Conditional deletion of Zeb1 in Csf1r+ cells reduces inflammatory response of the cornea to alkali burn.

ZEB1 is an essential factor in embryonic development. In adults, it is often highly expressed in malignant tumors with low expression in normal tissues. The major biological function of ZEB1 in developing embryos and progressing cancers is to transdifferentiate cells from an epithelial to mesenchymal phenotype; but what roles ZEB1 plays in normal adult tissues are largely unknown. We previously reported that the reduction of Zeb1 in monoallelic global knockout (Zeb1+/-) mice reduced corneal inflammation-associated neovascularization following alkali burn. To uncover the cellular mechanism underlying the Zeb1 regulation of corneal inflammation, we functionally deleted Zeb1 alleles in Csf1r+ myeloid cells using a conditional knockout (cKO) strategy and found that Zeb1 cKO reduced leukocytes in the cornea after alkali burn. The reduction of immune cells was due to their increased apoptotic rate and linked to a Zeb1-downregulated apoptotic pathway. We conclude that Zeb1 facilitates corneal inflammatory response by maintaining Csf1r+ cell viability.

Insoluble low-impedance organic battery cathode enabled by graphite grafting towards potassium storage.

Organic electrode materials are extensively applied for potassium storage as their sustainability and low cost. However, the organic electrodes' (i) solubility (such as naphthalene-1,4,5,8-tetracarboxylic dianhydride, NTCDA; 2,6-diaminoanthanthraquinone, DAQ, which are easily soluble in organic solvents) and (ii) intrinsic poor conductivity often result in high impedance and inferior electrochemical performance. Herein, the monomers of NTCDA and DAQ were polymerized (PND) to obtain an insoluble organic cathode, and a 5 wt% graphite (G) was also used to graft the PND sheet and increase its conductivity. Consequently, the as-prepared organic cathode (PND-G) achieved a long-life cycling performance of over 1500 cycles at 100 mA g-1. This work may provide guidelines for designing and developing insoluble and high conductive organic electrode materials.

Association between diabetes mellitus and primary restenosis following endovascular treatment: a comprehensive meta-analysis of randomized controlled trials.

IMPORTANCE: Diabetes mellitus (DM) is thought to be closely related to arterial stenotic or occlusive disease caused by atherosclerosis. However, there is still no definitive clinical evidence to confirm that patients with diabetes have a higher risk of restenosis. OBJECTIVE: This meta-analysis was conducted to determine the effect of DM on restenosis among patients undergoing endovascular treatment, such as percutaneous transluminal angioplasty (PTA) or stenting. DATA SOURCES AND STUDY SELECTION: The PubMed/Medline, EMBASE and Cochrane Library electronic databases were searched from 01/1990 to 12/2022, without language restrictions. Trials were included if they satisfied the following eligibility criteria: (1) RCTs of patients with or without DM; (2) lesions confined to the coronary arteries or femoral popliteal artery; (3) endovascular treatment via PTA or stenting; and (4) an outcome of restenosis at the target lesion site. The exclusion criteria included the following: (1) greater than 20% of patients lost to follow-up and (2) a secondary restenosis operation. DATA EXTRACTION AND SYNTHESIS: Two researchers independently screened the titles and abstracts for relevance, obtained full texts of potentially eligible studies, and assessed suitability based on inclusion and exclusion criteria.. Disagreements were resolved through consultation with a third researcher. Treatment effects were measured by relative ratios (RRs) with 95% confidence intervals (CIs) using random effects models. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. MAIN OUTCOMES AND MEASURES: The main observation endpoint was restenosis, including > 50% stenosis at angiography, or TLR of the primary operation lesion during the follow-up period. RESULTS: A total of 31,066 patients from 20 RCTs were included. Patients with DM had a higher risk of primary restenosis after endovascular treatment (RR = 1.43, 95% CI: 1.25-1.62; p = 0.001). CONCLUSIONS AND RELEVANCE: This meta-analysis of all currently available RCTs showed that patients with DM are more prone to primary restenosis after endovascular treatment.

Transcriptomic analysis reveals the inhibitory effect of beta-sitosterol on proliferation of bovine preadipocytes.

