Zn Single-Atom Catalysts Enable the Catalytic Transfer Hydrogenation of α,ß-Unsaturated Aldehydes.

Highly active nonprecious-metal single-atom catalysts (SACs) toward catalytic transfer hydrogenation (CTH) of α,ß-unsaturated aldehydes are of great significance but still are deficient. Herein, we report that Zn-N-C SACs containing Zn-N3 moieties can catalyze the conversion of cinnamaldehyde to cinnamyl alcohol with a conversion of 95.5% and selectivity of 95.4% under a mild temperature and atmospheric pressure, which is the first case of Zn-species-based heterogeneous catalysts for the CTH reaction. Isotopic labeling, in situ FT-IR spectroscopy, and DFT calculations indicate that reactants, coabsorbed at the Zn sites, proceed CTH via a "Meerwein-Ponndorf-Verley" mechanism. DFT calculations also reveal that the high activity over Zn-N3 moieties stems from the suitable adsorption energy and favorable reaction energy of the rate-determining step at the Zn active sites. Our findings demonstrate that Zn-N-C SACs hold extraordinary activity toward CTH reactions and thus provide a promising approach to explore the advanced SACs for high-value-added chemicals.

Limbal Stem Cell Dysfunction Induced by Severe Dry Eye via Activation of the p38 MAPK Signaling Pathway.

Severe dry eye (SDE) can cause grievous damage to the ocular surface and result in vision impairment and even blindness. To investigate the fate of limbal stem cells in SDE and the underlying mechanism, the current study established an SDE rat model by removing the extraorbital and infraorbital lacrimal glands and maintaining them in a low-humidity environment. One month after the surgery, aqueous tear secretion was reduced dramatically, blood vessels invaded into the central cornea, and inflammatory cells infiltrated into the limbal stroma. The expressions of keratin 12 and paired box gene 6 were down-regulated dramatically, while those of keratin 10, small proline-rich protein 1b, and mucin 5AC were up-regulated in the corneal epithelium of the SDE rats. Cell proliferation in the limbal epithelium was up-regulated, while the stem/progenitor marker adenosine 5'-triphosphate-binding cassette member 2 and the limbal epithelial colony-forming efficiency were decreased in the SDE condition. Furthermore, the p38 mitogen-activated protein kinase signaling pathway was activated in the limbal corneal epithelium of SDE rats. The abnormal differentiation and stemness loss in the corneal epithelium could be reversed upon treatment with a p38 inhibitor in a SDE in vivo model and in vitro hyperosmolar corneal epithelial culture conditions. These data suggest that SDE can lead to limbal stem cell dysfunction, and p38 mitogen-activated protein kinase signaling pathway activation plays an essential role in this process.

The Role of Ectodysplasin A on the Ocular Surface Homeostasis.

Ectodysplasin A (EDA), a ligand of the TNF family, plays an important role in maintaining the homeostasis of the ocular surface. EDA is necessary for the development of the meibomian gland, the lacrimal gland, as well as the proliferation and barrier function of the corneal epithelium. The mutation of EDA can induce the destruction of the ocular surface resulting in keratopathy, abnormality of the meibomian gland and maturation of the lacrimal gland. Experimental animal studies showed that a prenatal ultrasound-guided intra-amniotic injection or postnatal intravenous administration of soluble recombinant EDA protein can efficiently prevent the development of ocular surface abnormalities in EDA mutant animals. Furthermore, local application of EDA could restore the damaged ocular surface to some extent. Hence, a recombinant EDA-based therapy may serve as a novel paradigm to treat ocular surface disorders, such as meibomian gland dysfunction and corneal epithelium abnormalities.

A spectroscopic study of solvent effects on the formation of Cu(ii)-chloride complexes in aqueous solution.

A combination of electronic (UV-vis) and X-ray absorption (EXAFS, XANES) spectroscopies has been used to investigate the formation of copper(ii)/chloride complexes in concentrated aqueous solutions. It is established that lowering the water activity by the addition of Mg(ClO4)2 at a constant Cl-/Cu(ii) ratio results in the replacement of water molecules by Cl- ions in the primary coordination shell of Cu(ii). This behavior closely parallels the effect of increasing the Cl-/Cu(ii) ratio and demonstrates that full understanding of the stoichiometry and structures of the complexes formed in concentrated metal-ion chloride solutions requires explicit consideration of the role of the solvent.

