Therapeutic Effects of Hematopoietic Stem Cell Derived From Gene-Edited Mice on ß654-Thalassemia.

ß-thalassemia is an inherited blood disease caused by reduced or inadequate ß-globin synthesis due to ß-globin gene mutation. Our previous study developed a gene-edited mice model (ß654-ER mice) by CRISPR/Cas9-mediated genome editing, targeting both the ßIVS2-654 (C > T) mutation site and the 3' splicing acceptor site at 579 and corrected abnormal ß-globin mRNA splicing in the ß654-thalassemia mice. Herein, we further explored the therapeutic effect of the hematopoietic stem cells (HSCs) from ß654-ER mice on ß-thalassemia by consecutive HSC transplantation. The results indicated that HSC transplantation derived from gene-edited mice can significantly improve the survival rate of mice after lethal radiation doses and effectively achieve hematopoietic reconstruction and long-term hematopoiesis. Clinical symptoms, including hematologic parameters and tissue pathology of transplanted recipients, were significantly improved compared to the non-transplanted ß654 mice. The therapeutic effect of gene-edited HSC transplantation demonstrated no significant difference in hematological parameters and tissue pathology compared with wild-type mouse-derived HSCs. Our data revealed that HSC transplantation from gene-edited mice completely recovered the ß-thalassemia phenotype. Our study systematically investigated the therapeutic effect of HSCs derived from ß654-ER mice on ß-thalassemia and further confirmed the efficacy of our gene-editing approach. Altogether, it provided a reference and primary experimental data for the clinical usage of such gene-edited HSCs in the future.

Correction of Ito in human induced pluripotent stem Cell-derived cardiomyocyte carrying DPP6 mutation in early repolarization syndrome by CRISPR/Cas9 genome editing.

Early repolarization syndrome (ERS) is defined as occurring in patients with early repolarization pattern who have survived idiopathic ventricular fibrillation with clinical evaluation unrevealing for other explanations. The pathophysiologic basis of the ERS is currently uncertain. The objective of the present study was to examine the electrophysiological mechanism of ERS utilizing induced pluripotent stem cells (iPSCs) and CRISPR/Cas9 genome editing. Whole genome sequencing was used to identify the DPP6 (c.2561T > C/p.L854P) variant in four families with sudden cardiac arrest induced by ERS. Cardiomyocytes were generated from iPSCs from a 14-year-old boy in the four families with ERS and an unrelated healthy control subject. Patch clamp recordings revealed more significant prolongation of the action potential duration (APD) and increased transient outward potassium current (Ito) (103.97 ± 18.73 pA/pF vs 44.36 ± 16.54 pA/pF at +70 mV, P < 0.05) in ERS cardiomyocytes compared with control cardiomyocytes. Of note, the selective correction of the causal variant in iPSC-derived cardiomyocytes using CRISPR/Cas9 gene editing normalized the Ito, whereas prolongation of the APD remained unchanged. ERS cardiomyocytes carrying DPP6 mutation increased Ito and lengthen APD, which maybe lay the electrophysiological foundation of ERS.

Serum electrolyte concentrations and risk of atrial fibrillation: an observational and mendelian randomization study.

BACKGROUND: Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase the risk of AF, where the relationship between AF and serum electrolytes remains unclear. METHODS: A total of 15,792 individuals were included in the observational study, with incident AF ascertainment in the Atherosclerosis Risk in Communities (ARIC) study. The Cox regression models were applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for AF based on different serum electrolyte levels. Mendelian randomization (MR) analyses were performed to examine the causal association. RESULTS: In observational study, after a median 19.7 years of follow-up, a total of 2551 developed AF. After full adjustment, participants with serum potassium below the 5th percentile had a higher risk of AF relative to participants in the middle quintile. Serum magnesium was also inversely associated with the risk of AF. An increased incidence of AF was identified in individuals with higher serum phosphate percentiles. Serum calcium levels were not related to AF risk. Moreover, MR analysis indicated that genetically predicted serum electrolyte levels were not causally associated with AF risk. The odds ratio for AF were 0.999 for potassium, 1.044 for magnesium, 0.728 for phosphate, and 0.979 for calcium, respectively. CONCLUSIONS: Serum electrolyte disorders such as hypokalemia, hypomagnesemia and hyperphosphatemia were associated with an increased risk of AF and may also serve to be prognostic factors. However, the present study did not support serum electrolytes as causal mediators for AF development.

