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Diabetic retinopathy(DR)is one of the common causes of visual impairment and blindness in adults, which is caused by various pathogenesis. Although the mechanism of DR has not been elucidated yet, the destruction of blood-retinal barrier is a key process. As a highly endothelial-specific factor in promoting the growth of vascular endothelial cell, vascular endothelial growth factor(VEGF)plays a crucial role in the formation of pathological retinal neovascularization and the destruction of blood-retinal barrier. Therefore, a comprehensive understanding of the etiology and pathogenesis of blood-retinal barrier damage promoted by VEGF is critical for exploring the pathogenesis of DR. In this study, the underlying relationship between VEGF and the mechanism of blood-retinal barrier damage, including retinal vascular endothelial cell permeability, vascular inflammatory response, apoptosis, oxidative stress, mitochondrial damage and endoplasmic reticulum stress, with a view to providing a reference for the study in VEGF in the pathogenesis of blood-retinal barrier damage in DR.

The interdecadal variability of tropical cyclone precipitation (TCP) over the western North Pacific (WNP) has not been thoroughly explored in previous studies. Here, we show that the TCP variations are modulated by both the Atlantic Multidecadal Oscillation (AMO) and Interdecadal Pacific Oscillation (IPO) as evidenced by reanalysis data and model experiments. A clustering analysis of tropical cyclone tracks shows that the AMO dominates a dipole pattern of TCP anomalies in the South China Sea and along the coastal eastern China. Meanwhile, the IPO dominates TCP over the southeastern WNP. Further analyses show that the AMO, particularly its extratropical component, affects TCP over the WNP by triggering an eastward‐propagating Rossby‐wave train, resulting in a pair of anomalous gyres over the WNP. Contrastly, the IPO modulates TCP by stimulating tropical circulation anomalies via the tropical pathway. These findings shed light on improving near‐term TCP forecast and its regional influence on East Asia. Plain Language Summary: Tropical cyclone precipitation (TCP) is a topic of great concern owing to its destructive nature. Here, we find that TCP over the western North Pacific (WNP) exhibits significantly interdecadal variability and regional characteristics, a departure from the previous studies focusing on the entire WNP. The Atlantic Multidecadal Oscillation (AMO) mainly causes a dipole response of decadal changes in TCP over the South China Sea and coastal eastern China. Moreover, the AMO primarily affects TCP over the sub‐regional WNP through the extra‐tropical pathway by exciting a Rossby wave train. On the other hand, the Interdecadal Pacific Oscillation (IPO) predominantly affects TCP over the southeastern part of the WNP through the tropical pathway, inducing significant circulation anomalies over the tropical WNP. These findings offer valuable insights for future research and forecasting of TCP. Key Points: The Atlantic Multidecadal Oscillation (AMO) contributes to the dipole pattern of interdecadal tropical cyclone precipitation (TCP) anomalies over the South China Sea and coastal eastern ChinaThe AMO affects TCP by triggering a westerly jet‐guided Rossby‐wave train via the extra‐tropical pathwayThe Interdecadal Pacific Oscillation dominates the TCP anomalies over the southeastern part of western North Pacific by modulating tropical circulation anomalies [ABSTRACT FROM AUTHOR]

During the winter of 2019, the global outbreak of COVID-19 prompted extensive research on urban air pollution under lockdown measures. However, these studies predominantly focused on winter conditions, thereby limiting investigations into changes in urban air pollutants during other seasons that were also subject to lockdown restrictions. Shanghai, China, has undergone two COVID-19 lockdown periods in two seasons: winter 2019 and spring 2022. The seasonal variations and human activities were represented by meteorological factors and nighttime light brightness in this paper, respectively. The reduction in human-related emissions during the two lockdown periods was estimated based on the targets outlined in China's Air Pollution Prevention and Control Action Plan. The results showed significant reductions in NO2 and PM particles during the two lockdown periods, both accompanied by a notable increase in O3 concentration. In comparison to the winter lockdown, there was an approximate 40% decrease in the NO2 and PM2.5 concentrations in the spring, while the O3 concentration exhibited an increase of 48.81%. Furthermore, due to shifting wind patterns during the two lockdowns from winter to spring, the high-pollution core areas shifted 20–25 km southeastward in the spring. The PM particles and NO2 concentrations exhibited a considerable impact from human activities, whereas the O3 concentration was affected mostly by seasonal change and interactions among air pollutants. Compared to the corresponding non-lockdown condition, the concentration of CO decreased during the winter lockdown; however, it increased during the spring lockdown. The different change in CO concentration during the two lockdown periods was found to have a lower effect on the O3 concentration than that caused by changes in meteorological factors and nitrogen oxide (NO, NO2) concentrations. In summary, the impact of COVID-19 lockdown periods on urban air pollutants was more pronounced in spring compared to winter, and the interactions among air pollutants also underwent alterations. [ABSTRACT FROM AUTHOR]