Fat deposition affects beef quantity and quality via preadipocyte proliferation. Beta-sitosterol, a natural small molecular compound, has various functions, such as anti-inflammation, antibacterial, and anticancer properties. The mechanism of action of Beta-sitosterol on bovine preadipocytes remains unclear. This study, based on RNA-seq, reveals the impact of Beta -sitosterol on the proliferation of bovine preadipocytes. Compared to the control group, Beta-sitosterol demonstrated a more pronounced inhibitory effect on cell proliferation after 48 hours of treatment than after 24 hours, as evidenced by the results of EdU staining and flow cytometry. RNA-seq and Western Blot analyses further substantiated these findings. Our results suggest that the impact of Beta-sitosterol on the proliferation of bovine preadipocytes is not significant after a 24-hour treatment. It is only after extending the treatment time to 48 hours that Beta-sitosterol may induce cell cycle arrest at the G2/M phase by suppressing the expression of CCNB1, thereby inhibiting the proliferation of bovine preadipocytes.

Body mass index influences age-related cataracts: an updated meta-analysis and systemic review.

PURPOSE: Visual impairment and blindness caused by cataracts are major public health problems. Several factors are associated with an increased risk of age-related cataracts, such as age, smoking, alcohol consumption, and ultraviolet radiation. This meta-analysis aimed to assess the association between body mass index and age-related cataracts. METHODS: Studies on weight and age-related cataracts published from January 2011 to July 2020 were reviewed by searching PubMed, Medline, and Web of Science databases. The random-effects and fixed-effects models were used for the meta-analysis, and the results were reported as odd ratios. RESULTS: A total of nine studies were included in the meta-analysis. No correlation was found between underweight and nuclear cataracts (OR=1.31, 95% CI [-0.50 to 3.12], p=0.156). The results of the random-effects model showed that overweight was significantly associated with age-related cataracts and reduced the risk of age-related cataracts (OR=0.91, 95% CI [0.80-1.02], p<0.0001; I2=62.3%, p<0.0001). Significant correlations were found between overweight and cortical, nuclear, and posterior subcapsular cataracts (OR=0.95, 95% CI [0.66-1.24], p<0.0001; OR=0.92, 95% CI (0.76-1.08), p<0.0001; OR=0.87, 95% CI [0.38-1.02], p<0.0001). Significant correlations were found between obesity and cortical, nuclear, and posterior subcapsular cataracts (OR=1.00, 95% CI [0.82-1.17], p<0.0001; OR=1.07, 95% CI [0.92-1.22], p<0.0001; OR=1.14, 95% CI [0.91-1.37], p<0.0001). CONCLUSION: This finding suggested a significant correlation between body mass index and age-related cataracts, with overweight and obesity reducing or increasing the risk of age-related cataracts, respectively.

Enhanced Alkaline Hydrogen Evolution Reaction via Electronic Structure Regulation: Activating PtRh with Rare Earth Tm Alloying.

Developing high-performance electrocatalysts for alkaline hydrogen evolution reaction (HER) is crucial for producing green hydrogen, yet it remains challenging due to the sluggish kinetics in alkaline environments. Pt is located near the peak of HER volcano plot, owing to its exceptional performance in hydrogen adsorption and desorption, and Rh plays an important role in H2O dissociation. Lanthanides (Ln) are commonly used to modulate the electronic structure of materials and further influence the adsorption/desorption of reactants, intermediates, and products, and noble metal-Ln alloys are recognized as effective platforms where Ln elements regulate the catalytic properties of noble metals. Here Pt1.5Rh1.5Tm alloy is synthesized using the sodium vapor reduction method. This alloy demonstrates superior catalytic activity, being 4.4 and 6.6 times more effective than Pt/C and Rh/C, respectively. Density Functional Theory (DFT) calculations reveal that the upshift of d-band center and the charge transfer induced by alloying promote adsorption and dissociation of H2O, making Pt1.5Rh1.5Tm alloy more favorable for the alkaline HER reaction, both kinetically and thermodynamically.

Multipathway Regulation for Targeted Atherosclerosis Therapy Using Anti-miR-33-Loaded DNA Origami.

