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Inflammation is actively involved in the clinical manifestation of peripheral artery disease (PAD). Sonodynamic therapy (SDT), a novel non-invasive, plaque-based, macrophage-targeted anti-inflammatory regimen for atherosclerosis has the potential to improve walking performance by reducing plaque inflammation.This phase-2, randomized, sham-controlled, double-blind clinical trial enrolled 32 participants with symptomatic femoropopliteal PAD. The primary outcome was the 30-day change in the target-to-background ratio (TBR) within the most diseased segment (MDS) of the femoropopliteal artery assessed through positron emission tomography/computed tomography (PET/CT). The secondary outcomes were changes in walking performance, limb perfusion, lesional morphology and quality of life measurements.The mean age was 64.7 years and 63% were male. Thirty-one completed follow-up. SDT significantly decreased the MDS TBR by 0.53 (95% CI, -0.70 to -0.36, P 0.001) compared with control. Furthermore, SDT increased peak walking time by 118.6 s (95% CI, 74.3 to 163.0, P 0.001), increased ankle-brachial index by 0.11 (95% CI, 0.07 to 0.14, P 0.001), decreased lesional diameter and area stenosis by 7.2% (95% CI, -8.6 to -4.5, P 0.001) and 9.6% (95% CI, -24.5 to -5.3, P = 0.005), respectively, and increased the walking speed score of the Walking Impairment Questionnaire by 16.1 (95% CI, 2.6 to 29.5, P = 0.021) and the physical functioning score of the 36-item Short-Form Health Survey by 10.0 (95% CI, 5.0 to 20.0, P = 0.003) compared with control. These improvements were maintained in the SDT group up to 6-month.SDT rapidly reduced plaque inflammation and improved walking performance among patients with symptomatic PAD.Clinical Trials NCT03457662.

Hollow nano-/micromaterials with tunable shell architectures and compositions are becoming increasingly important and attractive for electrochemical energy conversion and storage. Here, we report carbon-incorporated mixed anionic nickel phosphorus-selenium (Ni0.85Se|P) hollow yolk-shell microspheres synthesized by simultaneous selenization and phosphatization of Ni-based metal organic framework (Ni-MOF). Our experimental results indicated that P-doping reduces the synthesis temperature of the system and enhances the crystallinity of Ni0.85Se. As a result, this unique structure (Ni0.85Se|P) with better crystallinity and higher Ni2+/Ni3+ ratio shows outstanding specific capacity of 506 C g−1 at 1 A g−1. And the assembled Ni0.85Se|P//AC hybrid supercapacitor shows high power density of 20.7 Wh kg−1 at energy density of 798.7 W kg−1. Meanwhile, Ni0.85Se|P exhibits smaller Tafel slope of 90 mV dec−1 and lower onset overpotential of 179 mV versus reversible hydrogen electrode (RHE) for hydrogen evolution reaction (HER) than that of NiP2 and Ni0.85Se, which demonstrates the modulated electronic structure of Ni0.85Se|P. Our study will provide a new strategy for combining P-doped induced high crystallinity mixed anion transition metal complexes with MOF of hollow structures for energy storage device and HER.

