Correlation between pupillary size and depth of focus after the implantation of extended depth of focus intraocular lenses.

PURPOSE: To evaluate whether depth of focus after the implantation of extended depth of focus (EDoF) intraocular lenses (IOLs) correlates with pupillary size. METHODS: This retrospective case series study evaluated eyes undergoing cataract surgery with implantation of EDoF IOLs. At least one month postoperatively, the depth of focus (DoF) was measured to determine the correlation with pupillary size, age, anterior chamber depth (ACD), axial length (AXL), and corneal spherical aberrations (SA). RESULTS: The study evaluated 64 eyes of 49 patients. The mean depth of focus was 2.67 diopters (D). The mean preoperative photopic pupil size was 3.36 mm. A significant negative association was found between preoperative photopic pupil size and depth of focus (r = 0.30, Pearson's correlation coefficient) and between preoperative mesopic pupil size and depth of focus (r = 0.274, Pearson's correlation coefficient).

Impacts of Spatial Resolution and XCO2 Precision on Satellite Capability for CO2 Plumes Detection.

Greenhouse gas satellites can provide consistently global CO2 data which are important inputs for the top-down inverse estimation of CO2 emissions and their dynamic changes. By tracking greenhouse gas emissions, policymakers and businesses can identify areas where reductions are needed most and implement effective strategies to reduce their impact on the environment. Monitoring greenhouse gases provides valuable data for scientists studying climate change. The requirements for CO2 emissions monitoring and verification support capacity drive the payload design of future CO2 satellites. In this study, we quantitatively evaluate the performance of satellite in detecting CO2 plumes from power plants based on an improved Gaussian plume model, with focus on impacts of the satellite spatial resolution and the satellite-derived XCO2 precision under different meteorological conditions. The simulations of CO2 plumes indicate that the enhanced spatial resolution and XCO2 precision can significantly improve the detection capability of satellite, especially for small-sized power plants with emissions below 6 Mt CO2/yr. The satellite-detected maximum of XCO2 enhancement strongly varies with the wind condition. For a satellite with a XCO2 precision of 0.7 ppm and a spatial resolution of 2 km, it can recognize a power plant with emissions of 2.69 Mt CO2/yr at a wind speed of 2 m/s, while its emission needs be larger than 5.1 Mt CO2/yr if the power plant is expected to be detected at a wind speed of 4 m/s. Considering the uncertainties in the simulated wind field, the satellite-derived XCO2 measurements and the hypothesized CO2 emissions, their cumulative contribution to the overall accuracy of the satellite's ability to identify realistic enhancement in XCO2 are investigated in the future. The uncertainties of ΔXCO2 caused by the uncertainty in wind speed is more significant than those introduced from the uncertainty in wind direction. In the case of a power plant emitting 5.1 Mt CO2/yr, with the wind speed increasing from 0.5 m/s to 4 m/s, the simulated ΔXCO2 uncertainty associated with the wind field ranges from 3.75 ± 2.01 ppm to 0.46 ± 0.24 ppm and from 1.82 ± 0.95 ppm to 0.22 ± 0.11 ppm for 1 × 1 km2 and 2 × 2 km2 pixel size, respectively. Generally, even for a wind direction with a higher overall uncertainty, satellite still has a more effective capability for detecting CO2 emission on this wind direction, because there is more rapid growth for simulated maximal XCO2 enhancements than that for overall uncertainties. A designed spatial resolution of satellite better than 1 km and a XCO2 precision higher than 0.7 ppm are suggested, because the CO2 emission from small-sized power plants is much more likely be detected when the wind speed is below 3 m/s. Although spatial resolution and observed precision parameters are not sufficient to support the full design of future CO2 satellites, this study still can provide valuable insights for enhancing satellite monitoring of anthropogenic CO2 emissions.

A Deep Learning Based Platform for Remote Sensing Images Change Detection Integrating Crowdsourcing and Active Learning.

Remote sensing images change detection technology has become a popular tool for monitoring the change type, area, and distribution of land cover, including cultivated land, forest land, photovoltaic, roads, and buildings. However, traditional methods which rely on pre-annotation and on-site verification are time-consuming and challenging to meet timeliness requirements. With the emergence of artificial intelligence, this paper proposes an automatic change detection model and a crowdsourcing collaborative framework. The framework uses human-in-the-loop technology and an active learning approach to transform the manual interpretation method into a human-machine collaborative intelligent interpretation method. This low-cost and high-efficiency framework aims to solve the problem of weak model generalization caused by the lack of annotated data in change detection. The proposed framework can effectively incorporate expert domain knowledge and reduce the cost of data annotation while improving model performance. To ensure data quality, a crowdsourcing quality control model is constructed to evaluate the annotation qualification of the annotators and check their annotation results. Furthermore, a prototype of automatic detection and crowdsourcing collaborative annotation management platform is developed, which integrates annotation, crowdsourcing quality control, and change detection applications. The proposed framework and platform can help natural resource departments monitor land cover changes efficiently and effectively.

