Long-term real-world outcomes of retinal microvasculature changes in proliferative diabetic retinopathy treated with panretinal photocoagulation vs. intravitreal conbercept.

PURPOSE: To compare long-term real-world outcomes of retinal microvasculature changes in proliferative diabetic retinopathy (PDR) treated with panretinal photocoagulation (PRP) vs. intravitreal conbercept (IVC) and to explore the potential factors affecting these changes. METHODS: This study retrospectively included 96 treatment-naïve PDR eyes of 96 type 2 diabetes mellitus patients [59 PRP and 37 IVC]. Baseline characteristics and treatment details were collected. Optical coherence tomography angiography (OCTA) data of macular vessel density (VD) and optic disc capillary density (CD) at baseline and at the last follow-up were compared between groups. The differences between the baseline and the last follow-up OCTA data in each group were also tested for significance. The correlation between the change in each OCTA parameter from baseline and each baseline characteristic/treatment parameter was investigated in each group. RESULTS: During a mean follow-up of two years, greater superficial (SCP) (p = 0.004) and deep capillary plexus (DCP) VD (p < 0.001) were observed in the foveal area in the PRP than in the IVC. Compared to the baseline, SCP VD in the foveal area increased in the PRP (p = 0.012), while an increased SCP VD in some sectors in the parafoveal and perifoveal areas (p < 0.05), rather than the foveal area (p = 0.908), was seen in the IVC. For both groups, eyes with a higher VD/CD at baseline tended to develop capillary dropout more intensively (all p < 0.05). In the IVC group, foveal avascular zone (FAZ) area change showed a negative correlation with baseline FAZ area (p = 0.020), and complementary PRP exerted a negative influence on FAZ area change (p = 0.002). In the PRP group, SCP VD change was positively correlated with follow-up frequency, and was negatively correlated with diastolic blood pressure (all p < 0.05); DCP VD change showed a positive correlation with PRP shot number (p = 0.019). CONCLUSION: The aforementioned microvasculature changes should be considered when PRP or IVC is adopted in PDR long-term management.

Multiverruca sinensis gen. nov., sp. nov., a thermotolerant fungus isolated from soil in China.

During a survey of thermotolerant fungi in China, three isolates were obtained from soil samples. Phylogenetic analysis of a combined internal transcribed spacer and large subunit dataset showed that these isolates belong to the same species, which form a well-separated lineage distinct from the other genera in Latoruaceae. Morphologically, the isolates are characterized by having globose and smooth conidiogenous cells, verruculose mycelium and cymbiform conidia. Combining the phylogenetic analyses and morphological characteristics, Multiverruca gen. nov. is proposed and introduced to accommodate a single new species, Multiverruca sinensis sp. nov. Detailed descriptions, illustrations and notes are provided for the new genus and species.

ERp29 Attenuates Nicotine-Induced Endoplasmic Reticulum Stress and Inhibits Choroidal Neovascularization.

Nicotine-induced endoplasmic reticulum (ER) stress in retinal pigment epithelium (RPE) cells is thought to be one pathological mechanism underlying age-related macular degeneration (AMD). ERp29 attenuates tobacco extract-induced ER stress and mitigates tight junction damage in RPE cells. Herein, we aimed to further investigate the role of ERp29 in nicotine-induced ER stress and choroidal neovascularization (CNV). We found that the expression of ERp29 and GRP78 in ARPE-19 cells was increased in response to nicotine exposure. Overexpression of ERp29 decreased the levels of GRP78 and the C/EBP homologous protein (CHOP). Knockdown of ERp29 increased the levels of GRP78 and CHOP while reducing the viability of ARPE-19 cells under nicotine exposure conditions. In the ARPE-19 cell/macrophage coculture system, overexpression of ERp29 decreased the levels of M2 markers and increased the levels of M1 markers. The viability, migration and tube formation of human umbilical vein endothelial cells (HUVECs) were inhibited by conditioned medium from the ERp29-overexpressing group. Moreover, overexpression of ERp29 inhibits the activity and growth of CNV in mice exposed to nicotine in vivo. Taken together, our results revealed that ERp29 attenuated nicotine-induced ER stress, regulated macrophage polarization and inhibited CNV.

