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In ruminants, the signal (interferon-tau, IFNT) for the maternal recognition of pregnancy has effects on maternal extrauterine organs, and progesterone plays a key role during pregnancy. However, it is unclear that early pregnancy has effects on the expression of interferon-stimulated genes (ISGs), progesterone receptors (PGRs), and progesterone-induced blocking factor (PIBF) in ovine small intestine. In this study, small intestines were obtained at day 16 of the estrous cycle, days 13, 16, and 25 of pregnancy, and RT-qPCR assay, Western blot, and immunohistochemistry were used to analyze the effects of early pregnancy on the expression of ISGs, PGR, and PIBF in the small intestine. The results indicated that expression levels of ISG15-conjugated protein, signal transducer and activator of transcription 1 (STAT1), myxovirus resistance protein 1, and interferon-gamma-inducible protein 10 (IP-10) at day 13 of pregnancy were the lowest. However, expression levels of PGR isoforms (60 kDa and 40 kDa), PIBF, STAT1 and 2′,5′-oligoadenylate synthetase 1 upregulated, but the expression value of IP-10 downregulated at day 25 of pregnancy compared with day 16 of the estrous cycle. In conclusion, early pregnancy modulated the expression of ISGs, PGR, and PIBF in ovine duodenum, which was implicated in immunoregulation and nutrient absorption of the small intestine in ewes. • Early pregnancy modulates expression of ISGs in the duodenum. • Upregulation of PGR isoforms in the duodenum during early pregnancy. • Upregulation of PIBF in the duodenum during early pregnancy. [ABSTRACT FROM AUTHOR]

Background: Pregnancy-induced immunological changes contribute to the maternal immune tolerance. Nuclear factor kappa B (NF-κB) pathway participates in regulating both innate and adaptive immunities, and lymph nodes play key roles in adaptive immune reaction. However, it is unclear whether early pregnancy changes the expression of NF-κB family in maternal lymph node in sheep. Methods: In this study, the samples of inguinal lymph nodes were collected from ewes on day 16 of the estrous cycle, and on days 13, 16 and 25 of pregnancy, and expression of NF-κB family, including NF-κB p105 (NFKB1), NF-κB p100 (NFKB2), p65 (RELA), RelB (RELB) and c-Rel (REL), were analyzed through real-time quantitative PCR, Western blot and immunohistochemical analysis. Results: The expression levels of NF-κB p105 and c-Rel downregulated, but NF-κB p100 upregulated on day 25 of pregnancy. The expression levels of p65, RelB and c-Rel peaked at day 13 of pregnancy, and expression level of RelB was higher during early pregnancy comparing to day 16 of the estrous cycle. In addition, p65 protein was located in the subcapsular sinus and lymph sinuses. Conclusion: This paper reported for the first time that early pregnancy has effects on the expression of NF-κB family, which may contribute to the maternal immunoregulation through blood circulation and lymph circulation during early pregnancy in sheep. [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]

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]

