Altered gut microbiota and metabolite profiles provide clues in understanding resistant hypertension.

BACKGROUND: Resistant hypertension is a severe phenotype in hypertension that may be driven by interactions between genetic and environmental factors. Specific changes in gut microbiota and metabolites have been shown to influence cardiovascular disease progression. However, microbial and metabolomic changes associated with resistant hypertension remain elusive. METHODS: In this study, the gut microbiome of 30 participants with resistant hypertension, 30 with controlled hypertension, and 30 nonhypertension was characterized using 16S rRNA amplicon sequencing. In addition, the serum metabolome of the same population was assessed by untargeted metabolomics. RESULTS: The alpha diversity of microbiome in the resistant hypertension decreased, and changes were also observed in the composition of the gut microbiota. The resistant hypertension group was characterized by elevated levels of Actinobacteitia and Proteobacteria. Twenty-three genera were found to have significantly different abundances between resistant hypertension and controlled hypertension, as well as 55 genera with significantly different abundances between resistant hypertension and nonhypertension. Compared with the controlled hypertension group, the genera Rothia and Sharpea in resistant hypertension were more abundant. Compared with the nonhypertension group, the genera Escherichia-Shigella , Lactobacillus , Enterococcus were more abundant. Untargeted metabolomics provided distinctly different serum metabolic profiles for the three groups and identified a range of differential metabolites. These metabolites were mainly associated with the pathway of glycerophospholipid metabolism. Furthermore, correlation analysis provided evidence of new interactions between gut microbiota and metabolites in the resistant hypertension. CONCLUSION: In conclusion, our study provides a comprehensive understanding of the resistant hypertension gut microbiota and metabolites, suggesting that treatment resistance in resistant hypertension patients may be related to the gut microbiota and serum metabolites.

Increased indexed proximal aortic diameter is a predictor of poor prognosis in maintenance hemodialysis patients.

Background: Recent studies have shown that the baseline values of absolute aortic root diameter (ARD) and indexed diameter are associated with all-cause mortality and cardiovascular events in the general population, even in the absence of aneurysmal aortic disease. However, there is limited available data on the association between ARD and prognosis in end-stage renal disease (ESRD) patients receiving maintenance hemodialysis (MHD). Accordingly, the purpose of this study is to investigate the predictive value of ARD for all-cause mortality and cardiovascular events in this specific population.Methods: ARD was measured by echocardiography at the level of the sinuses of Valsalva at end diastole and indexed to body surface area (BSA). The primary endpoint was all-cause mortality. The secondary endpoint was major adverse cardiovascular events (MACE), including cardiovascular mortality, myocardial infarction and stroke. Cox proportional hazards models were conducted to evaluate the association between baseline ARD/BSA and clinical outcomes.Results: A total of 391 patients were included in this study. The primary endpoint occurred in 95 (24.3%) patients while the secondary endpoint occurred in 71 (18.2%) patients. Multivariate Cox regression analysis showed that ARD/BSA was an independent prognostic factor for all-cause mortality (HR, per 1-SD increase, 1.403; 95% CI, 1.118-1.761; p = 0.003) as well as MACE (HR, per 1-SD increase, 1.356; 95% CI, 1.037-1.772; p = 0.026).Conclusions: Our results show that ARD/BSA is predictive of all-cause mortality and MACE in MHD patients with ESRD and support the view that assessment of ARD/BSA may refine risk stratification and preventive strategies in this population.

Characterization, biogenesis model, and current bioinformatics of human extrachromosomal circular DNA.

Human extrachromosomal circular DNA, or eccDNA, has been the topic of extensive investigation in the last decade due to its prominent regulatory role in the development of disorders including cancer. With the rapid advancement of experimental, sequencing and computational technology, millions of eccDNA records are now accessible. Unfortunately, the literature and databases only provide snippets of this information, preventing us from fully understanding eccDNAs. Researchers frequently struggle with the process of selecting algorithms and tools to examine eccDNAs of interest. To explain the underlying formation mechanisms of the five basic classes of eccDNAs, we categorized their characteristics and functions and summarized eight biogenesis theories. Most significantly, we created a clear procedure to help in the selection of suitable techniques and tools and thoroughly examined the most recent experimental and bioinformatics methodologies and data resources for identifying, measuring and analyzing eccDNA sequences. In conclusion, we highlighted the current obstacles and prospective paths for eccDNA research, specifically discussing their probable uses in molecular diagnostics and clinical prediction, with an emphasis on the potential contribution of novel computational strategies.