The differences between the two global warming targets of the Paris Agreement, 1.5 °C and 2 °C above pre-industrial levels, have drawn much attention from the scientific community. However, there is a remaining gap to distinguish regional climate responses in these two most typical pathways, i.e., transient and stabilization simulations, toward specific warming levels. In this study, we discern the East Asia summer monsoon (EASM) responses between these two types of simulations at low-warming targets, based on the fully coupled community Earth system model (CESM). The two types of responses display a similar increase pattern in the EASM precipitation. However, the quantitative differences between these two types of responses are as large as those between the 1.5 °C and 2 °C warming scenarios. The moist budget analysis reveals that the EASM precipitation differences are mainly caused by the thermodynamic, dynamic, and transient eddy effects. Specifically, the thermodynamic effect contributes to the precipitation increment in the coastal area of East Asia in both types of responses, with the enhanced low-level specific humidity. The dynamic contribution shows tripolar and bipolar patterns in East Asia in the transient and stabilization responses, respectively. Remarkably, the transient eddy effect contribution emerges only in the stabilization responses. Further, we reveal the dominant role of the East Asian subtropical jet (EASJ) in determining the contributions from dynamic and transient eddy effects. The changes in the EASJ's position and intensity are greatly regulated by the temperature change patterns at the mid-high levels in response to different greenhouse gas emission pathways. Our study highlights the differences between transient and stabilization climate states on a regional scale. [ABSTRACT FROM AUTHOR]

Simple Summary: The thymus is implicated in central immune tolerance and plays essential roles during normal pregnancy. The inhibitor of the NF-κB (IκB) family is a key component of the NF-κB pathway; however, the modulation of the κB family in the maternal thymus by early gestation has not been fully understood. It has been found that there changes in the expression of the IκB family in the maternal thymus take place during early pregnancy, suggesting that IκB proteins are involved in modulating immunologic tolerance and pregnancy establishment. The thymus is an essential component of maternal immune systems that play key roles in recognizing the placenta as immunologically foreign. The inhibitor of the NF-κB (IκB) family has essential effects on the NF-κB pathway; however, it is unclear whether early pregnancy modulates the expression of the IκB family in the thymus. In this study, maternal thymuses were sampled on day 16 of nonpregnancy and different gestation stages in the ovine, and the expression of IκB proteins was analyzed. The data showed that B cell leukemia-3 and IκBβ increased; however, IκBα, IκBε, and IKKγ deceased during gestation. Furthermore, there was an increase in IκBNS and IκBζ expression values on day 13 of pregnancy; however, this decreased on day 25 of gestation. In summary, the expression of the IκB family was modulated in the thymus during early gestation, suggesting that the maternal thymus can be associated with maternal immunologic tolerance and pregnancy establishment in ewes. [ABSTRACT FROM AUTHOR]

