Nonlinear optical response of heme solutions.

Heme is the prosthetic group for cytochrome that exists in nearly all living organisms and serves as a vital component of human red blood cells (RBCs). Tunable optical nonlinearity in suspensions of RBCs has been demonstrated previously, however, the nonlinear optical response of a pure heme (without membrane structure) solution has not been studied to our knowledge. In this work, we show optical nonlinearity in two common kinds of heme (i.e., hemin and hematin) solutions by a series of experiments and numerical simulations. We find that the mechanism of nonlinearity in heme solutions is distinct from that observed in the RBC suspensions where the nonlinearity can be easily tuned through optical power, concentration, and the solution properties. In particular, we observe an unusual phenomenon wherein the heme solution exhibits negative optical nonlinearity and render self-collimation of a focused beam at specific optical powers, enabling shape-preserving propagation of light to long distances. Our results may have potential applications in optical imaging and medical diagnosis through blood.

Empagliflozin and liraglutide ameliorate HFpEF in mice via augmenting the Erbb4 signaling pathway.

Heart failure with preserved ejection fraction (HFpEF) is closely associated with metabolic derangement. Sodium glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) exert anti-HFpEF effects, but the underlying mechanisms remain unclear. In this study, we explored the anti-HFpEF effects of empagliflozin and liraglutide and the underlying molecular mechanisms in a mouse model of HFpEF. This model was established by high-fat diet (HFD) feeding plus Nω-nitro-L-arginine methyl ester (L-NAME) treatment. The mice were treated with empagliflozin (20 mg·kg-1·d-1, i.g.) or liraglutide (0.3 mg·kg-1·d-1, i.p.) or their combination for 4 weeks. At the end of the experimental protocol, cardiac function was measured using ultrasound, then mice were euthanized and heart, liver, and kidney tissues were collected. Nuclei were isolated from frozen mouse ventricular tissue for single-nucleus RNA-sequencing (snRNA-seq). We showed that administration of empagliflozin or liraglutide alone or in combination significantly improved diastolic function, ameliorated cardiomyocyte hypertrophy and cardiac fibrosis, as well as exercise tolerance but no synergism was observed in the combination group. Furthermore, empagliflozin and/or liraglutide lowered body weight, improved glucose metabolism, lowered blood pressure, and improved liver and kidney function. After the withdrawal of empagliflozin or liraglutide for 1 week, these beneficial effects tended to diminish. The snRNA-seq analysis revealed a subcluster of myocytes, in which Erbb4 expression was down-regulated under HFpEF conditions, and restored by empagliflozin or liraglutide. Pseudo-time trajectory analysis and cell-to-cell communication studies confirmed that the Erbb4 pathway was a prominent pathway essential for both drug actions. In the HFpEF mouse model, both empagliflozin and liraglutide reversed Erbb4 down-regulation. In rat h9c2 cells, we showed that palmitic acid- or high glucose-induced changes in PKCα and/or ERK1/2 phosphorylation at least in part through Erbb4. Collectively, the single-cell atlas reveals the anti-HFpEF mechanism of empagliflozin and liraglutide, suggesting that Erbb4 pathway represents a new therapeutic target for HFpEF. Effects and mechanisms of action of empagliflozin and liraglutide in HFpEF mice. HFpEF was induced with a high-fat diet and L-NAME for 15 weeks, and treatment with empagliflozin and liraglutide improved the HFpEF phenotype. Single nucleus RNA sequencing (snRNA-seq) was used to reveal the underlying mechanism of action of empagliflozin and liraglutide.

Design and optimization of GI-PCF supporting the orbital angular momentum modes based on negative curvature structure.

Based on the negative curvature structure, we design a graded-index photonic crystal fiber (GI-PCF) supporting the orbital angular momentum (OAM) mode transmission and discuss its optimization strategy. The core of the designed GI-PCF is sandwiched by three-layer inner air-hole arrays with gradually decreasing air-hole radii and a single outer air-hole array, where the inner side of the annular core forms a graded refractive index distribution. All these structures are clad with negative-curvature tubes. By optimizing characteristic structural parameters, including the air-filling fraction of the outer array, the air-hole radii of the inner arrays, and the thickness of the tubes, the GI-PCF can support 42 OAM modes and most of them have a purity greater than 85%. Compared with conventional structures, the present design of GI-PCF has better properties on an overall level, which can stably transmit multiple OAM modes with high mode purity. These results inject new interest in the flexible design of PCF and have potential applications in various fields, including but not limited to the mode division multiplexing system and terabit data transmission.

