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Purpose: To explore the efficacy and relevant mechanism of 0.05% cyclosporine A (CsA) eye drops (II) monotherapy in patients with allergic conjunctivitis-associated dry eye (ACDE). Methods: Prospective, randomized, controlled study. Fifty-three patients with mild-to-moderate ACDE were randomly assigned to two groups. The CsA group received 0.05% CsA eye drops (II) monotherapy four times daily. The control group received 0.1% olopatadine twice daily combined with 0.1% preservative-free artificial tears four times daily. Clinical symptoms and signs, tear total IgE, and lymphotoxin-α (LT-α) concentrations were assessed at pre- and post-treatment days 7, 30, and 60. And we further measured six tear cytokines levels using a microsphere-based immunoassay. Results: The CsA group showed significant improvement in symptoms (Ocular Surface Disease Index and itching scores) and signs (conjunctival hyperaemia, conjunctival oedema, conjunctival papillae, tear break-up time (TBUT), corneal fluorescein staining, and goblet cell density) at each follow-up period compared to pre-treatment (all P< 0.050). And its improvement in itching scores (P7th< 0.001, P30th= 0.039, and P60th= 0.031) and TBUT (P7th= 0.009, P30th= 0.003, and P60th= 0.005) was more significant than the control group at all follow-up periods. The tear total IgE, interleukin (IL)-5, IL-6, periostin, eotaxin-3, and MMP-9 levels significantly decreased in the CsA group at day 60 after treatment (all P< 0.050). And the changed values in tear total IgE were positively correlated with the change in itching scores. Conclusions: 0.05% CsA eye drops (II) monotherapy can rapidly improve the symptoms and signs, especially in ocular itching and TBUT, in patients with ACDE. And its efficacy is superior to 0.1% olopatadine combined with artificial tears. Moreover, CsA downregulates the expression levels of tear inflammatory cytokines, including tear total IgE, IL-5, IL-6, periostin, eotaxin-3, and MMP-9. Among that, the reduction in tear total IgE levels may reflect the improvement of ocular itching.

Light is an essential environmental signal perceived by a broad range of photoreceptors in plants. Among them, the red/far-red light receptor phytochromes function to promote photomorphogenesis, which is critical to the survival of seedlings after seeds germination. The basic-helix-loop-helix transcription factors phytochrome-interacting factors (PIFs) are the pivotal direct downstream components of phytochromes. H2A.Z is a highly conserved histone variant regulating gene transcription, and its incorporation into nucleosomes is catalyzed by SWI2/SNF2-related 1 complex, in which SWI2/SNF2-related 1 complex subunit 6 (SWC6) and actin-related protein 6 (ARP6) serve as core subunits. Here, we show that PIFs physically interact with SWC6 in vitro and in vivo, leading to the disassociation of HY5 from SWC6. SWC6and ARP6regulate hypocotyl elongation partly through PIFsin red light. PIFs and SWC6 coregulate the expression of auxin-responsive genes such as IAA6, IAA19, IAA20, and IAA29and repress H2A.Z deposition at IAA6and IAA19in red light. Based on previous studies and our findings, we propose that PIFs inhibit photomorphogenesis, at least in part, through repression of H2A.Z deposition at auxin-responsive genes mediated by the interactions of PIFs with SWC6 and promotion of their expression in red light.