With climate change, frequent forest fires and prolonged fire period occur all over the world. Moreover, carbon emission from forest fire affects the carbon cycle of the forest ecosystem. However, this effect varies by region with no uniform conclusions, and fewer comparative studies exist on such differences between regions. In this paper, net primary productivity (NPP) data MOD17A3 were used as an important parameter of forest carbon absorption, along with MODIS fire spot data MCD14DL and burned area data MCD64A1. Forest carbon lost under forest fire interference in the northeast and southwest natural forest areas of China was studied to explore the role of forest fire in the carbon cycle process and its differences in the unlike regions of China. Here, by means of kernel density analysis and M-K trend test, the characteristics of forest fires in China's southwest and northeast forests were calculated. Forest carbon emission under forest fire disturbance was quantified by reference to the forest fire emission factor list. We show that (1) the total number of forest fire spots in the southwest region from 2001 to 2020 was 1.06 × 105, 1.28 times that of Northeast China. However, the total burned area in the southwest was only 67.84% of that in the northeast. (2) The total carbon emissions from forest fires in the southwest from 2001 to 2020 was 37,559.94 Gg, 10.77% larger than the northeast forest, CH4 and CO2 were 13.52% and 11.29% larger respectively. Moreover, the carbon emissions of forest fire in the northeast showed a downward trend, R2 = 0.16 (p < 0.1), while it remained basically unchanged in the southwest. The contribution of carbon emissions from forest fires changed with forest types, it was shown as: evergreen needleleaf forest (14.98%) > evergreen broadleaf forest (10.81%) > deciduous needleleaf forest (6.52%) > deciduous broadleaf forest (5.22%). (3) From 2001 to 2020, under the premise that the NPP both manifested upward trends, the NPP of the burned areas showed a significant downward trend in the southwest forest, with R2 = 0.42 (p < 0.05), while it increased in the northeast forest, with R2 = 0.37 (p < 0.05). It showed negative correlation between NPP of burned areas and forest fire carbon emissions, and forest fire disturbance had no significant effect on forest NPP in Northeast China, while net carbon loss occurred in Southwest China. In general, under different forest fire characteristics, NPP, which represents forest carbon uptake, and carbon emissions from forest fires show differences. The impact of forest fire disturbance on forest carbon process varies with regions. The study can provide some ideas on the effects of forest fire disturbance on climate change. [ABSTRACT FROM AUTHOR]

Early pregnancy modulates the maternal immune system, including the spleen and lymph nodes, which participate in maternal innate and adaptive immune responses. Methods: Ovine spleens and lymph nodes were sampled at day 16 of the estrous cycle, and at days 13, 16 and 25 of gestation, and qRT-PCR, Western blot and immunohistochemistry analysis were used to analyze the expression of the IκB family, including BCL-3, IκBα, IκBβ, IκBε, IKKγ, IκBNS and IκBζ. Early pregnancy induced expression of BCL-3, IκBα, IκBε, IKKγ and IκBζ, and expression of BCL-3, IκBβ and IκBNS peaked at day 16 of pregnancy in the spleen. However, early pregnancy suppressed the expression of BCL-3 and IκBNS, but stimulated the expression of IκBβ and IκBζ, and expression levels of IκBα, IκBβ, IκBε and IKKγ peaked in lymph nodes at days 13 and/or 16 of pregnancy. Early pregnancy changed the expression of the IκB family in the maternal spleen and lymph node in a tissue-specific manner, suggesting that the modulation of the IκB family may be involved in regulation of maternal functions of the spleen and lymph nodes, which are necessary for the establishment of maternal immune tolerance during early pregnancy in sheep. [ABSTRACT FROM AUTHOR]

Simple Summary: An inhibitor of the NF-κB (IκB) family is involved in regulating innate immune responses. In this study, early pregnancy induces upregulation of IκBα, but changes and downregulates the expression of BCL-3, IκBε, IKKγ and IκBNS, and changes expression of IκBβ and IκBζ in the maternal liver, which are related to maternal peripheral tolerance and pregnancy establishment. During normal pregnancy, there is a dynamic regulation of the maternal immune system, including the liver, to accommodate the presence of the allogeneic foetus in the uterus. However, it was unclear that the expression of the IkappaB (IκB) family was regulated in the ovine maternal liver during early pregnancy. In this study, sheep livers were collected at day 16 of the oestrous cycle (NP16), and days 13, 16 and 25 of gestation (DP13, DP16 and DP25), and RT-qPCR, Western blot and immunohistochemistry analysis were used to analyse the expression of the IκB family, including B cell leukemia-3 (BCL-3), IκBα, IκBβ, IκBε, IKKγ, IκBNS and IκBζ. The results revealed that expression of BCL-3, IκBβ, IκBε and IKKγ peaked at DP16, and the expression of IκBα was increased during early pregnancy. In addition, the expression of IκBζ peaked at DP13 and DP16, and IκBNS peaked at DP13. IκBβ and IKKγ proteins were located in the endothelial cells of the proper hepatic arteries and portal veins, and hepatocytes. In conclusion, early pregnancy changed the expression of the IκB family, suggesting that the modulation of the IκB family may be related to the regulation of maternal hepatic functions, which may be favourable for pregnancy establishment in sheep. [ABSTRACT FROM AUTHOR]