Given the multifactorial pathogenesis of atherosclerosis (AS), a chronic inflammatory disease, combination therapy arises as a compelling approach to effectively address the complex interplay of pathogenic mechanisms for a more desired treatment outcome. Here, we present cRGD/ASOtDON, a nanoformulation based on a self-assembled DNA origami nanostructure for the targeted combination therapy of AS. cRGD/ASOtDON targets αvß3 integrin receptors overexpressed on pro-inflammatory macrophages and activated endothelial cells in atherosclerotic lesions, alleviates the oxidative stress induced by extracellular and endogenous reactive oxygen species, facilitates the polarization of pro-inflammatory macrophages toward the anti-inflammatory M2 phenotype, and inhibits foam cell formation by promoting cholesterol efflux from macrophages by downregulating miR-33. The antiatherosclerotic efficacy and safety profile of cRGD/ASOtDON, as well as its mechanism of action, were validated in an AS mouse model. cRGD/ASOtDON treatment reversed AS progression and restored normal morphology and tissue homeostasis of the diseased artery. Compared to probucol, a clinical antiatherosclerotic drug with a similar mechanism of action, cRGD/ASOtDON enabled the desired therapeutic outcome at a notably lower dosage. This study demonstrates the benefits of targeted combination therapy in AS management and the potential of self-assembled DNA nanoformulations in addressing multifactorial inflammatory conditions.

A 17-year-old student with ankle sprain to leg amputation.

Cutaneous mucormycosis with ischemic complications is a life-threatening condition with high mortality rates, particularly in immunocompromised individuals. The incidence of mucormycosis has increased during the COVID-19 pandemic due to reduced immunity. We present the case of a 17-year-old high school student who experienced a sprained left lower extremity, followed by worsening pain and swelling due to the topical application of unknown local herbs. Eighteen days after the injury, she was admitted to our department in a comatose state with left lower limb ischemia. The patient had a history of uncontrolled diabetes mellitus and displayed a necrotic lesion on her left ankle, suggestive of invasive infectious fungi disease. Diagnostic procedures, including tissue staining and molecular analysis, identified Rhizopus oryzae as the causative organism. Administering amphotericin B yielded marked improvement, but the patient necessitated a mid-thigh amputation to curtail the infection's advance, culminating in her successful discharge post-treatment.

Atlas of Cell Repertoire Within Neointimal Lesions Is Metabolically Altered in Hypertensive Rats.

BACKGROUND: High blood pressure has been suggested to accelerate vascular injury-induced neointimal formation and progression. However, little is known about the intricate relationships between vascular injury and hypertension in the context of arterial remodeling. METHODS: Single-cell RNA-sequencing analysis was used to depict the cell atlas of carotid arteries of Wistar Kyoto rats and spontaneously hypertensive rats with or without balloon injury. RESULTS: We found that hypertension significantly aggravated balloon injury-induced arterial stenosis. A total of 36 202 cells from carotid arteries with or without balloon injury were included in single-cell RNA-sequencing analysis. Cell composition analysis showed that vascular injury and hypertension independently induced distinct aortic cell phenotypic alterations including immune cells, endothelial cells (ECs), and smooth muscle cells. Specifically, our data showed that injury and hypertension-induced specific EC phenotypic alterations, and revealed a transition from functional ECs to hypermetabolic, and eventually dysfunctional ECs in hypertensive rats upon balloon injury. Importantly, our data also showed that vascular injury and hypertension-induced different smooth muscle cell phenotypic alterations, characterized by deferential expression of synthetic signatures. Interestingly, pathway analysis showed that dysregulated metabolic pathways were a common feature in monocytes/macrophages, ECs, and smooth muscle cells in response to injury and hypertension. Functionally, we demonstrate that inhibition of mitochondrial respiration significantly ameliorated injury-induced neointimal formation in spontaneously hypertensive rats. CONCLUSIONS: This study provides the cell landscape changes of the main aortic cell phenotypic alterations in response to injury and hypertension. Our findings suggest that targeting cellular mitochondrial respiration could be a novel therapeutic for patients with hypertension undergoing vascular angioplasty.

Aldehyde dehydrogenase 2 serves as a key cardiometabolic adaptation regulator in response to plateau hypoxia in mice.