Background and Objectives: No treatment modalities have been identified to prevent neuron damage induced by traumatic brain injury (TBI). The objective of this study was to investigate whether ginsenoside Rb1 (GS-Rb1) could be utilized to exert neuroprotective effects in TBI. Methods: Lateral fluid percussion injury (LFPI) was used to induce an experimental TBI model. Lewis rats were divided into a GS-Rb1 group (5, 10, 20 mg/kg, intraperitoneally injected daily), a sham group, and a vehicle group. Neurological impairments were assessed with brain water content, Evans blue extravasation, neurological deficit scores, and Morris water maze test. TUNEL and NeuN staining were utilized to detect neuron apoptosis. The relative expression of apoptosis- and autophagy-relevant molecules were assayed with real-time PCR and western blot. Results: GS-Rb1 inhibited TBI-induced brain edema and Evans blue extravasation in a dose-dependent manner. Furthermore, GS-Rb1 improved neurological impairments with diminished neurological deficit scores, decreased escape latencies, increased time in the target quadrant, and increased number of platform site crossings. GS-Rb1 protected against neuron apoptosis with downregulated Bax expression and upregulated Bcl-2 expression. It was worth noting that TBI increased the LC3II/LC3I ratio and upregulated the relative expression of Beclin-1, Atg-7, and Atg-3; moreover, TBI downregulated the relative expression of P62. The administration of GS-Rb1 further strengthened the relative expression of autophagy-related molecules. Conclusions: GS-Rb1 alleviates neurological impairments induced by TBI with upregulated autophagy.

Photocatalytic carbon dioxide (CO2) reduction (PCR) into syngas is one of the sustainable approaches for recycling CO2into value-added chemical feedstocks. However, the PCR efficiency is often limited by the insufficient light-harvesting and poor charge separation. Herein, we design a spike-like double yolk–shell structured TiO2@ZnIn2S4(D-Y-TiO2@ZnIn2S4) photocatalyst with superior PCR efficiency. The unique design not only integrates advantages of increasing active sites, surface areas and light-harvesting capacity induced by the hierarchical morphology, but also facilitates photo-induced charge separation based on the heterojunction of TiO2and ZnIn2S4. Owing to the combination of structural and compositional merits, the optimized D-Y-TiO2@ZnIn2S4photocatalyst shows superior PCR performance (325.29 μmol CO per g; 227.18 μmol H2per g) under visible light. In addition, the ratio of CO/H2can be tuned from 0.03 to 1.43 by changing the sacrificial hole capture condition. This work provides a prospective way to obtain efficient PCR photocatalysts.

To observe alterations in corneal morphology caused by repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF). Prospective cohort study. Seventy-seven eyes were treated with intravitreal injection of anti-VEGF from June 2021 to March 2023. There were 25 eyes of neovascular age-related macular degeneration (nAMD), 24 eyes of diabetic macular edema (DME), and 28 eyes of retinal vein occlusion (RVO). Aflibercept was used in 37 eyes and Ranibizumab was used in 40 eyes. 3 + PRN was used. Corneal endothelium and corneal thickness were measured using a corneal endothelial microscope. The data related to central corneal thickness, corneal endothelial cell density (ECD), average cell size, coefficient of variation (CV), proportion of hexagonal cells (Hex%) was collected. A comparison was also made between baseline and the dynamic changes of all indexes 1 year following the last injection. It was observed that in comparison to baseline, ECD and Hex% decreased significantly after the 3rd injection of Aflibercept and Ranibizumab. However, ECD did not decrease further and remained at the same level as after the last injection. Hex% and average cell size increased to a certain extent in comparison to the last injection. All the changes were found to be statistically significant (P< .01). After 3 injections, ECD in DME group was markedly lower than that in nAMD and RVO group, but the CV in DME group was higher than that in nAMD as well as RVO groups, and all the differences were statistically significant (P< .05). Following intravitreal anti-VEGF therapy, DME is more likely than other disorders to result in a decrease in ECD. Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex% and ECD to a certain extent. After the last injection, Hex% can progressively recover, and ECD can remain stable without further declining. After injections, ECD in DME group was found to be significantly lower than that in nAMD and RVO groups, but CV in DME group was significantly higher in comparison to the other 2 groups. In patients with macular edema, repeated intravitreal injections of anti-VEGF may have certain effects on corneal morphology. Patients with diabetes mellitus in particular should pay special attention to corneal safety following repeated intravitreal injections if they have significantly reduced ECD at baseline.