SPOCK2 modulates neuropathic pain by interacting with MT1-MMP to regulate astrocytic MMP-2 activation in rats with chronic constriction injury.

BACKGROUND: Neuropathic pain (NP) is a kind of intractable pain. The pathogenesis of NP remains a complicated issue for pain management practitioners. SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 2 (SPOCK2) are members of the SPOCK family that play a significant role in the development of the central nervous system. In this study, we investigated the role of SPOCK2 in the development of NP in a rat model of chronic constriction injury (CCI). METHODS: Sprague-Dawley rats were randomly grouped to establish CCI models. We examined the effects of SPOCK2 on pain hpersensitivity and spinal astrocyte activation after CCI-induced NP. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were used to reflects the pain behavioral degree. Molecular mechanisms involved in SPOCK2-mediated NP in vivo were examined by western blot analysis, immunofluorescence, immunohistochemistry, and co-immunoprecipitation. In addition, we examined the SPOCK2-mediated potential protein-protein interaction (PPI) in vitro coimmunoprecipitation (Co-IP) experiments. RESULTS: We founded the expression level of SPOCK2 in rat spinal cord was markedly increased after CCI-induced NP, while SPOCK2 downregulation could partially relieve pain caused by CCI. Our research showed that SPOCK2 expressed significantly increase in spinal astrocytes when CCI-induced NP. In addition, SPOCK2 could act as an upstream signaling molecule to regulate the activation of matrix metalloproteinase-2 (MMP-2), thus affecting astrocytic ERK1/2 activation and interleukin (IL)-1ß production in the development of NP. Moreover, in vitro coimmunoprecipitation (Co-IP) experiments showed that SPOCK2 could interact with membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP14) to regulate MMP-2 activation by the SPARC extracellular (SPARC_EC) domain. CONCLUSIONS: Research shows that SPOCK2 can interact with MT1-MMP to regulate MMP-2 activation, thus affecting astrocytic ERK1/2 activation and IL-1ß production to achieve positive promotion of NP.

Morphological and phylogenetic analyses reveal a new species of Anthracophyllum (Omphalotaceae, Agaricales) in Zhejiang Province, China.

During the investigations of macrofungi resources in Zhejiang Province, China, an interesting wood rot fungus was collected. Based on morphological and molecular phylogenetic studies, it is described as a new species, Anthracophyllum sinense. A. sinense is characterized by its sessile, charcoal black and pleurotoid pileus, sparse lamellae occasionally branching, clavate basidia with long sterigmata [(3-)6-7(-8) µm], and non-heteromorphous cystidia. A. sinense establishes a separate lineage close to A. archeri and A. lateritium in the phylogenetic tree.

Dielectric Liquid Microlens Array with Tunable Focal Length Based on Microdroplet Array Created via Dip-Coating Method.

A dielectric liquid microlens array (LMA) with a tunable focal length was fabricated by using a microdroplet array generated through the dip-coating method. The process began with treating the octadecyltrichlorosilane (OTS) layer with selective UV/O3 irradiation for 20 min to establish a hydrophilic-hydrophobic patterning surface. The substrate was subsequently immersed in glycerol and then withdrawn at a constant rate to create a microdroplet array. Upon filling the cell with matching oil (SL5267) and placing it within a square array of a 200 µm diameter glycerol microdroplet array, the LMA was produced. The focal length ranged from approximately -0.96 to -0.3 mm within a voltage range of 0 to 60 Vrms. The glycerol microdroplets, characterized by their shapes, sizes, curvatures, and filling factors, can be precisely controlled by designing an OTS patterning or adjusting the dip-coating speed. This approach offers a rapid and high-throughput method for preparation. Our approach to fabricating tunable LMA offers several advantages, including simplicity of fabrication, uniform structural properties, cost-effectiveness, polarization independence, and excellent optical performance. These focus-tunable LMAs hold significant potential for applications in image processing, 3D displays, medical endoscopy, and military technologies.