Keratinophyton chongqingense sp. nov. and Keratinophyton sichuanense sp. nov., from soil in China.

Keratinophyton is a genus of well-known keratinophilic fungi found in various terrestrial habitats. During a survey of keratinolytic fungi in China, a total of 12 isolates of Keratinophyton species, representing eight taxa, were obtained from the soil. Two of these isolates were described as new species based on their morphological characteristics and molecular analyses of the internal transcribed spacer region and the rRNA gene of the nuclear large subunit. Descriptions and illustrations of these two novel species, which are named Keratinophyton chongqingense sp. nov. and Keratinophyton sichuanense sp. nov., are provided herein.

New taxonomic framework for Arthrodermataceae: a comprehensive analysis based on their phylogenetic reconstruction, divergence time estimation, phylogenetic split network, and phylogeography.

The Arthrodermataceae, or dermatophytes, are a major family in the Onygenales and important from a public health safety perspective. Here, based on sequenced and downloaded from GenBank sequences, the evolutionary relationships of Arthrodermataceae were comprehensively studied via phylogenetic reconstruction, divergence time estimation, phylogenetic split network, and phylogeography analysis. These results showed the clades Ctenomyces, Epidermophyton, Guarromyces, Lophophyton, Microsporum, Paraphyton, and Trichophyton were all monophyletic groups, whereas Arthroderma and Nannizzia were polyphyletic. Among them, Arthroderma includes at least four different clades, Arthroderma I, III and IV are new clades in Arthrodermataceae. Nannizzia contains at least two different clades, Nannizzia I and Nannizzia II, but Nannizzia II was a new clade in Arthrodermataceae. The unclassified group, distributed in Japan and India, was incorrectly identified; it should be a new clade in Arthrodermataceae. The phylogenetic split network based on the ITS sequences provided strong support for the true relationships among the lineages in the reconstructed phylogenetic tree. A haplotype phylogenetic network based on the ITS sequences was used to visualize species evolution and geographic lineages relationships in all genera except Trichophyton. The new framework provided here for the phylogeny and taxonomy of Arthrodermataceae will facilitate the rapid identification of species in the family, which should useful for evaluating the results of preventive measures and interventions, as well as for conducting epidemiological studies.

[Community composition and ecological functional structural analysis of endophytic fungi in bark of Eucommia ulmoides in different areas].

Based on high-throughput sequencing and metagenomic technology,the community composition and ecological functions of endophytic fungi in the bark of Eucommia ulmoides from three producing areas,Fengxiang town in Zunyi county of Guizhou province,Lingyang town of Cili county of Hunan province and Mumen town of Wangcang county of Sichuan province,were analyzed. A total of110 865 effective sequences of endophytic fungi were obtained in the study. The corresponding fungal group of OTUs after clustering belonged to 3 phyla( Ascomycota,Basidiomycota,Zygomycota),10 classes,25 orders,41 families,57 genera and 74 species. Among them,the dominant genera of Sichuan Wangcang Bark of E. ulmoides( EWP) was an unclassified genus in the Nectriaceae of the Crimsonaceae,with a relative abundance of 54. 79%; The dominant species of Hunan Cili Bark of E. ulmoides( ECP) was the unclassified genus of Ascomycota,with a relative abundance of 39. 97% and the dominant species of Guizhou Zunyi bark( EZP) was Lophiostoma,and its relative abundance was 47. 07%. The analysis of α diversity indicated that the shannon diversity index of endophytic fungi from different places was as follows: ECP: 1. 340 2>EZP: 1. 380 4 > EWP: 1. 168 3. The simpson diversity index was: EWP( 0. 427 3) >EZP( 0. 332 5) > ECP( 0. 313 6). FUNGuild software platform analysis displayed that endophytic fungi of E. ulmoides bark from three producing areas contained the following 14 functional groups: plant pathogen,animal pathogen and endophyte et al.,the number of functional groups in the 3 samples of E. ulmoides reached up 8 genera and exceeded one half of the total number. Correlation analysis of Canonical correspondence analysis( CCA) between endophytic fungal community diversity and four active compounds of E. ulmoides were analyzed,the results showed that the contents of pinoresinol diglucoside and chlorogenic acid,to a certain extend,had a positive correlation with an unclassified genus of Davidiellaceae,Mortierella,Chaetomium and Pestalotiopsis from the endophytic fungi in EWP sample.