Traditional Chinese medicine has gained significant attention in recent years owing to its multi-component, multi-target, and multi-pathway advantages in treating various diseases. Forsythiae Fructus , derived from the dried fruit of Forsythia suspensa (Thunb.) Vahl, is one such traditional Chinese medicine with numerous in vivo and ex vivo therapeutic effects, including anti-inflammatory, antibacterial, and antiviral properties. Forsythiae Fructus contains more than 200 chemical constituents, with forsythiaside, forsythiaside A, forsythiaside B, isoforsythiaside, forsythin, and phillyrin being the most active ingredients. Forsythiae Fructus exerts neuroprotective effects by modulating various pathways, including oxidative stress, anti-inflammation, NF-κB signaling, 2-AG, Nrf2 signaling, acetylcholinesterase, PI3K-Akt signaling, ferroptosis, gut-brain axis, TLR4 signaling, endoplasmic reticulum stress, PI3K/Akt/mTOR signaling, and PPARγ signaling pathway. This review aims to highlight the potential therapeutic effects of Forsythiae Fructus on the central nervous system and summarize the current knowledge on the active ingredients of Forsythiae Fructus and their effects on different pathways involved in neuroprotection. In this review, we conducted a comprehensive search of databases (PubMed, Google Scholar, Web of Science, China Knowledge Resource Integrated, local dissertations and books) up until June 2023 using key terms such as Forsythia suspensa , Forsythiae Fructus , forsythiaside, isoforsythiaside, forsythin, phillyrin, Alzheimer′s disease, Parkinson's disease, ischemic stroke, intracerebral hemorrhage, traumatic brain injury, aging, and herpes simplex virus encephalitis. Our findings indicate that Forsythiae Fructus and its active ingredients own therapeutic effects on the central nervous system by modulating various pathways, including oxidative stress, anti-inflammation, NF-κB signaling, 2-AG, Nrf2 signaling, acetylcholinesterase, PI3K-Akt signaling, ferroptosis, the gut-brain axis, TLR4 signaling, endoplasmic reticulum stress, PI3K/Akt/mTOR signaling, and PPARγ signaling pathway. Forsythiae Fructus and its active ingredients have demonstrated promising neuroprotective properties. Future in vivo and clinical studies of Forsythiae Fructus and its active ingredients should be conducted to establish precise dosage and standard guidelines for a more effective application in the treatment of neurological disorders. Molecular pathways involved in the pharmacological properties of Forsythiae Fructus and its active ingredients. The arrows (→) represent elevation, and these symbol (┤)represent lowering. This figure was created using Biorender.Abbreviations: Aβ, β-amyloid; Ach, Acetylcholine; AD, Alzheimer′s disease; BCL-2, B-cell lymphoma-2; CAT, catalase; GFAP, glial fibrillary acidic protein; GLU, glutamate; GPX4, glutathione peroxidase 4; GSH, glutathione; GSH-Px, glutathione peroxidase; HSE, Herpes simplex virus encephalitis; HSV-1, Herpes simplex virus type I; HO-1, Heme oxygenase; H2O2, hydrogen peroxide; Iba1, ionized calcium-binding adaptor molecule-1; ICH, Intracerebral hemorrhage; IFN-γ, interferon-gamma; IKK, IκB kinase; IL, Interleukin 1; JIP-3, JNK-interacting protein-3; JNK, Jun NH2-terminal kinase; L-Glu, L-glutamate; MDA, malondialdehyde; NF-κB, nuclear factor kappa-B; NO, nitric oxide; NOS, nitric oxide synthase; Nrf2, Nuclear factor E2-related factor 2; NQO1,NAD(P)H quinone oxidoreductase-1; PD, Parkinson's disease; PGE2, Prostaglandin E2; PI3K/Akt/MTOR: Phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin; PPARγ, Peroxisome proliferator-activated receptor γ; ROS, reactive oxygen species; SOD, superoxide dismutase; TBI, Traumatic brain injury; TGF-β, transforming growth factor-β; TLR4, toll-like receptor 4; TNF-α, tumor necrosis factor alpha; T-SOD, total superoxide dismutase; WDFY1: WD Repeat and FYVE domain containing 1; 2-AG, 2-arachidonoylglycerol; 4-HNE, 4-hydroxy-2-nonenal; [Display omitted] • Forsythiae Fructus , derived from the dried fruit of Forsythia suspensa (Thunb.) Vahl , is a traditional Chinese medicine. • Forsythiae Fructus and its various active ingredients exert neuroprotective effects by modulating various pathways. • Forsythiae Fructus has demonstrated promising potential for the treatment of nervous system diseases. • The therapeutic effects and clinical applications of Forsythiae Fructus is needed to further explore. [ABSTRACT FROM AUTHOR]