Hg16O12(NO3)6F2(H2O): A Mercury-Rich Nitrate Oxyfluoride with Diverse Triple-Coordinated Mercury-Based Units That Exhibits an Unparalleled [(Hg16O12F2(H2O))6+]∞ Cationic Framework and a Large Birefringence.

Designing new compounds based on anion regulation has been widely favored due to the production of diverse crystal structures and excellent optical properties. Here, a new nitrate oxyfluoride, Hg16O12(NO3)6F2(H2O), has been obtained through a hydrothermal reaction. It crystallizes in the centric Ibca space group and shows a novel three-dimensional [(Hg16O12F2(H2O))6+]∞ cationic framework composed of interconnected HgO2F, HgO3, and HgO2(H2O) units, with isolated NO3- groups as balanced anions to build the whole structure. Notably, the HgO2F and HgO2(H2O) units are first presented here among mercury (Hg)-based compounds. Additionally, Hg16O12(NO3)6F2(H2O) exhibits a large birefringence of 0.17 at 546 nm. This work enriches the multiformity of Hg-based compounds and provides a route for developing promising birefringent materials.

Polymeric microlens array formed on a discontinuous wetting surface using a self-assembly technique.

In this paper, we demonstrate a facile way to prepare polymeric microlens arrays (MLAs) based on a discontinuous wetting surface using a self-assembly technique. A patterned hydrophobic-octadecyltrichlorosilane (OTS) surface was prepared by U V/O 3 irradiation through a shadow mask. The area exposed to U V/O 3 irradiation turned highly hydrophilic, whereas the area protected by the mask remained highly hydrophobic, generating the patterned OTS surface. The surface energy of the OTS/glass surface changed from 23 to 72.8 mN/m after 17 min of U V/O 3 treatment. The scribing of the optical glue-NOA 81 onto the microhole array enabled one to obtain the MLAs due to the generation of the NOA 81 droplet array via the surface tension. After UV light curing, the cured NOA 81 droplet array with uniform dimensions within a large area exhibited excellent MLA characteristics. Moreover, the method developed in this study is simple in operation, low-cost, and requires neither a clean room nor expensive equipment.

Conservative versus stent treatment for spontaneous isolated superior mesenteric artery dissection after the failure of initial 3 days' conservative treatment: A 10-year follow-up study.

OBJECTIVES: To compare the safety and effectiveness of conservative and stent treatment for spontaneous isolated superior mesenteric artery dissection (SISMAD) patients after the failure of initial 3 days' conservative treatment. METHODS: All newly diagnosed SISMAD patients between 2013 and 2017 were retrospectively reviewed. After the failure of 3 days' conservative treatment, all patients were recommended for stent treatment, but some patients refused to choose it. Their demographic, radiologic, and clinical data were compared. RESULTS: 57 patients were not improved after initial 3 days' conservative treatment. Among them, 19 patients were chose to receive stent placement and 38 patients were continually treated with conservative treatment. The median follow-up time was 92.0 (range 62.7-120.4) months. There were no bowel ischemia and arterial rupture. No significant difference was observed in clinical complete recovery (Conservative 31/38 vs Stent 12/19, p =.19) and hospitalization time (Conservative 8.3 ± 1.7 days vs Stent 7.2 ± 1.5 days, p =.59) between conservative and stent treatment groups. Significant statistical differences were found in radiological complete remodeling (6/38 vs 16/19, p < .01) and hospitalization expense (8662 ± 2886 China Yuan vs 32,935 ± 11,767 China Yuan, p < .01) between these two groups. CONCLUSIONS: Although undergoing the failure of initial 3 days' conservative treatment, continue conservative treatment still is safe and effective for SISMAD patients. Stent placement could be chosen as an alternative treatment, especially for patients potentially with bowel ischemia or arterial rupture.