High volumetric capacity silicon-based lithium battery anodes by nanoscale system engineering.

The nanostructuring of silicon (Si) has recently received great attention, as it holds potential to deal with the dramatic volume change of Si and thus improve lithium storage performance. Unfortunately, such transformative materials design principle has generally been plagued by the relatively low tap density of Si and hence mediocre volumetric capacity (and also volumetric energy density) of the battery. Here, we propose and demonstrate an electrode consisting of a textured silicon@graphitic carbon nanowire array. Such a unique electrode structure is designed based on a nanoscale system engineering strategy. The resultant electrode prototype exhibits unprecedented lithium storage performance, especially in terms of volumetric capacity, without the expense of compromising other components of the battery. The fabrication method is simple and scalable, providing new avenues for the rational engineering of Si-based electrodes simultaneously at the individual materials unit scale and the materials ensemble scale.

Vitreous Olink proteomics reveals inflammatory biomarkers for diagnosis and prognosis of traumatic proliferative vitreoretinopathy.

Background: The aim of this study was to identify inflammatory biomarkers in traumatic proliferative vitreoretinopathy (TPVR) patients and further validate the expression curve of particular biomarkers in the rabbit TPVR model. Methods: The Olink Inflammation Panel was used to compare the differentially expressed proteins (DEPs) in the vitreous of TPVR patients 7-14 days after open globe injury (OGI) (N = 19) and macular hole patients (N = 22), followed by correlation analysis between DEPs and clinical signs, protein-protein interaction (PPI) analysis, area under the receiver operating characteristic curve (AUC) analysis, and function enrichment analysis. A TPVR rabbit model was established and expression levels of candidate interleukin family members (IL-6, IL-7, and IL-33) were measured by enzyme-linked immunosorbent assay (ELISA) at 0, 1, 3, 7, 10, 14, and 28 days after OGI. Results: Forty-eight DEPs were detected between the two groups. Correlation analysis showed that CXCL5, EN-RAGE, IL-7, ADA, CD5, CCL25, CASP8, TWEAK, and IL-33 were significantly correlated with clinical signs including ocular wound characteristics, PVR scoring, PVR recurrence, and final visual acuity (R = 0.467-0.699, p < 0.05), and all with optimal AUC values (0.7344-1). Correlations between DEP analysis and PPI analysis further verified that IL-6, IL-7, IL-8, IL-33, HGF, and CXCL5 were highly interactive (combined score: 0.669-0.983). These DEPs were enriched in novel pathways such as cancer signaling pathway (N = 14, p < 0.000). Vitreous levels of IL-6, IL-7, and IL-33 in the rabbit TPVR model displayed consistency with the trend in Olink data, all exhibiting marked differential expression 1 day following the OGI. Conclusion: IL-7, IL-33, EN-RAGE, TWEAK, CXCL5, and CD5 may be potential biomarkers for TPVR pathogenesis and prognosis, and early post-injury may be an ideal time for TPVR intervention targeting interleukin family biomarkers.

Applying Resistant Starch to Improve the Gel and Water Retention of Reduced-Fat Pork Batter.

Emulsified meat products contain high animal fat content, and excessive intake of animal fat is not good for health, so people are paying more and more attention to reduced-fat meat products. This study investigated the impact of varying proportions of pork back-fat and/or resistant starch on the proximate composition, water and fat retention, texture properties, color, and rheology characteristic of pork batter. The results found that replacing pork back-fat with resistant starch and ice water significantly decreased the total lipid and energy contents of cooked pork batter (p < 0.05) while improving emulsion stability, cooking yield, texture, and rheology properties. Additionally, when the pork back-fat replacement ratio was no more than 50%, there was a significant increase in emulsion stability, cooking yield, hardiness, springiness, cohesiveness, chewiness, and L* and G' values (p < 0.05). Furthermore, resistant starch and ice water enhanced myosin head and tail thermal stability and increased G' value at 80 °C. However, the initial relaxation times significantly decreased (p < 0.05) and the peak ratio of P21 significantly increased from 84.62% to 94.03%, suggesting reduced fluidity of water. In conclusion, it is feasible to use resistant starch and ice water as a substitute for pork back-fat in order to produce reduced-fat pork batter with favorable gel and rheology properties.

