The measurement and correlation analysis of scleral and choroid thickness in branch retinal vein occlusion.

To use Optical Coherence Tomography (OCT) to measure scleral thickness (ST) and subfoveal choroid thickness (SFCT) in patients with Branch Retinal Vein Occlusion (BRVO) and to conduct a correlation analysis. A cross-sectional study was conducted. From May 2022 to December 2022, a total of 34 cases (68 eyes) of untreated unilateral Branch Retinal Vein Occlusion (BRVO) patients were recruited at the Affiliated Eye Hospital of Nanchang University. Among these cases, 31 were temporal branch vein occlusions, 2 were nasal branch occlusions, and 1 was a superior branch occlusion. Additionally, 39 cases (39 eyes) of gender- and age-matched control eyes were included in the study. Anterior Segment Optical Coherence Tomography (AS-OCT) was used to measure ST at 6 mm superior, inferior, nasal, and temporal to the limbus, while Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) was used to measure SFCT. The differences in ST and SFCT between the affected eye, contralateral eye, and control eye of BRVO patients were compared and analyzed for correlation. The axial lengths of the BRVO-affected eye, contralateral eye, and control group were (22.92 ± 0.30) mm, (22.89 ± 0.32) mm and (22.90 ± 0.28) mm respectively, with no significant difference in axial length between the affected eye and contralateral eye (P > 0.05). The SFCT and ST measurements in different areas showed significant differences between the BRVO-affected eye, contralateral eye in BRVO patients (P < 0.05). The CRT of BRVO-affected eyes was significantly higher than that of the contralateral eyes and the control eyes (P < 0.001). In comparison between BRVO-affected eyes and control eyes, there were no statistically significant differences in age and axial length between the two groups (P > 0.05). However, significant differences were observed in SFCT and temporal, nasal, superior, and inferior ST between the two groups (P < 0.05). The difference in temporal ST between the contralateral eyes and the control eyes was not statistically significant (t = - 0.35, P = 0.73). However, the contralateral group showed statistically significant increases in SFCT, nasal, superior and inferior ST compared to control eyes (t = - 3.153, 3.27, 4.21, 4.79, P = 0.002, 0.002, < 0.001, < 0.001). However, the difference between the CRT of the contralateral and control eyes was not statistically significant (P = 0.421). When comparing SFCT and ST between BRVO-affected eyes with and without macular edema, no statistically significant differences were found (t = - 1.10, 0.45, - 1.30, - 0.30, 1.00; P = 0.28, 0.66, 0.21, 0.77, 0.33). The thickness of SFCT and temporal ST in major BRVO group is higher than the macular BRVO group and the difference was statistically significant (t = 6.39, 7.17, P < 0.001 for all). Pearson correlation analysis revealed that in BRVO patients, there was a significant positive correlation between SFCT/CRT and temporal ST (r = 0.288, 0.355, P = 0.049, 0.04). However, there was no correlation between SFCT/CRT and nasal ST, superior ST, and inferior ST (P > 0.05). In BRVO patients, both SFCT/CRT and ST increase, and there is a significant correlation between SFCT/CRT and the ST at the site of vascular occlusion.

Single-Molecule Cross-Plane Conductance of Polycyclic Aromatic Hydrocarbon Derivatives.

In the cross-plane single-molecule junctions, the correlation between molecular aromaticity and conductance remained puzzling. Cross-plane break junction (XPBJ) provides new insight into understanding the role of aromaticity and conjugation to molecules on charge transport through the planar molecules. In this work, we investigated the modulation of cross-plane charge transport in pyrene derivatives by hydrogenation and substituents based on the XPBJ method that differs from those used in-plane transport. We measured the electrical conductance of the hydrogenated derivatives of the pyrenes and found that hydrogenation reduces conductance, and the fully hydrogenated molecule has the lowest conductance. Conductance of pyrene derivatives increased after substitution by both electron-donating and electron-withdrawing groups. By calculating, the trend in decreased conductance of hydrogenated pyrene was found to be consistent with the change in aromaticity. Electron-withdrawing substituents reduce the aromaticity of the molecule and narrow the HOMO-LUMO gap, while electron-donating groups increase the aromaticity but also narrow the gap. Our work reveals the potential of fine-tuning the structure of the pyrene molecule to control the cross-plane charge transport through the single-molecule junctions.

Regulating the Electrode-Electrolyte Interfaces of Lithium-High Nickel Batteries via a Multifunctional Additive.

