A feed-forward relay integrates the regulatory activities of Bicoid and Orthodenticle via sequential binding to suboptimal sites.

The K50 (lysine at amino acid position 50) homeodomain (HD) protein Orthodenticle (Otd) is critical for anterior patterning and brain and eye development in most metazoans. In Drosophila melanogaster, another K50HD protein, Bicoid (Bcd), has evolved to replace Otd's ancestral function in embryo patterning. Bcd is distributed as a long-range maternal gradient and activates transcription of a large number of target genes, including otd Otd and Bcd bind similar DNA sequences in vitro, but how their transcriptional activities are integrated to pattern anterior regions of the embryo is unknown. Here we define three major classes of enhancers that are differentially sensitive to binding and transcriptional activation by Bcd and Otd. Class 1 enhancers are initially activated by Bcd, and activation is transferred to Otd via a feed-forward relay (FFR) that involves sequential binding of the two proteins to the same DNA motif. Class 2 enhancers are activated by Bcd and maintained by an Otd-independent mechanism. Class 3 enhancers are never bound by Bcd, but Otd binds and activates them in a second wave of zygotic transcription. The specific activities of enhancers in each class are mediated by DNA motif variants preferentially bound by Bcd or Otd and the presence or absence of sites for cofactors that interact with these proteins. Our results define specific patterning roles for Bcd and Otd and provide mechanisms for coordinating the precise timing of gene expression patterns during embryonic development.

Abscisic acid inhibits primary root growth by impairing ABI4-mediated cell cycle and auxin biosynthesis.

Cell cycle progression and the phytohormones auxin and abscisic acid (ABA) play key roles in primary root growth, but how ABA mediates the transcription of cell cycle-related genes and the mechanism of crosstalk between ABA and auxin requires further research. Here, we report that ABA inhibits primary root growth by regulating the ABA INSENSITIVE4 (ABI4)-CYCLIN-DEPENDENT KINASE B2;2 (CDKB2;2)/CYCLIN B1;1 (CYCB1;1) module-mediated cell cycle as well as auxin biosynthesis in Arabidopsis (Arabidopsis thaliana). ABA induced ABI4 transcription in the primary root tip, and the abi4 mutant showed an ABA-insensitive phenotype in primary root growth. Compared with the wild type (WT), the meristem size and cell number of the primary root in abi4 increased in response to ABA. Further, the transcription levels of several cell-cycle positive regulator genes, including CDKB2;2 and CYCB1;1, were upregulated in abi4 primary root tips. Subsequent chromatin immunoprecipitation (ChIP)-seq, ChIP-qPCR, and biochemical analysis revealed that ABI4 repressed the expression of CDKB2;2 and CYCB1;1 by physically interacting with their promoters. Genetic analysis demonstrated that overexpression of CDKB2;2 or CYCB1;1 fully rescued the shorter primary root phenotype of ABI4-overexpression lines, and consistently, abi4/cdkb2;2-cr or abi4/cycb1;1-cr double mutations largely rescued the ABA-insensitive phenotype of abi4 with regard to primary root growth. The expression levels of DR5promoter-GFP and PIN1promoter::PIN1-GFP in abi4 primary root tips were significantly higher than those in WT after ABA treatment, with these changes being consistent with changes in auxin concentration and expression patterns of auxin biosynthesis genes. Taken together, these findings indicated that ABA inhibits primary root growth through ABI4-mediated cell cycle and auxin-related regulatory pathways.

PIF4 interacts with ABI4 to serve as a transcriptional activator complex to promote seed dormancy by enhancing ABA biosynthesis and signaling.

