Recovering intestinal redox homeostasis to resolve systemic inflammation for preventing remote myocardial injury by oral fullerenes.

The unbalanced immune state is the dominant feature of myocardial injury. However, the complicated pathology of cardiovascular diseases and the unique structure of cardiac tissue lead to challenges for effective immunoregulation therapy. Here, we exploited oral fullerene nanoscavenger (OFNS) to maintain intestinal redox homeostasis to resolve systemic inflammation for effectively preventing distal myocardial injury through bidirectional communication along the heart-gut immune axis. Observably, OFNS regulated redox microenvironment to repair cellular injury and reduce inflammation in vitro. Subsequently, OFNS prevented myocardial injury by regulating intestinal redox homeostasis and recovering epithelium barrier integrity in vivo. Based on the profiles of transcriptomics and proteomics, we demonstrated that OFNS balanced intestinal and systemic immune homeostasis for remote cardioprotection. Of note, we applied this principle to intervene myocardial infarction in mice and mini-pigs. These findings highlight that locally addressing intestinal redox to inhibit systemic inflammation could be a potent strategy for resolving remote tissue injury.

CCND2 Modified mRNA Activates Cell Cycle of Cardiomyocytes in Hearts With Myocardial Infarction in Mice and Pigs.

BACKGROUND: Experiments in mammalian models of cardiac injury suggest that the cardiomyocyte-specific overexpression of CCND2 (cyclin D2, in humans) improves recovery from myocardial infarction (MI). The primary objective of this investigation was to demonstrate that our specific modified mRNA translation system (SMRTs) can induce CCND2 expression in cardiomyocytes and replicate the benefits observed in other studies of cardiomyocyte-specific CCND2 overexpression for myocardial repair. METHODS: The CCND2-cardiomyocyte-specific modified mRNA translation system (cardiomyocyte SMRTs) consists of 2 modRNA constructs: one codes for CCND2 and contains a binding site for L7Ae, and the other codes for L7Ae and contains recognition elements for the cardiomyocyte-specific microRNAs miR-1 and miR-208. Thus, L7Ae suppresses CCND2 translation in noncardiomyocytes but is itself suppressed by endogenous miR-1 and -208 in cardiomyocytes, thereby facilitating cardiomyocyte-specific CCND2 expression. Experiments were conducted in both mouse and pig models of MI, and control assessments were performed in animals treated with an SMRTs coding for the cardiomyocyte-specific expression of luciferase or green fluorescent protein (GFP), in animals treated with L7Ae modRNA alone or with the delivery vehicle, and in Sham-operated animals. RESULTS: CCND2 was abundantly expressed in cultured, postmitotic cardiomyocytes 2 days after transfection with the CCND2-cardiomyocyte SMRTs, and the increase was accompanied by the upregulation of markers for cell-cycle activation and proliferation (eg, Ki67 and Aurora B kinase). When the GFP-cardiomyocyte SMRTs were intramyocardially injected into infarcted mouse hearts, the GFP signal was observed in cardiomyocytes but no other cell type. In both MI models, cardiomyocyte proliferation (on day 7 and day 3 after treatment administration in mice and pigs, respectively) was significantly greater, left-ventricular ejection fractions (days 7 and 28 in mice, days 10 and 28 in pigs) were significantly higher, and infarcts (day 28 in both species) were significantly smaller in animals treated with the CCND2-cardiomyocyte SMRTs than in any other group that underwent MI induction. CONCLUSIONS: Intramyocardial injections of the CCND2-cardiomyocyte SMRTs promoted cardiomyocyte proliferation, reduced infarct size, and improved cardiac performance in small and large mammalian hearts with MI.

Cryogenic Electron-Beam Writing for Perovskite Metasurface.

Halide perovskites (HPs) metasurfaces have recently attracted significant interest due to their potential to not only further enhance device performance but also reveal the unprecedented functionalities and novel photophysical properties of HPs. However, nanopatterning on HPs is critically challenging as they are readily destructed by the organic solvents in the standard lithographic processes. Here, we present a novel, subtle, and fully nondestructive HPs metasurface fabrication strategy based on cryogenic electron-beam writing. This technique allows for high-precision patterning and in situ imaging of HPs with excellent compatibility. As a proof-of-concept, broadband absorption enhanced metasurfaces were realized by patterning nanopillar arrays on CH3NH3PbI3 film, which results in photodetectors with approximately 14-times improvement on responsivity and excellent stability. Our findings highlight the great feasibility of cryogenic electron-beam writing for producing perovskite metasurface and unlocking the unprecedented photoelectronic properties of HPs.

