After implementing the proposed predictive control strategy based on a machine learning algorithm in an active heave compensation system, the heave motion of the payload is reduced considerably. This investigation is expected to contribute to the motion control strategy of floating structures.

ABSTRACTThe ongoing COVID-19 pandemic is causing huge impact on health, life, and global economy, which is characterized by rapid spreading of SARS-CoV-2, high number of confirmed cases and a fatality/case rate worldwide reported by WHO. The most effective intervention measure will be to develop safe and effective vaccines to protect the population from the disease and limit the spread of the virus. An inactivated, whole virus vaccine candidate of SARS-CoV-2 has been developed by Wuhan Institute of Biological Products and Wuhan Institute of Virology. The low toxicity, immunogenicity, and immune persistence were investigated in preclinical studies using seven different species of animals. The results showed that the vaccine candidate was well tolerated and stimulated high levels of specific IgG and neutralizing antibodies. Low or no toxicity in three species of animals was also demonstrated in preclinical study of the vaccine candidate. Biochemical analysis of structural proteins and purity analysis were performed. The inactivated, whole virion vaccine was characterized with safe double-inactivation, no use of DNases and high purity. Dosages, boosting times, adjuvants, and immunization schedules were shown to be important for stimulating a strong humoral immune response in animals tested. Preliminary observation in ongoing phase I and II clinical trials of the vaccine candidate in Wuzhi County, Henan Province, showed that the vaccine is well tolerant. The results were characterized by very low proportion and low degree of side effects, high levels of neutralizing antibodies, and seroconversion. These results consistent with the results obtained from preclinical data on the safety.

ABSTRACTIn the face of COVID-19 pandemic caused by the newly emerged SARS-CoV-2, an inactivated, Vero cell-based, whole virion vaccine candidate has been developed and entered into phase III clinical trials within six months. Biochemical and immunogenic characterization of structural proteins and their post-translational modifications in virions, the end-products of the vaccine candidate, would be essential for the quality control and process development of vaccine products and for studying the immunogenicity and pathogenesis of SARS-CoV-2. By using a panel of rabbit antisera against virions and five structural proteins together with a convalescent serum, the spike (S) glycoprotein was shown to be N-linked glycosylated, PNGase F-sensitive, endoglycosidase H-resistant and cleaved by Furin-like proteases into S1 and S2 subunits. The full-length S and S1/S2 subunits could form homodimers/trimers. The membrane (M) protein was partially N-linked glycosylated; the accessory protein 3a existed in three different forms, indicative of cleavage and dimerization. Furthermore, analysis of the antigenicity of these proteins and their post-translationally modified forms demonstrated that S protein induced the strongest antibody response in both convalescent and immunized animal sera. Interestingly, immunization with the inactivated vaccine did not elicit antibody response against the S2 subunit, whereas strong antibody response against both S1 and S2 subunits was detected in the convalescent serum. Moreover, vaccination stimulated stronger antibody response against S multimers than did the natural infection. This study revealed that the native S glycoprotein stimulated neutralizing antibodies, while bacterially-expressed S fragments did not. The study on S modifications would facilitate design of S-based anti-SARS-CoV-2 vaccines.

ABSTRACTThe emerging SARS-CoV-2 infection associated with the outbreak of viral pneumonia in China is ongoing worldwide. There are no approved antiviral therapies to treat this viral disease. Here we examined the antiviral abilities of three broad-spectrum antiviral compounds gemcitabine, lycorine and oxysophoridine against SARS-CoV-2 in cell culture. We found that all three tested compounds inhibited viral replication in Vero-E6 cells at noncytotoxic concentrations. The antiviral effect of gemcitabine was suppressed efficiently by the cytidine nucleosides. Additionally, combination of gemcitabine with oxysophoridine had an additive antiviral effect against SARS-CoV-2. Our results demonstrate that broad-spectrum antiviral compounds may have a priority for the screening of antiviral compounds against newly emerging viruses to control viral infection.

Two coordination polymers involving Cd(II), i.e., [Cd2(IDPA)2(bpe) (H2O)2]n·2n(H2O) (1) (H2IDPA is 5-(1-oxoisoindolin-2-yl)isophthalic acid, bpe is 1,2-bis(4-pyridyl)ethane, 4-bpmh is N, N-bis-pyridin-4-ylmethylene-hydrazine), and [Cd(IDPA)(4-bpmh)0.5(H2O)2]n·n(H2O) (2) are prepared under solvothermal conditions via tuning the auxiliary ligand from bpe to 4-bpmh. Moreover, the as-prepared complexes 1–2 reveal much stronger luminescence in contrast to that of the free organic ligands. Their preventive effect and mechanism on scar formation after cosmetic surgery was explored. First, the two complexes’ suppression of the viability of the human immortal keratinocyte line (HaCaT) cell line was examined via exploiting cell counting kit-8 (CCK-8) detection. The vascular endothelial growth factor (VEGF) signal pathway activation in HaCaT cells was detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) assay.