Lithium metal batteries with high nickel ternary (LiNixCoyMn1-x-yO2, x ≥ 0.8) as the cathode hold the promise to meet the demand of next-generation high energy density batteries. However, the unsatisfactory stability of electrode-electrolyte interfaces limits their practical applications. In this work, N-methyl-N-trimethylsilyltrifluoroacetamide (NMTFA) is suggested as a new functional electrolyte additive to stabilize the Li∥LiNi0.9Co0.05Mn0.05O2 chemistry by forming robust and effective electrode-electrolyte interphases, namely the anode-electrolyte interphase (AEI, or conventionally called SEI) and cathode-electrolyte interphase (CEI). The NMTFA-derived SEI/CEI greatly enhances the battery performance that a capacity retention of 82.1% after 200 cycles at 1C charge/discharge is achieved, significantly higher than that without NMTFA addition (52.5%). Moreover, the NMTFA also improves the thermal stability of the electrolyte and inhibits the hydrolysis of LiPF6. This work provides new clues for the optimization of electrolyte formulation for lithium-high nickel batteries through modulating interfaces.

Highly Reversible Molecular Photoswitches with Transition Metal Dichalcogenides Electrodes.

The molecule-electrode coupling plays an essential role in photoresponsive devices with photochromic molecules, and the strong coupling between the molecule and the conventional electrodes leads to/ the quenching effect and limits the reversibility of molecular photoswitches. In this work, we developed a strategy of using transition metal dichalcogenides (TMDCs) electrodes to fabricate the thiol azobenzene (TAB) self-assembled monolayers (SAMs) junctions with the eutectic gallium-indium (EGaIn) technique. The current-voltage characteristics of the EGaIn/GaOx //TAB/TMDCs photoswitches showed an almost 100% reversible photoswitching behavior, which increased by ∼28% compared to EGaIn/GaOx //TAB/AuTS photoswitches. Density functional theory (DFT) calculations showed the coupling strength of the TAB-TMDCs electrode decreased by 42% compared to that of the TAB-AuTS electrode, giving rise to improved reversibility. our work demonstrated the feasibility of 2D TMDCs for fabricating SAMs-based photoswitches with unprecedentedly high reversibility.

Identification of Balanol As a Potential Inhibitor of PAK1 That Induces Apoptosis and Cytoprotective Autophagy in Colorectal Cancer Cells.

Colorectal cancer (CRC) is a common malignancy of the gastrointestinal tract, often accompanied by poor prognosis and high incidence and mortality. p21 activated kinases (PAKs) have been used as therapeutic targets because of their central role in many oncogenic signaling networks. By exploring tumor databases, we found that PAK1 overexpression is associated with poor prognosis in colorectal cancer, and therefore, PAK1-targeted inhibition is a new potential therapeutic strategy for colorectal cancer. We identified that Balanol (compound 6, DB04098) can effectively target PAK1 by high-throughput virtual screening. In vitro, compound 6 exhibited favorable PAK1 inhibition with potent anti-proliferative and anti-migration activity in SW480 cells. Additionally, we also found that compound 6 induced apoptosis and cytoprotective autophagy in SW480 cells. Together, these results indicate that compound 6 is a potential novel PAK1 inhibitor, which would be utilized as a candidate compound for future CRC treatment.

Atomically well-defined nitrogen doping for cross-plane transport through graphene heterojunctions.

The nitrogen doping of graphene leads to graphene heterojunctions with a tunable bandgap, suitable for electronic, electrochemical, and sensing applications. However, the microscopic nature and charge transport properties of atomic-level nitrogen-doped graphene are still unknown, mainly due to the multiple doping sites with topological diversities. In this work, we fabricated atomically well-defined N-doped graphene heterojunctions and investigated the cross-plane transport through these heterojunctions to reveal the effects of doping on their electronic properties. We found that a different doping number of nitrogen atoms leads to a conductance difference of up to ∼288%, and the conductance of graphene heterojunctions with nitrogen-doping at different positions in the conjugated framework can also lead to a conductance difference of ∼170%. Combined ultraviolet photoelectron spectroscopy measurements and theoretical calculations reveal that the insertion of nitrogen atoms into the conjugation framework significantly stabilizes the frontier molecular orbitals, leading to a change in the relative positions of the HOMO and LUMO to the Fermi level of the electrodes. Our work provides a unique insight into the role of nitrogen doping in the charge transport through graphene heterojunctions and materials at the single atomic level.

Predictive model of chemotherapy-related toxicity in elderly Chinese cancer patients.