Interactions between caregiving and sex and the antibody response to COVID-19 vaccination.

OBJECTIVE: Antibody response to vaccination is a powerful paradigm for studying the effects of chronic stress on immune function. In the present study, we used this paradigm to examine the interaction between caregiving (as a type of chronic stress) and sex on the antibody response to a single dose of a COVID-19 vaccination; recent research has called for examination of sex differences on health outcomes among family caregivers. A three-way interaction between caregiving, sex and psychological distress was also examined. METHODS: COVID-19 antibody data was extracted from 165 caregivers (98 females) and 386 non-caregivers (244 females) from the UK's Understanding Society COVID-19 study. Relevant socio-demographics, health and lifestyle, and distress variables were gathered as potential covariates. RESULTS: In a 2 x 2 ANOVA we found the interaction between caregiving and sex was significant; male caregivers had a lower antibody response to the vaccine compared to female caregivers F (1,547), =24.82, p < .001, η2 = .043. Following adjustment, male caregivers had the lowest antibody response relative to all other groups. The three-way interaction model, controlling for covariates was also significant, R2 = .013, p = .049; the conditional effects for the three-way interaction revealed that male caregivers, compared to the other groups had a lower antibody response at both low and medium levels of psychological distress. CONCLUSION: This study found evidence of a three-way interaction between caregiving, sex and distress on antibody response. Male caregivers had poorer antibody response to a single shot of the COVID-19 vaccination than female caregivers and male and female non-caregivers and this was evident at low and medium levels of distress. Our findings will be discussed in relation to the caregiver-and sex interactions during the pandemic.

In silico analysis of intestinal microbial instability and symptomatic markers in mice during the acute phase of severe burns.

BACKGROUND: Severe burns may alter the stability of the intestinal flora and affect the patient's recovery process. Understanding the characteristics of the gut microbiota in the acute phase of burns and their association with phenotype can help to accurately assess the progression of the disease and identify potential microbiota markers. METHODS: We established mouse models of partial thickness deep III degree burns and collected faecal samples for 16 S rRNA amplification and high throughput sequencing at two time points in the acute phase for independent bioinformatic analysis. RESULTS: We analysed the sequencing results using alpha diversity, beta diversity and machine learning methods. At both time points, 4 and 6 h after burning, the Firmicutes phylum content decreased and the content of the Bacteroidetes phylum content increased, showing a significant decrease in the Firmicutes/Bacteroidetes ratio compared to the control group. Nine bacterial genera changed significantly during the acute phase and occupied the top six positions in the Random Forest significance ranking. Clustering results also clearly showed that there was a clear boundary between the communities of burned and control mice. Functional analyses showed that during the acute phase of burn, gut bacteria increased lipoic acid metabolism, seleno-compound metabolism, TCA cycling, and carbon fixation, while decreasing galactose metabolism and triglyceride metabolism. Based on the abundance characteristics of the six significantly different bacterial genera, both the XGboost and Random Forest models were able to discriminate between the burn and control groups with 100% accuracy, while both the Random Forest and Support Vector Machine models were able to classify samples from the 4-hour and 6-hour burn groups with 86.7% accuracy. CONCLUSIONS: Our study shows an increase in gut microbiota diversity in the acute phase of deep burn injury, rather than a decrease as is commonly believed. Severe burns result in a severe imbalance of the gut flora, with a decrease in probiotics and an increase in microorganisms that trigger inflammation and cognitive deficits, and multiple pathways of metabolism and substance synthesis are affected. Simple machine learning model testing suggests several bacterial genera as potential biomarkers of severe burn phenotypes.

Risk prediction for severe COVID-19 progressing to critical illness and death in the ICU and efficacy analysis of using traditional Chinese medicine.