Transcriptional regulation plays a key role in the control of seed dormancy, and many transcription factors (TFs) have been documented. However, the mechanisms underlying the interactions between different TFs within a transcriptional complex regulating seed dormancy remain largely unknown. Here, we showed that TF PHYTOCHROME-INTERACTING FACTOR4 (PIF4) physically interacted with the abscisic acid (ABA) signaling responsive TF ABSCISIC ACID INSENSITIVE4 (ABI4) to act as a transcriptional complex to promote ABA biosynthesis and signaling, finally deepening primary seed dormancy. Both pif4 and abi4 single mutants exhibited a decreased primary seed dormancy phenotype, with a synergistic effect in the pif4/abi4 double mutant. PIF4 binds to ABI4 to form a heterodimer, and ABI4 stabilizes PIF4 at the protein level, whereas PIF4 does not affect the protein stabilization of ABI4. Subsequently, both TFs independently and synergistically promoted the expression of ABI4 and NCED6, a key gene for ABA anabolism. The genetic evidence is also consistent with the phenotypic, physiological and biochemical analysis results. Altogether, this study revealed a transcriptional regulatory cascade in which the PIF4-ABI4 transcriptional activator complex synergistically enhanced seed dormancy by facilitating ABA biosynthesis and signaling.

TIM3/CEACAM1 pathway involves in myeloid-derived suppressor cells induced CD8+ T cells exhaustion and bone marrow inflammatory microenvironment in myelodysplastic syndrome.

Myeloid-derived suppressor cells (MDSC) induced cellular immune deficiency and bone marrow inflammatory microenvironment play an important role in the pathogenesis and progression of myelodysplastic syndrome (MDS), but the underlying mechanism remains unclear. Here, we revealed that immune checkpoint protein TIM3 and CEACAM1 were highly demonstrated on MDSC and CD8+ T cells in MDS patients. CD8+ T cells were reduced in number and function and presented a exhaustion state. The levels of pro-inflammatory cytokines (IL-1ß, IL-18) and CEACAM1 were raised in bone marrow supernatants and MDSC culture supernatants. Blocking or neutralizing TIM3/CEACAM1 and IL-1ß/IL-18 partially reversed exhaustion of CD8+ T cells. Moreover, TIM3 correlated with NF-κB /NLRP3 inflammatory pathway. The levels of NF-κB/NLRP3/Caspase-1/IL-1ß and IL-18 were all increased in MDSC of MDS. Co-culturing MDSC from MDS patients with rhCEACAM1 enhanced NF-κB/NLRP3/Caspase-1/IL-1ß and IL-18 levels, whereas blocking TIM3 could partially reverse the above manifestations. These results indicated that TIM3/CEACAM1 pathway involved in CD8+ T cells exhaustion and might activate the NF-κB/NLRP3/Caspase-1 pathway in MDSC, increasing pro-inflammatory cytokines secretion in MDS bone marrow microenvironment. This study provided a basis for applying immune checkpoint inhibitors that could simultaneously modulate pro-inflammatory cytokine secretion and enhance anti-tumour immune function in the treatment of MDS.

Corneal subbasal nerve analysis in patients with primary Sjogren's syndrome: a novel objective grading method and clinical correlations.

PURPOSE: To investigate corneal sub-basal nerve morphology changes in primary Sjogren's syndrome (SS) dry eye (SSDE) patients and determine the association with disease severity at microstructural level. METHODS: Twenty-eight eyes of 17 SSDE and 82 eyes of 47 age- and sex-matched non-SS dry eye (NSSDE) patients were included. The Ocular Surface Disease Index questionnaire (OSDI), Schirmer's test (ST), tear meniscus height (TMH), non-invasive breakup time (NIBUT), meibomian gland (MG) morphology, and ocular staining score (OSS) were assessed. In vivo confocal microscopy was performed to observe corneal sub-basal nerve morphology (length, reflectivity, width, and tortuosity). Associations between clinical features and nerve parameters were analysed. RESULTS: SSDE patients more frequently had increased nerve reflectivity (151.12 ± 17.07 vs. 139.37 ± 14.31 grey value), width (4.45 ± 0.87 vs. 3.92 ± 0.81 µm), tortuosity (132.90 ± 8.04 vs. 129.50 ± 7.33 degree), and higher reflectivity, width, and total nerve grades than NSSDE individuals (all P < 0.05). Significant associations were found between nerve reflectivity/width and anti-SSA [OR = 1.139 (1.013-1.281)/1.802 (1.013-4.465)]/labial gland biopsy [OR = 1.046 (1.002-1.161)/1.616 (1.020-3.243)]. Higher nerve width was associated with increased OSDI [ß = 0.284 (0.187-0.455)], MG score [ß = 0.185 (0.109-0.300)] and OSS [ß = 0.163 (0.020-0.345)], but decreased NIBUT [ß = - 0.247 (- 0.548 ~ - 0.154)]. Higher nerve total grade was associated with increased OSDI [ß = 0.418 (0.157-0.793)] and OSS [ß = 0.287 (0.027-0.547)], but decreased ST [ß = - 0.410 (-0.857 ~ - 0.138)]. CONCLUSIONS: Corneal nerve morphology changes associated with clinical features in SS patients. These changes may facilitate severity evaluation and management of the disease.