Nitric oxide mediates hypocrellin accumulation induced by fungal elicitor in submerged cultures of Shiraia bambusicola.

Multiple responses of Shiraia bambusicola, including nitric oxide (NO) generation, hypocrellins production and salicylic acid (SA) biosynthesis, were induced by a fungal elicitor prepared from the mycelium of Aspergillum niger. Both the NO donator, sodium nitroprusside, and SA enhanced hypocrellin production without the fungal elicitor. However, the NO scavenger, 2,4-carboxyphenyl-4,4, 5,5- tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) and the SA biosynthesis inhibitor, cinnamic acid (CA), inhibited hypocrellin accumulation in the presence of the elicitor. cPTIO also inhibited SA production induced by the A. niger elicitor. CA failed to inhibit NO production but it significantly inhibited hypocrellin accumulation. Aspergillum niger elicitor induced an NO burst, SA accumulation, and hypocrellin production in S. bambusicola. Therefore, the fungal elicitor was involved in the signaling pathway, which is a mechanism different from that of higher plants.

A randomized non-inferiority trial of 577nm subthreshold micropulse laser versus half-dose photodynamic therapy for acute central serous chorioretinopathy.

PURPOSE: To compare the effectiveness of 577nm subthreshold micropulse laser (SML) with half-dose photodynamic therapy (Hd-PDT) for acute central serous chorioretinopathy (CSC). METHOD: A non-inferiority clinical trial was performed with a non-inferiority margin of eight letters. Sixty-eight eyes of 68 patients with acute CSC were randomized to the Hd-PDT group or 577 nm SML group. Best-corrected visual acuity (BCVA ), the subretinal fluid (SRF), and the central foveal thickness (CFT) were evaluated at 6 months. RESULTS: The visual acuity significantly improved from 70.38 ± 10.37 at baseline to 83.24 ± 3.03 at 6 months after treatment in the SML group (P < 0.001), from 71.09 ± 10.50 to 84.35 ± 2.09 in the PDT group (P < 0.001). SML was non-inferior to the PDT (mean difference: -0.41, 95% CI: -5.51 - 4.68, P = 0.0021). At the endpoint, CFT was significantly reduced in the two groups, but no statistical difference (P = 0.7694). The complete resolution of SRF reached 82.35% (28/34) in the SML group and 91.18% (31/34) in the PDT group, respectively,but no statistical difference (P = 0.3724). CONCLUSIONS: SML was non-inferiority to half-dose PDT in improving the visual acuity for CSC, and it is a viable alternative, especially when the verteporfin in PDT is unavailable.

Two new species of Sordariomycetes (Chaetomiaceae and Nectriaceae) from China.

Rich and diverse fungal species occur in different habitats on the earth. Many new taxa are being reported and described in increasing numbers with the advent of molecular phylogenetics. However, there are still a number of unknown fungi that have not yet been discovered and described. During a survey of fungal diversity in different habitats in China, we identified and proposed two new species, based on the morphology and multi-gene phylogenetic analyses. Herein, we report the descriptions, illustrations and molecular phylogeny of the two new species, Bisifusariumkeratinophilumsp. nov. and Ovatosporasinensissp. nov.

Two new species and one new combination of Ophiocordyceps (Hypocreales, Ophiocordycipitaceae) in Guizhou.