To reveal the key factors influencing the progression of severe COVID-19 to critical illness and death in the intensive care unit (ICU) and to accurately predict the risk, as well as to validate the efficacy of treatment using traditional Chinese medicine (TCM), thus providing valuable recommendations for the clinical management of patients. A total of 189 patients with COVID-19 in 25 ICUs in Chongqing, China, were enrolled, and 16 eventually died. Statistical models shown that factors influencing the progression of COVID-19 to critical illness include the severity of illness at diagnosis, the mode of respiratory support, and the use of TCM. Risk factors for death include a history of metabolic disease, the use of antiviral drugs and TCM, and invasive endotracheal intubation. The area under curve of the noncollinearity model predicted the risk of progression to critical illness and the risk of death reached 0.847 and 0.876, respectively. The use of TCM is an independent protective factor for the prevention of the progression of severe COVID-19, while uncorrectable hypoxemia and invasive respiratory support are independent risk factors, and antiviral drugs can help reduce mortality. The multifactorial prediction model can assess the risk of critical illness and death in ICU COVID-19 patients, and inform clinicians in choosing the treatment options and medications.

Children's emotional intelligence and aggressive behavior: The mediating roles of positive affect and negative affect.

Objective: Although previous studies have noted that emotional intelligence (EI) might be a significant protective factor for aggressive behavior, the specific mechanisms involved is largely unknown. Based on the General Aggressive Model, this cross-sectional study aims to investigate whether EI will influence aggressive behavior through the mediating roles of positive affect (PA) and negative affect (NA). Methods: A total of 410 primary school students (45.4% females; Mage = 10.35, SD = 0.48, range from 10 to 11 years) from Shenzhen, China, completed questionnaires on EI, aggressive behavior, PA, and NA. SPSS 22.0 was used for reliability test and correlation analysis, and (Hayes, 2013) [1] PROCESS macro (Model 6) was used to examine the multiple mediation model. Results: The results show that (a) EI was negatively associated with children's aggressive behavior; (b) NA partially mediated the link between EI and aggressive behavior in children, and (c) PA and NA sequentially mediated the above link. Conclusion: This study would not only deepen our understanding of how EI is associated with aggressive behavior but also provide valuable suggestions for teachers and parents to more effectively prevent and intervene children's aggressive behavior.

Inhibition of NF-κB ameliorates aberrant retinal glia activation and inflammatory responses in streptozotocin-induced diabetic rats.

Background: To determine the anti-inflammatory effects of IMD-0354, a specific NF-κB blocker, on glial cells in rats with streptozotocin (STZ)-induced diabetic retinopathy (DR). Methods: The following four groups of rats were used: control, control + IMD-0354, STZ, and STZ + IMD-0354. After six weeks of STZ injection, diabetic rats and nondiabetic control rats received IMD-0354 (30 mg/kg) or an equal volume of 4% dimethyl sulfoxide (DMSO) in phosphate-buffered saline intraperitoneally for six consecutive weeks. The following four groups of primary rat retinal microglia and Müller cells were used: control (5 mM), control + IMD-0354, high glucose (20 mM), and high glucose + IMD-0354. The effects of IMD-0354 on nuclear factor-κB (NF-κB) activation, oxidative stress strength, expression of inflammatory cytokines and VEGF (vascular endothelial growth factor), activation of glial cells, and apoptosis of neuron cells were evaluated by immunohistochemistry, oxidative stress assays, western blot, enzyme linked immunosorbent assay (ELISA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining respectively. Results: Nuclear translocation of NF-κB was markedly increased in diabetic rat retina and high glucose treated glial cells. Systemic administration of IMD-0354 significantly inhibited NF-κB activation in both diabetic rat retina and high glucose treated glial cells, ameliorated oxidative injury, inflammatory responses, VEGF production and glial cell activation, and protected neurons from apoptosis. Conclusions: Our findings indicated that NF-κB activation is acritical step in the abnormal reactivity of glial cells in STZ-induced diabetic rats. Inhibition effect of IMD-0354 on NF-κB activation may represent a promising therapeutic strategy for DR via a variety of mechanisms, including inflammation reduction and glial cells regulation.

Trends and characteristics of multiple births in Baoan Shenzhen: A retrospective study over a decade.