Purpose: Older cancer patients are more likely to develop and die from chemotherapy-related toxicity. However, evidence on drug safety and optimal effective doses is relatively limited in this group. The aim of this study was to develop a tool to identify elderly patients vulnerable to chemotherapy toxicity. Patients and methods: Elderly cancer patients ≥60 years old who visited the oncology department of Peking Union Medical College Hospital between 2008 and 2012 were included. Each round of chemotherapy was regarded as a separate case. Clinical factors included age, gender, physical status, chemotherapy regimen and laboratory tests results were recorded. Severe (grade ≥3) chemotherapy-related toxicity of each case was captured according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Univariate analysis was performed by chi-square statistics to determine which factors were significantly associated with severe chemotherapy toxicity. Logistic regression was used to build the predictive model. The prediction model was validated by calculating the area under the curve of receiver operating characteristic (ROC). Results: A total of 253 patients and 1,770 cases were included. The average age of the patients was 68.9 years. The incidence of grade 3-5 adverse events was 24.17%. Cancer type (non-GI cancers), BMI<20 kg/m2, KPS<90%, severe comorbidity, polychemotherapy, standard dose chemotherapy, low white blood cells count, anemia, low platelet cells count, low creatine level and hypoalbuminemia were associated with severe chemotherapy-related toxicity. We used these factors to construct a chemotherapy toxicity prediction model and the area under the ROC curve was 0.723 (95% CI, 0.687-0.759). Risk of toxicity increased with higher risk score (11.98% low, 31.51% medium, 70.83% high risk; p < 0.001). Conclusion: We constructed a predictive model of chemotherapy toxicity in elderly cancer patients based on a Chinese population. The model can be used to guide clinicians to identify vulnerable population and adjust treatment regimens accordingly.

A van der Waals heterojunction strategy to fabricate layer-by-layer single-molecule switch.

Single-molecule electronics offer a unique strategy for the miniaturization of electronic devices. However, the existing experiments are limited to the conventional molecular junctions, where a molecule anchors to the electrode pair with linkers. With such a rod-like configuration, the minimum size of the device is defined by the length of the molecule. Here, by incorporating a single molecule with two single-layer graphene electrodes, we fabricated layer-by-layer single-molecule heterojunctions called single-molecule two-dimensional van der Waals heterojunctions (M-2D-vdWHs), of which the sizes are defined by the thickness of the molecule. We controlled the conformation of the M-2D-vdWHs and the cross-plane charge transport through them with the applied electric field and established that they can serve as reversible switches. Our results demonstrate that the M-2D-vdWHs, as stacked from single-layer 2D materials and a single molecule, can respond to electric field stimulus, which promises a diverse class of single-molecule devices with unprecedented size.

Unraveling the therapeutic potential of carbamoyl phosphate synthetase 1 (CPS1) in human diseases.

CPS1, the rate-limiting enzyme that controls the first reaction of the urea cycle, is responsible for converting toxic ammonia into non-toxic urea in mammals. While disruption of the functions of CPS1 leads to elevated ammonia and nerve damage in the body, mainly manifested as urea cycle disorder. Moreover, accumulating evidence has recently revealed that CPS1 is involved in a variety of human diseases, including CPS1D, cardiovascular disease, cancers, and others. In particular, CPS1 expression varies among cancers, being overexpressed in some cancers and downregulated in others, suggesting that CPS1 may be a promising cancer therapeutic target. In addition, some small-molecule inhibitors of CPS1 have been reported, which have not been confirmed experimentally in malignancies, meaning their future role is far from certain. In this review, we describe the structure and function of CPS1, highlight its important roles in various human diseases, and further discuss the potential diagnostic and therapeutic implications of small molecule compounds targeting CPS1.

Identification of lncRNAs Associated with the Pathogenesis of Diabetic Retinopathy: From Sequencing Analysis to Validation via In Vivo and In Vitro Experiments.

This study is aimed at screening for differentially expressed long noncoding RNAs (lncRNAs) associated with the pathogenesis of diabetic retinopathy and verifying the role of lncZNRD1 in high glucose-induced injury of retinal microvascular endothelial cells. The retinal tissues of normal and diabetic rats were collected for high-throughput sequencing of differentially expressed lncRNAs. Retinal microvascular endothelial cells were treated with 50 mM glucose for 4 h, 8 h, 24 h, 48 h, and 72 h. Our results showed that compared with the control group, there were 736 differentially expressed lncRNAs in the retina tissue of the model group, including 226 upregulated genes and 736 downregulated genes. Based on the differentially expressed lncRNAs, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the ErbB signaling pathway, transforming growth factor- (TGF-) ß signaling pathway, PI3K - Akt signaling pathway, cyclic adenosine 3,5-monophosphate (cAMP) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and hypoxia-inducible factor-1 (HIF-1) signaling pathway were likely involved in the regulation of diabetic retinopathy. Compared with the control group, the expression of lncZNRD1-AS1 was significantly increased in retinal microvascular endothelial cells after treatment with high glucose for 24 h. Silencing lncZNRD1 promoted high glucose-induced apoptosis of microvascular endothelial cells. Additionally, silencing lncZNRD1 increased the expression levels of ALDH7A1 and ALDH3A2. In conclusion, lncZNRD1-AS1 demonstrated potentially beneficial function against high glucose-induced retina cell injury by regulating ALDH7A1 and ALDH3A2 expressions.

