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Here, N-doped hollow carbon sphere (NHCS)-supported (1 1 1)-plane-engineered sub-5-nm Pt (Pt-NHCS) catalysts regulated precisely by imidazolium ionic liquids were synthesized successfully and used to catalyze oxygen reduction. The (1 1 1)-plane engineered Pt nanocrystals with a diameter of 4.5 ± 0.5 nm were homogeneously deposited on the 3-dimensional spherical nanoshells. The resulting Pt nanocrystals anchored on the carbon skeleton exhibit a stable configuration in both alkaline and acid electrolytes with the help of imidazolium cations and pyrolysis. Among all as-prepared catalysts, the optimized Pt-NHCS shows remarkable long-term durability. Specifically, Pt-NHCS maintains 95.3% of the original current density after 10,000 potential cycles, while Pt/C benchmarks exhibit a retention of 78.5%. Accelerated durability test results indicate that Pt-NHCS exhibits a high efficiency of 96 % in comparison with initial current density, while a value of 86% for Pt/C. Density functional theory calculations demonstrate that reactive Pt(1 1 1) planes with well-defined Schottky defects and vacancies adsorb and activate oxygen molecule rapidly while desorbing the reaction intermediates.

The poly(L-lactide-co-e-caprolactone) (PLCL) ureteral stent creeps and loses shape stability, increasing the risk of stent tube dislocation. The rubbery biodegradable cross-linked PLCL networks were prepared through gamma irradiation under vacuum in the presence of trimethylolpropane triacrylate (TMPTA), pentaerythritol tetraacrylate (PET4A), and pentaerythritol triacrylate (PETA). At a standard sterilization dose of 25 kGy, the gel content and network density of PLCL networks increased with increasing crosslinking agent content (1, 3, 5, 7 wt%), and crosslinking efficiency decreased in the order of PETA > PET4A > TMPTA. The average molecular weight ( M c ¯ ) between two crosslinks ranged from 2000 to 105 g/mol. To perform the beneficial semi-interpenetrated polymer network and characterized by the principle, the networks were processed in several doses (25, 50, 75, 100, and 125 kGy). In place of the Charlesby-Pinner equation, the irradiation cross-linking followed the Chen-Liu-Tang equation. The PLCL network with 7 wt% PETA had a gel fraction of 83%, tensile strength of 34.7 MPa, and tensile set value as low as 5%. Furthermore, degradation in vitro was slowed down. Thus, PLCL networks with appropriate elasticity and flexibility, inherent biodegradability, and excellent biocompatibility can provide a promising alternative method for soft tissue repair engineering, such as ureteral stents.

Tissue-engineered scaffolds acted as active natural extracellular matrices that allowed for cell attachment, migration, proliferation, and differentiation. To enhance the drug loading, degradation control, and mechanical features of tissue-engineered scaffolds used in bone regeneration applications, we synthesized novel poly(trimethylene carbonate) (PTMC)/modified HA nanoparticles (KHA NPs, modified by silane coupling agent)/vancomycin hydrochloride (VH) porous microspheres scaffold. The fabricated PTMC/KHA/VH scaffold has unique surface corrosion degradation, excellent surface properties, and high cytocompatibility. The novel PTMC/KHA/VH scaffold was characterized by 42% porosity, 100 μm pore size, and 208.2 MPa compressive modulus. After the treatment of a rat femur defect for 4, 8, and 12 weeks, the surface corrosion biodegraded of the PTMC/KHA/VH scaffold remarkably decreased inflammation response and promoted bone regeneration, suggesting its use as a bioactive structure in bone tissue engineering.

To investigate the impact of the COVID-19 outbreak on the behaviours, mental health and seizure control of adult patients with epilepsy (PWE) and to identify the correlation of seizure increase and the COVID-19 outbreak to guide the medical care of individuals with epilepsy during a public health crisis.This study was conducted at 28 centres from February 2020 to April 2020. Participants filled out a 62-item online survey including sociodemographic, COVID-19-related, epilepsy-related and psychological variables and were divided into two groups based on whether their seizure frequency increased during the COVID-19 pandemic. Chi-square tests and t-tests were used to test differences in significant characteristics. Multiple logistic regression analyses were used to identify risk factors for seizure worsening.A total of 1,237 adult PWE were enrolled for analysis. Of this sample, 31 (8.33%) patients experienced an increase in seizures during the pandemic. Multivariate logistic regression suggested that feeling nervous about the pandemic (P0.05), poor quality of life (P = 0.001), drug reduction/withdrawal (P = 0.032), moderate anxiety during the COVID-19 outbreak (P = 0.046) and non-seizure free before the COVID-19 outbreak (P0.05) were independently related to seizure increase during the pandemic.During the COVID-19 pandemic, PWE with poor quality of life and mental status, as well as AED reduction/withdrawal, were more likely to experience seizure increase. This observation highlights the importance of early identification of the population at high risk of seizure worsening and implementation of preventive strategies during the pandemic.