Honeycomb-Inspired Surface-Enhanced Raman Scattering Microarray for Large-Area Automated Testing of Urease in Saliva Samples.

Surface-enhanced Raman scattering (SERS) technology, as an important analytical tool, has been widely applied in the field of chemical and biomedical sensing. Automated testing is often combined with biochemical analysis technologies to shorten the detection time and minimize human error. The present SERS substrates for sample detection are time-consuming and subject to high human error, which are not conducive to the combination of SERS and automated testing. Here, a novel honeycomb-inspired SERS microarray is designed for large-area automated testing of urease in saliva samples to shorten the detection time and minimize human error. The honeycomb-inspired SERS microarray is decorated with hexagonal microwells and a homogeneous distribution of silver nanostars. Compared with the other four common SERS substrates, the optimal honeycomb-inspired SERS microarray exhibits the best SERS performance. The RSD of 100 SERS spectra continuously collected from saliva samples is 6.56%, and the time of one detection is reduced from 5 min to 10 s. There is a noteworthy linear relationship with a R2 of 0.982 between SERS intensity and urease concentration, indicating the quantitative detection capability of the urease activity in saliva samples. The honeycomb-inspired SERS microarray, combined with automated testing, provides a new way in which SERS technology can be widely used in biomedical applications.

Fragment-Fusion Transformer: Deep Learning-Based Discretization Method for Continuous Single-Cell Raman Spectral Analysis.

Raman spectroscopy has become an important single-cell analysis tool for monitoring biochemical changes at the cellular level. However, Raman spectral data, typically presented as continuous data with high-dimensional characteristics, is distinct from discrete sequences, which limits the application of deep learning-based algorithms in data analysis due to the lack of discretization. Herein, a model called fragment-fusion transformer is proposed, which integrates the discrete fragmentation of continuous spectra based on their intrinsic characteristics with the extraction of intrafragment features and the fusion of interfragment features. The model integrates the intrinsic feature-based fragmentation of spectra with transformer, constructing the fragment transformer block for feature extraction within fragments. Interfragment information is combined through the pyramid design structure to improve the model's receptive field and fully exploit the spectral properties. During the pyramidal fusion process, the information gain of the final extracted features in the spectrum has been enhanced by a factor of 9.24 compared to the feature extraction stage within the fragment, and the information entropy has been enhanced by a factor of 13. The fragment-fusion transformer achieved a spectral recognition accuracy of 94.5%, which is 4% higher compared to the method without fragmentation and fusion processes on the test set of cell Raman spectroscopy identification experiments. In comparison to common spectral classification models such as KNN, SVM, logistic regression, and CNN, fragment-fusion transformer has achieved 4.4% higher accuracy than the best-performing CNN model. Fragment-fusion transformer method has the potential to serve as a general framework for discretization in the field of continuous spectral data analysis and as a research tool for analyzing the intrinsic information within spectra.

An antifouling supramolecular polymer ophthalmic ointment alleviates symblepharon in rat alkali burn eyes.

Symblepharon is an adverse ocular disease resulting in ocular discomfort and impaired vision, severely dragging down a patient's quality of life. Due to the specificity of the ocular surface, the retention time of drugs on it is short, leading to limited therapeutic effects for ocular diseases. Therefore, it is imperative to design a novel drug delivery system, which can not only prolong the retention time of a drug but also play an anti-fibrosis role in symblepharon. Herein, an antifouling supramolecular polymer ophthalmic ointment consisting of poly(N-acryloyl alaninamide) (PNAAA), vitamin C (VitC) and levofloxacin (Levo) was developed (termed PNAVL ophthalmic ointment), which acted as a mucoadhesive and long-acting ocular delivery system. This antifouling PNAVL ophthalmic ointment improved the retention time of VitC and Levo, and simultaneously provided anti-inflammation and anti-fibrosis effects for mitigating symblepharon after ocular alkali burn injury.

The Facile Three-Dimensional Printing of the Composite of Copper Nanosized Powder and Micron Powder with Enhanced Properties.