Nucleotide-binding oligomerization domain receptors (NOD-like receptors, NLRs) are involved in modulating the innate immune responses of the trophoblast and the placenta in normal pregnancy. The thymus participates in regulation of innate and adaptive immune responses. However, it is unclear whether expression of NLR is modulated in the maternal thymus during early pregnancy. In this study, thymuses were sampled at day 16 of the estrous cycle, and at days 13, 16 and 25 of gestation (n = 6 for each group) from ewes after slaughter. Different stages were chosen because the maternal thymus was under the different effects of interferon-tau and/or progesterone or not. RT-qPCR, Western blot and immunohistochemistry analysis were used to analyze the expression of the NLR family, including NOD1; NOD2; major histocompatibility complex class II transactivator (CIITA); NLR family apoptosis inhibitory protein (NAIP); nucleotide-binding oligomerization domain and Leucine-rich repeat and Pyrin domain containing protein 1 (NLRP1), NLRP3 and NLRP7. The results showed that expression level of NOD1 was changed with the pregnancy stages, and expression levels of NOD2, CIITA, NAIP, NLRP1, NLRP3 and NLRP7 mRNA and proteins were peaked at day 13 of pregnancy. The levels of NOD2 and CIITA were increased during early pregnancy. The stainings for NOD2 and NLRP7 proteins were located in epithelial reticular cells, capillaries and thymic corpuscles. In summary, pregnancy stages changed expression of NLR family in the maternal thymus, which may be related to the modulation of maternal thymic immune responses, and beneficial for normal pregnancy in sheep. [ABSTRACT FROM AUTHOR]

Simple Summary: NOD receptors mediate adaptive immune responses and immune tolerance. In this study, the results demonstrated that early pregnancy increased expression of NOD1, CIITA, NLRP1, NLRP3 and NLRP7. However, early pregnancy inhibited NAIP expression in maternal lymph nodes. There is immune regulation of the lymph nodes, which is necessary during ovine gestation. NOD receptors (NLRs) mediate adaptive immune responses and immune tolerance. Nevertheless, it is not clear if gestation modulates the NLR signaling pathway in lymph nodes of ewes. In this study, lymph nodes of ewes were collected at day 16 of the estrous cycle, and at days 13, 16 and 25 of gestation (n = 6 for each group). RT-qPCR, Western blot and immunohistochemistry analysis were used to analyze the expression of the NLR family, including NOD1, NOD2, CIITA, NAIP, NLRP1, NLRP3 and NLRP7. The data showed that early gestation enhanced expression of NOD1, CIITA, NLRP1, NLRP3 and NLRP7 mRNA, as well as proteins at day 16 of gestation, and the expression levels of NOD2, CIITA, NLRP1 and NLRP7 were higher at days 13 and 25 of gestation than day 16 of the estrous cycle. However, NOD1 expression was lower on days 13 and 25 of gestation compared to day 16 of the estrous cycle, and early gestation suppressed NAIP expression. In summary, early pregnancy modulated expression of the NLR family in ovine lymph nodes, which participates in immune regulation, and this modulation may be necessary for pregnancy establishment in ewes. [ABSTRACT FROM AUTHOR]