Change patterns in the corneal sub-basal nerve and corneal aberrations in patients with dry eye disease: An artificial intelligence analysis.

We aimed to investigate the change patterns in corneal sub-basal nerve morphology and corneal intrinsic aberrations in dry eye disease (DED). Our study included 229 eyes of 155 patients with DED and 40 eyes of 20 healthy control. We used the Oculus keratograph and the ocular surface disease index questionnaire to assess their signs and symptoms. In vivo confocal microscopy was used to observe the corneal sub-basal nerves, corneal endothelial cells, and Langerhans cells (LCs). An artificial intelligence (AI) technique run by the deep learning model generated the sub-basal nerve fibre parameters. Furthermore, we used the Pentacam HR system to measure the corneal intrinsic aberrations and corneal surface regularity indices. DED patients more frequently had increased anterior and total corneal aberrations than controls (P < 0.05). In addition, DED had decreased average density and maximum length of corneal nerve. (Both P < 0.01) The LC number was significantly correlated with maximum length (CC = -0.19, P = 0.01) of the sub-basal nerve fibre. Furthermore, the corneal nerve average density was negatively correlated with IHD, and anterior, posterior, and total corneal aberrations (All P < 0.05) especially the higher-order aberrations. Significant correlations were seen between corneal nerve morphology changes, analysed by AI and corneal intrinsic aberrations, particularly higher-order aberrations.

Effects of anthropogenic landscapes on population maintenance of waterbirds.

Anthropogenic impacts have reduced natural areas but increased the area of anthropogenic landscapes. There is debate about whether anthropogenic landscapes (e.g., farmlands, orchards, and fish ponds) provide alternatives to natural habitat and under what circumstances. We considered whether anthropogenic landscapes can mitigate population declines for waterbirds. We collected data on population trends and biological traits of 1203 populations of 579 species across the planet. Using Bayesian generalized linear mixed models, we tested whether the ability of a species to use an anthropogenic landscape can predict population trends of waterbird globally and of species of conservation concern. Anthropogenic landscapes benefited population maintenance of common but not less-common species. Conversely, the use of anthropogenic landscapes was associated with population declines for threatened species. Our findings delineate some limitations to the ability of anthropogenic landscapes to mitigate population declines, suggesting that the maintenance of global waterbird populations depends on protecting remaining natural areas and improving the habitat quality in anthropogenic landscapes. Article impact statement: Protecting natural areas and improving the quality of anthropogenic landscapes as habitat are both needed to achieve effective conservation.