Intestinal stromal cells are known to modulate the propagation and differentiation of intestinal stem cells1,2. However, the precise cellular and molecular mechanisms by which this diverse stromal cell population maintains tissue homeostasis and repair are poorly understood. Here we describe a subset of intestinal stromal cells, named MAP3K2-regulated intestinal stromal cells (MRISCs), and show that they are the primary cellular source of the WNT agonist R-spondin 1 following intestinal injury in mice. MRISCs, which are epigenetically and transcriptomically distinct from subsets of intestinal stromal cells that have previously been reported3–6, are strategically localized at the bases of colon crypts, and function to maintain LGR5+intestinal stem cells and protect against acute intestinal damage through enhanced R-spondin 1 production. Mechanistically, this MAP3K2 specific function is mediated by a previously unknown reactive oxygen species (ROS)–MAP3K2–ERK5–KLF2 axis to enhance production of R-spondin 1. Our results identify MRISCs as a key component of an intestinal stem cell niche that specifically depends on MAP3K2 to augment WNT signalling for the regeneration of damaged intestine.

Cyclohexanol (CHOL), as a value-added chemical, has attracted much attention due to its huge application market. The hydrogenation of cyclohexyl acetate (CHA), derived from the esterification of acetic acid and cyclohexene, not only provides a novel route to yield CHOL and ethanol (EtOH), but also rationally utilizes excess acetic acid. In this work, a series of Zn-promoted Cu/Al2O3catalysts were prepared viaa deposition–precipitation method for the liquid-phase hydrogenation of CHA to yield CHOL and EtOH. As a result, the addition of Zn species with an optimal amount greatly improved the activity and selectivity to CHOL and EtOH. A Cu2Zn1.25/Al2O3catalyst, which contained 16.2 wt% Cu and 9.6 wt% Zn, exhibited superior catalytic performance with 93.9% conversion of CHA and 97.2% selectivity to EtOH along with 97.1% selectivity to CHOL in a batch reactor. The Cu2Zn1.25/Al2O3catalyst also showed excellent stability and there was no deactivation after five runs. Based on detailed characterization, it was revealed that the addition of Zn species increased the dispersion of Cu particles, adjusted the strength and amount of acid sites, and changed the electronic properties of Cu species and thus the ratio of Cu+/(Cu0+ Cu+).

Achieving high catalytic performance with Cu-based catalysts is crucial for the hydrogenation of CO2-derived ethylene carbonate (EC) to simultaneously yield methanol (MeOH) and ethylene glycol (EG). Although Cu-based catalysts are widely studied for the target reaction, there are still some issues to be clarified. In this study, we prepared a 29.1 wt% Cu/SiO2-MHT catalyst by a modified hydrothermal method and successfully applied it to the hydrogenation of EC. In comparison with its three analogues having similar Cu loading and comparable Cu particle size but prepared by different methods, we found that the catalytic performance of the Cu/SiO2catalysts, including the activity and the selectivity to MeOH, could be tuned by adjusting the Cu+/(Cu0+ Cu+) ratio viadifferent preparation methods. As a result, the Cu/SiO2-MHT catalyst furnished 89% MeOH yield and 37.6 h−1turnover frequency. To our best knowledge, these values are one of the highest among all heterogeneous Cu catalysts up to now. The results reveal that a cooperative effect exists between Cu0and Cu+. When the Cu0species are sufficient to activate H2, a more favorable formation of MeOH can be achieved with more Cu+species and greater Cu+surface areas. Furthermore, a greater amount of Lewis acid on the Cu/SiO2-MHT catalyst is also beneficial for MeOH formation.

A visible-light-mediated protocol for the hydroacylation of azobenzenes with α-keto acids has been developed. In the absence of any catalyst or additive, decarboxylative hydroacylation proceeded smoothly under visible-light irradiation at room temperature. A wide range of azobenzenes and α-keto acids were well-tolerated and afforded hydroacylation products in high to excellent yields. Preliminary investigations indicated that photoactive azobenzenes absorb visible light to enable the transformation.