The net heat flux and meridional temperature advection in the ocean are two factors in the North Pacific subtropical sea surface temperature front (NPSTF) frontogenesis occurring from October to the following February. However, the relative importance of these two factors has been rarely explored. In this study, frontogenesis of the NPSTF is examined quantitatively based on the mixed-layer heat budget equation to clarify the relative importance of net heat flux and meridional temperature advection and to further explore its connection with the atmosphere above. Diagnosis results show that the net heat flux dominates the frontogenesis from October to December, while the meridional temperature advection in the ocean contributes equally as or even more than the net heat flux in January and February. The atmosphere is critical to the frontogenesis of the NPSTF, including the direct effect of the net heat flux and the indirect effect through the Aleutian low. Further analyses demonstrate that the latent heat flux (the shortwave radiation) dominates the net heat flux in October (from November to February). The meridional temperature advection in the ocean is mostly due to the meridional Ekman convergence, which is related to the Aleutian low. Climatologically, the strengthening and southward migration of the Aleutian low from October to the following February are characterized by the acceleration and southward shift of the westerly wind to the south, respectively, which can drive southward ocean currents. Correspondingly, the southward ocean currents provide for colder meridional advection to the north of the NPSTF in January and February, favoring frontogenesis. In addition, the Aleutian low plays a role in transforming the dominant effect of the net heat flux into the joint effect of meridional temperature advection and net heat flux in January. [ABSTRACT FROM AUTHOR]

Abstract Interferon-tau (IFNT) is the main signal for the maternal recognition of pregnancy in ruminants, and exerts its effects by stimulating the expression of interferon-stimulated genes, including the expression of interferon-stimulated gene15 kDa protein (ISG15). Progesterone (P4) exerts significant immune effects on the uterus during early pregnancy in ruminants that are partly mediated by progesterone-induced blocking factor (PIBF). The thymus is necessary for the normal development of immunologic function. In this study, thymuses were obtained on day 16 of the estrous cycle and on days 13, 16 and 25 of pregnancy (n = 6 for each group) from ewes. Our results showed that the expression of ISG15, P4 receptor (PGR) and PIBF mRNA and the expression of ISG15 and ISG15-conjugated proteins were upregulated in the thymuses during early pregnancy, and the 89-kDa PGR isoform and the 80-kDa PIBF variant were expressed constantly in the thymuses. However, there was no expression of the 60-kDa PGR isoform and the 62-kDa PIBF variant on day 16 of the estrous cycle. ISG15 and ISG15-conjugated proteins were limited to the epithelial reticular cells, capillaries and thymic corpuscles. This paper reports for the first time that early pregnancy exerts its effects on the thymus through IFNT and P4 in sheep. Highlights • Upregulation expression of ISG15 mRNA and protein in the thymus during early pregnancy in sheep. • Upregulation expression of PGR mRNA and protein in the thymus during early pregnancy in sheep. • Upregulation expression of PIBF mRNA and protein in the thymus during early pregnancy in sheep. • ISG15 protein was limited to the epithelial reticular cells, capillaries and thymic corpuscles in the thymus. [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]

ABSTRACT: The North Pacific subtropical front (NPSTF) of sea surface temperature (SST) is an important subtropical feature in the North Pacific. In this study, we reveal that the inter‐annual variability of the spring NPSTF has a robust correlation with the El Niño‐Southern Oscillation (ENSO) in the following winter over the period of 1961–2016. When there is a strong spring NPSTF, anomalous cyclonic and anticyclonic circulations in the low troposphere occur to its north and south, respectively. The northeasterly wind anomaly associated with the anticyclonic circulation increases the climatological northeasterly wind over the subtropical Northeast Pacific, resulting in SST decrease via the wind–evaporation–SST feedback. The SST and wind perturbations propagate southwards from the subtropical to the eastern central equatorial Pacific in summer and grow via the Bjerknes feedback from summer to winter, eventually leading to a La Niña event in winter. A strong spring NPSTF induces an anomalous anticyclonic circulation to its south through both transient eddy activity and atmospheric heat source anomaly. The enhanced air temperature gradient due to a strong NPSTF increases the atmospheric baroclinicity, favouring an enhanced transient eddy activity over the NPSTF and to the north. The enhanced transient eddy activity triggers a significant negative height anomaly to the north via high‐frequency transient eddy feedback forcing, which is conductive to an anticyclonic circulation over the subtropical North Pacific through the downstream effect of Rossby waves. On the other hand, the convergence and increased atmospheric baroclinicity related to the strong NPSTF act to enhance precipitation over the NPSTF and to the north, corresponding to the increased atmospheric heat source, which can also excite an anomalous anticyclonic circulation over the subtropical North Pacific. [ABSTRACT FROM AUTHOR]