Gain optimization of an erbium-ytterbium co-doped amplifier via a Si3N4 photonic platform.

Erbium-doped waveguide amplifiers enable the integration of various active functions on a silicon platform. Er3+ can provide the basis for efficient optical amplification of photonic integrated circuits, but the gain is limited by cooperative upconversion leading to doping concentration limitations and insufficient optimization of the waveguide structure. In this paper, an erbium-ytterbium co-doped Al2O3 amplifier has been innovatively implemented on a low loss Si3N4 waveguide by careful design and optimization with the finite difference method. A more accurate and comprehensive theoretical model of erbium-ytterbium co-doping is established, with consideration of upconversions, energy transfer, amplified spontaneous radiation and propagation loss to perform optimization of the high-gain erbium-ytterbium co-doped waveguide amplifier. The optimized waveguide amplifier achieves a small-signal gain of more than 36 dB at 1550 nm under Er3+ concentration of 3 × 1020 cm-3 and Yb3+ concentration of 3 × 1021 cm-3. Endowing Si3N4 photonic integrated circuits with gain can enable the miniaturization of various on-chip based active devices.

Multiple flatbands and localized states in photonic super-Kagome lattices.

We demonstrate multiple flatbands and compact localized states (CLSs) in a photonic super-Kagome lattice (SKL) that exhibits coexistence of singular and nonsingular flatbands within its unique band structure. Specifically, we find that the upper two flatbands of an SKL are singular-characterized by singularities due to band touching with their neighboring dispersive bands at the Brillouin zone center. Conversely, the lower three degenerate flatbands are nonsingular and remain spectrally isolated from other dispersive bands. The existence of such two distinct types of flatbands is experimentally demonstrated by observing stable evolution of the CLSs with various geometrical shapes in a laser-written SKL. We also discuss the classification of the flatbands in momentum space, using band-touching singularities of the Bloch wave functions. Furthermore, we validate this classification in real space based on unit cell occupancy of the CLSs in a single SKL plaquette. These results may provide insights for the study of flatband transport, dynamics, and nontrivial topological phenomena in other relevant systems.

Photonic Realization of a Generic Type of Graphene Edge States Exhibiting Topological Flat Band.

Cutting a honeycomb lattice (HCL) ends up with three types of edges (zigzag, bearded, and armchair), as is well known in the study of graphene edge states. Here, we propose and demonstrate a distinctive twig-shaped edge, thereby observing new edge states using a photonic platform. Our main findings are (i) the twig edge is a generic type of HCL edge complementary to the armchair edge, formed by choosing the right primitive cell rather than simple lattice cutting or Klein edge modification; (ii) the twig edge states form a complete flat band across the Brillouin zone with zero-energy degeneracy, characterized by nontrivial topological winding of the lattice Hamiltonian; (iii) the twig edge states can be elongated or compactly localized at the boundary, manifesting both flat band and topological features. Although realized here in a photonic graphene, such twig edge states should exist in other synthetic HCL structures. Moreover, our results may broaden the understanding of graphene edge states, as well as new avenues for realization of robust edge localization and nontrivial topological phases based on Dirac-like materials.

Mitochondrial protein MPV17 promotes ß-cell apoptosis in diabetogenesis.

MPV17 is a mitochondrial inner membrane protein, and its deficiency can cause mitochondrial DNA (mtDNA) depletion, increase reactive oxygen species (ROS), and promote apoptosis in several cell types, suggesting that MPV17 plays a protective role in cells although the underlying mechanism remains unknown. To test whether MPV17 is also protective in diabetic kidney disease, we treated Mpv17-deficient mice with streptozotocin (STZ) and surprisingly found that they were resistant to diabetes. Mpv17 deficiency was also found to confer resistance to the diabetes induced by an insulin mutation (Ins2Akita), which represents a mouse model of monogenic diabetes characterized by proinsulin misfolding and ß-cell failure. In both STZ and Ins2Akita models, Mpv17 mutants had significantly less severe ß-cell loss and apoptosis compared with the wild-type mice. We next showed that MPV17 is expressed in ß-cells of mice normally, suggesting that MPV17 acts ß-cells autonomously to facilitate apoptosis. Consistently, Mpv17 knockdown improved the viability and ameliorated the apoptosis of cultured MIN6 cells treated with STZ and palmitic acid (PA), respectively, accompanied by prevention of caspase 3 activation. The proapoptotic effect of MPV17 in ß-cells is in contrast with its known anti-apoptotic effect in other cell types. Thus, we have identified a novel regulator of ß-cell death in diabetes development.