High-altitude heart disease (HAHD) is a complex pathophysiological condition related to systemic hypobaric hypoxia in response to transitioning to high altitude. Hypoxia can cause myocardial metabolic dysregulation, leading to an increased risk of heart failure and sudden cardiac death. Aldehyde dehydrogenase 2 (ALDH2) could regulate myocardial energy metabolism and plays a protective role in various cardiovascular diseases. This study aims to determine the effects of plateau hypoxia (PH) on cardiac metabolism and function, investigate the associated role of ALDH2, and explore potential therapeutic targets. We discovered that PH significantly reduced survival rate and cardiac function. These effects were exacerbated by ALDH2 deficiency. PH also caused a shift in the myocardial fuel source from fatty acids to glucose; ALDH2 deficiency impaired this adaptive metabolic shift. Untargeted/targeted metabolomics and transmission electron microscopy revealed that ALDH2 deficiency promoted myocardial fatty-acid deposition, leading to enhanced fatty-acid transport, lipotoxicity and mitochondrial dysfunction. Furthermore, results showed that ALDH2 attenuated PH-induced impairment of adaptive metabolic programs through 4-HNE/CPT1 signaling, and the CPT1 inhibitor etomoxir significantly ameliorated ALDH2 deficiency-induced cardiac impairment and improved survival in PH mice. Together, our data reveal ALDH2 acts as a key cardiometabolic adaptation regulator in response to PH. CPT1 inhibitor, etomoxir, may attenuate ALDH2 deficiency-induced effects and improved cardiac function in response to PH.

Fog controls biological cycling of soil phosphorus in the Coastal Cordillera of the Atacama Desert.

Soils in hyper-arid climates, such as the Chilean Atacama Desert, show indications of past and present forms of life despite extreme water limitations. We hypothesize that fog plays a key role in sustaining life. In particular, we assume that fog water is incorporated into soil nutrient cycles, with the inland limit of fog penetration corresponding to the threshold for biological cycling of soil phosphorus (P). We collected topsoil samples (0-10 cm) from each of 54 subsites, including sites in direct adjacency (<10 cm) and in 1 m distance to plants, along an aridity gradient across the Coastal Cordillera. Satellite-based fog detection revealed that Pacific fog penetrates up to 10 km inland, while inland sites at 10-23 km from the coast rely solely on sporadic rainfall for water supply. To assess biological P cycling we performed sequential P fractionation and determined oxygen isotope of HCl-extractable inorganic P δ 18 O HCl - P i $$ \mathrm{P}\ \left({\updelta}^{18}{\mathrm{O}}_{\mathrm{HCl}-{\mathrm{P}}_{\mathrm{i}}}\right) $$ . Total P (Pt ) concentration exponentially increased from 336 mg kg-1 to a maximum of 1021 mg kg-1 in inland areas ≥10 km. With increasing distance from the coast, soil δ 18 O HCl - P i $$ {\updelta}^{18}{\mathrm{O}}_{\mathrm{HCl}-{\mathrm{P}}_{\mathrm{i}}} $$ values declined exponentially from 16.6‰ to a constant 9.9‰ for locations ≥10 km inland. Biological cycling of HCl-Pi near the coast reached a maximum of 76%-100%, which could only be explained by the fact that fog water predominately drives biological P cycling. In inland regions, with minimal rainfall (<5 mm) as single water source, only 24 ± 14% of HCl-Pi was biologically cycled. We conclude that biological P cycling in the hyper-arid Atacama Desert is not exclusively but mainly mediated by fog, which thus controls apatite dissolution rates and related occurrence and spread of microbial life in this extreme environment.

Mn2+ recycling in hypersaline wastewater: unnoticed intracellular biomineralization and pre-cultivation of immobilized bacteria.