Background: Essential fatty acids (EFAs) n3 alpha-linolenic acid (ALA) and n6 linoleic acid (LA) have been shown to improve lipid metabolism, promote nervous system development, suppress inflammation, and are of benefit in diabetes mellitus and cancer. But the exact mechanism of their action(s) is not clear. In the present study, we evaluated the effects of ALA and LA on glucose homeostasis, circulating lipid profile, inflammatory markers, gut microbiome, and bile acids in streptozotocin (STZ)-induced type 1 diabetes with retinopathy in rats. We also measured vitreal LXA4 levels in patients with diabetic retinopathy since arachidonic acid (AA), the precursor of LXA4, is derived from LA. Methods: The study was performed in male Sprague Dawley rats. Type 1 DM was induced by intraperitoneal injection of STZ. The type 1 DM animals received LA or ALA 100 ug/day via intraperitoneal route on alternate days till the end of the study (21 days after the DM onset). In these animals, glucose homeostasis and lipid profile were evaluated. Plasma and retinal fatty acid profile by gas chromatography (GC), retinal histology by H&E staining, activities of desaturases in the retina and liver tissues and inflammatory markers by qRT-PCR, and composition of the gut microbiota by 16S rDNA sequencing technology of the fecal samples were performed. In addition, short-chain fatty acids (SCFAs) and bile acids (BAs) in the feces and liver of rats were assayed by GC and liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS), respectively. Human vitreal samples obtained from patients with proliferative diabetic retinopathy (PDR) were analyzed for their fatty acids profile and LXA4 levels and compared with those with macular hole (control). Findings: LA and ALA-treated STZ-induced type 1 DM animals showed significant reduction in their plasma glucose levels, pro-inflammatory cytokines (IL-6 and TNF-α), changes in the composition of gut microbiome in the form of an increase in the abundance of Ruminococcaceae (ALA-treated group), Alloprevotella, Prevotellaceae_Ga6A1_group, Ruminococcaceae_UCG_010 and Ruminococcus_1 (in LA-treated group) , an increase in acetic acid and butyric acid, and an increase in the fecal concentrations of CA, CDCA and TUDCA and a decrease in GCA. Concentrations of hepatic CDCA, TCDCA, and TUDCA were significantly increased in ALA treated animals while CDCA were elevated in those with LA treatment. STZ-treated animals showed significant decrease in plasma LA, GLA, and AA and ALA levels with no significant changes in retinal fatty acid composition. All these changes reverted to normal in LA and ALA treated group. The changes in the plasma fatty acid composition were accompanied by significant alterations in the expression of desaturases, COX-2 and 5-LOX and 12-LOX enzymes and pro- and anti-inflammatory cytokines. In addition, retinal LXA4 levels were found to be decreased in patients with PDR. Interpretation: The results of the present study suggest that ALA and LA administration can improve plasma glucose levels, suppress inflammation, and produce significant beneficial alterations in the gut microbiota, plasma lipid profile and EFAs metabolism. Decrease in retinal LXA4 levels in those with PDR agree with the suggestion that EFAs metabolism is altered in T1DM and DR. These results imply a significant role for EFAs and their metabolites in the pathobiology of type 1 DM and diabetic retinopathy. Funding Information: The project was funded by the National Natural Science Foundation of China (No. 82000886), and Natural Science Foundation of Zhejiang Province (No.LQ20H120011). Declaration of Interests: Authors have no conflicts of interest to declare. Ethics Approval Statement: This study was approved by the animal ethics committee of the Second Affiliated Hospital of Zhejiang University school of medicine. All experimental procedures using animals were performed in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. This study was approved by the Clinical Ethical Research Committee of the Second Affiliated Hospital of Zhejiang University school of medicine. The study was performed as per the tenets of Helsinki declaration. Informed consent obtained from all the participating patients.

In this study, bimetallic nickel cobalt selenides (NixCo1-x)0.85Se with different Ni to Co ratios were synthesized via one-pot hydrothermal treatment, and their electrochemical performance, as electrode materials for supercapacitors, were systematically studied for the first time. The bimetallic nickel cobalt selenides (NixCo1-x)0.85Se show more excellent electrochemical performance than that of the monometallic selenides Ni0.85Se and Co0.85Se. Meanwhile, through varying the Ni to Co ratio, the (Ni0.5Co0.5)0.85Se delivers the highest specific capacity, excellent rate capability, and good cycling stability. Upon analysis, the superior electrochemical performance of bimetallic nickel cobalt selenides (NixCo1-x)0.85Se, especially (Ni0.5Co0.5)0.85Se, ascribe to the synergistic effect between the more electrochemical active composition (Ni ions) and the faster transfer of electron (Co ions).

We establish a multiplicative Fredholm theory for a Dirac-type operator associated to a connection with point singularities. There are two applications. 1: over a closed 7-manifold, we develop a deformation theory for G 2 -instantons with isolated (point) singularities. 2: for any G 2 − structure defined near the origin in R 7 , and any Hermitian Yang–Mills connection A O on S 6 , we show that there exists a locally defined G 2 -monopole asymptotic to A O at the origin.