Drp1 knockdown represses apoptosis of rat retinal endothelial cells by inhibiting mitophagy.

Diabetic retinopathy (DR) is the leading clinical cause of blindness in diabetic patients. Mitophagy participates in the pathogenesis of DR. Dynamin related protein 1 (Drp1) is associated with mitophagy. Here, we investigated whether Drp1 can regulate mitophagy to affect the progression of DR. We constructed DR rat model by administration of streptozocin. Primary rat retinal endothelial cells (RECs) were treated with high glucose (HG) as a DR cell model. Drp1 was highly expressed in the retinal tissues of DR rats and HG-treated RECs. Drp1 knockdown inhibited HG-mediated increase of reactive oxygen species (ROS) levels and apoptosis in RECs. Moreover, Drp1 silencing inhibited the expression of autophagy-related proteins LC3-II/LC3-1 and Beclin-1 and reduced LC3 puncta in HG-treated RECs. The expression of mitochondrial marker Tom20 was reduced and the levels of mitophagy were increased in the HG-treated RECs, which was rescued by Drp1 silencing. Drp1 knockdown repressed LC3-II expression in HG-treated RECs, indicating that autophagy flux was inhibited. Rapamycin (autophagy activator) enhanced ROS levels and apoptosis in HG-treated RECs by activating autophagy, which was rescued by Drp1 knockdown. In conclusion, these data demonstrated that Drp1 knockdown repressed apoptosis of rat retinal endothelial cells by inhibiting mitophagy. Thus, this work suggests that targeted regulation of Drp1 may become a treatment for DR.

Leaching kinetics and interface reaction of LiNi0.6Co0.2Mn0.2O2 materials from spent LIBs using GKB as reductant.

The application of green reductant is signification to recycling of cathode materials from spent lithium ions batteries. Here, ginkgo biloba was developed for enhancing leaching of spent LiNi0.6Co0.2Mn0.2O2 materials with systematically analysis of leaching kinetics and interface reaction. The leaching efficiencies of Ni, Mn, Co, and Li reach respectively 98.65 %, 98.25 %, 98.41 % and 99.99 % under optimal condition of 1.8 mol/L H2SO4 concentration, 9 g/L ginkgo biloba, 80 °C leaching temperature, 40 min time and 15 g/L pulp density. The apparent activation energies for leaching of Ni, Co, Mn and Li determined as 74.63, 79.33, 73.14 and 23.43 kJ/mol, respectively, indicates that the leaching process was controlled by the surface chemical reaction during the leaching process. Meanwhile, the regenerated material with better electrochemical performance was obtained by co-precipitation and calcination from leachate. Finally, the process is environmental friendly and economical feasible for recycling of spent lithium-ion batteries.

Therapeutic of Candesartan and Music Therapy in Diabetic Retinopathy with Depression in Rats.

This study aimed to investigate the therapeutic effects of candesartan combined with music therapy on diabetic retinopathy with depression and to assess the molecular mechanisms. Associated animal model of diabetes mellitus and depression was established in rats. Pathological changes in the hippocampus were detected by haematoxylin eosin (H&E) staining. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) was used to detect retinal cell apoptosis. Angiotensin II (Ang II) in peripheral blood and neurotransmitters, including serotonin (5-HT), dopamine (DA), and norepinephrine (NE) in the hippocampus, was measured by enzyme linked immunosorbent assay (ELISA). Fluorescence quantitative PCR and western blotting were used to detect the expression of brain-derived neurotrophic factor (BDNF) and c-fos in the hippocampus. Our data showed that chromatin aggregation and cytoplasmic vacuolation were observable in the hippocampal cells of the rats in the model group, while candesartan and music therapy could reduce morphological changes in the hippocampus of diabetic rats with depression. Compared with the control group, the apoptosis of retinal cells was significantly higher, the contents of 5-HT, DA, and NE in the hippocampus were significantly lower, Ang II level in peripheral blood was significantly higher, and the expression of BDNF and c-fos in the hippocampus decreased significantly in the model group. By contrast, candesartan or candesartan + music therapy ameliorated the changes in retina cell apoptosis, reduction of neurotransmitters, increase in AII, and the expression of c-fos and BDNF. Especially, music therapy further improved the effects of candesartan on retina cell apoptosis and neurotransmitter release in diabetic retinopathy rats with depression. In conclusion, candesartan and music therapy have an additive effect in DM with both visual impairment and depression, which might serve a potential alternative treatment for this complex disease.