Microbially induced manganese carbonate precipitation has been utilized for the treatment of wastewater containing manganese. In this study, Virgibacillus dokdonensis was used to remove manganese ions from an environment containing 5% NaCl. The results showed a significant decrease in carbonic anhydrase activity and concentrations of carbonate and bicarbonate ions with increasing manganese ion concentrations. However, the levels of humic acid analogues, polysaccharides, proteins, and DNA in EPS were significantly elevated compared to those in a manganese-free environment. The rhodochrosite exhibited a preferred growth orientation, abundant morphological features, organic elements including nitrogen, phosphorus, and sulfur, diverse protein secondary structures, as well as stable carbon isotopes displaying a stronger negative bias. The presence of manganese ions was found to enhance the levels of chemical bonds O-C=O and N-C=O in rhodochrosite. Additionally, manganese in rhodochrosite exhibited both + 2 and + 3 valence states. Rhodochrosite forms not only on the cell surface but also intracellularly. After being treated with free bacteria for 20 days, the removal efficiency of manganese ions ranged from 88.4 to 93.2%, and reached a remarkable 100% on the 10th day when using bacteria immobilized on activated carbon fiber that had been pre-cultured for three days. The removal efficiency of manganese ions was significantly enhanced under the action of pre-cultured immobilized bacteria compared to non-pre-cultured immobilized bacteria. This study contributes to a comprehensive understanding of the mineralization mechanism of rhodochrosite, thereby providing an economically and environmentally sustainable biological approach for treating wastewater containing manganese.

Remote Ischemic Conditioning Mediates Cardio-protection After Myocardial Ischemia/Reperfusion Injury by Reducing 4-HNE Levels and Regulating Autophagy via the ALDH2/SIRT3/HIF1α Signaling Pathway.

Remote ischemic conditioning (RIC) can be effectively applied for cardio-protection. Here, to clarify whether RIC exerts myocardial protection via aldehyde dehydrogenase 2 (ALDH2), we established a myocardial ischemia/reperfusion (I/R) model in C57BL/6 and ALDH2 knockout (ALDH2-KO) mice and treated them with RIC. Echocardiography and single-cell contraction experiments showed that RIC significantly improved myocardial function and alleviated I/R injury in C57BL/6 mice but did not exhibit its cardioprotective effects in ALDH2-KO mice. TUNEL, Evan's blue/triphenyl tetrazolium chloride, and reactive oxygen species (ROS) assays showed that RIC's effect on reducing myocardial cell apoptosis, myocardial infarction area, and ROS levels was insignificant in ALDH2-KO mice. Our results showed that RIC could increase ALDH2 protein levels, activate sirtuin 3 (SIRT3)/hypoxia-inducible factor 1-alpha (HIF1α), inhibit autophagy, and exert myocardial protection. This study revealed that RIC could exert myocardial protection via the ALDH2/SIRT3/HIF1α signaling pathway by reducing 4-HNE secretion.

Ischemia‒Reperfusion accelerates neointimal hyperplasia via IL-1ß-mediated pyroptosis after balloon injury in the rat carotid artery.

Background: Ischemia‒reperfusion (IR) is a pathological process that causes secondary damage to blood vessels. However, whether IR can further worsen neointima formation after balloon injury and the detailed mechanism are unclear. Methods: An in vivo model of balloon injury to the rat carotid artery was established to study the effect of IR following balloon injury on neointima formation. Smooth muscle cells (SMCs) were isolated from rat aortas and exposed to hypoxia-reoxygenation to mimic the IR process in vitro. The in vitro cell model was used to investigate the mechanism of IR-mediated neointima formation after balloon injury, which was further confirmed in an in vivo rat model. Results: IR aggravated neointima formation in the rat carotid artery 2 weeks after balloon injury compared with that observed in the absence of balloon injury (P < 0.001). Compared with that of normal SMCs in the rat carotid artery, the expression of IL-1ß, a key proinflammatory cytokine associated with pyroptosis, was increased more than 3-fold in the IR-induced neointima (P < 0.0001) and contributed to the proliferation and migration of rat primary aortic SMCs (P < 0.0001). This process was alleviated by the antioxidant acetylcysteine (NAC), suggesting its partial dependence on intracellular ROS. In the rat model of IR following balloon injury in the carotid artery, the carotid artery that was locally transfected with AAV carrying sh-IL-1ß or sh-caspase-1, which alleviated neointima formation, as indicated by a reduction in intima-media thickness in the rat carotid artery (P < 0.0001). Conclusion: Our results suggested that IR could promote IL-1ß production in SMCs in the carotid artery after balloon injury and aggravate neointimal hyperplasia, which was alleviated by silencing caspase-1/IL-1ß signaling in SMCs in the carotid artery. These results suggest that IL-1ß may be an effective target to combat IR-related neointima formation.

Enhanced Alkaline Hydrogen Evolution Reaction through Lanthanide-Modified Rhodium Intermetallic Catalysts.