Efectos de los Paisajes Antropogénicos sobre la Conservación de Poblaciones de Aves Acuáticas Resumen Los impactos antropogénicos han reducido las áreas naturales, pero han incrementado el área de los paisajes antropogénicos. Existe un debate sobre si los paisajes antropogénicos (p. ej.: campos de cultivo, huertos, estanques de peces) proporcionan alternativas al hábitat natural y bajo cuáles circunstancias. Consideramos si los paisajes antropogénicos pueden mitigar las declinaciones poblacionales de las aves acuáticas. Recolectamos datos sobre las tendencias poblacionales y las características biológicas de 1203 poblaciones de 579 especies de aves de todo el mundo. Mediante modelos bayesianos generalizados lineales mixtos, analizamos si la habilidad de una especie para usar un paisaje antropogénico puede pronosticar las tendencias poblacionales de las aves acuáticas a nivel mundial y de las especies de interés para la conservación. Los paisajes antropogénicos beneficiaron a la conservación de las poblaciones de especies comunes, pero no para las especies menos comunes. Por otro lado, el uso de paisajes antropogénicos estuvo asociado con las declinaciones poblacionales en las especies amenazadas. Nuestros descubrimientos delinean algunas limitaciones que tienen los paisajes antropogénicos para mitigar las declinaciones poblacionales, lo que sugiere que la conservación mundial de las poblaciones de aves acuáticas depende de la protección de las áreas naturales remanentes y del mejoramiento de la calidad del hábitat en los paisajes antropogénicos.

CD7 CAR T bridging to allo-HSCT in R/R T-ALL: A case report.

BACKGROUND: Refractory/relapsed T-cell acute lymphoblastic leukemia (R/R T-ALL) is a hematological malignancy with a poor prognosis. The current treatment strategy has not benefited most patients, and the treatment methods are still being explored. CASE PRESENTATION: An 8-year-old boy with R/R T-ALL achieved CR after multiple chemotherapies, followed by the first allo-HSCT. Unfortunately, 1 year and 3 months later, he relapsed. After recurrence, the patient underwent multiple chemotherapies, but the NOTCH1 gene and MRD were still positive. FCM and immunohistochemistry revealed abnormally high expression of CD7, so we considered bridging the second allo-HSCT after CD7 CAR T-cells treatment. The patient has low toxic and side effects and is still in CR, findings from this case report have more important therapeutic significance for R/R T-ALL. CONCLUSION: In conclusion, CD7 CAR T-cells bridging to allo-HSCT is a safe and effective approach for R/R T-ALL, resulting in durable CR and longer survival.

The expression and clinical significance of CD59 and FLAER in Chinese adult AML patients.

BACKGROUND: The role of CD59 and fluorescently labeled aerolysin (FLAER) in acute myeloid leukemia (AML) remains unclear and requires further investigation. To explore the relationship between CD59, FLAER, and AML, we investigated CD59 and FLAER expression in AML and analyzed their relationship with clinical characteristics of AML patients. METHODS: We employed flow cytometry (FCM) to analyze CD59 and FLAER expression in 161 AML patients at Tianjin Medical University General Hospital and evaluated its association with sex, white blood cell (WBC) count, platelet (PLT) count, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-Dimer(D-D), and lactate dehydrogenase (LDH), followed by analyzing its connection with disease progression and complete remission (CR). RESULTS: CD59 and FLAER deficiencies were identified in AML patients. Compared with CR group, non-CR group patients revealed more CD59 and FLAER deficiency. Compared with non-acute promyelocytic leukemia (M3) group, M3 group patients had more CD59 and FLAER deficiency. CD59- level in primordial cells of M3 patients was positively correlated with primordial cell ratio (r = 0.660, p = 0.003). Additionally, we discovered that the decline in CD59 and FLAER levels might be linked to higher D-D and LDH in AML patients. The difference was statistically significant (p < 0.05). CONCLUSIONS: We demonstrated that the decline in CD59 and FLAER levels was associated with leukemia cell proliferation and abnormal coagulation function in AML, suggesting that they could serve as a predictor of AML coagulation dysfunction, particularly in M3.

Associations between home renovation and asthma, allergic rhinitis, and eczema among preschool children in Wuhan, China.