This study concerns atmospheric responses to the North Pacific subtropical front (NPSTF) in boreal spring over the period 1982-2014. Statistical results show that a strong NPSTF in spring can significantly enhance the East Asian jet stream (EAJS). Both transient eddy activity and the atmospheric heat source play important roles in this process. The enhanced atmospheric temperature gradient due to a strong NPSTF increases atmospheric baroclinicity, resulting in an intensification of transient eddy and convection activities. On the one hand, the enhanced transient eddy activities can excite an anomalous cyclonic circulation with a quasi-baraotropical structure in the troposphere to the north of the NPSTF. Accordingly, the related westerly wind anomalies around 30°N can intensify the component of the EAJS over the Northeast Pacific. On the other hand, an enhanced atmospheric heat source over the NPSTF, which is related to increased rainfall, acts to excite an anomalous cyclonic circulation system in the troposphere to the northwest of the NPSTF, which can explain the enhanced component of the EAJS over the Northwest Pacific. The two mechanisms may combine to enhance the EAJS. [ABSTRACT FROM AUTHOR]

A fetus changes immune responses in the uterus and the maternal immune system, and lymph nodes are associated with regulating maternal adaptive immunity. Complement activation is associated with abnormal pregnancy in mice and humans. The aim of the present study was to explore the expression levels of complement components in maternal lymph nodes during early pregnancy in sheep. Maternal inguinal lymph nodes were sampled on day 16 of the estrous cycle, and days 13, 16 and 25 of gestation in ewes. Reverse transcription-quantitative PCR, western blotting and immunohistochemical analyses were used to detect the expression levels of complement components C1q, C1r, C1s, C2, C3, C4a, C5b and C9 in the lymph nodes. The results revealed that the protein and mRNA levels of C1q, C1s and C5b were enhanced during early pregnancy, and that C1r and C4a were upregulated at day 25 of pregnancy. The mRNA and protein levels of C2 and C9 peaked at day 16 of pregnancy, but C3 was decreased at day 25 of pregnancy. C3 protein was located in the subcapsular sinuses and lymph sinuses of the maternal lymph node. In summary, the present study detected changes in the expression levels of complement components in maternal lymph nodes, which may be associated with maternal immune regulation during early pregnancy in sheep. [ABSTRACT FROM AUTHOR]

Abstract: Understanding the local CNS immune response to neoplasms is essential in the development of immune-based treatments for malignant brain tumors. Using rodent glioma models, we have recently found tumor-associated microglia/macrophages (MG/MP) to be less responsive to known MG/MP activators such as CpG, LPS and IFN-γ. To understand the mechanism of MG/MP suppression, nuclear extracts from rodent intracranial C6 gliomas, C6 glioma-associated MG/MP, normal brain, and normal MG/MP were obtained and studied using Electrophoretic Mobility Shift Assay (EMSA). Among the nuclear factors studied (AP-1, IRF, USF-1 and Stat-1) only USF-1, which is constitutively expressed in most cells, was down-regulated in tumor-associated MG/MP, but not normal MG/MP. Because tumor-associated MG/MP had higher expression of IL-10 (but not TNF-α or TGF-β), we evaluated the role of USF-1 on IL-10 expression. siRNA mediated inhibition of USF-1 expression in primary MG/MP cultures resulted in up-regulation of IL-10 mRNA but not TNF-α or TGF-β. These findings suggest that USF-1 may play a role in IL-10 regulation in MG/MP in brain tumors. [Copyright &y& Elsevier]