Three-dimensional (3D) printing of Cu items is a new way to build up the structured Cu materials, but 3D printing of Cu items is usually a challenge because of the high melting point, high thermal conductivity, and high light reflection rate of Cu material. In this study, the composite of Cu microspheres powder and Cu nanoparticles (micro/nano Cu powder) is used to realize the 3D printing of Cu items with the selective laser melting technology. The sintering temperature and the thermal conductivity of micro/nano Cu powder are evidently decreased due to Cu nanoparticles' addition in the micron Cu powder. The results reveal that the 3D printing of 50%/50% micro/nano Cu powder needs laser power range of 100-240 W, which is in contrast to 200-340 W for 3D printing of 100% Cu microspheres powder. Furthermore, the conductivity, mechanical strength, and density of 3D-printed Cu items are improved with the addition of Cu nanoparticles into the micron Cu powder. The increasement of 34% on electrical conductivity and 17% on tensile strength are reached by the addition of 50% Cu nanoparticles with the laser power of 240 W.

Lifetime over 10000 hours for organic solar cells with Ir/IrOx electron-transporting layer.

The stability of organic solar cells is a key issue to promote practical applications. Herein, we demonstrate that the device performance of organic solar cells is enhanced by an Ir/IrOx electron-transporting layer, benefiting from its suitable work function and heterogeneous distribution of surface energy in nanoscale. Notably, the champion Ir/IrOx-based devices exhibit superior stabilities under shelf storing (T80 = 56696 h), thermal aging (T70 = 13920 h), and maximum power point tracking (T80 = 1058 h), compared to the ZnO-based devices. It can be attributed to the stable morphology of photoactive layer resulting from the optimized molecular distribution of the donor and acceptor and the absence of photocatalysis in the Ir/IrOx-based devices, which helps to maintain the improved charge extraction and inhibited charge recombination in the aged devices. This work provides a reliable and efficient electron-transporting material toward stable organic solar cells.

Design, Synthesis, and Biological Evaluation of Novel Thioureidobenzamide (TBA) Derivatives as HBV Capsid Assembly Modulators.

Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a promising therapeutic approach for the treatment of HBV infection. In this study, we designed and synthesized five series of benzamide derivatives based on a multisite-binding strategy at the tolerant region and diversity modification in the solvent-exposed region. Among them, thioureidobenzamide compound 17i exhibited significantly increased anti-HBV activity in HepAD38 (EC50 = 0.012 µM) and HBV-infected HLCZ01 cells (EC50 = 0.033 µM). Moreover, 17i displayed a better inhibitory effect on the assembly of HBV capsid protein compared with NVR 3-778 and a inhibitory effect similar to the clinical drug GLS4. In addition, 17i showed moderate metabolic stability in human microsomes, had excellent oral bioavailability in Sprague-Dawley (SD) rats, and inhibited HBV replication in the HBV carrier mice model, which could be considered as a promising candidate drug for further development.

High-efficiency and room-temperature reduction of graphene oxide: a facile green approach towards flexible graphene films.

A novel, green, and highly efficient strategy for room-temperature reduction of solid-state graphene oxide films has been successfully developed using hydrogen-involved reduction with the assistance of a small amount of Pd catalyst. Based on this approach, flexible reduced graphene oxide films with high conductivity can be achieved and a roll-to-roll technique is expected.

Crosslinking-Induced Corneal Endothelium Dysfunction and Its Protection by Topical Ripasudil Treatment.

PURPOSE: To investigate the changes of corneal endothelium under different crosslinking conditions and the protective effect of ripasudil. METHODS: Corneal crosslinking groups were infiltrated with riboflavin and subsequently irradiated with 0.54 J/cm2 or 1.08 J/cm2 UVA, while noncrosslinking groups included neither UVA nor riboflavin treatment, only 1.08 J/cm2 UVA and only riboflavin treatment. Corneal opacity, variations in corneal endothelial cells, and corneal thickness of all groups were observed by slit lamp, in vivo confocal microscopy, and optical coherence tomography. Immunofluorescence staining and scanning electron microscopy were performed to evaluate changes in the structure and function of the corneal endothelium. The mice that received a corneal crosslinking dose of 1.08 J/cm2 were instilled with ripasudil to explore its protective effect on the corneal endothelium. RESULTS: Treatment with UVA and riboflavin caused an increase in corneal opacity and corneal thickness and decreased endothelial cell density. Furthermore, treatment with UVA and riboflavin caused endothelial cell DNA damage and destroyed the tight junction and pump function of the endothelium, while riboflavin or the same dose of UVA alone did not affect the endothelium. Ripasudil reduced DNA damage in endothelial cells, increased the density of cells, and protected the endothelium's integrity and function. CONCLUSION: Riboflavin combined with UVA can damage the corneal endothelium's normal functioning. The corneal endothelium's wound healing is dose-dependent, and the ROCK inhibitor ripasudil maintains the endothelium's pump and barrier functions.