Background: Shenzhen has the largest and youngest foreign population among all cities in China. The reproductive health of pregnant women from different backgrounds is a social issue that deserves attention. In the past decade, China has liberalized its population policies to stimulate population growth, and the proportion of multiple births has continued to increase. Method: This retrospective cohort included 526,654 newborns born in Baoan, Shenzhen, from January 1, 2009, to December 31, 2019, including 515,016 singletons and 11,638 twins or triplets. Univariate regression models were used to analyze the effects of maternal sociodemographic characteristics, physiological characteristics, medical history, antenatal care and other factors associated with single vs. multiple births and to elucidate the changing trends of different factors affecting multiple births in the past 11 years. Additionally, fetal development in multiple births was analyzed by generalized linear mixed models. Results: The rates of pregnancy complications, preterm birth, and advanced-age pregnancy were significantly higher in the multiple birth mothers than in single birth mothers, and more multiple pregnancies were achieved through assisted reproductive technologies. The rates of adverse outcomes such as stillbirth, malformation, hypoxia, and ultralow body weight in multiple fetuses were significantly higher than that in singleton fetuses. The trend analysis from 2009 to 2019 showed that the socioeconomic status and health level of mothers with multiple births improved over time, and the risk during pregnancy generally decreased. Simultaneously, the development indicators of multiple fetuses have improved year by year, and the proportion of adverse outcomes has also decreased significantly. A low pre-natal care utilization rate was shown to be detrimental to the development of multiple fetuses. Independent risk factors for hypoxia and very low birth weight were also identified. The differences in secular trends between two birth groups were further revealed by time series models. Conclusion: This study presented a comprehensive survey of multiple pregnancies in the area with the largest population inflow in China. This study identified the factors that affect the health of multiple birth mothers and their fetuses, particularly suggesting that preterm birth rates and the use of assisted reproduction remain high. The findings provide a basis for the formulation of individualized pre-natal care, assisted reproductive guidance and healthcare policies for multiple births.

MoSSe/Hf(Zr)S2 heterostructures used for efficient Z-scheme photocatalytic water-splitting.

Direct Z-scheme water-splitting is a promising route to enhancing the photocatalytic performance due to the effective separation of photogenerated carriers while simultaneously preserving the strong oxidation activity of holes and reduction activity of electrons. In this work, the MoSSe/XY2 (X = Hf, Zr; S, Se) heterostructures (HSs) with different contacts are proposed for Z-scheme photocatalytic water-spitting by first principles calculation. The separation of photogenerated carriers for HfSe2/SMoSe and ZrSe2/SMoSe HSs is limited by the type-I band alignment, while the hydrogen production ability of HfSe2/SeMoS and ZrSe2/SeMoS HSs is limited by the lower conduction band edge positions relative to the water reduction potential. The HfS2/SMoSe, HfS2/SeMoS, ZrS2/SMoSe, and ZrS2/SeMoS HSs are direct Z-scheme water-splitting photocatalysts with the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) occurring at the Hf(Zr)S2 layer and MoSSe layer, respectively. More excitingly, the S (or Se) vacancies effectively lower the HER overpotentials. Besides, the solar-to-hydrogen efficiencies are 6.1%, 5.9%, 6.4%, and 6.3% for HfS2/SMoSe, HfS2/SeMoS, ZrS2/SMoSe, and ZrS2/SeMoS HSs, respectively. This work paves the way for designing highly efficient overall water-splitting photocatalysts using 2D materials.

Three Monthly Injections Versus One Initial Injection of Ranibizumab for the Treatment of Macular Edema Secondary to Branch Retinal Vein Occlusion: 12-Month Results of a Prospective Randomized Study.

INTRODUCTION: To compare three monthly injections versus one initial injection of intravitreal ranibizumab (IVR) followed by pro re nata (PRN) dosing to treat macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: Seventy-four patients were randomized (1:1) to the 3 + PRN or 1 + PRN groups. Patients underwent monthly evaluations and additional IVR injections were administered if the retreatment criteria were met. The functional and anatomical outcomes were recorded. The factors associated with the improvement in best-corrected visual acuity (BCVA) were analyzed. RESULTS: Sixty-nine patients (93.2%) completed the study. At 12 months, the mean gain in BCVA was 12.9 letters in the 3 + PRN group and 14.3 letters in the 1 + PRN group, which was not significant (P = 0.59). The mean reduction in central macular thickness was 297.8 µm in the 3 + PRN group and 300.2 µm in the 1 + PRN group (P = 0.96). The macular vascular density changes of the superficial and deep capillary plexuses were not significantly different between the two groups (P = 0.99 and 0.70, respectively). The mean number of IVR injections was 5.0 in the 3 + PRN group and 4.2 in the 1 + PRN group (P = 0.17). The incidence of retinal neovascularization was similar in both groups (P = 0.67). The baseline BCVA, but not the treatment regimen, was significantly associated with the change in BCVA (P < 0.01). CONCLUSION: Significant gains in BCVA and maintenance of macular perfusion were achieved in BRVO eyes treated with the 3 + PRN or 1 + PRN regimens. Baseline BCVA was a prognostic factor for the visual improvement. TRIAL REGISTRATION: A prospective randomized controlled trial to compare the 1 + PRN and 3 + PRN regimen in the treatment of macular edema secondary to branch retinal vein occlusion (ChiCTR2000038086).