High-resolution atmospheric mercury emission from open biomass burning in China: Integration of localized emission factors and multi-source finer resolution remote sensing data.

Mercury (Hg) emissions from open biomass burning represent one of the largest Hg inputs to the atmosphere, with considerable effects on the atmospheric Hg budget. However, there is currently large uncertainty in the inventory of Hg emissions from open biomass burning in China due to limitations on the coarse resolution of burned area products, rough biomass data, and the unavailability of suitable emission factors (EFs). In this study, we developed high tempo-spatial resolution (30 m) and long time-series (2000-2019) atmospheric Hg emission inventories from open biomass burning using the Global Annual Burned Area Map (GABAM) product, high-resolution biomass map, Landsat-based tree cover datasets as well as local EFs in China. The results showed that the average annual Hg emission from open biomass burning in China amounted to 172.6 kg during 2000-2019, with a range of 63-398.5 kg. The largest Hg emissions were found in cropland (72%), followed by forest (25.9%), and grassland (2.1%). On a regional level, Northeast China (NE) and Southwest China (SW) were the two main contributors, together accounting for more than 60% of total Hg emissions. The temporal distribution of Hg emissions showed that the peaks occurred in 2003 and 2014. This is a comprehensive estimation of Hg emissions from open biomass burning in China by integrating various high-resolution remotely sensed data and nationwide localized EFs, which has important implications for understanding the role of open biomass burning in China in regional and global atmospheric Hg budget.

Investigation of biogenic volatile organic compounds emissions in the Qinghai-Tibetan Plateau.

Biogenic volatile organic compounds (BVOCs), which are produced and emitted by plants, have significant chemical reactivity in the atmosphere and impacting climate change. Qinghai Province, a vital component of the plateau, has abundant vegetation resources, primarily grasslands and forests, yet BVOCs emissions and their impact on air quality remain understudied. In this study, the emissions rates and compositions of BVOCs from seven dominant vegetation types in Qinghai Province were sampled and analyzed using a closed-loop stripping dynamic headspace sampling approach combined with GC-MS, and the total emissions of BVOCs in Qinghai province in 2021 were estimated by using G95 model. At the same time, the emission characteristics of various vegetation types were also analyzed. The results showed that the emissions rates and compositions of BVOCs differed significantly among vegetation types, with monoterpenes being the dominant emission composition in coniferous forests, which accounted for >70 % of the total BVOCs emissions, while isoprene being the main composition in alpine meadow, accounting for 84.96 %. The emissions of three typical vegetation types, Picea asperata, alpine meadow and alpine steppe, were monitored daily, revealing significant diurnal and clear unimodal patterns. The study also found that the annual average BVOCs emissions from vegetation sources in Qinghai Province were estimated to be 1550.63 Gg yr-1, with isoprene contributing the highest proportion of emissions, accounting for 56.94 %. Grassland was the largest BVOCs emission source in Qinghai Province, with an annual average emission of 1438.52 Gg yr-1. Additionally, BVOCs emissions in Qinghai Province showed strong seasonal and daily variation patterns, with the highest emissions occurring in summer, with the peak in July. These findings provide the characteristics of BVOCs emissions from vegetation sources in the Tibetan Plateau, which will contribute to a better understanding of their impact on atmospheric chemistry and climate change.

Suppression of cAMP/PKA/CREB signaling ameliorates retinal injury in diabetic retinopathy.

The blood-retinal barrier (BRB), homeostasis, neuronal integrity, and metabolic processes are all directly influenced by Müller cells, the most important retinal glial cells. We isolated primary Müller cells from Sprague-Dawley (SD) neonatal rats and treated them with glucose at varying doses. CCK-8 was used to quantify cellular viability, and a TUNEL assay was performed to detect cell apoptosis. ELISA, immunofluorescence, and western blotting were used to assess cAMP/PKA/CREB signaling, Kir4.1, AQP4, GFAP, and VEGF levels, respectively. H&E staining was used to examine histopathological alterations in diabetic retinopathy (DR)-affected retinal tissue in rats. As glucose concentration increases, gliosis of Müller cells became apparent, as evidenced by a decline in cell activity, an increase in apoptosis, downregulation of Kir4.1 level, and overexpression of GFAP, AQP4, and VEGF. Treatments with low, intermediate, and high glucose levels led to aberrant activation of cAMP/PKA/CREB signaling. Interestingly, blocking cAMP and PKA reduced high glucose-induced Müller cell damage and gliosis by a significant amount. Further in vivo results suggested that cAMP or PKA inhibition significantly improved edema, bleeding, and retinal disorders. Our findings showed that high glucose exacerbated Müller cell damage and gliosis via a mechanism involving cAMP/PKA/CREB signaling.