Postextrasystolic repolarization changes of ventricular premature beats correlate with structural heart disease and suggest prognostic implications.

Ventricular premature beats (VPBs) can potentially lead to life-threatening arrhythmias, especially in patients with structural heart disease (SHD). However, identifying dangerous VPBs has always been a topic and challenge in clinical research. This study aimed to evaluate the relationship of postextrasystolic repolarization changes of VPBs with SHD and its possible additional prognostic value. 125 cases of frequent VPBs with SHD and 156 cases without SHD were included. VPBs were stratified selected from 24 h Holter recording according to the scale of heart rate. Average QTDV (difference value of QT interval between the first beat follow VPB with beats preceding VPB) and max QTDV were significantly longer in SHD group than that in the non-SHD group. For identifying patients with SHD, the best cutoff value were 19 ms for average QTDV (AUC = 0.931) and 29 ms for max QTDV (AUC = 0.910) respectively. For Tu morphology analysis, PT2 (postextrasystolic T wave amplitude change ≥2 mV), reversed T wave, and Pu (postextrasystolic u wave) change were all highly specific, but low sensitive as identification of SHD. Compared with average QTDV < 19 ms patients, average QTDV ≥ 19 ms patients had significantly larger left heart size and wores left cardiac function. The presence of non-persistent ventricular tachycardia runs was higher in average QTDV ≥ 19 ms group and positive Pu change group than that in control groups. The findings indicated that postextrasystolic repolarization changes of VPBs correlated with SHD and suggested potential value in prognosis asssessment.

Halogen Bond Unlocks Ultra-High Birefringence.

Anisotropy is crucial for birefringence (Δn) in optical materials, but optimizing it remains a formidable challenge (Δn > 0.3). Supramolecular frameworks incorporating π-conjugated components are promising for achieving enhanced birefringence since their structural diversity and inherent anisotropy. Herein, we first synthesized (C6H6NO2)+Cl- (NAC). And then constructed a halogen bonded supramolecular framework I+(C6H4NO2)- (INA) by halogen aliovalent substitution of Cl- with I+. The organic moieties are protonated and deprotonated nicotinic acid (NA), respectively. The antiparallel arrangement of birefringent-active units in NAC and INA leads to significant differences in bonding characteristics between interlayer and intralayer domains. Moreover, [O···I+···N] halogen bond in 1D [I+(C6H4NO2)-] chain exhibits stronger interactions and stricter directionality, resulting in a more pronounced in-plane anisotropy between the intrachain and interchain directions. Consequently, INA exhibits exceptional birefringent performance, with a value of 0.778 at 550 nm, twice that of NAC (0.363 at 550 nm). This value significantly exceeds those of commercial birefringent crystals, such as CaCO3 (0.172 at 546 nm), and is the highest reported value among ultraviolet birefringent crystals. This work presents a novel design strategy that employs halogen bonds as connection sites and modes for birefringent-active units, opening new avenues for developing high-performance birefringent crystals.

A novel polymer enabled by polymerized small molecule strategy for tumor photothermal and photodynamic therapy.

Photothermal therapy (PTT) and photodynamic therapy (PDT) are effective method for tumor treatment. However, the limited variety and quantity of photothermal agents (PTAs) and photosensitizer (PSs) are still major challenges. Moreover, the cell apoptosis mechanism induced by PDT and PTT is still elusive. A fused-ring small molecule acceptor-donor acceptor' donor-acceptor (A-DA'D-A) type of Y5 (Scheme 1) has a narrow band-gap and strong light absorption. Herein, we used Y5 to polymerize with thiophene unit to obtain polymer PYT based on polymerized small molecule strategy, and PYT nanoparticles (PYT NPs) was prepared via one-step nanoprecipitation strategy with DSPE-PEG2000. PYT NPs had excellent biocompatibility, good photostability, high photothermal conversion efficiency (67%) and reactive oxygen species (ROS) production capacity under 808 nm laser irradiation (PYT NPs + NIR). In vitro and in vivo experiments revealed that PYT NPs + NIR had the ability to completely ablate tumor cells. It was demonstrated that cell apoptosis induced by PYT NPs + NIR was closely related to mitochondrial damage. This study provides valuable guidance for constructing high-performance organic PTAs and PSs for tumor treatment. Scheme 1 PYT enabled by polymerized small molecule strategy for tumor photothermal and photodynamic therapy.

