Real-World Weekly Efficacy Analysis of Faricimab in Patients with Age-Related Macular Degeneration.

Objectives: This study entailed a weekly analysis of real-world data (RWD) on the safety and efficacy of intravitreal (IVT) faricimab in neovascular age-related macular degeneration (nAMD). Methods: A retrospective, single-centre clinical trial was conducted at the Department of Ophthalmology, University Hospital Zurich, University of Zurich, Switzerland, approved by the Cantonal Ethics Committee of Zurich, Switzerland. Patients with nAMD were included. Data from patient charts and imaging were analysed. The safety and efficacy of the first faricimab injection were evaluated weekly until 4 weeks after injection. Results: Sixty-three eyes with a complete 4-week follow-up were enrolled. Six eyes were treatment-naïve; fifty-seven eyes were switched to faricimab from another treatment. Neither group showed signs of retinal vasculitis during the 4 weeks after injection. Central subfield thickness (CST) and volume (CSV) showed a statistically significant decrease compared to the baseline in the switched group (CST: p = 0.00383; CSV: p = 0.00702) after 4 weeks. The corrected visual acuity returned to the baseline level in both groups. The macular neovascularization area decreased in both groups, but this was not statistically significant. A complete resolution of sub- and intraretinal fluid after 4 weeks was found in 40% (switched) and 75% (naïve) of the treated patients. Conclusions: The weekly follow-ups reflect the structure-function relationship beginning with a fast functional improvement within two weeks after injection followed by a return to near-baseline levels after week 3. The first faricimab injection in our cohort showed a high safety profile and a statistically significant reduction in macular oedema in switched nAMD patients.

Factors Associated with Success of Switching to Faricimab for Neovascular Age-Related Macular Degeneration Refractory to Intravitreal Aflibercept.

We investigated the factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The primary endpoint was a more than two-week extension of the treatment interval after 6 months. In addition, factors related to the success or failure of extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes from 43 patients. Extended dosing intervals of >2 weeks were identified in 14 eyes (32.6%). A short dosing interval before switching, absence of polypoidal lesions, and thin central choroidal thickness before switching were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend existing dosing intervals.

The Inhibitory Effect of Resveratrol from Reynoutria japonica on MNV-1, a Human Norovirus Surrogate.

As a natural nonflavonoid polyphenol compound, resveratrol is the main functional component of Reynoutria japonica and has anti-inflammatory, antioxidant, antiviral, and other physiological activities. In this study, the effect of resveratrol on the viability of RAW264.7 cells was examined, and murine norovirus (MNV-1) was used as a surrogate for human norovirus to evaluate the inhibitory effect of resveratrol. The concentrations of resveratrol resulting in 50% cytotoxicity (CC50) for RAW264.7 cells were 21.32 and 24.97 µg/mL after 24 and 48 h of incubation, respectively, and resveratrol at a concentration lower than the half-effective inhibitory concentration (EC50) could not damage cell DNA. The EC50 of resveratrol on MNV-1 in infected RAW264.7 cells was determined to equal 5.496 µg/mL. After RAW264.7 cells, virus, and a fresh mixture of virus and RAW264.7 cells were treated with resveratrol solution for 1 h (denoted cell pre-treatment, virus pre-treatment, and mixture coprocessing), the RAW264.7 cells obtained after cell pre-treatment exhibited lower virus infection, and MNV-1 obtained after virus pre-treatment and mixture coprocessing showed a decreased infectious capacity. The inhibition ratio of resveratrol on MNV-1 did not significantly differ between the treatments at 4 and 25 °C or among the various pH values except for the lower acidic condition (pH 2). TEM revealed significant changes in the morphology of MNV-1 after treatment with resveratrol, and molecular docking indicated that resveratrol strongly binds to the viral capsid protein of MNV-1. In addition, resveratrol regulated the expression of cytokine that protects against MNV-1 infection. Therefore, at a lower concentration, resveratrol, a natural component from Reynoutria japonica, exerts an inhibitory effect on MNV-1 growth and could be used as a safe additive in food products to improve the nutritional status and control norovirus.

Synergistic Strain Suppressing and Interface Engineering in Na4MnV(PO4)3/C for Wide-Temperature and Long-Calendar-Life Sodium-Ion Storage.