Estimation of ground-level O3 concentration in the Yangtze River Delta region based on a high-performance spatiotemporal model MixNet.

In recent years, the escalating ozone (O3) concentration has significantly damaged human health. The machine learning models are widely used to estimate ground-level O3 concentrations, but the spatial and temporal features in the data are less considered. To address the issue, this study proposed a novel framework named MixNet to estimate daily O3 concentration from 2020 to 2021 over the Yangtze River Delta. The MixNet utilized image convolution to extract the potential spatial information related to O3 fully. The temporal features were extracted by a Long Short-Term Memory (LSTM). A U-Net, a new jump connection method with an attention mechanism and residual blocks, facilitated a more comprehensive extraction of spatial features in the data. The extracted temporal and spatial features were fused to estimate ground-level O3. Meanwhile, a novel training method was proposed to enhance the accuracy of MixNet. The daily mean O3 maps have high validation results in comparison with ground-level O3 measurement, with R2 (RMSE) of 0.903 (14.511 µg/m3) for sample-based validation, 0.831 (19.036 µg/m3) for site-based validation, and 0.712 (25.108 µg/m3) for time-based validation. The season-average maps indicate that O3 concentration is summer > autumn > spring > winter. The highest value was 137.41 µg/m3 in the summer of 2021 over the Yangtze River Delta urban agglomeration, and the lowest value was 52.73 µg/m3 in winter 2020. The MixNet showed better performance compared with other models, and thus the "point-plane image thinking" will contribute to future studies in developing better methods to estimate atmospheric pollutants.

Preventive effects of the Rehmannia glutinosa Libosch and Cornus officinalis Sieb herb couple on chronic kidney disease rats via modulating the intestinal microbiota and enhancing the intestinal barrier.

CKD is a clinical syndrome with slow development and gradual deterioration of renal function. At present, modern medicine still lacks an ideal treatment method for this disease, while TCM has accumulated rich clinical experience in the treatment of CKD, which can effectively improve renal function and delay renal failure, and has unique advantages. RC is widely used in clinical practice to treat CKD, especially the "Kidney-Yin" deficiency syndrome. However, the compatibility mechanisms responsible for its effects in experimental studies, including preclinical and clinical research studies, are still not fully understood. Adenine-induced CKD rats were used to investigate the preventive effect of RC on CKD rats. Based on the high-throughput 16S rRNA gene sequencing results from Illumina, we discussed the intestinal flora abundance in rats in different treatment groups. According to a PCA and a PCoA based on a distance matrix, there was a clear separation of gut microbiome profiles between normal rats and model rats in terms of beta diversity. The abundance of Firmicutes in CKD rats was relatively increased, while that of Bacteroidetes was decreased. It is clear that the plot for the RC group was closer to that of the normal group, suggesting that the RC group had higher similarities among bacterial members with N rats. Ussing chamber, Western blot, and PCR assays were used to investigate the effects of RC on intestinal barrier function and its molecular mechanism in model animals. The results indicated that the protein expressions of ZO-1, claudin-1, and occludin-1 were decreased significantly in chronic kidney disease rats with the induction of adenine. With the treatment of RG, CO, and RC, the intestinal barrier was repaired due to the upregulated expressions of the aforementioned proteins in CKD rats. Based on our findings, RC appears to strengthen the intestinal barrier and modulate gut microbiota in adenine-induced CKD rats. This project revealed the compatibility mechanism of RC in regulating the intestinal microecology and barrier function to intervene in CKD and provided the basis and ideas for the clinical application of RC and the development of innovative drugs for CKD.