Investigating the synergistic effects of amitriptyline and H. pylori eradication on depressive-like behaviors and inflammatory cytokines in mice.

BACKGROUND: Recent research has highlighted the potential role of Helicobacter pylori in the pathogenesis of psychiatric disorders. This study aimed to evaluate the potential synergistic effects of an antidepressant drug and H. pylori eradication therapy in a mouse model. METHODS: Male C57BL/6 mice were divided into four groups: control, H. pylori infection, antidepressant treatment, and combined treatment. H. pylori infection was induced by oral gavage with a clinically relevant strain, and the antidepressant drug was administered via intraperitoneal injections. Behavioral tests including the forced swim test, sucrose preference test, and open field test were conducted to assess depressive-like behaviors and locomotor activity. RESULTS: The study demonstrated that H. pylori infection induced depressive-like behaviors in mice, as evidenced by increased immobility time in the forced swim test and reduced sucrose preference. Antidepressant treatment alone partially ameliorated these behavioral changes. Strikingly, the combined treatment of the antidepressant drug and H. pylori eradication therapy led to a significantly greater reduction in depressive-like behaviors compared to either treatment alone. Furthermore, the combined treatment group exhibited increased locomotor activity in the open field test, suggesting a potential improvement in overall psychomotor functioning. ELISA assays revealed alterations in inflammatory cytokines in the H. pylori-infected mice, which were partially attenuated by the combined treatment. CONCLUSION: The study provides novel evidence for the potential synergistic effects of an antidepressant drug and H. pylori eradication therapy in alleviating depressive-like behaviors in a mouse model.

Unveiling the role of KRAS in tumor immune microenvironment.

Kirsten rats sarcoma viral oncogene (KRAS), the first discovered human oncogene, has long been recognized as "undruggable". KRAS mutations frequently occur in multiple human cancers including non-small cell lung cancer(NSCLC), colorectal cancer(CRC) and pancreatic ductal adenocarcinoma(PDAC), functioning as a "molecule switch" determining the activation of various oncogenic signaling pathways. Except for its intrinsic pro-tumorigenic role, KRAS alteration also exhibits an unique immune signature characterized by elevated PD-L1 level and high tumor mutational burden(TMB). KRAS mutation shape an immune suppressive microenvironment by impeding effective T cells infiltration and recruiting suppressive immune cells including myeloid-derived suppressor cells(MDSCs), regulatory T cells(Tregs), cancer associated fibroblasts(CAFs). In immune checkpoint inhibitor(ICI) era, NSCLC patients with mutated KRAS tend to be more responsive to ICI than patients with intact KRAS. The hallmark for KRAS mutation is the existence of multiple kinds of co-mutations. Different types of co-alterations have distinct tumor microenvironment(TME) signatures and responses to ICI. TP53 co-mutation possess a "hot" TME and achieve higher response to immunotherapy while other loss of function mutation correlated with a "colder" TME and a poor outcome to ICI-based therapy. The groundbreaking discovery of KRAS G12C inhibitors significantly improved outcomes for this KRAS subtype even though efficacy was limited to NSCLC patients. KRAS G12C inhibitors also restore the suppressive TME, creating an opportunity for combinations with ICI. However, an inevitable challenge to KRAS inhibitors is drug resistance. Promising combination strategies such as combination with SHP2 is an approach deserve further exploration because of their immune modulatory effect.

Complementary to Multiple Labels: A Correlation-Aware Correction Approach.