A Na4MnV(PO4)3 (NMVP) cathode is regarded as a promising cathode candidate for sodium-ion batteries (SIBs). However, issues such as low electronic conductivity and partial cation dissolution contribute to high polarization and structure distortion. Herein, we engineered the local electron density and reaction kinetic properties of NMVP cathodes with varying oxygen vacancies by introducing varying amounts of Zr doping and carbon coating. The optimized sample exhibited a high-rate capacity of 71.8 mAh g-1 at 30 C (83.1% capacity retention after 1000 cycles) and excellent performance over a wide temperature range (84.1 mAh g-1 at 60 °C and 61.4 mAh g-1 at -30 °C). In situ X-ray diffraction technology confirmed a redox solid solution and a two-phase reaction mechanism, revealing minor changes in cell volume and slight strain variations after Zr doping, effectively suppressing the structural distortion. Theoretical calculations illustrated that Zr doping largely shrinks the band gap of NMVP, enriches local electron density, and slightly alters the local element distribution and bond lengths. Moreover, full-cells have shown high energy density (259.9 Wh kg-1) and outstanding cycling stability (200 cycles). The work provides fresh insights into the synergistic effect of strain suppressing and interface engineering in promoting the development of wide temperature range and long-calendar-life SIBs.

Effect of Pro Re Nata Regimen with Anti-VEGF on Type 3 Macular Neovascularization: Long-Term Outcomes.

INTRODUCTION: The purpose of this study was to investigate long-term outcomes of intravitreal injections (IVI) of antivascular endothelial growth factor (VEGF) in neovascular age-related macular degeneration (nAMD) with type 3 macular neovascularization (MNV). METHODS: This retrospective study included 19 eyes of 17 patients with nAMD and type 3 MNV treated with anti-VEGF IVI with a loading dose and a PRN regimen. Best corrected visual acuity (BCVA), central macular thickness (CMT), presence of macular intraretinal fluid (IRF) and subretinal fluid (SRF), flow area (FA), subfoveal choroidal thickness (CT), and macular atrophy (MA) were assessed at baseline (T0) and during follow-up (T1, post-loading phase; T2, 1 year; T3, 2 years; T4 >2 years). The correlations between MA at the last follow-up and standard deviation (SD) values of CMT and CT during follow-up were assessed. The influence of the number of injections on the change in MA over time was also analyzed. MA differences at T4 were assessed for pseudodrusen presence. RESULTS: BCVA improved significantly during follow-up (p = 0.013) particularly increasing from baseline to post-loading phase and then did not modify significantly thereafter. CMT significantly reduced from T0 to T1 and remained stable during follow-up (p = <0.001). MNV flow area showed a trend toward an increase in the post-loading phase that was not statistically significant (p = 0.082) and CT decreased significantly during follow-up (p < 0.001). MA changed significantly during follow-up (p < 0.001) with a significant increase from T0 to T3 and from T0 to T4 (p < 0.010). A Cochran-Armitage test for trend showed a significant reduction (p = 0.001) of macular IRF and SRF during follow-up. MA at T4 showed a significant positive correlation with SD (standard deviation) values of CMT (p = 0.040) and CT (p = 0.020). Indeed, the number of injections did not influence the change over time of MA (p = 0.709). MA at T4 was not statistically significantly different between patients with pseudodrusen at baseline (p = 0.497). CONCLUSIONS: Intravitreal anti-VEGF injections with PRN regimen in MNV type 3 showed functional and anatomical benefits. Variations of retinal thickness and choroidal thickness during treatment were related to MA modification over time.

Fibronectin binds integrin α5ß1 to regulate macular neovascularization through the Wnt/ß-catenin signaling pathway.