Ovalbumin-Induced Allergic Inflammation Diminishes Cross-Linked Collagen Structures in an Experimental Rabbit Model of Corneal Cross-Linking.

Background: Allergic conjunctivitis (AC) is one of the reported potential risk factors of progression in keratoconus patients after corneal cross-linking surgery; however, the causal relationship is still inconclusive. Recent studies have indicated that various inflammatory cytokines play a vital role in the development of primary keratoconus. It is still unclear whether these inflammatory mediators also trigger CXL failures. This study aimed to investigate the impact of AC on the rabbit corneas after trans-epithelial corneal cross-linking (TCXL). Methods: A total of six rabbits were kept untreated as the normal control (NC) group. A total of 18 rabbits were treated by TCXL and divided into three groups (six in each group), namely, no treatment (TCXL group); induction of AC (TCXL + AC group); and induction of AC plus topical prednisolone acetate (TCXL + AC + PA group), according to additional treatment. AC was induced by topical application of ovalbumin after intraperitoneal pre-sensitization with ovalbumin. Rabbits were evaluated by slit lamp, in vivo laser scanning confocal microscopy, anterior segment optical coherence tomography, and measurement of corneal biomechanics. The cornea specimens were collected for the transmission electron microscope, the collagenase I digestion test, and PCR assay for TNF-α, IL-6, IL-1ß, matrix metalloproteinase 9 (MMP-9), lysyl oxidase (LOX), and tissue inhibitor of metalloproteinases 1 (TIMP-1) on the day (D) 28. Results: On D28, the TNF-α, IL-6, IL-1ß, MMP-9, and LOX levels were significantly increased while the TIMP-1 was decreased in the TCXL + AC group when compared with the TCXL and TCXL + AC + PA groups. In vivo confocal microscopy revealed that at a depth of 150-210 µm, a trabecular patterned hyperdense structure surrounded by elongated needle-like processes could be observed in the TCXL and TCXL + AC + PA groups, but hardly seen in the TCXL + AC group. The demarcation lines were indistinct and blurred in the TCXL + AC group. An electron microscope demonstrated less interlacing fibril lamellae and higher interfibrillar spacing in the TCXL + AC group. The stability of corneal biomechanics and resistance to collagenase were decreased in the TCXL + AC group. Conclusion: The corneal microstructures induced by TCXL and biomechanical stability were diminished in rabbits with AC but could be maintained by topical anti-inflammatory treatment. Our results supported the causal relationship between altered cytokine profiles and corneal microstructure after primary corneal cross-linking.

General Strategy toward Hydrophilic Single Atom Catalysts for Efficient Selective Hydrogenation.

Well dispersible and stable single atom catalysts (SACs) with hydrophilic features are highly desirable for selective hydrogenation reactions in hydrophilic solvents towards important chemicals and pharmaceutical intermediates. A general strategy is reported for the fabrication of hydrophilic SACs by cation-exchange approach. The cation-exchange between metal ions (M = Ni, Fe, Co, Cu) and Na+ ions introduced in the skeleton of metal oxide (TiO2 or ZrO2 ) nanoshells plays the key role in forming M1 /TiO2 and M1 /ZrO2 SACs, which efficiently prevents the aggregation of the exchanged metal ions. The as-obtained SACs are highly dispersible and stable in hydrophilic solvents including alcohol and water, which greatly facilitates the catalysis reaction in alcohol. The Ni1 /TiO2 SACs have been successfully utilized as catalysts for the selective C=C hydrogenation of cinnamaldehyde to produce phenylpropanal with 98% conversion, over 90% selectivity, good recyclability, and a turnover frequency (TOF) of 102 h-1 , overwhelming most reported catalysts including noble metal catalysts.