To investigate the potential associations between household renovation and allergic diseases among preschool children in Wuhan, we conducted a large cross-sectional questionnaire survey among 9455 preschool children aged 3-6 years in Wuhan during November to December 2019. Data on demographics, health status, and home decoration conditions were analysed based on a questionnaire. Compared with tiles/stone/cement floor covering, the use of composite floor significantly increased the risk of diagnosed rhinitis and eczema among children (rhinitis: AOR, 95% CI: 1.36, 1.06-1.73; eczema: AOR, 95% CI: 1.47, 1.17-1.85). Household renovation had significant associations with diagnosed eczema (within 1 year before pregnancy: AOR, 95% CI: 1.34, 1.20-1.50; during pregnancy: AOR, 95% CI: 1.25, 1.08-1.44). This study suggests that use of artificial synthetic materials in home renovation during early childhood and pregnancy may be potential risk factors for childhood asthma, allergic rhinitis, and eczema.

Visual functional defects in patients with type 2 diabetes mellitus: a questionnaire based cross-sectional study.

PURPOSE: To determine the impact of type 2 diabetes mellitus (T2DM) on visual functions, identify different modifiers as risk or protective factors, and find out how these factors affect patients' visual symptoms and visual functions as a whole. METHODS: We performed an online survey among 1030 participants (400 patients, 630 non-patients). Demographic features and severity of disease were documented, while visual functions were evaluated using National Eye Institute Visual Functioning questionnaire-25 (NEI VFQ-25). Independent t-test, analysis of variance, linear and nonlinear regression models were used to assess all data. RESULTS: Scores other than color vision among T2DM patients were significantly lower compared with non-T2DM participants. There was significant difference after stratification of age and education, but no significant difference between different genders was observed. Parameters including duration of T2DM, fasting plasma glucose (FPG) and glycosylated hemoglobin A1c (HbA1c) negatively impacted on the scores, with 20 years' of diabetic duration, 10 mmol/L of FPG, 7.5% of HbA1c being potential cut-off points. Poorer best corrected visual acuity (BCVA) and diagnosis of diabetic retinopathy were risk factors, while they simultaneously produced mediation effect, contributing 5%-78% of effect in the deterioration of visual functions caused by longer diabetic duration and higher blood glucose. CONCLUSION: Significant visual impairments and faster deterioration in visual functions were seen in T2DM patients, with older age, lower educational level, longer diabetic duration, poorer blood glucose administration, limited BCVA, and the presence of diabetic retinopathy identified as risk factors. Average BCVA and diabetic retinopathy also yielded mediation effect as diabetic duration lengthened and blood glucose elevated.

The spatiotemporal evolution of rural landscape patterns in Chinese metropolises under rapid urbanization.

Understanding the evolution of rural landscapes in metropolises during rapid urbanization is crucial for formulating policies to protect the rural ecological environment. In this study, remote sensing and geographical information system data, as well as applied landscape index analysis, are used to examine the spatiotemporal evolution of rural landscape patterns in the Beijing-Tianjin region of China, which has experienced rapid urbanization. The relationships between land use/land cover changes and changes in rural landscape patterns are explored. The results revealed significant spatial differences in the rural landscapes in the Beijing-Tianjin region; farmland and forestland were the main types of landscapes, creating a "mountain-field-sea" natural landscape pattern. The conversion of rural landscapes in the Beijing-Tianjin region involved mainly the conversion of farmland to urban areas, with few exchanges between other landscape types. The urban areas in the Beijing-Tianjin region increased by 3% per decade; farmland decreased at the same rate. Additionally, the rural landscape patterns in the Beijing-Tianjin region were dominated by fragmentation, dispersion, and heterogeneity and moved from complex to regular. Water bodies displayed the most fragmented natural landscape; their number of patches increased by 36%, though their network characteristics were maintained. Forestland was the most concentrated natural landscape. In this study, theoretical support and a scientific reference for the optimization of rural landscape patterns and the improvement in rural living environments in rapidly urbanizing areas are provided.