Age-related macular degeneration (AMD) is a progressive, degenerative disease of the macula. The formation of macular neovascularization (MNV) and subretinal fibrosis of AMD is the most classic cause of the loss of vision in older adults worldwide. While the underlying causes of MNV and subretinal fibrosis remain elusive, the common feature of many common retinal diseases is changes the proportions of protein deposition in extracellular matrix (ECM) when compared to normal tissue. In ECM, fibronectin (FN) is a crucial component and plays a pivotal part not only in fibrotic diseases but also in the process of angiogenesis. The study aims to understand the role of ligand FN and its common integrin receptor α5ß1 on MNV, and to understand the molecular mechanism involved. To study this, the laser-induced MNV mouse model and the rhesus macaque choroid-retinal endothelial cell line (RF/6A) chemical hypoxia mode were established, and the FN-α5ß1 expression levels were detected by immunohistochemistry (IHC) and quantitative real-time PCR analysis (qRT-PCR). Fibronectin expression was silenced using small interfering RNA (siRNA) targeting FN. The tube formation and vitro scratch assays were used to assess the ability to form blood vessels and cell migration. To measure the formation of MNV, immunofluorescence, and Western blot assays were used. These results revealed that the expressions of FN and integrin α5ß1 were distinctly increased in the laser-induced MNV mouse model and in the RF/6A cytochemically induced hypoxia model, and the expression tendency was identical. After the use of FN siRNA, the tube formation and migration abilities of the RF/6A cells were lower, the ability of endothelial cells to proliferate was confined and the scope of damage caused by the laser in animal models was significantly cut down. In addition, FN gene knockdown dramatically inhibited the expression of Wnt/ß-catenin signal. The interaction of FN with the integrin receptor α5ß1 in the constructed model, which may act through the Wnt/ß-catenin signaling pathway, was confirmed in this study. In conclusion, FN may be a potential new molecular target for the prevention and treatment of subretinal fibrosis and MNV.

Long term follow up of patients with MNV3 treated with intra-vitreal Aflibercept.

PURPOSE: MNV3 or Retinal angiomatous proliferation is a subtype of neovascular age-related macular degeneration (nAMD). We present the 5 year long term visual and anatomical outcomes of patients with MNV3 lesions treated with intravitreal Aflibercept. METHODS: This is a prospective study of treatment naïve patients with reading centre graded MNV3 lesions. After the loading phase, the patients received intravitreal Aflibercept as per the View study up to year 3, thereafter it was given on a prn basis. At each visit, best corrected visual acuity (BCVA) and optical coherence tomography (OCT) central macular thickness (CMT) was measured. RESULTS: Thirty one patients reached study completion. Mean BCVA of treated eyes had decreased by 0.6 ETDRS letters at the end of year 5 compared with baseline. At study completion, 81% of eyes had stable vision while 19% of eyes had gained 15 letters or more. At study end, 26% of eyes had BCVA of 6/12 or better, while 19% had lost 15 letters or more (all had central foveal photoreceptor loss). There was a maximal mean reduction in CMT of 164 microns (p = <0.0001) while 68% of maculae were fluid free at study completion. Eighty seven percent of treated eyes developed nascent GA, of which in 74% of eyes was involving the fovea. DISCUSSION: Despite initial improvement in mean BCVA, the improvement in BCVA was not maintained despite good overall control of the MNV3 lesions. The loss of BCVA was most likely due to the majority of eyes developing centre involving macular atrophy.

Short-Term Outcomes of 3 Monthly intravitreal Faricimab On Different Subtypes of Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate the efficacy and safety of faricimab injections for treatment-naïve neovascular age-related macular degeneration (nvAMD) patients, including subtypes and pachychoroid phenotypes, and identify predictive factors for visual outcomes. Methods: nvAMD patients were prospectively recruited, receiving three monthly faricimab (6 mg) injections. Best-corrected visual acuity (BCVA) two months after the last injection (month 4) was compared between subtypes, and between pachychoroid neovasculopathy (PNV) and non-PNV eyes. Regression analysis determined factors influencing month 4 BCVA. Results: The study involved 23 patients (12 typical AMD [tAMD], 10 polypoidal choroidal vasculopathy [PCV], 1 retinal angiomatous proliferation [RAP]). Eleven exhibited PNV phenotype. Significant BCVA (P = 4.9 × 10-4) and central retinal thickness (CRT) (P = 1.3 × 10-5) improvements were observed post-faricimab treatment. The therapy demonstrated favourable results for both tAMD and PCV eyes, and non-PNV and PNV eyes. Faricimab achieved dry macula in 77.3% of eyes, with subretinal fluid resolution in most cases, although intraretinal fluid (IRF) often persisted. Multivariable analysis identified external limiting membrane (ELM) presence and IRF as BCVA contributors at month 4. Conclusion: Faricimab demonstrated significant effectiveness and safety in treatment-naïve nvAMD patients, particularly for PCV and PNV eyes. ELM presence and IRF is predictive of visual outcomes.

Changes in the Murine Microbiome and Bacterial Extracellular Vesicle Production in Response to Antibiotic Treatment and Norovirus Infection.