Berberine regulates mesangial cell proliferation and cell cycle to attenuate diabetic nephropathy through the PI3K/Akt/AS160/GLUT1 signalling pathway.

High glucose (HG) is one of the basic factors of diabetic nephropathy (DN), which leads to high morbidity and disability. During DN, the expression of glomerular glucose transporter 1 (GLUT1) increases, but the relationship between HG and GLUT1 is unclear. Glomerular mesangial cells (GMCs) have multiple roles in HG-induced DN. Here, we report prominent glomerular dysfunction, especially GMC abnormalities, in DN mice, which is closely related to GLUT1 alteration. In vivo studies have shown that BBR can alleviate pathological changes and abnormal renal function indicators of DN mice. In vitro, BBR (30, 60 and 90 µmol/L) not only increased the proportion of G1 phase cells but also reduced the proportion of S phase cells under HG conditions at different times. BBR (60 µmol/L) significantly reduced the expression of PI3K-p85, p-Akt, p-AS160, membrane-bound GLUT1 and cyclin D1, but had almost no effect on total protein. Furthermore, BBR significantly declined the glucose uptake and retarded cyclin D1-mediated GMC cell cycle arrest in the G1 phase. This study demonstrated that BBR can inhibit the development of DN, which may be due to BBR inhibiting the PI3K/Akt/AS160/GLUT1 signalling pathway to regulate HG-induced abnormal GMC proliferation and the cell cycle, supporting BBR as a potential therapeutic drug for DN.

Adjunctive Er:YAG laser in non-surgical periodontal therapy of patients with inadequately controlled type 2 diabetes mellitus: A split-mouth randomized controlled study.

BACKGROUND AND OBJECTIVE: Limited studies are available comparing the outcomes of non-surgical periodontal therapy (NSPT) with or without adjunctive Er:YAG laser (ERL) in patients with type 2 diabetes mellitus (T2DM). This study evaluated the effects of ERL adjunctive NSPT on single-rooted teeth of inadequately controlled T2DM patients with periodontitis. METHODS: Twenty-two inadequately controlled T2DM participants with periodontitis were recruited. Adopting a double-blinded split-mouth design and under block randomization, we investigated the effects of ERL in calculus removal then degranulation mode, or a sham treatment, adjunct NSPT, which included two visits of full-mouth root surface debridement delivered within 4-10 days, to test or control single-rooted teeth (Wuxi Stomatology Hospital, trial 2017-016). We followed periodontal parameters (plaque %, bleeding on probing [BOP] %, probing pocket depth [PPD], probing attachment level [PAL]) and selected systemic parameters (fasting plasma glucose [FPG], glycosylated hemoglobin [HbA1c%], high sensitivity C-reactive protein) at baseline, one, three, and six months after periodontal treatment. RESULTS: The study was completed as planned. Periodontal parameters, FPG and HbA1c% of the 22 participants appeared significantly improved at six months (p < 0.001). The 44 ERL treated, compared to 44 sham treated single-rooted teeth exhibited significant improvement in BOP, mean PPD, and mean PAL at various postoperative follow-up time points (effect size ≥0.44; p < 0.001). No adverse event was reported. CONCLUSION: Periodontal treatment outcomes in the T2DM patients with inadequate glycemic control were better in the single-rooted teeth received ERL adjunct NSPT. Further studies are warranted to confirm the observations reported in this short-term clinical study.

19 F NMR Allows the Investigation of the Fate of Platinum(IV) Prodrugs in Physiological Conditions.

PtIV prodrugs can overcome resistance and side effects of conventional PtII anticancer therapies. By 19 F-labeling of a PtIV prodrug (Pt-FBA, FBA=p-fluorobenzoate), the activation under physiological conditions could be investigated. Unlike single-electron reductants, multi-electron agents can efficiently promote the two electrons reduction of PtIV to PtII . The activation of Pt-FBA in cell lysate is highly dependent upon the type of cancer cells. When administered to E. coli, Pt-FBA is reduced intracellularly and free FBA can shuttle out of the cell. The reduction rate greatly increases by inducing metallothionein overexpression and is lowered by addition of ZnII ions. When injected into mice, Pt-FBA undergoes fast reduction in the bloodstream accompanied by metabolic degradation of FBA; nevertheless, unreduced Pt-FBA can accumulate to detectable levels in liver and kidneys. The 19 F NMR approach has the advantage of avoiding the interference of all background signals.