Reduced serum high-density lipoprotein cholesterol levels and aberrantly expressed cholesterol metabolism genes in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a common malignant tumor of the gastrointestinal tract. Lipid metabolism, as an important part of material and energy circulation, is well known to play a crucial role in CRC. AIM: To explore the relationship between serum lipids and CRC development and identify aberrantly expressed cholesterol metabolism genes in CRC. METHODS: We retrospectively collected 843 patients who had confirmed CRC and received surgical resection from 2013 to 2015 at the Cancer Hospital of the Chinese Academy of Medical Sciences as our research subjects. The levels of serum total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL-C/HDL-C and clinical features were collected and statistically analyzed by SPSS. Then, we used the data from Oncomine to screen the differentially expressed genes (DEGs) of the cholesterol metabolism pathway in CRC and used Gene Expression Profiling Interactive Analysis to confirm the candidate DEGs. PrognoScan was used to analyze the prognostic value of the DEGs, and Search Tool for the Retrieval of Interacting Genes was used to construct the protein-protein interaction network of DEGs. RESULTS: The serum HDL-C level in CRC patients was significantly correlated with tumor size, and patients whose tumor size was more than 5 cm had a lower serum HDL-C level (1.18 ± 0.41 mmol/L vs 1.25 ± 0.35 mmol/L, P < 0.01) than their counterparts. In addition, TC/HDL (4.19 ± 1.33 vs 3.93 ± 1.26, P < 0.01) and LDL-C/HDL-C (2.83 ± 1.10 vs 2.61 ± 0.96, P < 0.01) were higher in patients with larger tumors. The levels of HDL-C (P < 0.05), TC/HDL-C (P < 0.01) and LDL-C/HDL-C (P < 0.05) varied in different stages of CRC patients, and the differences were significant. We screened 14 differentially expressed genes (DEGs) of the cholesterol metabolism pathway in CRC and confirmed that lipoprotein receptor-related protein 8 (LRP8), PCSK9, low-density lipoprotein receptor (LDLR), MBTPS2 and FDXR are upregulated, while ABCA1 and OSBPL1A are downregulated in cancer tissue. Higher expression of LDLR (HR = 3.12, 95%CI: 1.77-5.49, P < 0.001), ABCA1 (HR = 1.66, 95%CI: 1.11-2.48, P = 0.012) and OSBPL1A (HR = 1.38, 95%CI: 1.01-1.89, P = 0.041) all yielded significantly poorer DFS outcomes. Higher expression of FDXR (HR = 0.7, 95%CI: 0.47-1.05, P = 0.002) was correlated with longer DFS. LDLR, ABCA1, OSBPL1A and FDXR were involved in many important cellular function pathways. CONCLUSION: Serum HDL-C levels are associated with tumor size and stage in CRC patients. LRP8, PCSK9, LDLR, MBTPS2 and FDXR are upregulated, while ABCA1 and OSBPL1A are downregulated in CRC. Among them, LDLR, ABCA1, OSBPL1A and FDXR were valuable prognostic factors of DFS and were involved in important cellular function pathways.

OMI formaldehyde column constrained emissions of reactive volatile organic compounds over the Pearl River Delta region of China.

In recent years, surface ozone (O3) concentration was high and became the primary air pollutant in the Pearl River Delta (PRD) region. However, as precursors of tropospheric O3, the emissions of reactive nonmethane volatile organic compounds (NMVOCs) were reported to have large uncertainties. Here, combined with the simulated formaldehyde (HCHO) columns from the RAMS-CMAQ modeling system, formaldehyde (HCHO) columns derived from the Ozone Monitoring Instrument (OMI) were used as the constraints to improve the emission estimates of the reactive NMVOCs through the linear regression method over the PRD region in March of 2017. The observed highest HCHO concentration was 2-4 times as high as the original simulated results over the PRD region mostly due to the underestimation in the reactive NMVOC emissions, especially the anthropogenic sources. With the regression coefficients calculated through five sensitivity simulation cases as well as the observed HCHO column, the better quantified emissions of reactive NMVOCs were obtained over the PRD region. It showed that the total emissions of reactive NMVOCs were improved by a factor of 2.1. The emissions derived from anthropogenic, biomass burning and biogenic sources increased from 0.0329, 4.69 × 10-4 and 0.0524 Tg/month to 0.0959, 0.0215 and 0.0620 Tg/month, respectively. As a result, the difference between the observed and modeled high HCHO column decreased to 1-2.5 times, which may be dominated by the enhanced reactive NMVOC emissions derived from anthropogenic sources. Besides, the great improvement in the emissions of reactive NMVOCs contributed to an increase of 20-40 µg/m3 in the maximum daily 8-h average (MDA8) O3 concentration over the PRD region.

Machine learning-based estimation of ground-level NO2 concentrations over China.