Immune checkpoints represent a promising breakthrough in targeted therapy and prognosis of myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a hematological malignancy of undetermined etiology, possibly linked to chromosomal structural alterations, genetic mutations, presentation and carcinogenicity of variant antigens on cell surface, and the generation of pro-inflammatory microenvironment in the bone marrow. Current drugs are unable to cure this disease, and therefore, decreasing the survival and proliferation of malignant cells to delay disease progression and extend the survival time of patients becomes the primary approach to management. In recent years, the immune system has received increasing attention for its potential role in the occurrence and development of MDS, leading to the emergence of immunoregulation as a viable treatment option. The current review provides a brief overview of pathogenesis of MDS and current treatment principles. In the meantime, the significance of immune proteins in treatment and prognosis of MDS is also discussed.

Binocular dynamic visual acuity in dry eye disease patients.

Purpose: To investigate binocular dynamic visual acuity (DVA) for patients with dry eye disease (DED). Methods: The prospective study included DED patients. The binocular DVA at 40 and 80 degrees per second (dps), Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), tear film break-up time first (TBUTF), corneal fluorescein staining (CFS), eyelid margin abnormalities and meibomian gland (MG) abnormalities morphology and function were evaluated. A deep learning model was applied to quantify the MG area proportion. The correlation between DVA and DED parameters was analyzed. Results: A total of 73 DED patients were enrolled. The age, OSDI, CFS, MG expressibility, secretion quality, and eyelid margin abnormalities were significantly positively correlated with the DVA for 40 and 80 dps (all P < 0.05). The MG area proportion in the upper eyelid was negatively correlated with DVA at 40 dps (R = -0.293, P < 0.001) and at 80 dps (R = -0.304, P < 0.001). Subgroup analysis by MG grade demonstrated that the DVA of patients with severe MG dropout (<25% of the total area) was significantly worse than other mild and moderate groups, both in 40 and 80 dps (all P < 0.05). The patients with CFS showed worse 40 (P < 0.001) and 80 dps (P < 0.001) DVA than the patients without CFS. Conclusion: Binocular DVA is significantly associated with DED symptoms and signs. The DED patients with CFS and severe MG dropout and dysfunction have worse DVA.

Evaluation of visual performance and eye movements in patients with blue light-filtering intraocular lenses versus ultraviolet light-filtering intraocular lenses.

Background: Eye movement plays an important role in visual perception and provides essential visual information for everyday tasks. Our previous study indicated that the visual performance and eye movement pattern were impaired in age-related cataract patients and could be improved after cataract surgery, but the impact of different intraocular lens (IOL) types was obscure. Previous studies found that blue light might affect the eye movement pattern and cognitive function. In this study, we explored the visual performance and eye movement pattern in post-cataract surgery patients implanted with blue light-filtering IOLs or ultraviolet (UV) light-filtering IOLs to further understand the impact of different types of IOLs on and daily visual performance and eye movement pattern and to help ophthalmologists and patients make the personalized option of IOL types in future. Methods: Patients after both-eye cataract surgeries were included in this study. Eye movement behaviors were automatically recorded by an eye tracker while performing three performance-based everyday tasks (non-social object search, face recognition, and reading). Visual performance and eye movement parameters were compared between participants with blue light-filtering IOLs and UV light-filtering IOLs. The correlation between visual performance and eye movement parameters was explored to determine which eye movement parameters had a significant influence on visual performance outcomes. Results: A total of 30 patients (16 with blue light-filtering IOLs and 14 with UV light-filtering IOLs) were included. In this study, we found that the eye movement pattern was slightly different with these two IOLs: during non-social object visual search task, time to first fixation and fixation counts before first fixation were notably increased in yellow-tinted blue light-filtering IOL patients. During reading task, a higher total fixation count was also found in blue light-filtering IOL patients. However, the visual performance of these two IOLs was close, except for a quicker search of the target object with clear UV light-filtering IOLs. Conclusion: Both blue light-filtering and UV light-filtering IOLs were able to successfully restore visual function and yield satisfactory outcomes after cataract surgery. Although subtle, yellow-tinted IOLs did have a slight but significant impact on visual performance and the eye movement pattern of elderly patients when handling everyday tasks.