Given an elliptic operator $P$ on a non-compact manifold (with proper asymptotic conditions), there is a discrete set of numbers called indicial roots. It's known that $P$ is Fredholm between weighted Sobolev spaces if and only if the weight is not indicial. We show that an elliptic theory exists even when the weight is indicial. We also discuss some simple applications to Yang-Mills theory and minimal surfaces., Comment: 16 pages, no figure. Comments are welcome

A hybrid approach is beneficial to simultaneously exploit the characteristics of capacitive and transition materials to increase the energy density and power density of supercapacitors. In order to achieve optimal electrochemical performance, by means of a facile hydrothermal co-synthesis, we synthesize a three-dimensional porous aerogel consisting of MoS2 nanosheets and reduced graphene oxide (rGO) with a controllable composition and morphological structure. The MoS2/rGO porous aerogel hybrids working as electrode material for supercapacitors, can efficiently enhance surface charge transport, provide more chemical reaction sites, shorten the migration path for electrons and ions, and facilitate the electrolyte diffusion. Using electrochemical feature in two-electrode configurations and symmetric cell devices, we obtain a specific capacitance of 472 F/g with excellent rate capability and cycling stability (98.9% retention after 30,000 cycles) at the current density of 1.0 A/g. Additionally, our designed supercapacitors are flexible under mechanical deformations, which are useful for the next generation wearable electronic devices.

Hydrogen evolution reaction (HER) through water splitting at low overpotential is an appealing technology to produce renewable energy, wherein the design of stable electrocatalysts is very critical. To achieve optimal electrochemical performance, a highly efficient and stable noble-metal-free HER catalyst is synthesized by means of a facile hydrothermal co-synthesis. It consists of Ni3S4 nanosheets and MoS2 nanolayers supported on N-doped reduced graphene oxide (Ni3S4/MoS2@N-rGO). The optimized sample provides a large amount of active sites that benefit electron transfer in 3D conductive networks. Thanks to the strong synergistic effect in the catalyst network, we achieved a low overpotential of 94 mV, a small Tafel slope of 56 mV/dec and remarkable durability in an acidic medium.

The hybrid material of Mn-doped molybdenum disulfide/reduced graphene oxide (Mn-MoS 2 /rGO) is successfully fabricated through a one-pot hydrothermal method. The hybrid material, evaluated as electrochemical catalyst for the hydrogen evolution reaction (HER), exhibits improved catalytic activity and good stability for the HER in acidic medium with small overpotential (approximately 110 mV). Through analyses, it can be concluded that the improvement for electrochemical HER performance of the hybrid catalyst is ascribed not only to high conductivity mainly from reduced graphene oxide, but also to fundamental catalytic activity enhancement generated by Mn ions doping into the S-edge of MoS 2 with a portion of Mo ions replacement. These results verify the facilitation effect of Mn-doping on HER activities, and the Mn-MoS 2 /rGO hybrid prepared in this work could be employed as a promising alternative to noble metal catalysts in HER.

Glaucoma is a neuropathic disease that causes optic nerve damage, loss of retinal ganglion cells (RGCs), and visual field defects. Most glaucoma patients have no early signs or symptoms. Conventional pharmacological glaucoma medications and surgeries that focus on lowering intraocular pressure are not sufficient; RGCs continue to die, and the patient's vision continues to decline. Recent evidence has demonstrated that neuroprotective approaches could be a promising strategy for protecting against glaucoma. In the case of glaucoma, neuroprotection aims to prevent or slow down disease progression by mitigating RGCs death and optic nerve degeneration. Notably, new pharmacologic medications such as antiglaucomatous agents, antibiotics, dietary supplementation, novel neuroprotective molecules, neurotrophic factors, translational methods such as gene therapy and cell therapy, and electrical stimulation-based physiotherapy are emerging to attenuate the death of RGCs, or to make RGCs resilient to attacks. Understanding the roles of these interventions in RGC protection may offer benefits over traditional pharmacological medications and surgeries. In this review, we summarize the recent neuroprotective strategy for glaucoma, both in clinical trials and in laboratory research.

An increase in oxidative stress is an important pathological mechanism of heart injury induced by doxorubicin (DOX). Tranilast is an anti-allergy drug that has been shown to possess good antioxidant activity in previous studies. The overexpression and secretion of chymase by mast cells (MCs) increase the pathological overexpression of angiotensin II (Ang II), which plays a crucial role in myocardial hypertrophy and the deterioration of heart disease. The MC stabilizer tranilast (N-(3,4-dimethoxycinnamoyl) anthranilic acid; tran) prevents mast cells from degranulating, which may reduce DOX-induced Ang II synthesis. Therefore, in the present study, we hypothesized that tranilast will protect rats from DOX-induced myocardial damage via its antioxidant activity, thereby inhibiting Ang II expression. Thirty male Wistar rats were divided into three groups (n = 10 in each group) that received DOX, a combination of DOX and tranilast or saline (the control group) to test this hypothesis. Tranilast suppressed chymase expression, reduced Ang II levels and prevented the myocardial hypertrophy and the deterioration of heart function induced by DOX. Based on the findings of the present study, the suppression of chymase-dependent Ang-II production and the direct effect of tranilast on the inhibition of apoptosis and fibrosis because of its antioxidant stress capacity may contribute to the protective effect of tranilast against DOX-induced myocardial hypertrophy.