Complementary label learning (CLL) requires annotators to give irrelevant labels instead of relevant labels for instances. Currently, CLL has shown its promising performance on multi-class data by estimating a transition matrix. However, current multi-class CLL techniques cannot work well on multi-labeled data since they assume each instance is associated with one label while each multi-labeled instance is relevant to multiple labels. Here, we show theoretically how the estimated transition matrix in multi-class CLL could be distorted in multi-labeled cases as they ignore co-existing relevant labels. Moreover, theoretical findings reveal that calculating a transition matrix from label correlations in multi-labeled CLL (ML-CLL) needs multi-labeled data, while this is unavailable for ML-CLL. To solve this issue, we propose a two-step method to estimate the transition matrix from candidate labels. Specifically, we first estimate an initial transition matrix by decomposing the multi-label problem into a series of binary classification problems, then the initial transition matrix is corrected by label correlations to enforce the addition of relationships among labels. We further show that the proposal is classifier-consistent, and additionally introduce an MSE-based regularizer to alleviate the tendency of BCE loss overfitting to noises. Experimental results have demonstrated the effectiveness of the proposed method.

The association between atherogenic index of plasma and metabolic dysfunction-associated fatty liver disease as detected by FibroScan.

Introduction: Objectives: this study aimed to explore the potential of the atherogenic index of plasma (AIP) as a predictor of metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: a cross-sectional study, including data from 4473 participants in the National Health and Nutrition Examination Survey (NHANES) 2017-2018, was performed. A control attenuation parameter (CAP) ≥ 285 dB/m was used to confirm hepatic steatosis. Degrees of liver stiffness were confirmed according to liver stiffness measurement (LSM). Weighted multivariate logistic regression models were used to assess the association between AIP and the risk for MAFLD and liver fibrosis. Finally, receiver operating characteristic (ROC) curve analysis was used to test the accuracy of AIP in predicting MAFLD. Results: the association between AIP and the prevalence of MAFLD was positive in all three multivariate logistic regression models (model 1, odds ratio (OR), 18.2 (95 % confidence interval (CI), 14.4-23.1); model 2, OR, 17.0 (95 % CI, 13.3-21.8); model 3, OR, 5.2 (95 % CI, 3.9-7.0)). Moreover, this positive relationship was found to be significant in patients of different sexes and whether they had diabetes. However, no significant differences were observed between AIP and significant fibrosis or cirrhosis as assessed by different liver fibrosis indices. Finally, ROC curve analysis demonstrated that the AIP index also demonstrated positive diagnostic utility (area under the ROC curve, 0.733 (95 % CI, 0.718-0.747); p < 0.001). Conclusion: This study revealed a positive association between AIP and MAFLD among American adults. Furthermore, this association persisted in different sexes and whether they had diabetes.

Introducción: Objetivos: este estudio tuvo como objetivo explorar el potencial del índice aterogénico del plasma (AIP) como predictor de enfermedad hepática grasa asociada a disfunción metabólica (MAFLD). Métodos: se realizó un estudio transversal que incluyó datos de 4473 participantes de la encuesta nacional de exémenes de salud y nutrición (NHANES) 2017-2018. Se utilizó un parámetro de atenuación de control (CAP) ≥ 285 dB/m para confirmar la esteatosis hepática. Los grados de rigidez hepática se confirmaron de acuerdo con la medición de rigidez hepática (LSM). Se utilizaron modelos de regresión logística multivariponderponderados para evaluar la asociación entre AIP y el riesgo de MAFLD y fibrosis hepática. Por último, se utilizó el análisis de la curva ROC para probar la precisión de la AIP en la predicción de la MAFLD. Resultados: la asociación entre AIP y prevalencia de MAFLD fue positiva en los tres modelos de regresión logística multivariable (modelo 1, odds ratio (OR): 18,2 (intervalo de confianza (IC) del 95 %: 14,4-23,1); Modelo 2, OR: 17,0 (IC del 95 %: 13,3-21,8); Modelo 3, OR: 5,2 (IC del 95 %: 3,9-7,0)). Además, esta relación positiva se encontró significativa en pacientes de diferentes sexos ya tuvieran o no diabetes. Sin embargo, no se observaron diferencias significativas entre la AIP y la fibrosis o cirrosis significativa evaluada por diferentes índices de fibrosis hepática. Finalmente, el análisis de la curva ROC demostró que el índice AIP también demostró utilidad diagnóstica positiva (área bajo la curva ROC = 0,733 (IC del 95 %: 0,718-0,747); p < 0,001). Conclusión: este estudio reveló una asociación positiva entre AIP y MAFLD en los adultos estadounidenses. Además, esta asociación persistió en los diferentes sexos ya tuvieran o no diabetes.