Liquid metal (LM) has been used as flexible electrodes for high performance triboelectric nanogenerators (TENGs), however it is unclear how the LM in tribo-layers would affect the performance of TENGs. Here, we report the investigation on the effects of LM particles incorporated into a tribo-layer on the performance of TENGs. The TENGs consist of a polyacrylonitrile (PAN) electrospinning nanofiber membrane, and a polytetrafluoroethylene (PTFE) thin film. LM particles with different concentrations are incorporated into PAN polymer matrix, and used to make the PAN nanofibers membranes by electrospinning. Result shows that the outputs of TENGs become much larger with the increase in LM content. Specifically, the current density increases by about 40%, and both the charge density and output voltage increase by nearly 70%. The overall output power is approximately 2 times higher for the TENG with 1.5 wt% LM concentration, as compared to those of TENGs with pure PAN tribo-layer. However, the output of PAN/LM-PTFE TENGs deteriorates drastically when the LM mass content is increased to 2.5 wt%, at which the composite contains a high density of LM spheroid and spindle particles, deteriorating the generation of triboelectric charge.

To investigate the potential effect of repeated intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs on corneal nerves. A total of 64 patients were treated with intravitreal injection of anti-VEGF drugs. There were 19 cases of neovascular age-related macular degeneration (AMD), 20 cases of diabetic macular edema (DME) and 25 cases of retinal vein occlusion (RVO). Twenty-nine cases were treated with aflibercept (2 mg/0.05 mL) whereas 35 cases were managed with ranibizumab (0.5 mg/0.05 mL). A corneal confocal microscope was used to collect images of corneal subbasal nerve plexus, and Image J was used for image analysis. The changes in corneal nerve were compared between 1 month after each injection and before injection. There were no significant differences in the density and length of corneal nerve at specific time after the surgery in comparison with baseline in patients who were given 3 intravitreal injections. There was no significant correlation between the numbers of injections and the changes of the corneal nerves. After 3rd injection, the nerve length of the DME group was markedly lower than that of AMD and RVO groups, the difference was statistically significant (P< .05). The nerve density of the DME group was not significantly different from that of AMD and RVO groups, whereas the nerve length and nerve density of the AMD and RVO groups were not statistically significant between each other also. The corneal nerve length after the 2nd and 3rd injections of Aflibercept were lower than that before surgery, the difference was statistically significant. There were no significant differences in nerve density and nerve length at each time point after Ranibizumab injection. The length and density of the corneal nerve after multiple injections in contralateral eye displayed no significant changes compared with the baseline. Repeated intravitreal anti-VEGF drug can reduce the length of corneal nerves. For patients who need repeated intravitreal injections of anti-VEGF drugs, especially in DM, attention should be paid on the changes affecting the corneal nerves. It is also needed to strengthen the local anti-inflammatory therapy to avoid infection and to use artificial tears to protect the microenvironment of the ocular surface after the surgery.

Background:Mutations in the surfactant protein C gene (SFTPC) result in interstitial lung disease (ILD). Our objective was to report a novel SFTPC mutation and evaluate the effect of this mutant on protein synthesis and processing.Methods:Genomic DNA was extracted from whole blood of a Chinese infant with ILD and candidate genes associated with ILD were sequenced by next-generation sequencing. Subclones of wild-type and mutant SFTPC were transiently transfected into A549 cells. The functional characterization of mutant surfactant protein C (SP-C) was evaluated by Western blotting, transmission electron microscopy, and immunofluorescence.Results:A novel heterozygous mutation SFTPC: c.337T>T/C, p.Y113H was identified in this ILD infant. Neither of the parents carries this mutation. Using A549 cells expressing wild-type and mutant SP-C isoforms, Western blotting revealed a significant reduction of proSP-C and a band with abnormal molecular weight in the mutant SP-C compared to the wild-type. Ultrastructural analysis showed abnormal cytoplasmic organelles. Immunofluorescence demonstrated mutant SP-C was scarcely trafficked to lamellar bodies but localized well to early endosomes, which was in marked contrast to the wild type protein.Conclusion:We detected a novel mutation in SFTPC causing ILD in infancy. The mutation results in aberrant proSP-C processing and altered subcellular localization.