Norovirus infection is influenced by the presence of commensal bacteria, and both human and murine norovirus (MNV) bind to these bacteria. These virus-bacterial interactions, as well as MNV infection, promote the increased production of bacterial extracellular vesicles (bEVs). However, no correlation has been made between specific bacterial groups, their vesicles, and their impact on norovirus infection. The current study evaluated the impact of select bacterial compositions of murine microbiomes using antibiotic (ABX) cocktails on MNV infection and bEV production. The goal of this research was to determine if increases in bEVs following MNV infection in mice were associated with changes in specific bacterial populations. Bacterial taxa were found to be differentially abundant in both ABX-treated and untreated mice, with the greatest change in bacterial taxa seen in mice treated with a broad-spectrum ABX cocktail. Specifically, Lachnospiraeae were found to be differentially abundant between a variety of treatment factors, including MNV infection. Overall, these results demonstrate that MNV infection can alter the abundance of bacterial taxa within the microbiota, as well as their production of extracellular vesicles, and that the use of selective antibiotic treatments can allow the detection of viral impacts on the microbiome that might otherwise be masked.

Amino acid substitutions in norovirus VP1 dictate host dissemination via variations in cellular attachment.

IMPORTANCE: All viruses initiate infection by utilizing receptors to attach to target host cells. These virus-receptor interactions can therefore dictate viral replication and pathogenesis. Understanding the nature of virus-receptor interactions could also be important for the development of novel therapies. Noroviruses are non-enveloped icosahedral viruses of medical importance. They are a common cause of acute gastroenteritis with no approved vaccine or therapy and are a tractable model for studying fundamental virus biology. In this study, we utilized the murine norovirus model system to show that variation in a single amino acid of the major capsid protein alone can affect viral infectivity through improved attachment to suspension cells. Modulating plasma membrane mobility reduced infectivity, suggesting an importance of membrane mobility for receptor recruitment and/or receptor conformation. Furthermore, different substitutions at this site altered viral tissue distribution in a murine model, illustrating how in-host capsid evolution could influence viral infectivity and/or immune evasion.

[Long-term outcome of macular neovascularization secondary to choroidal osteoma with and without intravitreal anti-VEGF(vascular endothelial growth factor)- treatment]. / Langzeitverlauf von makulären Neovaskularisationen bei chorioidalen Osteomen mit und ohne intravitreale Anti-VEGF(vascular endothelial growth factor)-Therapie.

BACKGROUND: Choroidal osteoma (CO) is a benign ossifying ocular tumor, which is unilateral in most cases. The CO may cause severe visual impairment, especially in the case of a secondary macular neovascularization (MNV). OBJECTIVE: Based on a case series of patients with MNV secondary to CO, the variability of the clinical course with and without intravitreal anti-vascular endothelial growth factor (VEGF) treatment is presented. METHODS: All patients diagnosed with secondary MNV due to CO between 2007 and 2023 were retrospectively assessed with respect to the clinical course. RESULTS: In this study 7 eyes of 5 patients (4 women, 1 man) were diagnosed with secondary MNV due to CO. Intravitreal anti-VEGF treatment was carried out in 2 patients with unilateral MNV and 1 patient was treated in both eyes for bilateral MNV. In another case with bilateral MNV, only 1 eye was treated because of fibrosis in the other eye. A further case with unilateral CO and MNV scars at the initial diagnosis was left untreated. Overall, in 3 out of 5 eyes treated with intravitreal VEGF inhibition stabilization or improvement of visual acuity could be achieved. CONCLUSION: In our case series intravitreal anti-VEGF treatment attained a functional stabilization or improvement in 3 out of 5 treated eyes. In one case of CO-associated MNV fibrosis rapidly developed without treatment. Therefore, the clarification for patients with CO about the lifelong risk for development of a secondary MNV is essential in individual cases for early treatment. As no standardized treatment scheme for intravitreal VEGF antibodies for CO-related MNV exists, the treatment is planned on an individual basis.

Dome-shaped macula with protrusion of inner part of sclera.

Purpose: To report our findings in a patient with a two layered dome shaped macula (DSM) in which only the inner layer of the sclera protruded anteriorly. Observations: An 84-year-old woman with high myopia had a DSM in both eyes. The optical coherence tomographic (OCT) image of the left eye showed a uniform thickening of the foveal sclera, but the DSM of the right eye was split into an inner and outer layer by intrascleral blood vessels running between the two layers. OCT showed that only the inner layer of the sclera protruded anteriorly while the outer layer remained in its normal position. Conclusions and importance: The two layered DSM suggests that the etiology of DSMs may be more complex.