Design of highly efficient electrocatalysts for alkaline hydrogen evolution reaction (HER) is of paramount importance for water electrolysis, but still a considerable challenge because of the slow HER kinetics in alkaline environments. Alloying is recognized as an effective strategy to enhance the catalytic properties. Lanthanides (Ln) are recognized as an electronic and structural regulator, attributed to their unique 4f electron behavior and the phenomenon known as lanthanide contraction. Here, a new class of Rh3 Ln intermetallics (IMs) are synthesized using the sodium vapor reduction method. The alloying process induced an upshift of the d-band center and electron transfer from Ln to Rh, resulting in optimized adsorption and dissociation energies for H2 O molecules. Consequently, Rh3 Tb IMs exhibited outstanding HER activity in both alkaline environments and seawater, displaying an overpotential of only 19 mV at 10 mA cm-2 and a Tafel slope of 22.2 mV dec-1 . Remarkably, the current density of Rh3 Tb IMs at 100 mV overpotential is 8.6 and 5.7 times higher than that of Rh/C and commercial Pt/C, respectively. This work introduces a novel approach to the rational design of HER electrocatalysis and sheds light on the role of lanthanides in electrocatalyst systems.

L-type calcium ion channel-mediated activation of autophagy in vascular smooth muscle cells via thonningianin A (TA) alleviates vascular calcification in type 2 diabetes mellitus.

Vascular calcification (VC) is associated with increased morbidity and mortality, especially among people with type 2 diabetes mellitus (T2DM). The pathogenesis of vascular calcification is incompletely understood, and until now, there have been no effective therapeutics for vascular calcification. The L-type calcium ion channel in the cell membrane is vital for Ca2+ influx. The effect of L-type calcium ion channels on autophagy remains to be elucidated. Here, the natural compound thonningianin A (TA) was found to ameliorate vascular calcification in T2DM via the activation of L-type calcium ion channels. The results showed that TA had a concentration-dependent ability to decrease the transcriptional and translational expression of the calcification-related proteins runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2) and osteopontin (OPN) (P < 0.01) via ATG7-dependent autophagy in ß-glycerophosphate (ß-GP)- and high glucose (HG)-stimulated primary mouse aortic smooth muscle cells (MASMCs) and alleviate aortic vascular calcification in VitD3-stimulated T2DM mice. However, nifedipine, an inhibitor of L-type calcium ion channels, reversed TA-induced autophagy and Ca2+ influx in MASMCs. Molecular docking analysis revealed that TA was located in the hydrophobic pocket of Cav1.2 α1C and was mainly composed of the residues Ile, Phe, Ala and Met, which confirmed the efficacy of TA in targeting the L-type calcium channel of Cav1.2 on the cell membrane. Moreover, in an in vivo model of vascular calcification in T2DM mice, nifedipine reversed the protective effects of TA on aortic calcification and the expression of the calcification-related proteins RUNX2, BMP2 and OPN (P < 0.01). Collectively, the present results reveal that the activation of cell membrane L-type calcium ion channels can induce autophagy and ameliorate vascular calcification in T2DM. Thonningianin A (TA) can target and act as a potent activator of L-type calcium ion channels. Thus, this research revealed a novel mechanism for autophagy induction via L-type calcium ion channels and provided a potential therapeutic for vascular calcification in T2DM.

A Multicenter Prospective Randomized Controlled Study of a New Corneal Wetting Agent During Ophthalmologic Surgery.