Lin28a cardiomyocyte-specific modified mRNA translation system induces cardiomyocyte cell division and cardiac repair.

The mammalian heart has a limited regenerative capacity. Previous work suggested the heart can regenerate during development and immediately after birth by inducing cardiomyocyte (CM) proliferation; however, this capacity is lost seven days after birth. modRNA gene delivery, the same technology used successfully in the two mRNA vaccines against SARS-CoV-2, can prompt cardiac regeneration, cardiovascular regeneration and cardiac protection. We recently established a novel CM-specific modRNA translational system (SMRTs) that allows modRNA translation only in CMs. We demonstrated that this system delivers potent intracellular genes (e.g., cell cyclepromoting Pkm2), which are beneficial when expressed in one cell type (i.e., CMs) but not others (non-CMs). Here, we identify Lin28a as an important regulator of the CM cell cycle. We show that Lin28a is expressed in CMs during development and immediately after birth, but not during adulthood. We describe that specific delivery of Lin28a into CM, using CM SMRTs, enables CM cell division and proliferation. Further, we determine that this proliferation leads to cardiac repair and better outcome post MI. Moreover, we identify the molecular pathway of Lin28a in CMs. We also demonstrate that Lin28a suppress Let-7 which is vital for CM proliferation, partially due to its suppressive role on cMYC, HMGA2 and K-RAS.

Perfect Excitation of Topological States by Supersymmetric Waveguides.

Topological photonic states provide intriguing strategies for robust light manipulations, however, it remains challenging to perfectly excite these topological eigenstates due to their complicated mode profiles. In this work, we propose to realize the exact eigenmode of the topological edge states by supersymmetric (SUSY) structures. By adiabatically transforming the SUSY partner to its main topological structure, the edge modes can be perfectly excited with simple single-site input. We experimentally verify our strategy in integrated silicon waveguides in telecommunication wavelength, showing a broad working bandwidth. Moreover, a shortcut-to-adiabaticity strategy is further applied to speed up the adiabatic pump process by inverse-design approaches, thus enabling fast mode evolutions and leading to reduced device size. Our method is universal and beneficial to the topology-based or complex eigenmodes systems, ranging from photonics and microwaves to cold atoms and acoustics.

Bound-Extended Mode Transition in Type-II Synthetic Photonic Weyl Heterostructures.

Photonic structures with Weyl points (WPs), including type I and type II, promise nontrivial surface modes and intriguing light manipulations for their three-dimensional topological bands. While previous studies mainly focus on exploring WPs in a uniform Weyl structure, here we establish Weyl heterostructures (i.e., a nonuniform Weyl lattice) with different rotational orientations in the synthetic dimension by nanostructured photonic waveguides. In this work, we unveil a transition between bound and extended modes on the interface of type-II Weyl heterostructures by tuning their rotational phases, despite the reversed topological order across the interface. This mode transition is also manifested from the total transmission to total reflection at the interface. All of these unconventional effects are attributed to the tilted dispersion of type-II Weyl band structure that can lead to mismatched bands and gaps across the interface. As a comparison, the type-I Weyl heterostructures lack the phase transition due to the untilted band structure. This work establishes a flexible scheme of artificial Weyl heterostructures that opens a new avenue toward high-dimensional topological effects and significantly enhances our capabilities in on-chip light manipulations.

Metasurface-Enabled On-Chip Manipulation of Higher-Order Poincaré Sphere Beams.