Most current scientific research on NO2 remote sensing focuses on tropospheric NO2 column concentrations rather than ground-level NO2 concentrations; however, ground-level NO2 concentrations are more related to anthropogenic emissions and human health. This study proposes a machine learning estimation method for retrieving the ground-level NO2 concentrations throughout China based on the tropospheric NO2 column concentrations from the TROPOspheric Monitoring Instrument (TROPOMI) and multisource geographic data from 2018 to 2020. This method adopts the XGBoost machine learning model characterized by a strong fitting ability and complex model structure, which can explain the complex nonlinear and high-order relationships between ground-measured NO2 and its influencing factors. The R2 values between the retrievals and the validation and test datasets are 0.67 and 0.73, respectively, which suggests that the proposed method can reliably retrieve the ground-level NO2 concentrations across China. The distribution characteristics, seasonal variations and interannual differences in ground-level NO2 concentrations are further analyzed based on the retrieval results, demonstrating that the ground-level NO2 concentrations exhibit significant geographical and seasonal variations, with high concentrations in winter and low concentrations in summer, and the highly polluted regions are concentrated mainly in Beijing-Tianjin-Hebei (BTH), the Yangtze River Delta (YRD), the Pearl River Delta (PRD), Cheng-Yu District (CY) and other urban agglomerations. Finally, the interannual variation in the ground-level NO2 concentrations indicates that pollution decreased continuously from 2018 to 2020.

Lizhong Decoction Ameliorates Ulcerative Colitis in Mice via Regulation of Plasma and Urine Metabolic Profiling.

OBJECTIVE: To elucidate the mechanism of Lizhong Decoction (LZD) in treating dextran sodium sulfate (DSS)-induced colitis in mice based on metabonomics. METHODS: Thirty-six mice were randomly divided into 6 groups, including normal, model, low- (1.365 g/kg), medium- (4.095 g/kg) and high dose (12.285 g/kg) LZD and salazosulfadimidine (SASP) groups, 6 mice in each group. Colitis model mice were induced by DSS admistration for 7 days, and treated with low, medium and high dose LZD extract and positive drug SASP. Metabolic comparison of DSS-induced colitis and normal mice was investigated by using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) combined with Metabolynx™ software. RESULTS: The metabolic profiles of plasma and urine in colitis mice were distinctly ameliorated after LZD treatment (P<0.05). Potential biomarkers (9 in serum and 4 in urine) were screened and tentatively identified. The endogenous metabolites were mainly involved in primary bile acid, sphingolipid, linoleic acid, arachidonic acid, amino acids (alanine, aspartate, and glutamate), butanoate and glycerophospholipid metabolism in plasma, and terpenoid backbone biosynthesis, glycerophospholipid and tryptophan metabolism in urine. After LZD treatment, these markers notably restored to normal levels. CONCLUSIONS: The study revealed the underlying mechanism of LZD on amelioration of ulcerative colitis based on metabonomics, which laid a foundation for further exploring the pathological and physiological mechanism, early diagnosis, and corresponding drug development of colitis.

RNF6 promotes colorectal cancer invasion and migration via the Wnt/ß-catenin pathway by inhibiting GSK3ß activity.

BACKGROUND: The purpose of this study was to explore the molecular mechanism underlying the interaction between ring finger protein 6 (RNF6) and glycogen synthase kinase 3ß (GSK3ß) in colorectal cancer (CRC). METHODS: In this study, cell models of overexpressed or silenced RNF6 were established by liposome transfection, and IM-12 was used as the inhibitor of GSK3ß. Real-time quantitative PCR and western blots were used to detect the expression of RNF6, p-GSK3ß, GSK3ß, and ß-catenin, and MTT assays were used to quantify cell proliferation. The tumorigenicity of cells was observed by plate clonal formation assay; the invasiveness of cells was examined in Transwell Boyden chambers, and the migratory capacity of cells was tested by scratch wound assays. The rat CRC model was induced by AOM/DSS, in which we verified activity in the Wnt/ß-catenin pathway by examining GSK3ß phosphorylation. RESULTS: RNF6 was upregulated in CRC samples and cell lines. Silencing or overexpressing RNF6 in colorectal cancer cells inhibited or promoted, respectively, the proliferation, tumorigenicity, invasion and migration of CRC cells, as well as expression of p-GSK3ß, GSK3ß and ß-catenin. IM-12 reversed the Wnt/ß-catenin-activated state change induced by RNF6 silencing and the inhibition of cell proliferation, tumorigenicity, invasion and migration. The same results were observed in vivo in the rat CRC model. CONCLUSIONS: Overexpression of RNF6 in CRC increased the GSK3ß phosphorylation level, which led to activation of the Wnt/ß-catenin pathway and promoted the invasion and migration of CRC cells, suggesting that RNF6 may be a novel target for the treatment of CRC.