Graphitic carbon nitride (g-CN) as a two-dimensional photocatalyst has received considerable attention. Tri-s-triazine-based crystalline carbon nitride nanosheets (CCN-nanosheets) with a thickness from 2 to 5 nm have been synthesized by a thermal procedure. The number of amino groups in the as-obtained samples significantly decreases compared with the samples before treatment (bulk-CCN), which optimizes the grain boundaries and narrows the band gap. Meanwhile, density functional theory (DFT) calculation demonstrates the distinct adjustment for the electronic structure of the sample from deamination. Combining the characteristics of two-dimensional morphology with high crystallinity, CCN-nanosheets demonstrates a high specific surface area of 154.2 m2 g−1, a suitable conductive band potential, improved photo-generated electron-hole pairs separation rate and high carrier transport efficiency. As a consequence, CCN-nanosheets exhibits an outstanding hydrogen evolution rate of 203 μmol h−1 (18 times higher than that of bulk-CCN and 20 times than that of pristine g-CN) and excellent cycling stability. It is anticipated that this facile and effective strategy for tailoring nanostructure and grain boundary would open up a new way for improving the photocatalytic performance of g-CN.

Following Donaldson's openness theorem on deforming a conical Kahler–Einstein metric, we prove a parabolic Schauder-type estimate with respect to conical metrics. As a corollary, we show that the conical Kahler–Ricci flow exists for short time. The key is to establish the relevant heat kernel estimates, where we use the Weber formula on Bessel function of the second kind and Carslaw's heat kernel representation in [8] .

Graphitic carbon nitride (g-CN) typifies organic semiconducting photocatalyst, but it suffers from inefficient charge transfer and unconsummated polymerization at a certain level. In order to develop an optimal setup of charge distribution in a specific crystal plane, we attempted to realize both crystallinity and doping at the same time. Taking account into three different types of melem-based precursors (melem, oligomelem and melon), we systematically investigated a Zn-doped conjugated system using a two-step thermal polymerization strategy of a molten salts bath. The as-prepared Zn-doped crystalline carbon nitrides (Zn-CCN) show a highly ordered crystal structure with an extended tri-s-triazine-based intraplanar network, improved light harvesting and significantly suppressed electron-hole recombination. In addition, the density functional theory (DFT) calculations revealed that the Zn atoms prefer to dwell in the cave of the (100) plane, and their 4s-orbital electrons directly participate in the formation of the conduction band. This unique Zn-doped electronic structure notably reduces the in-planar charge density when Zn atoms act as a rope ladder urging electrons to escape from the N-encircled cave. When Zn-CCN is tailored with these unique layouts, it exhibits dramatically enhanced visible-light photocatalytic hydrogen evolution and excellent cycling stability, exceeding most of other metal-induced crystalline carbon nitrides. It is anticipated that this work can pave a novel research path in future studies of g-CN-based and other two-dimensional photocatalysts with ameliorated performances.

The coupling model proposed more than a decade ago for the description of relaxations in complex correlated systems by one of us (KLN) have been shown repeatedly to be applicable to amorphous polymers, viscous liquids, the glassy state, metallic glasses, glassy ionic conductors and etc. In these examples, the relaxing species are dense packed and mutually interacting. As a consequence, the constraints between them have a strong influence on the relaxation dynamics. Very recent quasielastic neutron scattering experimental data as well as molecular dynamics simulation results which provide dramatic proof of the validity of the coupling model will be discussed. The applicability of the coupling model to some relaxations in metals including precipitates and the Snoek—Koster relaxation is less obvious but has recently been proposed, justified and demonstrated to be relevant by one of us (YNW). The applicability of the coupling model to these and other problems of immediate interest to participants of ICIFUAS-10 will be summarized and discussed. For Snoek—Koster relaxation, additional experimental data in ultra-high purity iron containing low concentration of carbon obtained by one of us (LBM) show characteristics that cannot be explained by Seeger's model of thermally activated formation of kink pairs on screw dislocations in the presence of foreign interstitial atoms, but are consistent with the coupling model.