INTRODUCTION: A multicenter prospective randomized controlled study was used to investigate the effect and safety of a new corneal wetting agent called the Corneal Surface Viscoelastic Protector (CsVisc, Success Bio-Tech Co., Ltd, China), on the corneal epithelium during ophthalmic surgery by comparison with the commercially available Cornea Protect (CP, Valeant Med Sp. zo. o. Leobendorf, Austria). METHODS: This multicenter prospective randomized controlled study comprised patients scheduled for cataract surgery and pars plana vitrectomy. The patients were randomly assigned to receive either a new corneal wetting agent (CsVisc) or Cornea Protect (CP, Valeant Med Sp. zo. o. Leobendorf, Austria). Optical clarity during surgery, application frequency, duration of effect, diffusion time of corneal wetting agents, fluorescein staining, intraocular pressure (IOP), tear-film break-up time (TBUT), and Schirmer I test (SIT) were assessed. Adverse events were noted on the designated patient case report forms. RESULTS: A total of 149 eyes (149 patients, mean age 62 years; range 25-80 years) were included in the study. There were 74 eyes in the control group and 75 eyes in the study group. In patients who underwent vitrectomy, the frequency of application was 1.62 ± 1.03 in the study group and 1.39 ± 0.66 in the control group, with no significant difference (P = 0.399), and the duration of effect was 19.16 ± 6.94 min in the study group and 19.06 ± 7.22 min in the control group, with no significant difference (P = 0.835). The optical clarity of the study group was not significantly different from that of the control group (P = 0.485). In patients who underwent cataract surgery, the frequency of application was 1.10 ± 0.38 in the study group and 1.07 ± 0.26 in the control group, and the difference was not significant (P = 0.950). The difference between the duration of effect in the study group (8.32 ± 2.50 min) and the control group (7.63 ± 2.52 min) was not significant (P = 0.310). The difference in optical clarity scores between the two groups was not statistically significant (P = 0.600). Among all patients in this study, the diffusion time of the corneal wetting agent was 14.97 ± 10.07 s in the control group and 11.23 ± 8.41 s in the study group, with a statistically significant difference (p = 0.008). The frequency of adverse events was 20.00% (15/75) in the study group and 14.86% (11/74) in the control group, with no statistically significant difference (P = 0.409). There were no serious adverse events related to the test medical device or causing patients to withdraw from the study. CONCLUSIONS: The CsVisc is safe and effective in preventing intraoperative corneal epithelial damage due to corneal dryness and can be comparable to the CP. In addition, the CsVisc has a shorter diffusion time.

Autophagy reduces aortic calcification in diabetic mice by reducing matrix vesicle body-mediated IL-1ß release.

Vascular calcification (VC) is a common pathological process of cardiovascular disease that occurs in patients with type 2 diabetes mellitus (T2DM). However, the molecular basis of VC progression remains unknown. A GEO dataset (GSE146638) was analyzed to show that microbodies and IL-1ß may play important roles in the pathophysiology of VC. The release of matrix vesicle bodies (MVBs) and IL-1ß and the colocalization of IL-1ß with MVBs or autophagosomes were studied by immunofluorescence in an in vivo diabetes mouse model with aortic calcification and an in vitro high glucose cell calcification model. MVB numbers, IL-1ß levels and autophagy were increased in calcified mouse aortas and calcified vascular smooth muscle cells (VSMCs). IL-1ß colocalized with MVBs and autophagosomes. The MVBs from calcified VSMCs induced the calcification of normal recipient VSMCs, and this effect was alleviated by silencing IL-1ß. The autophagy inducer rapamycin reduced IL-1ß expression and calcification in VSMCs, while these processes were induced by the autophagy inhibitor chloroquine. In conclusion, our results suggested that MVBs could carry IL-1ß out of cells and induce VC in normal VSMCs, and these processes could be counteracted by autophagy. These results suggested that MVB-mediated IL-1ß release may be an effective target for treating vascular calcification.

Mitochondrial transplantation ameliorates doxorubicin-induced cardiac dysfunction via activating glutamine metabolism.

Doxorubicin is a wildly used effective anticancer agent. However, doxorubicin use is also related to cardiotoxic side effect in some patients. Mitochondrial damage has been shown to be one of the pathogeneses of doxorubicin-induced myocardial injury. In this study, we demonstrated that mitochondrial transplantation could inhibit doxorubicin-induced cardiotoxicity by directly supplying functional mitochondria. Mitochondrial transplantation improved contractile function and respiratory capacity, reduced cellular apoptosis and oxidative stress in cardiomyocytes. Mitochondria isolated from various sources, including mouse hearts, mouse and human arterial blood, and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), all exerted similar cardioprotective effects. Mechanically, mitochondrial transplantation activates glutamine metabolism in doxorubicin-treated mice heart and blocking glutamine metabolism attenuated the cardioprotective effects of mitochondrial transplantation. Overall, our study demonstrates that mitochondria isolated from arterial blood could be used for mitochondrial transplantation, which might serve as a feasible promising therapeutic option for patients with doxorubicin-induced cardiotoxicity.