Hyperglycemia Induces Meibomian Gland Dysfunction.

Purpose: Patients diagnosed with diabetes are inclined to have abnormalities on stability of tear film and disorder of meibomian gland (MG). This study aims to explore the pathological change of MG induced by diabetes in a rat model. Methods: Sprague-Dawley (SD) rats were intraperitoneally injected with streptozotocin (STZ) to establish a diabetic animal model. Lipid accumulation in MG was detected by Oil Red O staining and LipidTox staining. Cell proliferation status was determined by Ki67 and P63 immunostaining, whereas cell apoptosis was confirmed by TUNEL assay. Gene expression of inflammatory cytokines and adhesion molecules IL-1α, IL-1ß, ELAM1, ICAM1, and VCAM1 were detected by RT-PCR. Activation of ERK, NF-κB, and AMPK signaling pathways was determined by Western Blot analysis. Oxidative stress-related factors NOX4, 4HNE, Nrf2, HO-1, and SOD2 were detected by immunostaining or Western Blot analysis. Tom20 and Tim23 immunostaining and transmission electron microscopy were performed to evaluate the mitochondria functional and structure change. Results: Four months after STZ injection, there was acini dropout in MG of diabetic rats. Evident infiltration of inflammatory cells, increased expression of inflammatory factors, and adhesion molecules, as well as activated ERK and NF-κB signaling pathways were identified. Oxidative stress of MG was evident in 4-month diabetic rats. Phospho-AMPK was downregulated in MG of 2-month diabetic rats and more prominent in 4-month rats. After metformin treatment, phospho-AMPK was upregulated and the morphology of MG was well maintained. Moreover, inflammation and oxidative stress of MG were alleviated after metformin intervention. Conclusions: Long-term diabetes may lead to Meibomian gland dysfunction (MGD). AMPK may be a therapeutic target of MGD induced by diabetes.

Downregulation of p38 MAPK Signaling Pathway Ameliorates Tissue-Engineered Corneal Epithelium.

Tissue-engineered corneal epithelium transplantation is effective treatment for severe limbal stem cell deficiency (LSCD), while epithelial terminal differentiation, tans-differentiation, and insufficient stem cell during construction affect the quality of tissue-engineered corneal epithelium. In this study, we applied SB203580 in the culture medium to downregulate the p38 mitogen-activated protein kinase (MAPK) signaling pathway during construction of tissue-engineered corneal epithelium. With application of SB203580, tissue-engineered corneal epithelium showed enhanced strength and condensed structure. The expression of progenitor cell markers ATP-binding cassette sub-family G member 2, tumor protein p63, keratin 14, and Wnt family member 7A was increased, differentiation markers keratin 12, paired box 6, keratin 10, and keratin 13 and trans-differentiation markers actin alpha 2, smooth muscle and snail family transcriptional repressor 1 was decreased, while cell junction markers claudin 1 and cadherin 1 was increased in the tissue-engineered corneal epithelium. The Wnt/catenin beta 1 signaling pathway was upregulated in the epithelium after p38 MAPK inhibition. Transplantation of tissue-engineered corneal epithelium treated with SB203580 to rabbit LSCD model showed faster wound healing and improved epithelial quality. We conclude that downregulation of p38 MAPK signaling pathway helps maintain the stemness and prevent terminal differentiation and abnormal differentiation of corneal epithelial cells during epithelium construction process, and thus can improve the quality of tissue-engineered corneal epithelium. Impact statement Downregulation of p38 MAPK signaling pathway helps maintain the self-renewal of limbal stem cells and prevents terminal differentiation and abnormal differentiation of corneal epithelial cells. Small molecules modulating p38 MAPK signaling pathway ameliorate tissue-engineered corneal epithelium.

Pt@polydopamine nanoparticles as nanozymes for enhanced photodynamic and photothermal therapy.

Polydopamine nanoparticles were used to stabilize a nano-Pt catalyst to relieve tumour hypoxia in photodynamic therapy (PDT). Polydopamine not only provides a platform for carrying nano-Pt and photosensitizers but is also used as a photothermal reagent for photothermal therapy (PTT). The system presented an enhanced anti-tumor therapy effect through a combined PDT and PTT mechanism.