Impaired wound healing represents an unsolved medical need with a high impact on patients´ quality of life and global health care. Even though its causes are diverse, ischemic-hypoxic conditions and exacerbated inflammation are shared pathological features responsible for obstructing tissue restoration. In line with this, it has been suggested that promoting a normoxic pro-regenerative environment and accelerating inflammation resolution, by reinstating the lymphatic fluid transport, could allow the wound healing process to be resumed. Our group was first to demonstrate the functional use of scaffolds seeded with photosynthetic microorganisms to supply tissues with oxygen. Moreover, we previously proposed a photosynthetic gene therapy strategy to create scaffolds that deliver other therapeutic molecules, such as recombinant human growth factors into the wound area. In the present work, we introduce the use of transgenic Synechococcus sp. PCC 7002 cyanobacteria (SynHA), which can produce oxygen and lymphangiogenic hyaluronic acid, in photosynthetic biomaterials. We show that the co-culture of lymphatic endothelial cells with SynHA promotes their survival and proliferation under hypoxic conditions. Also, hyaluronic acid secreted by the cyanobacteria enhanced their lymphangiogenic potential as shown by changes to their gene expression profile, the presence of lymphangiogenic protein markers and their capacity to build lymph vessel tubes. Finally, by seeding SynHA into collagen-based dermal regeneration materials, we developed a viable photosynthetic scaffold that promotes lymphangiogenesis in vitro under hypoxic conditions. The results obtained in this study lay the groundwork for future tissue engineering applications using transgenic cyanobacteria that could become a therapeutic alternative for chronic wound treatment. Statement of significance In this study, we introduce the use of transgenic Synechococcus sp. PCC 7002 (SynHA) cyanobacteria, which were genetically engineered to produce hyaluronic acid, to create lymphangiogenic photosynthetic scaffolds for dermal regeneration. Our results confirmed that SynHA cyanobacteria maintain their photosynthetic capacity under standard human cell culture conditions and efficiently proliferate when seeded inside fibrin-collagen scaffolds. Moreover, we show that SynHA supported the viability of co-cultured lymphatic endothelial cells (LECs) under hypoxic conditions by providing them with photosynthetic-derived oxygen, while cyanobacteria-derived hyaluronic acid stimulated the lymphangiogenic capacity of LECs. Since tissue hypoxia and impaired lymphatic drainage are two key factors that directly affect wound healing, our results suggest that lymphangiogenic photosynthetic biomaterials could become a treatment option for chronic wound management.

In the current study, to support the safety pharmacology assessment of Ethanamizuril as a new potent anticoccidial agent of triazine compounds, the effects of Ethanamizuril on the central nervous system, cardiovascular system and respiratory system were investigated. Using locomotor activity test, climbing behavior test and nembutal subthreshold hypnotic test at each time point after oral administration of Ethanamizuril to mice, the effects on the central nervous system were evaluated. An assessment of Ethanamizuril effects on the cardiovascular and respiratory system were performed by the use of a telemetry system in conscious beagle dogs. The results showed that the treatment of Ethanamizuril had no effects on motor activity, behavioral changes, coordination, and sensory/motor reflex responses in mice. There were also no changes in heart rate, blood pressure, and electrocardiogram at all doses and each time points in beagle dogs. Our data suggested that Ethanamizuril showed no adverse effects on the central nervous system, cardiovascular system, and respiratory system.

Purpose To explore the molecular mechanisms of PM2.5-induced dysfunction in human corneal epithelial cells (HCECs) and the potential role of the plasminogen activator inhibitor type-2 (PAI-2) in PM2.5-induced autophagy in vitro and in vivo. Methods RNA-Seq was performed to identify the differentially expressed genes (DEGs) in PM2.5-exposed HCECs compared to unexposed condition, followed by validation via real-time PCR (qRT-PCR). Corneal fluorescein staining and tear secretion were assessed in the PM2.5-exposed rat model. The expression of PAI-2 and autophagy-related markers were examined via immunoblotting, immunofluorescence staining and/or qRT-PCR in PM2.5-exposed or unexposed HCECs and rat corneas. PAI-2-knockdown HCECs were generated to study PAI-2's role in the PM2.5-induced autophagy in HCECs. Results A total of 434 DEGs—240 up-regulated and 194 down-regulated—were identified in PM2.5-exposed HCECs rather than unexposed HCECs. The expression of a few genes related to proliferation, inflammation, and aryl hydrocarbon stimulation were significantly altered by PM2.5 exposure. PAI-2 expression was up-regulated in PM2.5-exposed HCECs, sharing a similar fluctuation trend with autophagy-related markers LC3B II and BECN1 according to various exposure periods. Moreover, PAI-2 knockdown significantly suppressed the expression of LC3B and BECN1 in PM2.5-exposed HCECs. The corneal fluorescein staining was enhanced and tear secretion was significantly reduced in PM2.5-exposed rat eyes. PAI-2 expression was also increased in PM2.5-exposed rat corneas, together with the up-regulation of several autophagy-related markers. Conclusion The present study identified the altered expression of hundreds of genes in PM2.5-exposed HCECs, which suggests the importance of PM2.5 for cornea health. The involvement of PAI-2 was discovered in the PM2.5-induced autophagy in HCECs as well as likely in rat corneas, which implied that PAI-2 may become a potential target of clinical treatment of PM2.5-associated ocular surface diseases.