The calculated results in the literature for the decomposition of formic acid into CO on Pt(111) cannot rationalize the well-known facile CO poisoning of Pt-based catalysts. The present work reexamines formic acid decomposition on Pt(111) by considering both the monomer and dimer pathways both in the absence and in the presence of water molecules. Upon a thorough search, we locate some new adsorption configurations of formic acid for the subsequent C–H or O–H cleavage, which were ignored in previously published literature. From the calculated minimum energy pathways (MEPs), we propose that formic acid decomposition on Pt(111) is initiated by C–H bond cleavage rather than O–H bond cleavage. Monomeric formic acid preferentially decomposes to CO2regardless of the absence or presence of water, while the dimeric form favors the formation of CO in the gas phase, but competitively reacts to form CO and CO2in the presence of water molecules. The surrounding water molecules and the second formic acid molecule in the dimer play substantial roles in the process of formic acid decomposition, and can be regarded as promoters, assisting formic acid decomposition on Pt(111). In all situations, that is, regardless of the presence of a monomer or dimer, or the presence or absence of water, the calculated barrier differences in the rate-determining steps of CO2and CO formation are much smaller than those reported in previously published studies. These results improve our understanding of the mechanism of formic acid oxidation catalyzed by Pt-based catalysts, and rationalize the performance durability problem of Pt-based catalysts used in direct formic acid fuel cells.

While the high performance for electrooxidation of formic acid (HCOOH) has been recognized, Pd-based catalysts still suffer from CO poisoning, even though they are much more tolerant than Pt-based catalysts. Existing theoretical studies on the decomposition of HCOOH on Pd(111) surface cannot rationalize the catalyst poisoning effect. By performing density functional theory calculations, the present work reexamined the decomposition of HCOOH on Pd(111) along with the dual-path mechanism consisting of indirect and direct pathways. Two new adsorption configurations of HCOOH on Pd(111) are presented, from which the formation of CO is found to be either the same or more favorable in comparison with the formation of CO2. The present results are in distinct contrast to previous calculations where the barrier for the formation of CO2was much lower than that for the formation of CO. Furthermore, this work also discussed the formation of CO through the reduction of CO2and the effects of coadsorbed HCOOH and H2O molecules on the reactivity. From calculated results, it seems that the newly formed CO2on Pd(111) can return to the surface to interact with adsorbed H atoms, partly contributing to the formation of CO. Coadsorbed HCOOH and H2O molecules are found to importantly affect the initial adsorption configuration and the decomposition mechanism of HCOOH on Pd(111). These results provide new insight into the reactivity of HCOOH on the Pd(111) surface and rationalize CO poisoning of Pd-based catalysts.

To characterize the endothelial progenitor cell mobilization in the models of moderate and severe lung injury, we hypothesized that there were differences in endothelial progenitor cell levels and mobilizing cytokines between moderate and severe lung injury.

Hierarchical, three-fold symmetrical dendritic gold was prepared in an aqueous solution of the quaternary ammonium cationic surfactant dodecyltrimethylammonium bromide (DTAB). Similar surfactants with different head groups and hydrocarbon chain lengths were also used for comparison. Two-fold and one-fold symmetrical dendritic gold nanostructures were obtained in N-dodecyl-N-methylpyrrolidinium bromide (C12-MPB) and dodecyltriethylammonium bromide (DTEAB) aqueous solutions, respectively. Longer hydrocarbon chain lengths were unfavorable for the formation of dendritic nanostructures. The interaction energies between the individual surfactants and Au (111) plane were calculated using molecular dynamics simulations. Based on a series of contrast experiments and molecular dynamics simulations, the possible growth mechanism and fabrication process of the dendritic structures were proposed. The DTAB-capped, three-fold gold dendrites exhibited good surface-enhanced Raman scattering (SERS) sensitivity toward rhodamine 6G (R6G), indicating their potential for use in SERS-based detections and analysis. This work provides a simple and effective strategy for fabricating dendritic gold nanostructures in aqueous solutions.