MiR-375 mitigates retinal angiogenesis by depressing the JAK2/STAT3 pathway.

Aberrant neovascularization in the retina is an important threat to vision and closely related to several retinal diseases, such as wet form of age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity. However, the pathogenesis remains largely unknown. MicroRNAs (miRNAs) have been demonstrated to play critical regulatory roles in angiogenesis. Therefore, we aimed to identify the key miRNAs that regulate retinal neovascularization and elucidate the potential underlying mechanisms. In the present study, we performed RNA sequencing of microRNAs in the retina and found that miR-375 was significantly downregulated in the retina of oxygen-induced retinopathy mice. In retinal microvascular endothelial cells (RMECs), overexpression of miR-375 inhibited cell proliferation and angiogenesis. Conversely, inhibition of miR-375 had the opposite effects. Moreover, our results showed that miR-375 negatively regulated the protein expression of JAK2 by inhibiting its translation. The promoting effects of anti-miR-375 on cell proliferation and angiogenesis were attenuated by an inhibitor of STAT3. These results indicate that miR-375 mitigates cell proliferation and angiogenesis, at least in part, through the JAK2/STAT3 pathway in RMECs, which implies an important underlying mechanism of retinal angiogenesis and provides potential therapeutic targets for retinal microangiopathy.

Wide-field swept-source OCT angiography of the periarterial capillary-free zone before and after anti-VEGF therapy for branch retinal vein occlusion.

BACKGROUND: The aim of the study was to investigate the changes in the periarterial capillary-free zone (paCFZ) after anti-vascular endothelial growth factor (VEGF) therapy in patients with branch retinal vein occlusion (BRVO) by wide-field swept-source optical coherence tomography angiography (SS-OCTA) and assess their associations with clinical outcomes. METHODS: In this retrospective observational study of 54 treatment-naïve BRVO patients with macular edema, we reviewed the findings of 12 × 12 mm2 SS-OCTA at baseline, 3, 6, and 12 months after intravitreal ranibizumab injections. The paCFZ and major retinal artery areas were measured on SS-OCTA images. The paCFZ area to artery area (P/A) ratio was calculated. RESULTS: The paCFZ areas and P/A ratios of first- and second-order arteries were significantly greater in BRVO eyes than in contralateral eyes (all P < 0.01), but there were no differences in the first- and second-order artery areas (P = 0.20 and 0.25, respectively). The paCFZ areas and P/A ratios decreased significantly at 3, 6, and 12 months after anti-VEGF therapy (all P < 0.01). The baseline P/A ratio was significantly correlated with the baseline best-corrected visual acuity (BCVA), central retinal thickness, and their improvements at 3, 6, and 12 months (all P < 0.05). Baseline BCVA and P/A ratios of first- and second-order arteries were independently associated with the final BCVA in multivariate linear regression. CONCLUSIONS: Wide-field SS-OCTA shows that anti-VEGF therapy can lead to a significant improvement in the paCFZ parameters in BRVO. Smaller baseline P/A ratios on SS-OCTA tend to predict better visual outcomes at 12 months after anti-VEGF therapy.

Ocular Manifestations in a Chinese Pedigree of Familial Amyloidotic Polyneuropathy Carrying the Transthyretin Mutation c.401A>G (p.Tyr134Cys)

Familial amyloid polyneuropathy (FAP) caused by a genetic mutation in transthyretin (TTR) is an autosomal dominant hereditary disease. The retrospective, observational case series study presents the ocular clinicopathological findings of five cases carrying the TTR mutation c.401A>G (p.Tyr134Cys). Multimodal retinal imaging and electrophysiological examination, Congo red staining and immunohistochemical analysis of specimens, and genetic analyses were performed. Cases 1 and 2 were symptomatic with vitreous and retinal amyloid deposition and poor visual recovery. Case 3 had a symptomatic vitreous haze in the left eye with good postoperative visual recovery. The right eye of case 3 and the eyes of cases 4 and 5 were asymptomatic. Thicker retinal nerve fiber layer, retinal venous tortuosity with prolonged arteriovenous passage time on fluorescein angiography and retinal dysfunction detected by multifocal electroretinogram occurred even in asymptomatic eyes. Moreover, the internal limiting membrane from patients with FAP was stained positive for Congo red and transforming growth factor-ß1. The results highlight the amyloid deposition of mutant TTR in the optic disc and retina, even in the asymptomatic stage. The deposited amyloid leads to increased resistance to venous return and retinal functional abnormalities. Therefore, careful follow-up of structural and functional changes in the retina is needed, even in asymptomatic patients with FAP.