Quality Evaluation of Artemisia capillaris Thunb. Based on Qualitative Analysis of the HPLC Fingerprint and UFLC-Q-TOF-MS/MS Combined with Quantitative Analysis of Multicomponents.

In this study, a new method was developed for the comprehensive quality evaluation (QE) of Artemisia capillaris Thunb. (A. capillaris, named Yinchenhao in Chinese), which is one of the most commonly used herbal medicines (HMs). First, fingerprints of 31 batch samples of A. capillaris were determined by HPLC, the reference fingerprint was established, and the common peaks were assigned. Second, the components of common peaks in the HPLC fingerprints were identified by ultrafast liquid chromatography- (UFLC-) Q-TOF-MS/MS. Finally, the contents of the components unambiguously confirmed by reference substances were determined, and the correlation between the contents of chlorogenic acid and the contents of others was analyzed. The results showed that there were 20 common peaks in the HPLC fingerprints of 31 batch samples. The components of these 20 common peaks were identified as ten organic acids, eight flavonoids, and two others. Among nine organic acids such as 1-caffeoylquinic acid, neochlorogenic acid, chlorogenic acid, caffeic acid, cryptochlorogenic acid, 1,3-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, and 4,5-dicaffeoylquinic acid, three flavonoids such as rutin, hyperoside, and isoquercetin, and one other p-hydroxyacetophenone, a total of 13 ones were unambiguously identified by comparison with reference substances; one caffeoylquinic acid glucoside and one flavone di-C-glucoside were detected in A. capillaris for the first time. There were some differences in the contents of 13 components in different samples; chlorogenic acid could be regarded as the quality marker of A. capillaris. The current established method in this study can be used for the comprehensive QE of A. capillaris and can also provide reference for the QE of the other HMs.

Activation of the STAT5 Signaling Pathway by Yiqi Jiedu Formula Induces Regulatory T Cell-Mediated Alleviation of Corneal Immunopathological Damage in Mice With Recurrent Herpes Simplex Keratitis.

This study aimed to investigate the effect of Yiqi Jiedu (YQJD) formula on the repair of corneal lesions in mice with recurrent herpes simplex virus keratitis (HSK). Sixty female BALB/c mice were randomly divided into three groups: a normal control group (Naive), a recurrence model group (Re), and a YQJD group. After inducing recurrence by ultraviolet irradiation, the ocular surfaces of different groups of mice were observed using a slit lamp and photographed, and ocular surface scores were calculated. The abundance of CD4+CD25+Foxp3+ regulatory T (Treg) cells was determined by flow cytometry in peripheral blood and spleen cells. The CD4+Foxp3+ Tregs were assessed by immunofluorescence in the cornea. The levels of the cytokines IL-10 and TGF-ß in serum and splenocyte culture supernatants were detected by enzyme-linked immunosorbent assay. Furthermore, the activation status of the STAT5 signaling pathway was examined by protein blotting, and the effect of YQJD on Treg cells through inhibition of the STAT5 pathway was observed in vitro. YQJD alleviated corneal inflammation by enhancing the STAT5 signaling pathway, thereby promoting the differentiation of CD4+CD25+Foxp3+ Treg cells, increasing the levels of anti-inflammatory cytokines such as IL-10 and TGF-ß, and maintaining immune tolerance. YQJD increased the proportion of CD4+Foxp3+ Treg cells; also, in the cornea, YQJD inhibited the aggregation of macrophages and CD4+ cells and reduced the proportion of Th17 cells and other pro-inflammatory cells. Moreover, YQJD promoted the secretion of IL-4 to protect the cornea, leading to the mitigation of corneal immunopathological damage. YQJD reduced corneal lesions in recurrent HSK mice by stimulating Treg cells, inducing immune tolerance, and inhibiting corneal immunopathological responses via modulation of the STAT5 signaling pathway.