An integrated way to generate and manipulate higher-order Poincaré sphere beams (HOPBs) is a sought-after goal in photonic integrated circuits for high-capacity communication systems. Here, we demonstrate a novel method for on-chip generation and manipulation of HOPBs through combining metasurface with optical waveguides on lithium niobate on insulator platform. With phase modulation by a diatomic geometric metasurface, guided waves are extracted into free space with a high signal-to-noise ratio in the form of two orthogonal circularly polarized optical vortices which are linearly superposed into HOPBs. Meanwhile, a dual-port waveguide crossing is established to reconfigure the output states into an arbitrary point on a higher-order Poincaré sphere based on in-plane interference of two guided waves. Our approach provides a promising solution to generate and manipulate the HOPBs in a compact manner, which would be further enhanced by employing the electro-optical modulation on a lithium niobate waveguide to access a fully tunable scheme.

Topological and Stacked Flat Bands in Bilayer Graphene with a Superlattice Potential.

We show that bilayer graphene in the presence of a 2D superlattice potential provides a highly tunable setup that can realize a variety of flat band phenomena. We focus on two regimes: (i) topological flat bands with nonzero Chern numbers, C, including bands with higher Chern numbers |C|>1 and (ii) an unprecedented phase consisting of a stack of nearly perfect flat bands with C=0. For realistic values of the potential and superlattice periodicity, this stack can span nearly 100 meV, encompassing nearly all of the low-energy spectrum. We further show that in the topological regime, the topological flat band has a favorable band geometry for realizing a fractional Chern insulator (FCI) and use exact diagonalization to show that the FCI is in fact the ground state at 1/3 filling. Our results provide a realistic guide for future experiments to realize a new platform for flat band phenomena.

Identification and evaluation of potential probiotics against skin-ulceration disease in the Chinese tongue sole (Cynoglossus semilaevis).

In this study, three highly pathogenic bacterial strains (Vibrio harveyi TB6, Vibrio alginolyticus TN1, and Vibrio parahaemolyticus TN3) were isolated from skin ulcers and intestines of diseased Chinese tongue sole (Cynoglossus semilaevis). The bacteria were investigated using hemolytic activity tests, in vitro co-culture with intestinal epithelial cells, and artificial infection of C. semilaevis. A further 126 strains were isolated from the intestines of healthy C. semilaevis. The three pathogens were used as indicator bacteria, and the antagonistic strains were identified from the 126 strains. The activities of exocrine digestive enzymes in the strains were also tested. Four strains with antibacterial and digestive enzyme activities were obtained and the best strains, Bacillus subtilis Y2 and Bacillus amyloliquefaciens Y9, were selected according to their ability to protect epithelial cells from infection. In addition, the effects of strains Y2 and Y9 at the individual level were investigated, finding that the activities of the immune-related enzymes superoxide dismutase, catalase, acid phosphatase, and peroxidase were significantly increased in the sera of the treatment group compared with the control group (p < 0.05). The specific growth rate (SGR, %) was also increased, especially in the Y2 group, and was significantly higher compared with the controls (p < 0.05). The result of the artificial infection test showed that the cumulative mortality within 72 h in the Y2 group was the lowest (50.5%), and in the Y9 group (68.5%) it was significantly lower than that in the control group (100%) (p < 0.05). Analysis of the intestinal microbial communities indicated that Y2 and Y9 could alter the composition of the intestinal flora, increasing both species richness and evenness, and inhibiting the growth of Vibrio in the intestine. These results suggested food supplemented with Y2 and Y9 could improve both immune function and disease resistance, as well as have a positive effect on the growth performance and the intestinal morphology of C. semilaevis.

Manipulating Dual Bound States in the Continuum for Efficient Spatial Light Modulator.

Spatial light modulators (SLMs) that could control diverse optical properties are highly demanded by many optoelectronic systems. Recently, the integration of nonlinear χ(2) materials and metasurfaces has been recognized as a promising strategy for next-generation SLMs. However, their modulation efficiency still encounters challenges due to low quality factor and weak light-matter interaction. Here, we demonstrate an efficient SLM by manipulating the dual bound state in continuum (BIC) with the assistance of a binary-pore anodic alumina oxide template technique. The coexistence of symmetry-protected BIC and Fabry-Pérot BIC is obtained by a desirable sandwich configuration with a BIC metasurface and EO polymer, which efficiently restrain radiative loss and generate a strong quasi-BIC resonance. The assembled SLM with large absorption and Q-factor delivers a modulation depth of 77% and an f3 dB of nearly 100 MHz. This dual BIC metasurface provides potential for applications including switches, LIDAR, augmented and virtual reality, and so on.