Polysaccharide was derived from Pueraria lobata (PPL) which was considered as one of the traditional Chinese medicinal and edible herbs. In the present study, PPL was administered in equal doses (12.5 mg/kg) to both normal mice and antibiotic-associated diarrhea (AAD) mice for two weeks, and was evaluated in terms of body weight, organ indices, gut structure, gut microbiota and short chain fatty acids. The results showed that normal mice treated with PPL not only reduced the isovaleric acid concentration (P 0.05), but also significantly increased the abundance of beneficial bacteria, involving Oscillospira and Anaerotruncus (P 0.05). In addition, PPL could relieve colonic pathological changes and gut microbiota dysbiosis caused by AAD. It indicated that PPL was a potential functional food ingredient by modulating gut microbiota.

DNA-encoded library (DEL) technology has been used as an ultra-high-throughput screening approach for hit identification of drug targets. This process is an affinity-based selection and requires incubation of DEL molecules with the target. Currently, in most reported cases, the input (i.e., the copy number) of individual DEL molecules varies from 105 to 107. With the ever-increasing DEL size and screening cost, lowering the input of DEL molecules while maintaining an appropriate signal-to-noise ratio in a selection is of paramount importance. In this article, we varied the input of DEL ranging from 103 to 105 in selections with two different protein targets to explore the lower limit of DEL molecule input. The results could facilitate the optimization of the DEL selection process and reduce costs related to library consumption.

Purpose The purpose of this study was to compare the perioperative parameters of quadrant, sextant, and grid lens fragmentation patterns in femtosecond laser-assisted cataract surgery (FLACS). Design Prospective randomized clinical trial. Methods S etting : Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. S tudy population : A total of 894 eyes in 661 patients with cataracts were enrolled. I ntervention or observation procedures : the nuclear density was graded according to the Emery-Little classification. Patients received lens fragmentation using a quadrant, sextant, or grid pattern after random allocation. Evaluations included intraoperative parameters, complications, and postoperative outcomes. M ain outcome measurements : effective phacoemulsification time (EPT), intraoperative complications, visual acuity and intraocular pressure at one day postoperatively, as well as endothelial cell density, endothelial cell loss, and central corneal thickness at 1 week postoperatively. Results In grade 1 nuclei, the mean EPT in the grid group was the shortest compared to those in the quadrant (P = 0.011) and sextant (P = 0.001) groups. In grade 2 nuclei, all 3 patterns showed no significant differences in the mean EPT (P > 0.05). In grade 3 nuclei, the sextant group revealed shorter mean EPT than the grid (P = 0.017) and quadrant (P > 0.05) groups. In grades 4 and 5 nuclei, the quadrant pattern had the shortest mean EPT among all 3 patterns (P Conclusions The grid and quadrant patterns allow for shorter EPT in soft (grade 1) and hard (grades 4 and 5) nuclei, respectively. All 3 patterns can be selected for treating grade 2 nuclei. The sextant pattern may be the best option when treating grade 3 nuclei. The grid pattern should be avoided in hard nuclei combined with glaucoma or glaucoma suspect.

Deep network recently has achieved promising performance for classification task with massive training samples. The behavior of this model, however, would be diminished obviously when the training set is small. Meanwhile, linear representation based classifiers have widely applied into many fields. These classifiers mostly attempt to take advantage of the correct class to code the test sample through appending l1-norm or nuclear norm which highly takes computation. Under these observations, we present a novel competitive and collaborative representation classification (Co-CRC) that employs the properties of training data with l2-norm regularization to create a competitive environment which enables the correct class to make more contribution to coding. Additionally, the proposed competitive weight in this paper enhances the competitive relation among all classes and is beneficial for the classifier to find the correct class. Extensive experimental results over popular benchmarks including object, scene and face images database indicate that the proposed algorithm totally based on l2-norm regularization takes less computation to obtain rather sparse coding and mostly outperforms several state-of-the-art approaches.