Ophiocordyceps is the largest genus in Ophiocordycipitaceae and has a broad distribution with high diversity in subtropical and tropical regions. In this study, two new species, pathogenic on lepidopteran larvae are introduced, based on morphological observation and molecular phylogeny. Ophiocordycepsfenggangensissp. nov. is characterised by having fibrous, stalked stroma with a sterile tip, immersed perithecia, cylindrical asci and filiform ascospores disarticulating into secondary spores. Ophiocordycepsliangiisp. nov. has the characteristics of fibrous, brown, stipitate, filiform stroma, superficial perithecia, cylindrical asci and cylindrical-filiform, non-disarticulating ascospores. A new combination Ophiocordycepsmusicaudata (syn. Cordycepsmusicaudata) is established employing molecular analysis and morphological characteristics. Ophiocordycepsmusicaudata is characterised by wiry, stipitate, solitary, paired to multiple stromata, yellowish, branched fertile part, brown stipe, immersed perithecia, cylindrical asci and cylindrical-filiform, non-disarticulating ascospores.

Long-Term Real-World Outcomes of Corneal Changes in Proliferative Diabetic Retinopathy: Panretinal Photocoagulation vs. Intravitreal Conbercept.

PURPOSE: To compare long-term real-world outcomes of corneal thickness (CT) alterations in proliferative diabetic retinopathy (PDR) patients treated with panretinal photocoagulation (PRP) and intravitreal conbercept (IVC). METHODS: This retrospective study included 69 eyes of 69 patients with PDR (42 PRP and 27 IVC). Full corneal thickness (FCT), corneal epithelial thickness (CET) and corneal stromal thickness (CST) measured by anterior segment optical coherence tomography at baseline were compared between groups. These CT changes at last follow-up from baseline were also compared between groups and within each group. RESULTS: During a mean follow-up of more than two years, the IVC group demonstrated a significantly increased corneal thickness from baseline compared to the PRP group in some areas (PRP vs. IVC: FCT 0-2 mm: -0.59 ± 9.31 vs. 5.59 ± 9.23 µm, p = 0.009; CST 0-2 mm: -2.05 ± 8.79 vs. 3.48 ± 7.52 µm, p = 0.015; CST 2-5 mm: -1.78 ± 13.27 vs. 5.68 ± 14.53 µm, p = 0.046). In within-group comparisons, a significantly increased FCT from baseline was found in the 0-2 mm area in the IVC group (p = 0.004), but no significant change was observed in the PRP group (p = 0.691). For CET changes, a significantly increased CT was observed in the 0-2 mm, 2-5 mm and 5-7 mm areas in both groups respectively (all p < 0.05). Regarding CST, an increased CT was found in the 0-2 mm area in the IVC group (p = 0.037), while a decreased trend was observed in 0-2 mm and 2-5 mm areas in the PRP group (all p > 0.05). CONCLUSION: When using PRP or IVC in the long-term management of PDR, CT changes should be considered. This may provide evidence for corneal protection during PDR treatment.

Culturable fungi from urban soils in China II, with the description of 18 novel species in Ascomycota (Dothideomycetes, Eurotiomycetes, Leotiomycetes and Sordariomycetes).

As China's urbanisation continues to advance, more people are choosing to live in cities. However, this trend has a significant impact on the natural ecosystem. For instance, the accumulation of keratin-rich substrates in urban habitats has led to an increase in keratinophilic microbes. Despite this, there is still a limited amount of research on the prevalence of keratinophilic fungi in urban areas. Fortunately, our group has conducted in-depth investigations into this topic since 2015. Through our research, we have discovered a significant amount of keratinophilic fungi in soil samples collected from various urban areas in China. In this study, we have identified and characterised 18 new species through the integration of morphological and phylogenetic analyses. These findings reveal the presence of numerous unexplored fungal taxa in urban habitats, emphasising the need for further taxonomic research in urban China.

Changes of microstructure of central serous chorioretinopathy on OCT and its relationship with prognosis.