Turning back the clock: A concise viewpoint of cardiomyocyte cell cycle activation for myocardial regeneration and repair.

Patients with acute myocardial infarction (MI) could progress to end-stage congestive heart failure, which is one of the most significant problems in public health. From the molecular and cellular perspective, heart failure often results from the loss of cardiomyocytes-the fundamental contractile unit of the heart-and the damage caused by myocardial injury in adult mammals cannot be repaired, in part because mammalian cardiomyocytes undergo cell-cycle arrest during the early perinatal period. However, recent studies in the hearts of neonatal small and large mammals suggest that the onset of cardiomyocyte cell-cycle arrest can be reversed, which may lead to the development of entirely new strategies for the treatment of heart failure. In this Viewpoint, we summarize these and other provocative findings about the cellular and molecular mechanisms that regulate cardiomyocyte proliferation and how they may be targeted to turn back the clock of cardiomyocyte cell-cycle arrest and improve recovery from cardiac injury and disease.

Multiparameter measurement sensor based on no-core fiber.

This paper proposes a no-core-single-mode-no-core Mach-Zehnder fiber sensor. In this sensor, two no-core fibers serve as input and output couplers, and the middle single-mode fiber serves as a sensing arm. Using finite element simulation and theoretical analysis, the optimal length of the couplers and the sensing arm are determined. High-order modes excited by no-core optical fiber propagate through the cladding of the single-mode fiber, which is affected by the ambient temperature and applied force. The trough of different interference orders of the transmission spectrum is selected as a research object to realize the measurement of curvature and temperature, strain and temperature with the sensing matrix.

Evaluation of penehyclidine for prevention of post operative nausea and vomitting in patients undergoing total thyroidectomy under total intravenous anaesthesia with propofol-remifentanil.

BACKGROUD: Postoperative nausea and vomiting (PONV) is one of the most common complications after total thyroidectomy under general anesthesia. Total intravenous anesthesia (TIVA) has been documented to prevent PONV in patients undergoing total thyroidectomy. Penehyclidine, an anticholinergic agent with an elimination half-life of over 10 h, is widely used as premedication to reduce glandular secretion. This study aimed to explore the preventative effects of penehyclidine with propofol-remifentanil-TIVA to single-TIVA on PONV in patients undergoing total thyroidectomy. METHODS: A total of 100 patients scheduled for total thyroidectomy were randomly assigned to either the penehyclidine group (n = 50) or TIVA group (n = 50). Propofol and remifentanil were was used for TIVA in all patients. No patients who received premedication. Patients were administrated with either 5 ml of normal saline or 0.5 mg of penehyclidine soon after anesthesia induction. The incidence of nausea and vomiting, the severity of nausea, the requirement of rescue antiemetics, and adverse effects were investigated during the first 24 h in two time periods (0-2 h and 2-24 h). RESULTS: The overall PONV incidence during the 24 h after surgery was significantly lower in the penehyclidine group compared with the TIVA group (12% vs 36%, P < 0.005). Besides, the incidence of nausea and the incidence of vomiting were significantly lower in the penehyclidine group compared with the TIVA group at 2-24 h after surgery. However, there was no significant difference between the two groups at 0-2 h after surgery. CONCLUSIONS: Administration of penehyclidine under TIVA with propofol-remifentanil is more effective for prevention of PONV than TIVA alone, especially 2-24 h after total thyroidectomy. TRIAL REGISTRATION: https://www.chictr.org.cn/edit.aspx?pid=132463&htm=4 (Ref: ChiCTR2100050278, the full date of first registration: 25/08/2021).

Bacterial dynamics and functions driven by bulking agents to enhance organic degradation in food waste in-situ rapid biological reduction (IRBR).