Physiological response of barley seedlings to salinity and artemisinin combined stresses under freeze-thaw environment.

In the Qinghai-Tibet Plateau, both the large daily temperature difference and soil salinization make plants susceptible to abiotic stresses such as freeze-thaw and salinity. Meanwhile, crops in this area can be affected by artemisinin, an antimalarial secondary metabolite produced in Artemisia. Under freeze-thaw and salinity stresses, artemisinin was induced as an allelopathy stress factor to explore the physiological response of highland barley, including the relative electrical conductivity (RC), soluble protein (SP) content, malondialdehyde (MDA) content, antioxidant enzyme activity, and water use efficiency (WUE). Compared with the control group, the contents of RC and MDA in seedling leaves under stress were significantly increased by 24.74-402.37% and 20.18-77.95%, indicating that cell membrane permeability was greatly damaged, and WUE was significantly decreased by 15.77-238.59%. The activity of enzymes increased under single stress and decreased under combined stress. Salinity, artemisinin, and freeze-thaw stress show a synergistic relationship; that is, compound stresses were more serious than single stress. In summary, the results of this study revealed the physiological and ecological responses of barley seedlings under different habitat stresses and the interactions among different stress factors.

One-Year Efficacy and Safety of Proton-Beam Irradiation Combined with Intravitreal Conbercept for Refractory or Recurrent Polypoidal Choroidal Vasculopathy: A Pilot Study.

INTRODUCTION: To investigate the efficacy and safety of proton-beam irradiation (PBI) combined with intravitreal conbercept (IVC) injection for refractory or recurrent polypoidal choroidal vasculopathy (PCV). METHODS: A prospective interventional clinical trial included 12 patients with refractory PCV (defined as persistent exudation or fluid after six consecutive injections at monthly intervals and/or photodynamic therapy) or recurrent PCV (defined as new exudative signs after six monthly injections and/or photodynamic therapy) treated between January 2019 and September 2020. Every patient underwent single PBI (14 GyE) with concomitant IVC (0.5 mg) within 1 week and further doses of IVC were administered pro re nata. RESULTS: By the 12-month follow-up, the subretinal fluid was completely absorbed in 9 eyes (81.8%). The angiographic regression and closure rates of the polyps were 60% (12/20) and 90% (18/20), respectively. The mean number of IVC injections was 3.1 ± 1.37. The mean BCVA improved by 20 letters (P = 0.006). The mean central macular thickness (CMT) decreased from 476.50 ± 123.63 µm to 317.70 ± 89.34 µm (P = 0.004). The areas of branching vascular networks and polyps decreased by 37.2% and 72.3%, respectively. Radiation retinopathy was observed in five eyes, but no systemic adverse events were observed. CONCLUSION: PBI combined with IVC appears to promote polyp regression and closure, reduce CMT, and improve BCVA, with a favorable safety profile, after 12 months. Therefore, PBI may be a useful adjuvant therapy for patients with refractory or recurrent PCV. TRIAL REGISTRATION: Proton-Beam Irradiation Combined with Intravitreal Conbercept for Refractory or Recurrent Polypoidal Choroidal Vasculopathy: Prospective Phase II Clinical Study (ChiCTR2000038987).

M1 Bone Marrow-Derived Macrophage-Derived Extracellular Vesicles Inhibit Angiogenesis and Myocardial Regeneration Following Myocardial Infarction via the MALAT1/MicroRNA-25-3p/CDC42 Axis.