RNA-sequencing expression profile and functional analysis of retinal pigment epithelium in atrophic age-related macular degeneration.

The retinal pigment epithelium (RPE) is fundamental to sustaining retinal homeostasis. RPE abnormality leads to visual defects and blindness, including age-related macular degeneration (AMD). Although breakthroughs have been made in the treatment of neovascular AMD, effective intervention for atrophic AMD is largely absent. The inadequate knowledge of RPE pathology is hindered by a lack of patient RPE datasets, especially at the single-cell resolution. In this study, we delved into a large-scale single-cell resource of AMD donors in which RPE cells were occupied in a substantial proportion. Bulk RNA-seq datasets of atrophic AMD were integrated to extract molecular characteristics of RPE in the pathogenesis of atrophic AMD. Both in vivo and in vitro models revealed that carboxypeptidase X, M14 family member 2 (CPXM2) was specifically expressed in the RPE cells of atrophic AMD, which might be induced by oxidative stress and involved in the epithelial-mesenchymal transition of RPE cells. Additionally, silencing of CPXM2 inhibited the mesenchymal phenotype of RPE cells in an oxidative stress cell model. Thus, our results demonstrate that CPXM2 plays a crucial role in regulating atrophic AMD and may serve as a potential therapeutic target for atrophic AMD.

Case report: A therapeutic attempt to treat Morbihan disease with Baricitinib.

A woman in her thirties who had been diagnosed with Morbihan disease did not notice a significant improvement in her condition after receiving years of treatment. Our decision to use Baricitinib helped her to achieve a better outcome. To our knowledge, this is the first study to use Baricitinib in Morbihan disease, although JAK inhibitors have already been successfully used before. It is hoped that our case report will provide new treatment options for Morbihan disease therapy.

OGG1 prevents atherosclerosis-induced vascular endothelial cell injury through mediating DNA damage repair.

OBJECTIVE: This study was designed to investigate the role of 8-oxoguanine DNA glycosylase 1 (OGG1) in preventing atherosclerosis-induced vascular EC injury, thereby providing a theoretical basis for the exploration of drug targets and treatment methods for atherosclerosis. METHODS: Human umbilical vein cell line (EA.hy926) was treated with ox-LDL to construct an in vitro atherosclerotic cell model. pcDNA3.1-OGG1 was transfected into EA.hy926 cells to overexpress OGG1. qRT-PCR, CCK-8 assay, flow cytometry, oil red O staining, ELISA, comet assay and western blot were used to evaluate the OGG1 expression, viability, apoptosis level, lipid droplet content, 8-OHdG level and DNA damage of cells in each group. RESULTS: Compared with the Control group, ox-LDL stimulation of endothelial cells significantly decreased cell viability, promoted apoptosis and DNA damage, and increased intracellular levels of 8-OHdG and γH2AX, while decreasing protein levels of PPARγ, FASN, FABP4, RAD51 and POLB. However, overexpression of OGG1 can significantly inhibit ox-LDL damage to endothelial cells, promote lipid metabolism, decrease lipid droplet content, and improve DNA repair function. CONCLUSION: Over-expression of OGG1 improves DNA repair. Briefly, OGG1 over-expression enhances the DNA damage repair of ECs by regulating the expression levels of γH2AX, RAD51 and POLB, thereby enhancing cell viability and reducing apoptosis.