Direct Observation of Flatband Loop States Arising from Nontrivial Real-Space Topology.

Topological properties of lattices are typically revealed in momentum space using concepts such as the Chern number. Here, we study unconventional loop states, namely, the noncontractible loop states (NLSs) and robust boundary modes, mediated by nontrivial topology in real space. While such states play a key role in understanding fundamental physics of flatband systems, their experimental observation has been hampered because of the challenge in realizing desired boundary conditions. Using a laser-writing technique, we optically establish photonic kagome lattices with both an open boundary by properly truncating the lattice, and a periodic boundary by shaping the lattice into a Corbino geometry. We thereby demonstrate the robust boundary modes winding around the entire edge of the open lattice and, more directly, the NLSs winding in a closed loop akin to that in a torus. We prove that the NLSs due to real-space topology persist in ideal Corbino-shaped kagome lattices of arbitrary size. Our results could be of great importance for our understanding of the singular flatbands and the intriguing physics phenomenon applicable for strongly interacting systems.

Influence of life-style factors, including second-hand smoke, on dental caries among 3-year-old children in Wuxi, China.

AIM: To examine the association of life-style factors, including second-hand smoke, with dental caries among 3-year-old children in Wuxi, China. METHODS: A multi-stage stratified random cluster sampling method was used, and 283 children were recruited. The prevalence of dental caries was 29.3% (83/283). RESULTS: Univariate analysis indicated that the possible related factors of dental caries included sleep duration, interest in snacks, candy, exposure to second-hand smoke and weight of birth (all P < 0.05). Meanwhile, multivariate logistic regression analysis suggested that children who had used fluoride were less susceptible to dental caries than those who had not used fluoride before (P < 0.05). Moreover, the risk of dental caries in children who were very interested in snacks was greater than those with little interest in snacks (P < 0.05). CONCLUSIONS: Life-style behaviours are crucial factors and should attract enough attention. There might be a potential negative effect of second-hand smoke on the deciduous caries, but it still requires further studies. A co-ordinated effort by health-care providers, policymakers and health institutions has successfully improved children's oral health and the awareness of hygiene knowledge among citizens in Wuxi city.

Valley Vortex States and Degeneracy Lifting via Photonic Higher-Band Excitation.

We demonstrate valley-dependent vortex generation in photonic graphene. Without breaking inversion symmetry, the excitation of two valleys leads to the formation of an optical vortex upon Bragg reflection to the third equivalent valley, with its chirality determined by the valley degree of freedom. Vortex-antivortex pairs with valley-dependent topological charge flipping are also observed and corroborated by numerical simulations. Furthermore, we develop a three-band effective Hamiltonian model to describe the dynamics of the coupled valleys and find that the commonly used two-band model is not sufficient to explain the observed vortex degeneracy lifting. Such valley-polarized vortex states arise from high-band excitation without a synthetic-field-induced gap opening. Our results from a photonic setting may provide insight for the study of valley contrasting and Berry-phase-mediated topological phenomena in other systems.

Observation of spatial optical diametric drive acceleration in photonic lattices.

We experimentally and theoretically demonstrate a spatial diametric drive acceleration of two mutually incoherent optical beams in 1D optical lattices under a self-defocusing nonlinearity. The two beams, exciting the modes at the top/bottom edges of the first Bloch band and hence experiencing normal/anomalous diffraction, can bind together and bend in the same direction during nonlinear propagation, analogous to the interplay between two objects with opposite signs of mass that breaks Newton's third law. Their spatial spectrum changes associated with the acceleration are analyzed for different lattice modulations. We find that the acceleration limit is determined by the beam exciting the top band edge that reaches a saturated momentum change prior to the other pairing beam.

Unconventional Flatband Line States in Photonic Lieb Lattices.

Flatband systems typically host "compact localized states" (CLS) due to destructive interference and macroscopic degeneracy of Bloch wave functions associated with a dispersionless energy band. Using a photonic Lieb lattice (LL), such conventional localized flatband states are found to be inherently incomplete, with the missing modes manifested as extended line states that form noncontractible loops winding around the entire lattice. Experimentally, we develop a continuous-wave laser writing technique to establish a finite-sized photonic LL with specially tailored boundaries and, thereby, directly observe the unusually extended flatband line states. Such unconventional line states cannot be expressed as a linear combination of the previously observed boundary-independent bulk CLS but rather arise from the nontrivial real-space topology. The robustness of the line states to imperfect excitation conditions is discussed, and their potential applications are illustrated.