Myocardial infarction (MI) is a severe cardiovascular disease. Some M1 macrophage-derived extracellular vesicles (EVs) are involved in the inhibition of angiogenesis and acceleration dysfunction during MI. However, the potential mechanism of M1 phenotype bone marrow-derived macrophages- (BMMs-) EVs (M1-BMMs-EVs) in MI is largely unknown. This study sought to investigate whether M1-BMMs-EVs increased CDC42 expression and activated the MEK/ERK pathway by carrying lncRNA MALAT1 and competitively binding to miR-25-3p, thus inhibiting angiogenesis and myocardial regeneration after MI. After EV treatment, the cardiac function, infarct size, fibrosis, angiogenesis, and myocardial regeneration of MI mice and the viability, proliferation and angiogenesis of oxygen-glucose deprivation- (OGD-) treated myocardial microvascular endothelial cells (MMECs) were assessed. MALAT1 expression in MI mice, cells, and EVs was detected. MALAT1 downstream microRNAs (miRs), genes, and pathways were predicted and verified. MALAT1 and miR-25-3p were intervened to evaluate EV effects on OGD-treated cells. In MI mice, EV treatment aggravated MI and inhibited angiogenesis and myocardial regeneration. In OGD-treated cells, EV treatment suppressed cell viability, proliferation, and angiogenesis. MALAT1 was highly expressed in MI mice, OGD-treated MMECs, M1-BMMs, and EVs. Silencing MALAT1 weakened the inhibition of EV treatment on OGD-treated cells. MALAT1 sponged miR-25-3p to upregulate CDC42. miR-25-3p overexpression promoted OGD-treated cell viability, proliferation, and angiogenesis. The MEK/ERK pathway was activated after EV treatment. Collectively, M1-BMMs-EVs inhibited angiogenesis and myocardial regeneration following MI via the MALAT1/miR-25-3p/CDC42 axis and the MEK/ERK pathway activation.

Microstructural Design of Necklace-Like Fe3O4/Multiwall Carbon Nanotube (MWCNT) Composites with Enhanced Microwave Absorption Performance.

In order to manufacture microwave absorbers with strong attenuation abilities and that are light weight, in this paper, ferromagnetic carbon matrix composites were prepared by the composite of carbon nanotubes with adjustable dielectric constant and Fe3O4. Fe3O4/MWCNT composites with well-designed necklace-like structure and controllable size in the range of 100-400 nm have been successfully achieved by a simple solvent thermal method. A series of samples were prepared by changing experimental parameters. The microwave absorption characteristics of these samples were studied from the dielectric constant and magnetic permeability in two aspects. The electromagnetic absorption properties of the composites show obvious differences with different microsphere sizes, different microsphere density and different proportion of additives. When the solvothermal time is 15 h and the microsphere size is 400 nm, the reflection loss reaches -38 dB. The interfacial polarization caused by the unique structural design and good impedance matching produce composites that possess excellent electromagnetic loss ability.

Wide-Field Swept-Source Optical Coherence Tomography Angiography Analysis of the Periarterial Capillary-Free Zone in Branch Retinal Vein Occlusion.

Purpose: To investigate the characteristics of the retinal periarterial capillary-free zone (paCFZ) with wide-field swept-source optical coherence tomography angiography (SS-OCTA) in eyes with branch retinal vein occlusion (BRVO). Methods: Seventy treatment-naïve eyes with BRVO and 35 healthy eyes were included. The paCFZ areas, artery calibers, and areas of the major arteries in the unaffected quadrants of BRVO eyes were measured in 12 × 12-mm SS-OCTA images and compared with those of the contralateral eyes and healthy eyes. Other multimodal imaging data were collected. Results: There were no significant differences in the unaffected artery caliber or area among the three groups (all P > 0.05). The unaffected paCFZ areas and the ratios of the unaffected paCFZ area to the counterpart artery area (paCFZ/artery area) of the major arteries were significantly larger than those in the contralateral or healthy eyes (all P < 0.05). Subgroup analysis revealed that the paCFZ/artery area value differed significantly between ischemic and nonischemic BRVO eyes (P < 0.01). The paCFZ/artery area value was positively correlated with logMAR best-corrected visual acuity, symptom duration, central macular thickness, and retinal nonperfusion area in BRVO. Conclusions: Quantitative SS-OCTA measurements confirmed enlarged paCFZs along the unaffected major retinal arteries in BRVO eyes. The paCFZ parameters were correlated with symptom duration, retinal ischemia, and visual function. Translational Relevance: Retinal periarterial capillary-free zones in BRVO can be non-invasively measured by SS-OCTA, assisting in clinically identifying retinal ischemia and evaluating visual function.