Spatial resolution of virus replication: RSV and cytoplasmic inclusion bodies.

Respiratory Syncytial Virus (RSV) is a major cause of respiratory illness in young children, elderly and immunocompromised individuals worldwide representing a severe burden for health systems. The urgent development of vaccines or specific antivirals against RSV is impaired by the lack of knowledge regarding its replication mechanisms. RSV is a negative-sense single-stranded RNA (ssRNA) virus belonging to the Mononegavirales order (MNV) which includes other viruses pathogenic to humans as Rabies (RabV), Ebola (EBOV), or measles (MeV) viruses. Transcription and replication of viral genomes occur within cytoplasmatic virus-induced spherical inclusions, commonly referred as inclusion bodies (IBs). Recently IBs were shown to exhibit properties of membrane-less organelles (MLO) arising by liquid-liquid phase separation (LLPS). Compartmentalization of viral RNA synthesis steps in viral-induced MLO is indeed a common feature of MNV. Strikingly these key compartments still remain mysterious. Most of our current knowledge on IBs relies on the use of fluorescence microscopy. The ability to fluorescently label IBs in cells has been key to uncover their dynamics and nature. The generation of recombinant viruses expressing a fluorescently-labeled viral protein and the immunolabeling or the expression of viral fusion proteins known to be recruited in IBs are some of the tools used to visualize IBs in infected cells. In this chapter, microscope techniques and the most relevant studies that have shed light on RSV IBs fundamental aspects, including biogenesis, organization and dynamics are being discussed and brought to light with the investigations carried out on other MNV.

Simulation of contamination and elimination of Escherichia coli, Listeria monocytogenes, and Murine norovirus 1 (MNV-1) from the washing process when handling of potatoes.

Root vegetables, which are in close contact with soil, are particularly vulnerable to soil contamination or decay as they can be contaminated from multiple sources, including primary production and processing. This study investigated effective washing conditions to reduce the microbial contamination of potatoes by using soaking and shaking in the washing process. The reduction of Escherichia coli, Listeria monocytogenes, and Murine norovirus 1 (MNV-1) in four washing processes (soaking only, shaking only, combined soaking-shaking I, and combined soaking-shaking I-shaking II) were compared. The numbers of E. coli and L. monocytogenes decreased by 0.55 and 0.49 log CFU/g after shaking only, 1.96 and 1.80 log CFU/g after soaking, 2.07 and 1.67 log CFU/g after soaking-shaking I, and 2.42 and 1.90 log CFU/g after soaking-shaking I-shaking II, respectively. The combined process reduced the microbial contamination more efficiently than shaking only. The reduction of E. coli in the washing process was higher than that of L. monocytogenes by approximately 0.5 logs. MNV-1 showed a reduction in the soaking and shaking steps by 1.34 and 1.98 log GC/100 g, with no significant reduction observed after the combination process. A combined process of soaking-shaking I-shaking II was effective to eliminate E. coli, L. monocytogenes, and MNV-1 from potatoes during the handling and washing process.

High-Rate-Capacity Cathode Based on Zn-Doped and Carbonized Polyacrylonitrile-Coated Na4MnV(PO4)3 for Sodium-Ion Batteries.

Na4MnV(PO4)3 (NMVP) is a promising cathode material for sodium-ion batteries (SIBs) because of its extraordinary three-dimensional structure that provides plenty of channels for sodium-ion migration. However, the unsatisfied electrical conductivity of NMVP limits its utilization in SIBs. Herein, Zn-doped NMVP with a uniform carbonized polyacrylonitrile (PAN) coating layer, named NMZVP@cPAN, was synthesized via a sol-gel method, and carbonized PAN was uniformly distributed on the surface of NMVP. Therefore, the NMZVP@cPAN cathodes exhibited an outstanding discharge capacity of 70.6 mA·h·g-1 at 30 C and remarkable cycling stability with an admirable retention of 89.64% after 1000 cycles at 5 C. Rietveld refinement and ex situ X-ray diffraction analyses were performed to determine the change in the crystal structure. Density functional theory calculations were performed to determine the effects of Zn doping on the density of states and the migration energy barriers. Finally, the NMZVP@cPAN cathodes were successfully modified and could be used in SIBs as NMVP cathodes.

Boosting cycling stability through Al(PO3)3 loading in a Na4MnV(PO4)3/C cathode for high-performance sodium-ion batteries.