Renoprotective effect of berberine via regulating the PGE2 -EP1-Gαq-Ca(2+) signalling pathway in glomerular mesangial cells of diabetic rats.

G-protein coupled receptor-mediated pathogenesis is of great importance in the development of diabetic complications, but the detailed mechanisms have not yet been clarified. Therefore, we aimed to explore the roles of the prostaglandin E2 receptor 1 (EP1)-mediated signalling pathway and develop a corresponding treatment for diabetic nephropathy (DN). To create the DN model, rats fed a high-fat and high-glucose diet were injected with a single dose of streptozotocin (35 mg/kg, i.p.). Then, rats were either treated or not with berberine (100 mg/kg per day, i.g., 8 weeks). Cells were isolated from the renal cortex and cultured in high-sugar medium with 20% foetal bovine serum. Prostaglandin E2 (PGE2 ) levels were determined by ELISA, and cells were identified by fluorescence immunoassay. We measured the biochemical characteristics and observed morphological changes by periodic-acid-Schiff staining. The expression of the EP1 receptor and the roles of GRK2 and ß-arrestin2 were identified using western blotting and flow cytometry. Downstream proteins were detected by western blot, while molecular changes were assessed by ELISA and laser confocal scanning microscopy. Berberine not only improved the majority of biochemical and renal functional parameters but also improved the histopathological alterations. A significant increase in PGE2 level, EP1 membrane expression and Gαq expression, and concentration of Ca(2+) were observed, accompanied by increased GRK2 and ß-arrestin2 levels soon afterwards. Berberine decreased the abnormal concentration of Ca(2+) , the increased levels of PGE2 , the high expression of EP1 and Gαq and suppressed the proliferation of mesangial cells. The EP1 receptor, a critical therapeutic target of the signalling pathway, contributed to mesangial cell abnormalities, which are linked to renal injury in DN. The observed renoprotective effects of berberine via regulating the PGE2 -EP1-Gαq-Ca(2+) signalling pathway indicating that berberine could be a promising anti-DN medicine in the future.

Observation of localized flat-band states in Kagome photonic lattices.

We report the first experimental demonstration of localized flat-band states in optically induced Kagome photonic lattices. Such lattices exhibit a unique band structure with the lowest band being completely flat (diffractionless) in the tight-binding approximation. By taking the advantage of linear superposition of the flat-band eigenmodes of the Kagome lattices, we demonstrate a high-fidelity transmission of complex patterns in such two-dimensional pyrochlore-like photonic structures. Our numerical simulations find good agreement with experimental observations, upholding the belief that flat-band lattices can support distortion-free image transmission.

G protein-coupled receptors: potential therapeutic targets for diabetic nephropathy.

Diabetic nephropathy, a lethal microvascular complication of diabetes mellitus, is characterized by progressive albuminuria, excessive deposition of extracellular matrix, thickened glomerular basement membrane, podocyte abnormalities, and podocyte loss. The G protein-coupled receptors (GPCRs) have attracted considerable attention in diabetic nephropathy, but the specific effects have not been elucidated yet. Likewise, abnormal signaling pathways are closely interrelated to the pathologic process of diabetic nephropathy, despite the fact that the mechanisms have not been explored clearly. Therefore, GPCRs and its mediated signaling pathways are essential for priority research, so that preventative strategies and potential targets might be developed for diabetic nephropathy. This article will give us comprehensive overview of predominant GPCR types, roles, and correlative signaling pathways in diabetic nephropathy.

Demonstration of flat-band image transmission in optically induced Lieb photonic lattices.

We present a simple, yet effective, approach for optical induction of Lieb photonic lattices, which typically rely on the femtosecond laser writing technique. Such lattices are established by judiciously overlapping two sublattices (an "egg-crate" lattice and a square lattice) with different periodicities through a self-defocusing photorefractive medium. Furthermore, taking advantage of the superposition of localized flat-band states inherent in the Lieb lattices, we demonstrate distortion-free image transmission in such two-dimensional perovskite-like photonic structures. Our experimental observations find good agreement with numerical simulations.