Immunophenotypic changes of monocytes in myelodysplastic syndrome and clinical significance.

BACKGROUND: Myelodysplastic syndrome (MDS) is a type of heterogeneous myeloid clonal disorder usually diagnosed based on a combination of multiple laboratory examinations, including analysis of peripheral blood cells, bone marrow cell morphology and cytogenetics. However, there is a certain difficulty in cases with no distinct changes in hematology and marrow cell morphology. METHODS: We adopt flow cytometry to quantitatively analyze the immunophenotypic changes of marrow monocytes according to the surface antigens and their combinations at different differentiation stages, so as to study the changes of monocytes during differentiation in patients with bone marrow failure. In the meantime, the relationship between the immunophenotypic changes of marrow monocytes and IPSS-R score and prognosis of MDS patients was analyzed. RESULTS: Our results demonstrated disorders of maturation and differentiation of monocytes in patients with MDS and clonal cytopenias of undetermined significance as compared to those with aplastic anemia and healthy individuals. In addition, the differentiation abnormality gradually increased with the disease progression. Furthermore, CD300e expression was found to show significant associations with the clinical stage and disease progression of MDS, and the progression-free survival and AML-free survival were much longer in MDS patients highly expressing CD300e on monocytes. CONCLUSIONS: CCUS and MDS patients have disorders of differentiation and maturation of monocytes, which tends to be more critical with MDS progression or transforms to AML. Moreover, high CD300e expression has the potential to be a favorable prognostic marker for MDS. This study provides important insights to the role of monocyte immunotyping in the diagnosis, differentiation and prognosis of MDS.

Comparison of dynamic defocus curve on cataract patients implanting extended depth of focus and monofocal intraocular lens.

BACKGROUND: The aim of the study was to compare the dynamic defocus curve on patients post-implantation of the extended depth-of-focus (EDOF) and monofocal intraocular lens (IOL). METHODS: A total of 62 age-related cataract patients receiving phacoemulsification with implantation of TECNIS Symfony (ZXR00) or monofocal IOLs were enrolled. The binocular static and dynamic defocus curves with corrected distance visual acuity were evaluated at one month postoperatively. RESULTS: The ZXR00 group achieved significantly better intermediate (P = 0.044) and near (P = 0.017) visual acuity (VA) than the monofocal group. Two groups had similar uncorrected and corrected distance VA (P > 0.05, respectively). The dynamic defocus curve revealed a smoother decline from 0.0 D to - 2.0 D in the ZXR00 group. Defocused dynamic VA in the ZXR00 group was significantly better (P < 0.05) except at 0.0 D (P = 0.724) and - 0.5 D (P = 0.176). The area under the curve (P = 0.002) and corrected dynamic vision accommodation (P = 0.001) derived from the dynamic defocus curves were better in the ZXR00 group. A positive correlation was observed between defocused dynamic and static VA in both groups (P < 0.001). Multiple linear regression analysis indicated that defocused static VA and corrected dynamic vision accommodation were significant influential factors for the defocused dynamic VA from - 1.0 D to - 3.0 D (P < 0.05). CONCLUSIONS: The EDOF IOL provided similar distance vision, better intermediate and near vision, and a better overall dynamic defocus curve than the monofocal IOL. The dynamic defocus curve may be comprehensively applied to evaluate the all-distance dynamic visual performance post-cataract surgery.

The impact of patient-reported visual disturbance on dynamic visual acuity in myopic patients after corneal refractive surgery.