Mn-based NASICON-type Na4MnV(PO4)3 (NMVP) has been widely investigated as one of the most promising alternatives to Na3V2(PO4)3 cathodes for sodium-ion batteries (SIBs) due to its higher energy density, higher abundance, and lower cost and toxicity compared to V. However, electrochemical performance for large-scale applications is limited by NMVP's inferior conductivity and structural degradation during cycling. Herein, a facile strategy to modify the surface/interphase properties of NMVP/C was reported using the thermally stable Al(PO3)3 precursor with a wet process followed by heat treatment to enhance the interface stability of electrodes. The nanomodified layer has the benefits of an ionic conductor (slight NaPO3) and robust composite (Al(PO3)3), which can facilitate the stability of Mn-based cathode materials and ionic conductivity. These merits endow 1 wt% Al(PO3)3-loaded NMVP/C cathodes with a high rate performance (102/61 mAh g-1 at 0.2/50 C) and impressive cyclability (88.5%/89.7% at 5 C/10 C after 3000/4000 cycles) in Na-ion batteries at 2.5-3.8 V. Moreover, when the cutoff voltage is raised to 4 V, improved electrochemical properties (111.6/50.8 mAh g-1 at 0.2/10 C and 71.4% after 1000 cycles at 5 C) are also realized. Such an enhancement indicates that facial surface modification engineering limits organic electrolyte erosion, inhibits transition metal dissolution and suppresses surface lattice degradation, which is confirmed by ex situ X-ray diffractometry and transmission electron microscopy. Therefore, the Al(PO3)3 surface modification strategy combined with mechanism analysis can provide a possible reference for advanced electrochemical properties in energy storage devices.

Impact of irrigation water quality on human norovirus surrogate survival during leafy green production.

Introduction: The impact of water quality on the survival of human norovirus (NoV) was determined in irrigation water field run-off (tail water) and well water from a representative Central Coast vegetable production site in the Salinas Valley, California. Methods: Tail water, well water, and ultrapure water samples were inoculated separately with two surrogate viruses for human NoV-Tulane virus (TV) and murine norovirus (MNV)-to achieve a titer of 1×105 plaque forming units (PFU)/ml. Samples were stored at 11, 19, and 24°C for 28 days. Additionally, inoculated water was applied to soil collected from a vegetable production site in the Salinas Valley or to the surface of growing romaine lettuce leaves, and virus infectivity was evaluated for 28 days in a growth chamber. Results: Virus survival was similar for water stored at 11, 19, and 24°C and there was no difference in infectivity based on water quality. After 28 days, a maximum 1.5 log reduction was observed for both TV and MNV. TV decreased by 1.97-2.26 log and MNV decreased by 1.28- 1.48 logs after 28 days in soil; infectivity was not influenced by water type. Infectious TV and MNV were recovered from lettuce surfaces for up to 7 and 10 days after inoculation, respectively. Across the experiments there was no significant impact of water quality on the stability of the human NoV surrogates. Discussion: Overall, the human NoV surrogates were highly stable in water with a less than 1.5 log reduction over 28 days and no difference observed based on the water quality. In soil, the titer of TV declined by approximately 2 logs over 28 days, while MNV declined by 1 log during the same time interval, suggesting surrogate-specific inactivation dynamics in the soil tested in this study. A 5-log reduction in MNV (day 10 post inoculation) and TV (day 14 post inoculation) was observed on lettuce leaves, and the inactivation kinetics were not significantly impacted by the quality of water used. These results suggest that human NoV would be highly stable in water, and the quality of the water (e.g., nutrient content, salinity, and turbidity) does not significantly impact viral infectivity.

Inhibition of AIF-1 alleviates laser-induced macular neovascularization by inhibiting endothelial cell proliferation via restrained p44/42 MAPK signaling pathway.