ABSTRACTChikungunya virus (CHIKV), a mosquito-borne alphavirus, has become an important re-emerging pathogen with its rapid spread to many non-endemic areas. The lack of effective vaccines and antiviral agents is largely attributed to the elusive infection and dissemination dynamics in vivo. In this study, we designed and developed a novel, replication-competent, CHIKV reporter virus (CHIKV-iRFP) encoding a near infrared fluorescent protein (iRFP). In vitro and in vivo characterization demonstrated that CHIKV-iRFP retained similar replication and virulence phenotypes to its parental virus. Neonatal BABL/c mice and IFNAR−/− A129 mice were highly susceptible to CHIKV-iRFP infection. Following intracranial (i.c.) inoculation, CHIKV-iRFP efficiently replicated and disseminated into whole body, resulting in rapid death in an age-dependent manner. Remarkably, upon footpad injection, CHIKV-iRFP readily disseminated from footpad to head and whole skeleton, with a specific tropism for bone marrow. Taken together, this novel reporter virus provides a powerful tool to track real time CHIKV replication and to test the in vivo efficacy of vaccines and antiviral therapeutics.

The flavivirus NS5 harbors both a methyltransferase (MTase) and an RNA-dependent RNA polymerase (RdRP). Both enzyme activities of NS5 are critical for viral replication. Recently, the full-length NS5 crystal structure of Japanese encephalitis virus reveals a conserved MTase-RdRP interface that features two conserved components: a six-residue hydrophobic network and a GTR sequence. Here we showed for the first time that these key interface components are essential for flavivirus replication by various reverse genetics approaches. Interestingly, some replication-impaired variants generated a common compensatory NS5 mutation outside the interface (L322F), providing novel routes to further explore the crosstalk between MTase and RdRP.

Chikungunya virus (CHIKV), a member of the Alphavirus genus, is an important human emerging/re-emerging pathogen. Currently, there are no effective antiviral drugs or vaccines against CHIKV infection. Herein, we construct an infectious clone of CHIKV and an eGFP reporter CHIKV (eGFP-CHIKV) with an isolated strain (assigned to Asian lineage) from CHIKV-infected patients. The eGFP-CHIKV reporter virus allows for direct visualization of viral replication through the levels of eGFP expression. Using a known CHIKV inhibitor, ribavirin, we confirmed that the eGFP-CHIKV reporter virus could be used to identify inhibitors against CHIKV. Importantly, we developed a novel and reliable eGFP-CHIKV reporter virus-based neutralization assay that could be used for rapid screening neutralizing antibodies against CHIKV.

Objective To explore the effect of ginsenoside Rb1 (gRb1) on oxidative damage of human umbilical vein endothelial cells (HUVECs) resulted from hydrogen peroxide (H2O2). Methods HUVECs were divided into control group, H2O2 group and gRb1 group. MTT assay was used to determine cell survival; annexin V-FITC/PI double staining was used to detect cell apoptosis; SOD1 activity was measured with xanthine oxidase method; MDA concentration was detected by thibatituric acid assay; protein expression of ICAM-1 and VCAM-1 was analysed by Western blot. Results Compared with control group, the apoptosis rate, MDA production and the protein level of ICAM-1 and VCAM-1 significantly increased, but the cell viability and SOD1 activity decreased. Compared with H2O2 group, gRb1 reversed the parameters mentioned above. Conclusions gRb1 can alleviate oxidative damage of HUVECs by reducing cell apoptosis, oxidative stress and protein expression of ICAM-1 and VCAM-1.

A zero-valent iron/rectorite nanocomposite (NZVI/rectorite) was developed as a heterogeneous H2O2 catalyst for P-chlorophenol degradation. The physicochemical properties of NZVI/rectorite were characterized by various techniques including X-ray diffraction, scanning electron microscopy, transmission electron microscopy, energy-dispersive spectrometry, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and Brunauer–Emmett–Teller analysis. Results showed that NZVI sphere nanoparticles were successfully loaded on the rectorite surface with less aggregation and good dispersion. Moreover, compared with acid-leached rectorite (30.91 m2/g), the NZVI/rectorite appeared to have larger surface area (50.75 m2/g). In addition, the effects of pH, reaction time, initial P-chlorophenol concentration, catalyst amount, and H2O2 dosage on the P-chlorophenol degradation were systematically investigated. Results showed that NZVI/rectorite presents better properties for the degradation and mineralization of P-chlorophenol compared with pristine NZVI due to the large surface area, low aggregation, and good dispersion of the former. The degradation mechanisms of P-chlorophenol by NZVI/rectorite were adsorption and reduction coupled with a Fenton-like reaction. Four successive runs of the stability and regeneration study also showed that the NZVI/rectorite were unchanged even after 100% of P-chlorophenol degradation ratio. This study has extended the application of NZVI/rectorite as environment function material for the removal of P-chlorophenol from the environment. Keywords: Nano zero-valent iron, Rectorite, Heterogeneous Fenton oxidation, P-chlorophenol degradation