The multi‐model ensemble mean sea surface temperature (SST) of CMIP5 models shows an El Niño‐like Pacific warming (PW) trend, contradictory with the observational result which manifests a La Niña‐like PW pattern. Here, we demonstrate that these two SST PWs coexist in the CMIP5 models and they are largely determined by the model's tropical Indo‐Pacific SST gradient. When the Pacific warms faster than the Indian Ocean (IO), the model tends to project an El Niño‐like PW pattern. In contrast, a La Niña‐like warming trend prevails if a more rapid IO warming is simulated. We suggest that the PW pattern in an individual model is nonstationary and may transform from a La Niña‐like to an El Niño‐like when its interbasin SST gradient changes with more robust warming in the Pacific, and vice versa. Our conclusions shed great light on the future SST PW pattern change projected by the coupled models. Plain Language Summary: Previous studies demonstrate that an El Niño‐like SST warming pattern prevails in a majority of CMIP5 models. But a La Niña‐like warming pattern is detected based on historical SST records. This inconsistency between the observations and model simulation triggers an intense debate in the climate community. In this study, we find that both El Niño‐like and La Niña‐like SST warming patterns can be identified in the CMIP5 model simulations. The warming pattern is largely determined by the SST gradient between the Indian and Pacific oceans. Distinct from previous studies, an El Niño‐like pattern in an individual model can shift to a La Niña‐like pattern when the Indian warming is stronger than the Pacific warming trend, and vice versa. Key Points: El Niño‐like and La Niña‐like Pacific sea surface temperature warming patterns coexist and are interchangeable in climate model projectionsThe tropical Pacific warming pattern is primarily determined by a zonal gradient in the Indo‐Pacific sea surface warmingThis Pacific warming pattern diversity sheds light on future sea surface temperature change under greenhouse gases concentrations [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) participate in maternal immune regulation at multiple maternal-fetal interfaces. The liver is crucial for innate and adaptive immunity during pregnancy. The objective of this study was to measure the expression of genes and proteins related to TLR signaling. In this study, livers were obtained from ewes on day 16 of the estrous cycle, and on days 13, 16 and 25 of gestation, and RT-qPCR, western blot and immunohistochemistry were employed to measure the expression of genes and proteins related to TLR signaling, including TLR2, TLR3, TLR4, TLR5, TLR7, TLR9, myeloid differentiation primary-response protein 88 (MyD88), tumor necrosis factor receptor associated factor 6 (TRAF6) and interleukin-1-receptor-associated kinase 1 (IRAK1). Our data showed that the expression levels of TLR2, TLR3, TLR5, TLR9 and TRAF6 were increased, but those of TLR4 and TLR7 were decreased in the liver during early pregnancy. In addition, the expression levels of MyD88 and IRAK1 were the highest on days 13 and 16 of pregnancy, respectively, and the MyD88 protein was located in endothelial cells of proper hepatic arteries and portal veins and in hepatocytes. In conclusion, early pregnancy modulates TLR signaling in the maternal liver in sheep, which may participate in maternal immune regulation. [ABSTRACT FROM AUTHOR]

The study focused on the automatic segmentation of Magnetic Resonance Imaging (MRI) images of stroke patients and the therapeutic effects of Mental Imagery on motor and neurological functions after stroke. First, the traditional fuzzy c-means (FCM) algorithm was optimized, and the optimized one was defined as filter-based FCM (FBFCM). 62 stroke patients were selected as the research subjects and randomly divided into the experimental group and the control group. The control group accepted the conventional rehabilitation training, and the experimental group accepted Mental Imagery on the basis of the control group. They all had the MRI examination, and their brain MRI images were segmented by the FBFCM algorithm. The MRI images before and after treatment were analyzed to evaluate the therapeutic effects of Mental Imagery on patients with motor and nerve dysfunction after stroke. The results showed that the segmentation coefficient of the FBFCM algorithm was 0.9315 and the segmentation entropy was 0.1098, which were significantly different from those of the traditional fuzzy c-means (FCM) algorithm. (P < 0.05), suggesting that the FBFCM algorithm had good segmentation effects on brain MRI images of stroke patients. After Mental Imagery, it was found that the patient's Function Independent Measure (FIM) score was 99.04 ± 8.19, the Modified Barthel Index (MBI) score was 51.29 ± 4.35, the Fugl-Meyer (FMA) score was 61.01 ± 4.16, the neurological deficit degree in stroke (NFDS) score was 11.48 ± 2.01, the NIH Stroke Scale (NIHSS) score was 10.36 ± 1.69, and the clinical effective rate was 87.1%, all significantly different from those of the conventional rehabilitation training group (P < 0.05). Additionally, the brain area activated by Mental Imagery was more extensive. In conclusion, the FBFCM algorithm demonstrates superb capabilities in segmenting MRI images of stroke patients and is worth promotion in clinic. Mental Imagery can promote the neurological rehabilitation of patients by activating relevant brain areas of patients. [ABSTRACT FROM AUTHOR]