This study investigated the effects of different bulking agents (i.e., sawdust, wheat straw, rice straw, and corncob) on bacterial structure and functions for organic degradation during food waste in-situ rapid biological reduction (IRBR) inoculated with microbial agent. Results showed that the highest organic degradation (409.5 g/kg total solid) and volatile solids removal efficiency (41.0%) were achieved when wheat straw was used, largely because the degradation of readily degradable substrates and cellulose was promoted by this bulking agent. Compared with other three bulking agents, the utilization of wheat straw was conducive to construct a more suitable environmental condition (moisture content of 18.0-28.2%, pH of 4.91-5.87) for organic degradation during IRBR process, by virtue of its excellent structural and physiochemical properties. Microbial community analysis suggested that the high-moisture environment in rice straw treatment promoted the growth of Staphylococcus and inhibited the activity of the inoculum. By contrast, lowest bacterial richness was observed in corncob treatment due to the faster water loss. Compared with these two bulking agents, sawdust and wheat straw treatment led to a more stable bacterial community structure, and the inoculated Bacillus gradually became the dominant genus (36.6-57.8%) in wheat straw treatment. Predicted metagenomics analysis showed that wheat straw treatment exhibited the highest carbohydrate metabolism activity which improved the pyruvate, amino sugar and nucleotide sugar metabolism, and thereby promoted the organic degradation and humic substrate production. These results indicated that wheat straw was a more desirable bulking agent, and revealed the potential microbial organics degradation mechanism in IRBR process.

Yangonin treats inflammatory osteoporosis by inhibiting the secretion of inflammatory factors and RANKL expression.

OBJECTIVES: As the main cause of osteoporosis, abnormal activity of osteoclasts could disrupt the balance between bone resorption and formation. Moreover, up-regulation of nuclear factor-kappa ligand (RANKL) expression by chronic inflammation-mediated inflammatory factors might contribute to the differentiation of osteoclast precursor cells. Therefore, an anti-inflammatory agent named yangonin was presented for inhibiting osteoclast and relieving inflammatory osteoporosis through down-regulating inflammatory factors. METHODS: We established a model of macrophage inflammation and then verified the anti-inflammatory effect of yangonin. The inhibitory effect of yangonin on osteoclasts was detected by tartrate-resistant acid phosphatase (TRAP) staining, Western blotting and quantitative real-time PCR (qRT-PCR). Finally, micro-CT, TRAP and hematoxylin-eosin (HE) staining were used to show the effect of yangonin on inflammatory osteoporosis in vivo. RESULTS: Our results suggested that yangonin was able to reduce the secretion of inflammatory factors, down-regulate osteoclast-related genes such as TRAP, RANKL, cathepsin K (CTSK) and nuclear factor-activated T-cell 1 (NFATc1). Furthermore, it was demonstrated that yangonin could suppress the function of inflammatory cytokines in osteoclast differentiation and reporting, wherein NF-κB, AKT and downstream c-Fos/NFATc1 signaling pathways were involved. In an in vivo study, we implied that yangonin has a relieving effect on inflammatory osteoporosis. CONCLUSION: Our research shows that yangonin down-regulates inflammatory factors and inhibits the bone-breaking effect of inflammation through NF-κB, AKT and downstream c-Fos/NFATc1 signaling pathways to achieve the purpose of treating inflammatory osteoporosis.

Penehyclidine mitigates postoperative nausea and vomiting and intraoperative oculocardiac reflex in patients undergoing strabismus surgery: a prospective, randomized, double-blind comparison.

BACKGROUND: Postoperative nausea and vomiting (PONV) is one of the most frequent complications following strabismus surgery. Penehyclidine, an anticholinergic agent, is widely used as premedication. This study investigated the effect of preoperative penehyclidine on PONV in patients undergoing strabismus surgery. METHODS: In this prospective, randomized, double-blind study, patients scheduled for strabismus surgery under general anesthesia were randomly assigned to either penehyclidine (n = 114) or normal saline (n = 104) group. Penehyclidine was administrated immediately after anesthesia induction, and normal saline was substituted as control. PONV was investigated from 0 to 48 h after surgery. Intraoperative oculocardiac reflex (OCR) was also recorded. RESULTS: Compared with normal saline, penehyclidine significantly reduced PONV incidence (30.7% vs. 54.8%, P < 0.01) and mitigated PONV severity as indicated by severity scoring (P < 0.01). Compared with normal saline, penehyclidine also significantly reduced OCR incidence (57.9% vs. 77.9%, P < 0.01) and mitigated OCR severity, as indicated by the requirement for atropine rescue (77.3% vs. 90.1%, P < 0.05) and the maximum decrease of heart rate during OCR (23.1 ± 9.4 bpm vs. 27.3 ± 12.4 bpm, P < 0.05). The recovery course did not differ between groups. CONCLUSIONS: Penehyclidine administrated after anesthesia induction significantly reduced the incidence of PONV and alleviated intraoperative OCR in patients undergoing strabismus surgery. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04054479 ). Retrospectively registered August 13, 2019.