Hypoxia-induced downregulation of B-cell translocation gene 3 confers resistance to radiation therapy of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is now a major human cancer, and B-cell translocation gene 3 (BTG3) has been reported as a tumor-suppressor in CRC, but its upstream regulator has not been identified. METHODS: Endogenous expression levels of BTG3 were compared between normal colorectal cell line CCD-18Co and two CRC cell lines SW480 and HT29, as well as between CRC patient tumor and adjacent normal tissues. Analysis of BTG3 genomic region was performed which identified a putative hypoxia response element (HRE). Effects of hypoxia condition, BTG3 overexpression, and their combination on the radiation sensitivity of CRC cell lines were assessed. RESULTS: BTG3 was downregulated in CRC cell lines and patient tumor samples, via the HRE in its promoter region. Hypoxia and BTG3 overexpression could both induce radiation resistance in CRC cells. Combining hypoxia with BTG3 overexpression effectively rendered the resistance of CRC cells to radiation to a level lower than hypoxia alone and higher than normoxia alone, indicating the essential role of BTG3 in hypoxia-induced radiation resistance of CRC cells. CONCLUSION: We therefore propose a novel signaling cascade involving hypoxia/BTG3 to be a potential risk factor for CRC patients undergoing radiation therapy, which could possibly serve as therapeutic targets among CRC patients with acquired radiotherapy resistance.

Functional Neuroanatomy of the Human Accommodation Response to an "E" Target Varying from -3 to -6 Diopters.

Background: We aimed to identify the functional brain networks involved in the regulation of visual accommodation by contrasting the cortical functional areas evoked by foveal fixation to an "E" target, which were subservient to the accommodation responses to a -3/-6 diopter stimulus. Methods: Neural activity was assessed in healthy volunteers by changes in blood oxygen level-dependent (BOLD) signals measured with functional magnetic resonance imaging (fMRI). Twenty-five right-handed subjects viewed the "E" target presented in a hierarchical block design. They participated in two monocular tasks: (i) sustained foveal fixation upon an "E" target on a white background at 33 cm (-3.03D accommodative demand); and (ii) sustained fixation through an attached -3D concave lens (-6D accommodative demand) in front of the fixated eye; each condition cycled through a standard alternating 30-s eye open/30-s eye closed design to provide the BOLD contrast. The total sustained period was 480 s. Results: The contrast between the -3D and the rest condition revealed activation in the occipital lobe (Lingual gyrus, Cuneus, Calcarine_L, and Calcarine_R); cerebellum (Cerebellum_Crus1_L and Cerebellum_6_L); precentral lobe (Precentral_R); frontal lobe (Frontal_Inf_Oper_R and Frontal_Mid_R); and cingulate cortex (Cingulum_Ant_L). With the -3D concave lenses (-6D accommodative demand) in front of the fixated eye, the voxel size and peak intensity of activation in the occipital lobe and cerebellum were greater than with the -3D accommodative demand; emergent activated brain areas included the parietal lobe (bilateral precuneus gyrus and right supramarginal gyrus); the precentral lobe and cingulate cortex failed to reach the threshold in the -6D vs. rest contrast. In the -3D and -6D contrast comparison, the frontal lobe (Frontal_Sup_Medial_L) and parietal lobe (Precuneus_L and Precuneus_R) passed the significance threshold of cluster-level family-wise error (FWE) correction. The mean activation in the -3D and -6D contrast revealed an incremental summation of the activations than that found in the previous -3D vs. rest and -6D vs. rest comparisons. Conclusions: Neural circuits were selectively activated during the -3D/-6D accommodative response to blur cues. Cognitive-perceptual processing is involved in signal regulation of ocular accommodative functions.

Farnesoid X Receptor-Mediated Cytoplasmic Translocation of CRTC2 Disrupts CREB-BDNF Signaling in Hippocampal CA1 and Leads to the Development of Depression-Like Behaviors in Mice.

BACKGROUND: We recently identified neuronal expression of farnesoid X receptor (FXR), a bile acid receptor known to impair autophagy by inhibiting cyclic adenosine monophosphate response element-binding protein (CREB), a protein whose underfunctioning is linked to neuroplasticity and depression. In this study, we hypothesize that FXR may mediate depression via a CREB-dependent mechanism. METHODS: Depression was induced in male C57BL6/J mice via chronic unpredictable stress (CUS). Subjects underwent behavioral testing to identify depression-like behaviors. A variety of molecular biology techniques, including viral-mediated gene transfer, Western blot, co-immunoprecipitation, and immunofluorescence, were used to correlate depression-like behaviors with underlying molecular and physiological events. RESULTS: Overexpression of FXR, whose levels were upregulated by CUS in hippocampal CA1, induced or aggravated depression-like behaviors in stress-naïve and CUS-exposed mice, while FXR short hairpin RNA (shRNA) ameliorated such symptoms in CUS-exposed mice. The behavioral effects of FXR were found to be associated with changes in CREB-brain-derived neurotrophic factor (BDNF) signaling, as FXR overexpression aggravated CUS-induced reduction in BDNF levels while the use of FXR shRNA or disruption of FXR-CREB signaling reversed the CUS-induced reduction in the phosphorylated CREB and BDNF levels. Molecular analysis revealed that FXR shRNA prevented CUS-induced cytoplasmic translocation of CREB-regulated transcription coactivator 2 (CRTC2); CRTC2 overexpression and CRTC2 shRNA abrogated the regulatory effect of FXR overexpression or FXR shRNA on CUS-induced depression-like behaviors. CONCLUSIONS: In stress conditions, increased FXR in the CA1 inhibits CREB by targeting CREB and driving the cytoplasmic translocation of CRTC2. Uncoupling of the FXR-CREB complex may be a novel strategy for depression treatment.