Intravitreal dexamethasone implant - a new treatment for idiopathic posterior scleritis: A case report.

BACKGROUND: Posterior scleritis is one of the most easily missed and misdiagnosed diseases in ophthalmology. In this case we treated a patient with intravitreal dexamethasone implant that has not been extensively studied before. CASE SUMMARY: A 40-year-old female patient who had anxiety, palpitation, and insomnia presented with eye pain and decreased vision in the left eye. An eye examination indicated that her visual acuity (VA) was 40/100. Her left eye presented conjunctival edema, mild exophthalmos, clear cornea, KP(-), and clear aqueous humor. In the fundus, there was a cinerous retinal protuberance. Ultrasonography showed "T-sign" and no systemic association was detected in laboratory examination. One month after injection of dexamethasone implant, the patient exhibited VA of 20/20, fundus serous retinal detachment disappeared, and intraocular pressure of both eyes was at the normal level. CONCLUSION: Intravitreal injection of dexamethasone implant may be a safe and effective treatment for patients with idiopathic posterior scleritis.

miR-7 Reduces High Glucose Induced-damage Via HoxB3 and PI3K/AKT/mTOR Signaling Pathways in Retinal Pigment Epithelial Cells.

BACKGROUND: Diabetic retinopathy (DR) is a common complication of diabetes. This study investigated the effect of miR-7 in the regulation of cell proliferation via the HoxB3 gene and PI3K/AKT/mTOR signaling pathways in DR. METHODS: Human retinal pigment epithelial cell line (ARPE-19) cultured in normal medium (Control) and high glucose medium (25mM glucose, HG) was transfected with mimics NC (HG+ mimics NC), miR-7 mimics (HG+miR-7 mimics), inhibitor NC (HG+ inhibitor NC), and miR-inhibitor (HG+miR-7 inhibitor). The cells were assayed for viability, apoptosis, and expression of genes. RESULTS: HG reduced cell viability and increased apoptosis. However, miR-7 mimics reduced the apoptosis. PCR results showed that miR-7 was significantly upregulated after transfection with miR-7 mimics. The expression of Hoxb3, mTOR, p-PI3K, and p- AKT was significantly downregulated at mRNA and protein levels after miR-7 mimics transfection, while no difference was observed for PI3K and AKT expression. CONCLUSION: Our findings demonstrate that miR-7 regulates the growth of retinal epithelial cells through various pathways and is a potential therapeutic target for the prevention and treatment of diabetic retinopathy.

Targeting human 8-oxoguanine DNA glycosylase to mitochondria protects cells from high glucose-induced apoptosis.

PURPOSE: Diabetic retinopathy (DR) is a major vision threatening disease mainly induced by high glucose. Despite great efforts were made to explore the etiology of DR, the exact mechanism responsible for its pathogenesis remains elusive. METHODS: In our study, we constructed diabetic rats via Streptozotocin (STZ) injection. TUNEL assay was employed to examine retinal cell apoptosis. The levels of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were analyzed via flow cytometry. The mRNA and protein levels of mitochondrial respiratory chain were investigated by RT-qPCR and western blot. RESULTS: Compared with normal rats, the retinal cell apoptosis rate in diabetic rats was significantly upregulated. What's more, the signals of 8-OHdG and the levels of Cytochrome C in diabetic rats were enhanced; however, the MnSOD signals and NADPH-1 levels were reduced. We investigated the effect of mitochondrialy targeted hOGG1 (MTS-hOGG1) on the primary rRECs under high glucose. Compared with vector-transfected cells, MTS-hOGG1-expressing cells blocked high glucose-induced cell apoptosis, the loss of MMP and the overproduction of ROS. In addition, under high glucose, MTS-hOGG1 transfection blocked the expression of Cytochrome C, but enhanced the expression of cytochrome c oxidase subunit 1 and NADPH-1. CONCLUSIONS: These findings indicated that high glucose induced cell apoptosis by causing the loss of MMP, the overproduction of ROS and mtDNA damage. Targeting DNA repair enzymes hOGG1 in mitochondria partly mitigated the high glucose-induced consequences, which shed new light for DR therapy.