Age-related macular degeneration (AMD) is a leading blinding disease worldwide, and macular neovascularization (MNV) is a common complication encountered in the advanced stages of AMD. While the underlying causes of MNV remain elusive, aberrant multiplication of choroidal endothelial cells (CECs) and increased vascular endothelial growth factor (VEGF) are thought to play significant roles in the occurrence and development of MNV. Allograft inflammatory factor-1(AIF-1) is a crucial regulatory factor of vascular tubular structure formation and growth, involving the proliferation and migration of vascular endothelial cells and various tumor cells. This study aimed to understand how AIF-1 effects the proliferation of CECs and the subsequent progression of MNV. To study this, a mouse MNV model was established through laser injury, and the AIF-1 expression levels were then measured using western blot and immunohistochemistry. AIF-1 siRNA was intravitreally injected to silence AIF-1 gene expression. Western blot and choroidal flat mount were performed to measure the progression of MNV and proliferation of the CECs. These results showed that the protein expression of AIF-1 was significantly elevated in the laser-induced mouse MNV model, and the expression trend was consistent with VEGF. The protein level of AIF-1 was significantly decreased after the intravitreal injection of AIF-1 siRNA, the damage range of laser lesions was significantly reduced, and the proliferation of endothelial cells was inhibited. Knockdown of the AIF-1 gene significantly inhibited the expression of mitogen-activated protein kinase p44/42 in MNV lesions. In summary, this research demonstrates that AIF-1 promoted MNV progression by promoting the proliferation of CECs and that silencing AIF-1 significantly ameliorates MNV progression in mouse models, which may act through the p44/42 MAPK signaling pathway. AIF-1 could be a new potential molecular target for MNV.

OCTA Biomarker Search in Patients with nAMD: Influence of Retinal Fluid on Time-Dependent Biomarker Response.

PURPOSE: Previous studies have identified a link between optical coherence tomography (OCT)-derived and OCT angiography (OCTA)-based parameters in patients with neovascular AMD (nAMD); the latter may serve as direct biomarkers for macular neovascularization (MNV) activity. The aim of this study was to assess the individual influence of retinal thickness (RT) as well as intra- and sub-retinal fluid (IRF, SRF) presence on the treatment response over time as assessed by previously identified OCTA-derived MNV vascular parameters. METHODS: During the first 3 months of anti-VEGF therapy patients were prospectively followed. RT, SRF and IRF were determined from SSOCT/A (PlexElite, Zeiss) images and using the semi-automated AngioTool software, vessel area (VA), total vessel length (TVL), total number of junctions (TNJ), junction density (JD), vessel density (VD) as well as MNV area were exported. IRF and SRF were identified manually on OCT volume scans .The associations between RT, IRF, and SRF and SSOCTA vascular parameters were analyzed using linear mixed models. RESULTS: 31 eyes of 31 patients with treatment-naïve and OCTA-positive nAMD MNV were included in this analysis. VA, TVL, TNJ, and MNV area show a statistically significant change over time in response to anti-VEGF treatment, even after correcting for the presence of SRF, IRF, or RT (all p < 0.05). This is not the case for JD and VD (both p > 0.05). CONCLUSIONS: OCTA-based parameters VA, TVL, TNJ, and MNVarea show a strong response to anti-VEGF therapy over time, independent of the presence of IRF, SRF or RT. We conclude that the above listed OCTA parameters could contribute to our understanding of MNV biology and to guide individualized treatment in the future. TRIAL REGISTRY: The authors confirm that all ongoing and related trials are registered. ClinicalTrials.gov Number: NCT02521142.

Ultrafast Charge-Discharge Capable and Long-Life Na3.9 Mn0.95 Zr0.05 V(PO4 )3 /C Cathode Material for Advanced Sodium-Ion Batteries.

Na4 MnV(PO4 )3 /C (NMVP) has been considered an attractive cathode for sodium-ion batteries with higher working voltage and lower cost than Na3 V2 (PO4 )3 /C. However, the poor intrinsic electronic conductivity and Jahn-Teller distortion caused by Mn3+ inhibit its practical application. In this work, the remarkable effects of Zr-substitution on prompting electronic and Na-ion conductivity and also structural stabilization are reported. The optimized Na3.9 Mn0.95 Zr0.05 V(PO4 )3 /C sample shows ultrafast charge-discharge capability with discharge capacities of 108.8, 103.1, 99.1, and 88.0 mAh g-1 at 0.2, 1, 20, and 50 C, respectively, which is the best result for cation substituted NMVP samples reported so far. This sample also shows excellent cycling stability with a capacity retention of 81.2% at 1 C after 500 cycles. XRD analyses confirm the introduction of Zr into the lattice structure which expands the lattice volume and facilitates the Na+ diffusion. First-principle calculation indicates that Zr modification reduces the band gap energy and leads to increased electronic conductivity. In situ XRD analyses confirm the same structure evolution mechanism of the Zr-modified sample as pristine NMVP, however the strong ZrO bond obviously stabilizes the structure framework that ensures long-term cycling stability.