Precipitation fluctuations are continuously threatening the environment and may cause huge economic losses. In present study, the precipitation over China has been evaluated under five principal shared socioeconomic pathways (SSPs) scenarios during 2015–2099 based on eight CMIP6 models bias-corrected by the method of Equidistant Cumulative Distribution Functions. The results showed that (1) the simulated precipitation in China was in good agreement with observed precipitation for the eight CMIP6 models during 1961–2014, especially for the UKESM1-0-LL and MIROC6. However, the simulated annual mean precipitation has been significantly overvalued in the Southwest River basin (> 50%), while it was undervalued in the higher elevations of the Northwest River basin (< − 60%); (2) the annual mean precipitation will show a fluctuating upward trend during 2015–2099 over China under all the SSPs scenarios for the eight CMIP6 models. The rate of precipitation increase over north China will be higher than that in south China, especially in the Northwest River basin (reach 57.44% in the 2090s under the SSP5-8.5 for the ensemble mean). This increase of the precipitation in north China might alleviate the shortage of water there, but will not change the pattern of more rain in the south and less in the north; (3) in the southeastern basins, the precipitation of the multi-model ensemble (MME) and MIROC6 during 2011–2020 will be lower than that of 1961–2010 (− 6.53 to − 0.06%) under all SSPs scenarios. While the precipitation will increase obviously under all the SSPs scenarios, especially for the SSP5-8.5 scenario after the year of 2060; (4) the bias of the MME was much lower than that of individual CMIP6 models, and the bias of lower SSPs scenarios will be relatively lower. Generally, uncertainty ranges of precipitation fluctuations in north China (15.31–79.26%) will be higher than those in south China (16.06–7.55%). These findings revealed the projections and uncertainties of CMIP6 precipitation over China, which will be helpful for a better understanding of the future evolution of precipitation in China at large scale and in other regions of the world. [ABSTRACT FROM AUTHOR]

Complement pathways participate in the regulation of innate immune system, and complement activation is inhibited in normal pregnancy. The liver plays key roles in the modulation of immunity and tolerance, but it is unclear that early pregnancy induces the changes in expression of complement components in the ovine maternal liver. The aim of the present study was to explore the expression of complement components in the liver using quantitative real‐time polymerase chain reaction (PCR), Western blot, and immunohistochemistry. Maternal livers were collected on Day 16 of the estrous cycle and Days 13, 16, and 25 of gestation. The results indicated that early pregnancy suppressed the expression of C1q, C1r, C1s, C2, C4a, C5b, and C9 in the maternal liver, but C3 expression was increased. In addition, C3 protein was located in the endothelial cells of the proper hepatic arteries and portal veins and hepatocytes. In summary, the downregulaltion of C1q, C1r, C1s, C2, C4a, C5b, and C9 may be involved in the suppression of complement activation, and upregulation of C3 is related to the modulation of maternal immune tolerance in ovine liver. [ABSTRACT FROM AUTHOR]

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Summary: As a pineal gland hormone, melatonin acts through its receptors to modulate the immune system. The immune system is composed of primary and secondary organs, and immune organs are adapted to the presence of the fetal alloantigen during pregnancy. However, it is unclear whether melatonin affects maternal immune organs during early pregnancy in sheep. In this study, the ovine thymus, lymph node, spleen and liver were sampled at day 16 of the oestrous cycle, and at days 13, 16 and 25 of pregnancy. The expression of melatonin receptor 1A (MT1), melatonin receptor 1B (MT2) and cluster of differentiation 4 (CD4) was detected by quantitative real‐time polymerase chain reaction, Western blot and immunohistochemistry experiments. Our results showed that during early pregnancy there was an upregulation of MT1 mRNA and protein in the thymus, lymph node and liver, and there was a downregulation in the spleen. The expression of MT2 mRNA and protein was increased in the thymus but decreased in the spleen and liver, and there was no significant change in the lymph node during early pregnancy. CD4 protein was upregulated in the thymus, lymph node and liver, but there were no significant changes in the spleen during early pregnancy. In conclusion, early pregnancy induces tissue‐specific expression of MT1, MT2 and CD4, which may be due to the different functions of the thymus, lymph node, spleen and liver. Further, melatonin is involved in immune regulation of the maternal thymus, lymph node, spleen and liver during early pregnancy in sheep. [ABSTRACT FROM AUTHOR]