Celastrol exerts anti-inflammatory effect in liver fibrosis via activation of AMPK-SIRT3 signalling.

Celastrol, a pentacyclic tritepene extracted from Tripterygium Wilfordi plant, showing potent liver protection effects on several liver-related diseases. However, the anti-inflammatory potential of celastrol in liver fibrosis and the detailed mechanisms remain uncovered. This study was to investigate the anti-inflammatory effect of celastrol in liver fibrosis and to further reveal mechanisms of celastrol-induced anti-inflammatory effects with a focus on AMPK-SIRT3 signalling. Celastrol showed potent ameliorative effects on liver fibrosis both in activated hepatic stellate cells (HSCs) and in fibrotic liver. Celastrol remarkably suppressed inflammation in vivo and inhibited the secretion of inflammatory factors in vitro. Interestingly, celastrol increased SIRT3 promoter activity and SIRT3 expression both in fibrotic liver and in activated HSCs. Furthermore, SIRT3 silencing evidently ameliorated the anti-inflammatory potential of celastrol. Besides, we found that celastrol could increase the AMPK phosphorylation. Further investigation showed that SIRT3 siRNA decreased SIRT3 expression but had no obvious effect on phosphorylation of AMPK. In addition, inhibition of AMPK by employing compound C (an AMPK inhibitor) or AMPK1α siRNA significantly suppressed SIRT3 expression, suggesting that AMPK was an up-stream protein of SIRT3 in liver fibrosis. We further found that depletion of AMPK significantly attenuated the inhibitory effect of celastrol on inflammation. Collectively, celastrol attenuated liver fibrosis mainly through inhibition of inflammation by activating AMPK-SIRT3 signalling, which makes celastrol be a potential candidate compound in treating or protecting against liver fibrosis.

Analysis of 72 patients with colorectal high-grade neuroendocrine neoplasms from three Chinese hospitals.

BACKGROUND: Colorectal high-grade neuroendocrine neoplasms (HGNENs) are rare and constitute less than 1% of all colorectal malignancies. Based on their morphological differentiation and proliferation identity, these neoplasms present heterogeneous clinicopathologic features. Opinions regarding treatment strategies for and improvement of the clinical outcomes of these patients remain controversial. AIM: To delineate the clinicopathologic features of and explore the prognostic factors for this rare malignancy. METHODS: This observational study reviewed the data of 72 consecutive patients with colorectal HGNENs from three Chinese hospitals between 2000 and 2019. The clinicopathologic characteristics and follow-up data were carefully collected from their medical records, outpatient reexaminations, and telephone interviews. A survival analysis was conducted to evaluate their outcomes and to identify the prognostic factors for this disease. RESULTS: According to the latest recommendations for the classification and nomenclature of colorectal HGNENs, 61 (84.7%) patients in our cohort had poorly differentiated neoplasms, which were categorized as high-grade neuroendocrine carcinomas (HGNECs), and the remaining 11 (15.3%) patients had well differentiated neoplasms, which were categorized as high-grade neuroendocrine tumors (HGNETs). Most of the neoplasms (63.9%) were located at the rectum. More than half of the patients (51.4%) presented with distant metastasis at the date of diagnosis. All patients were followed for a median duration of 15.5 mo. In the entire cohort, the median survival time was 31 mo, and the 3-year and 5-year survival rates were 44.3% and 36.3%, respectively. Both the univariate and multivariate analyses demonstrated that increasing age, HGNEC type, and distant metastasis were risk factors for poor clinical outcomes. CONCLUSION: Colorectal HGNENs are rare and aggressive malignancies with poor clinical outcomes. However, patients with younger age, good morphological differentiation, and without metastatic disease can have a relatively favorable prognosis.