PURPOSE: To quantitatively evaluate the relationship between retinal microstructure and prognosis in patients with central serous chorioretinopathy(CSC) using optical coherence tomography(OCT). METHODS: Three hundred and ninty-eight affected eyes of patients with central serous chorioretinopathy were included in this retrospective study. The OCT images of all patients were analyzed in baseline, and logistic regression analysis were performed with 11 independent variables, and subretinal fluid absorption in 3 months after therapy as dependent variable. The correlation between shortage of ellipsoid baseline and height of foveal subretinal fluid, width of foveal subretinal fluid were analyzed respectively. The difference of duration and baseline logMAR visual acuity in eyes with and without double layer sign or subretinal hyper-reflective materials were analyzed respectively. The difference of therapeutic outcome among different therapeutic methods was also analyzed in eyes with double-layer sign and subretinal hyper-reflective materials respectively. RESULTS: In the regression analysis with subretinal fluid absorption in 3 months after therapy as dependent variable, disintegrity of ellipsoid zone was statistically significant(P<0.0001,B=1.288). There is no correlation between disintegrity of the ellipsoid zone and the width or height of subretinal fluid. The duration of disease in eyes with double layer sign or subretinal hyper-reflective materials was longer than those without these features(P<0.001, P<0.0001). In the eyes with the double-layer sign or subretinal hyper-reflective material, the difference of logMAR visual acuity 3 months after treatment between 2 therapeutic methods was not statistically significant. CONCLUSIONS: Using optical coherence tomography to evaluate microstructure changes in eyes with central serous chorioretinopathy quantitatively, we found that subretinal fluid was easier to absorb completely in eyes with less disintegrity of ellipsoid zone. Double layer sign and subretinal hyper-reflective materials are more common in eyes with longer duration of disease.

Study on species diversity of Akanthomyces (Cordycipitaceae, Hypocreales) in the Jinyun Mountains, Chongqing, China.

Akanthomyces species have only been reported from Guizhou and Qinghai Province, with few reports from other regions in China. In this research, the species diversity of Akanthomyces in the Jinyun Mountains, Chongqing was investigated. Fourteen infected spider specimens were collected and two new species (A.bashanensis and A.beibeiensis) and a known species (A.tiankengensis) were established and described according to a multi-locus phylogenetic analysis and the morphological characteristics. Our results reveal abundant Akanthomyces specimens and three species were found at Jinyun Mountain. Due to its being an important kind of entomopathogenic fungi, further attention needs to be paid to the diversity of other entomopathogenic fungi in Chongqing, China.

Two new species of Samsoniella (Cordycipitaceae, Hypocreales) from the Mayao River Valley, Guizhou, China.

Samsoniella species have been often found in the forest habitat and rarely found in special karst eco-environments, such as Tiankeng, valleys and caves. In this research, eleven cordyceps specimens were collected from Mayao River Valley. A known species (S.haniana) and two new species (S.duyunensis and S.vallis) were established and described according to a multilocus phylogenetic analysis and morphological characteristics. Our results provide insight that the richness of Samsoniella species in karst eco-environments and further attention should be paid to entomopathogenic fungi in such habitats.

Twenty-year outcome in neovascular age-related macular degeneration treated with photodynamic therapy and intravitreal bevacizumab/ranibizumab injections: A case report.

A 64-year-old female presented with acute painless vision loss in the left eye was diagnosed with neovascular age-related macular degeneration. During the 20-year follow-up, the patient experienced subretinal fluid, subretinal hemorrhage, pigmentary epithelium detachment, intraretinal fluid, subretinal scar formation and macular atrophy. A total of 3 PDT treatments, 3 intravitreal bevacizumab and 16 ranibizumab injections were performed in the left eye. At the last visit, she remained best-corrected visual acuity of 20/200 with foveal macular atrophy and subfoveal fibrotic scar.

Taxonomy and Phylogeny of Eight New Acrophialophora Species (Sordariales, Chaetomiaceae) from China.