Purpose: To investigate the impact of patient-reported visual disturbance on dynamic visual acuity in myopic patients after corneal refractive surgery. Methods: This is a prospective nonrandomized study. Adult myopic patients receiving bilateral laser-assisted sub-epithelial keratomileusis (LASEK), femtosecond laser-assisted in situ keratomileusis (FS-LASIK), or small incision lenticule extraction (SMILE) with Plano target were included. Eight types of patient-reported visual disturbance were evaluated regarding frequency, severity and bothersome and dynamic visual acuity (DVA) of 40 and 80 degrees per second (dps) was measured postoperatively at 3 months. Results: The study enrolled 95 patients with an average age of 27.6 ± 6.4 years. The most frequently reported visual disturbance was the fluctuation in vision (70.5%), followed by glare (66.3%) and halo (57.4%). Postoperative DVA at 80 dps was significantly associated with the total score of haloes (p = 0.038) and difficulty in judging distance (p = 0.046). Significant worse postoperative DVA at 40 dps was observed in patients with haloes than those without (p = 0.024). The DVA at 80 dps for patients without haloes or difficulty in judging distance was significantly better than that with the symptoms (haloes, p = 0.047; difficulty in judging distance, p = 0.029). Subgroup analysis by surgical procedures demonstrated that the significant difference in DVA between patients with and without visual disturbance was only observed in patients receiving FS-LASIK. Conclusion: Postoperatively, myopic patients undergoing corneal refractive surgery with haloes or difficulty in judging distance have significantly worse low and high-speed DVA than those without the symptoms. The present study provided the basis for postoperative guidance in daily tasks involving dynamic vision when patients have visual disturbances.

Procyanidins Extracted from the Lotus Seedpod Ameliorate Cognitive Impairment through CREB-BDNF Pathway Mediated LTP in APP/PS1 Transgenic Mice.

BACKGROUND: Alzheimer's disease (AD) is an age-related neurodegenerative disease and is featured by cognitive impairment. Procyanidins have been shown to have a potential protective effect against neurodegenerative diseases, but the underlying mechanism is not comprehensive enough. OBJECTIVE: To further investigate the effects of procyanidins from lotus seedpod (LSPC) on cognition in AD. METHODS: The APP/PS1 transgenic mice were administered with LSPC (100 mg/kg body weight) for five months. The Morris water maze test was used to assess learning and memory function, the long-term potentiation (LTP) was measured, and the expressions of Aß, pCREB/CREB and BDNF were quantified by western blot. RESULTS: LSPC significantly ameliorated cognitive dysfunction, reduced Aß deposition and reversed the remarkable reduction of the phosphorylation of CREB and the expression of BDNF, and then enhanced the effect of LTP in APP/PS1 mice. CONCLUSION: These results revealed that LSPC could ameliorate cognitive impairment through the CREB-BDNF pathway that mediates the enhancement of LTP in APP/PS1 transgenic mice.

Chromosome-scale genomes reveal genomic consequences of inbreeding in the South China tiger: A comparative study with the Amur tiger.

The South China tiger (Panthera tigris amoyensis, SCT) is the most critically endangered subspecies of tiger due to functional extinction in the wild. Inbreeding depression is observed among the captive population descended from six wild ancestors, resulting in high juvenile mortality and low reproduction. We assembled and characterized the first SCT genome and an improved Amur tiger (P. t. altaica, AT) genome named AmyTig1.0 and PanTig2.0. The two genomes are the most continuous and comprehensive among any tiger genomes yet reported at the chromosomal level. By using the two genomes and resequencing data of 15 SCT and 13 AT individuals, we investigated the genomic signature of inbreeding depression of the SCT. The results indicated that the effective population size of SCT experienced three phases of decline, ~5.0-1.0 thousand years ago, 100 years ago, and since captive breeding in 1963. We found 43 long runs of homozygosity fragments that were shared by all individuals in the SCT population and covered a total length of 20.63% in the SCT genome. We also detected a large proportion of identical-by-descent segments across the genome in the SCT population, especially on ChrB4. Deleterious nonsynonymous single nucleotide polymorphic sites and loss-of-function mutations were found across genomes with extensive potential influences, despite a proportion of these loads having been purged by inbreeding depression. Our research provides an invaluable resource for the formulation of genetic management policies for the South China tiger such as developing genome-based breeding and genetic rescue strategy.