GABA negatively regulates adventitious root development in poplar.

γ-Aminobutyric acid (GABA) influences plant growth, but little is known about how this metabolite regulates adventitious root (AR) development. Here, we investigate the effects of GABA on ARs using poplar lines overexpressing glutamate decarboxilase 2 (GAD2) and by treating poplar stem cuttings with exogenous GABA or vigabatrin (VGB; a specific GABA transaminase inhibitor). Endogenous GABA accumulation not only inhibited AR growth, but it also suppressed or delayed AR formation. Anatomical observations revealed that the GABA and VGB treatments resulted in a 1 d delay in the formation of AR primordia and the appearance of ARs. This delay coincided with changes in primary metabolism, including transient increases in hexose and amino acid levels. GABA-dependent changes in the expression of genes related to hormone synthesis and signalling, as well as analysis of hormone levels revealed that ethylene-dependent pathways were decreased at the earliest stage of AR formation. In contrast, auxin and abscisic acid were increased at 1-5 d as well as GA4 over a 5 d period of AR formation. These results demonstrate that GABA plays a crucial role in AR development. Evidence is presented demonstrating that GABA can interact with hormone-related pathways as well as carbon/nitrogen metabolism. These findings also elucidate the functions of GABA in plant development.

One-step synthesis of high photocatalytic graphitic carbon nitride porous nanosheets.

As a metal-free photocatalyst, graphitic carbon nitride (g-C3N4) has attracted tremendous attention. Preparation of porous few-layer g-C3N4 nanosheets has been proven to be an effective strategy to obtain high photocatalytic performance. At present, most methods are expensive, time-consuming or complicated. Here, a low-cost, facile and environment-friendly one-step synthesis method of porous few-layer g-C3N4 nanosheets is designed by introducing water in the precursor. Straightforward calcination of the precursor, which decomposes to form ammonia, can produce g-C3N4 nanosheets with the assistance of water. Under the visible light (>400 nm), the photocatalytic H2 evolution performance of the so-obtained nanosheets is 3214 µmol · g-1 · h-1, which is 17.3 times of the original bulk g-C3N4. The apparent quantum yield is 27% under the 380 nm monochromatic light irradiation.

Responses of GABA shunt coupled with carbon and nitrogen metabolism in poplar under NaCl and CdCl2 stresses.

The γ-aminobutyric acid (GABA) shunt is closely associated with plant tolerance; however, little is known about its mechanism. This study aimed to decipher the responses of the GABA shunt and related carbon-nitrogen metabolism in poplar seedlings (Populus alba × Populus glandulosa) treated with different NaCl and CdCl2 concentrations for 30 h. The results showed that the activities of glutamate decarboxylase (GAD) and GABA-transaminase (GABA-T) were activated, as well as α-ketoglutarate dehydrogenase (α-KGDH) and succinate dehydrogenase (SDH) activities were enhanced by NaCl and CdCl2 stresses, except for SDH under CdCl2 stress. Meanwhile, the expression levels of GADs, GABA-Ts SDHs, succinyl-CoA ligases (SCSs), and succinic acid aldehyde dehydrogenases (SSADHs) were also increased. Notably, significant increases in the key components of GABA shunt, Glu and GABA, were observed under both stresses. Soluble sugars and free amino acids were enhanced, whereas citrate, malate and succinate were almost inhibited by both NaCl and CdCl2 stresses except that citrate was not changed or just increased by 50-mM NaCl stress. Thus, these results suggested that the carbon-nitrogen balance could be altered by activating the GABA shunt when main TCA-cycle intermediates were inhibited under NaCl and CdCl2 stresses. This study can enhance the understanding about the functions of the GABA shunt in woody plants under abiotic stresses and may be applied to the genetic improvement of trees for phytoremediation.