The genus Acrophialophora belongs to the family Chaetomiaceae. With the addition of new species and transferred species from other genera, the genus Acrophialophora has expanded. In this study, eight new species related to Acrophialophora were isolated from soil samples in China. Using muti-locus phylogenetic (ITS, LSU, tub2 and RPB2) analysis combined with morphological characteristics, eight new species (Acrophialophora curvata, A. fujianensis, A. guangdongensis, A. longicatenata, A. minuta, A. multiforma, A. rhombica, and A. yunnanensis) are described. Descriptions, illustrations, and notes of the new species are also provided.

Retinal and Choroidal Alterations in Diabetic Retinopathy Treatment using Subthreshold Panretinal Photocoagulation with Endpoint Management Algorithm: A Secondary Analysis of a Randomized Clinical Trial.

INTRODUCTION: The aim of this study was to compare retinal and choroidal alterations in eyes with severe nonproliferative diabetic retinopathy (NPDR) after panretinal photocoagulation (PRP), using conventional pattern scan laser (PASCAL) and PASCAL with endpoint management (EPM). METHODS: This was a post hoc analysis of a paired randomized clinical trial. Bilateral treatment-naïve eyes of an individual with symmetric severe NPDR were randomly allocated into the threshold PRP group and subthreshold EPM PRP group. Patients had follow-up visits at 1, 3, 6, 9, and 12 months post-treatment. The retinal thickness (RT), choroidal thickness (CT), choroidal area, and choroidal vascularity index (CVI) were compared between the two groups and among different time points within the same group. RESULTS: Seventy eyes of 35 patients with diabetes mellitus (DM) were finally included for analysis at the 6- and 12-month visits, respectively. At 3 and 6 months post-treatment, the RT in the subthreshold EPM PRP group was significantly thinner than that in the threshold PRP group. CT, stromal area, and luminal area were reduced earlier in the threshold PRP group than in the subthreshold EPM PRP group. CVI was not significantly different within the same group or between groups at most time points. CONCLUSION: At 12 months post-treatment, retinal thickening and choroidal disturbance may be slightly less severe and more delayed in eyes receiving PRP using PASCAL with EPM than in those receiving PRP using conventional PASCAL. The EPM algorithm may be a good alternative in PRP when treating severe NPDR. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01759121.

Assessing the Association Between Lead Pollution and Risk of Alzheimer's Disease by Integrating Multigenomics.

Alzheimer's disease (AD) is a life-threatening neurodegenerative disease of the elderly. In recent observations, exposure to heavy metals environmental may increase the risk of AD. However, there are few studies on the causal relationship between heavy metal exposure and AD. In this study, we integrated two large-scale summaries of AD genome-wide association study (GWAS) datasets and a blood lead level GWAS dataset and performed the two-sample Mendelian randomization analysis to assess the causality of blood lead level and AD risk. The results showed that there is a significantly positive causality between blood lead level and AD risk both in the inverse-variance weighted (IVW) model and the weighted median estimator (WME) model. An independent additional verification also reached a consistent conclusion. These findings further confirm the conclusions of previous studies and improve the understanding of the relationship between AD pathogenesis and the toxicity of lead in environmental pollution.

Multigene phylogeny, phylogenetic network, and morphological characterizations reveal four new arthropod-associated Simplicillium species and their evolutional relationship.

Simplicillium species are widely distributed and commonly found on various substrates. A minority of species are associated with arthropods. A spider-associated species Simplicillium araneae, and three insect-associated species, Simplicillium coleopterorum, Simplicillium guizhouense, and Simplicillium larvatum, are proposed as novel species based on a multi-locus phylogenetic analysis and morphological characteristics. These Simplicillium species completely fit the nutritional model of Hypocreales fungi and could be used as a model to study their evolutionary relationship. A phylogenetic network analysis based on ITS sequences suggests that a host jump was common among Simplicillium species, and S. araneae may have originally come from an insect host and then jumped to a spider host. However, the evolutionary relationship of S. coleopterorum, S. guizhouense, and S. larvatum was not clear in the phylogenetic network and more sequencing information should be added to the network. In addition, strain CBS 101267 was identified as Simplicillium subtropicum.