Introduction [68Ga]Ga-EDTA ([68Ga]Ga-ethylenediaminetetraacetic acid) was previously reported as a renal imaging agent for measuring GFR (glomerular filtration rate). In an effort to provide new agents with better in vivo characteristics for renal imaging, [68Ga]Ga-HBED-CC-DiAsp (Di-Aspartic acid derivative of N,N′-bis [2-hydroxy-5-(carboxyethyl)benzyl]-ethylenediamine-N,N′-diacetic acid) was prepared and tested. Method HBED-CC-DiAsp was synthesized and labeled with [68Ga]GaCl4− at room temperature. Plasma protein and red blood cells (RBC) binding were also evaluated. Biodistribution and dynamic PET imaging studies were performed in mice and rats, respectively. Results [68Ga]Ga-HBED-CC-DiAsp was radiolabeled at room temperature by a one-step kit formulation in high purity without any purification (radiochemical purity >98%). Previous reports suggested that Ga-HBED-CC exhibited a higher stability constant and rapid chelating formation rate than that of Ga-EDTA (logKGaL = 38.5 vs 22.1, respectively). In vitro stability studies indicated that it was stable up to 120 min. The log DOW value, partition coefficient between n-octanol and water, was found to be −2.52 ± 0.08. Plasma protein and RBC binding was similar to that observed for [68Ga]Ga-EDTA. Biodistribution and dynamic PET/CT imaging studies in rats revealed a rapid clearance primarily through the renal–urinary pathway. The PET-derived [68Ga]Ga-HBED-CC-DiAsp renograms in rats showed an average time-to-peak of 3.6 ± 0.7 min which was similar to that observed for [68Ga]Ga-EDTA (3.1 ± 0.5 min). The time-to-half-maximal activity was also comparable to that of [68Ga]Ga-EDTA (8.8 vs 8.2 min, respectively). Pretreatment of probenecid, a renal tubular excretion inhibitor, showed no significant effect on renal excretion. Conclusions [68Ga]Ga-HBED-CC-DiAsp could be prepared quickly at room temperature in high yield and purity. Results of in vitro studies and in vivo biodistribution in mice and rats suggested that [68Ga]Ga-HBED-CC-DiAsp might be useful as a PET imaging agent for measurement of GFR.

Apolipoprotein A-I (apoA-I) is cross-linked and dysfunctional in human atheroma. Although multiple mechanisms of apoA-I cross-linking have been demonstrated in vitro, the in vivo mechanisms of cross-linking are not well-established. We have recently demonstrated the highly selective and efficient modification of high-density lipoprotein (HDL) apoproteins by endogenous oxidized phospholipids (oxPLs), including γ-ketoalkenal phospholipids. In the current study, we report that γ-ketoalkenal phospholipids effectively cross-link apoproteins in HDL. We further demonstrate that cross-linking impairs the cholesterol efflux mediated by apoA-I or HDL3 in vitro and in vivo. Using LC-MS/MS analysis, we analyzed the pattern of apoprotein cross-linking in isolated human HDL either by synthetic γ-ketoalkenal phospholipids or by oxPLs generated during HDL oxidation in plasma by the physiologically relevant MPO-H(2)O(2)-NO(2)(−) system. We found that five histidine residues in helices 5–8 of apoA-I are preferably cross-linked by oxPLs, forming stable pyrrole adducts with lysine residues in the helices 3–4 of another apoA-I or in the central domain of apoA-II. We also identified cross-links of apoA-I and apoA-II with two minor HDL apoproteins, apoA-IV and apoE. We detected a similar pattern of apoprotein cross-linking in oxidized murine HDL. We further detected oxPL cross-link adducts of HDL apoproteins in plasma and aorta of hyperlipidemic LDLR(−/−) mice, including cross-link adducts of apoA-I His-165–apoA-I Lys-93, apoA-I His-154–apoA-I Lys-105, apoA-I His-154–apoA-IV Lys-149, and apoA-II Lys-30–apoE His-227. These findings suggest an important mechanism that contributes to the loss of HDL's atheroprotective function in vivo.

Targeting microglial activation has been shown to ameliorate early brain injury (EBI) after subarachnoid hemorrhage (SAH). Ferroptosis is a new form of programmed cell death after SAH, but these molecular features were not recognized as evidence of microglial function so far. In this study, we constructed microglial S100A8-specific knockdown and established the SAH model in vivo and in vitro. Multi-technology strategies, including high throughput sequencing, adeno-associated virus gene gene-editing and several molecular biotechnologies to validate the effects of S100A8 on microglial autophagy and ferroptosis after SAH. Our results revealed that the expression of S100A8 was significantly increased in brain tissue after SAH. Targeted microglial S100A8 inhibition improved neural function and neuronal apoptosis in mice after SAH. Further mechanism exploration found that favourable effects of S100A8 depletion in EBI may be through the inhibition of microglia autophagy-dependent ferroptosis. In conclusion, S100A8 may be a potential intervention target for microglial ferroptosis in EBI after SAH.