Cyp1B1 is expressed constitutively in many extrahepatic cells and is induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). An enhancer region (AhER-810 to –1075 of the mouse Cyp1B1 promoter), which mediates aryl hydrocarbon receptor (AhR) regulation of transcription, contains three consensus XRE sequences (designated XRE1, XRE4, and XRE5) and a central Ebox. XRE5 is essential for both basal and induced activity in C3H10T1/2 cells. AhR/ARNT binding to XRE1, XRE4, and the Ebox complex function in combination to support the AhR/ARNT complex at XRE5. The identical 12 base cores of XRE1 and XRE4 differ from the core of XRE5 by two bases outside of the consensus XRE. These sites bind a constitutive complex slightly smaller than AhR/ARNT (anomalous complex; anC), which is not formed at XRE5 or six Cyp1A1 XREs. Exchange of these bases (m3 mutations) restores selective AhR/ARNT binding at XRE1/XRE4 and introduces anC binding at XRE5. The activities of multimeric XRE1 and XRE5 luciferase reporters responded in parallel to the extent of AhR/ARNT binding. The consensus anC binding sequence ((C/T)GCG(C/T)GCGC(C/A)GC) overlaps the XRE1/XRE4 AhR/ARNT element. Gel mobility analyses show that anC binds to XRE1/XRE4 under basal conditions, while AhR/ARNT partially displaces anC following TCDD induction. Selective depletion of anC with biotin-oligonucleotides increases AhR/ARNT binding. M3-mutations at, respectively, XRE1 and XRE4 of the AhER sequence, had opposite effects on luciferase reporters. Activities increased for the XRE1 mutation and decreased for the XRE4 mutation, but also depended on the level of AhR transfected into AhR −/− fibroblasts. AnC compete with AhR at XRE1 while playing an activating role at XRE4. This positive effect of constitutive anC binding at XRE4 may contribute to the characteristic basal Cyp1B1 expression in embryo fibroblasts, which is mediated by low constitutive activities of AhR. [Copyright &y& Elsevier]

Using observational data covering 1948–2020, the environmental factors controlling the winter precipitation in California were investigated. Empirical orthogonal function (EOF) analysis was applied to identify the dominant climate regimes contributing to the precipitation. The first EOF mode described a consistent change, with 70.1% variance contribution, and the second mode exhibited a south–east dipole change, with 11.7% contribution. For EOF1, the relationship was positive between PC1(principal component) and SST (sea surface temperature) in the central Pacific Ocean, while it was negative with SST in the southeast Indian Ocean. The Pacific–North America mode, induced by the positive SST and precipitation in the central Pacific Ocean, leads to California being occupied by southwesterlies, which would transport warm and wet flow from the ocean, beneficial for precipitation. As for the negative relationship, California is controlled by biotrophically high pressure, representing part of the Rossby wave train induced by the positive SST in the Indian ocean, which is unfavorable for the precipitation. For EOF2, California is controlled by positive vorticity at the upper level, whereas at the lower level, there is positive vorticity to the south and negative vorticity to the north, the combination of which leads to the dipole mode change in the precipitation. [ABSTRACT FROM AUTHOR]

Previous studies have documented the significant influences of the North Pacific subtropical sea surface temperature (SST) front (NPSTF) on the overlying atmospheric circulation. However, whether and how the NPSTF could affect remote circulations has not been well addressed. Here, we demonstrate that the enhanced NPSTF can induce a southward shift of the downstream North Atlantic westerly jet stream (NAWJS) in winter. A strong NPSTF with an increased meridional SST gradient induces a positive (negative) air temperature anomaly in its south (north) flank through the heat flux, leading to a direct thermal wind response and an indirect transient eddy feedback. The direct thermal wind response benefits a negative height anomaly south of Gulf of Alaska below 250 hPa and a positive one above 200 hPa, while the transient eddy activity could locally enhance and tilt northward with height. The kinetic energy significantly grows from the baroclinic energy conversion below 250 hPa over the NPSTF and from the barotropic energy conversion north of the NPSTF at the upper levels. This enhanced transient eddy activity gives rise to a negative height anomaly south of Gulf of Alaska through high-frequency transient eddy feedback forcing at all levels dominated by transient eddy vorticity flux. The anomalous low south of Gulf of Alaska favors an anomalous high over Canada and an anomalous low over the United States through Rossby energy propagation, causing the southward shift of the NAWJS. The numerical model further verifies the downstream influences of the NPSTF on the NAWJS in winter. • In addition to local effects, NPSTF can deliver its effect further downstream and modulate the meridional shift in NAWJS. • The height response south of Alaska Bay fosters downstream wind and height anomalies via Rossby energy propagation. • The transient eddy activity jointly induced by BTEC and BCEC dominates the local atmospheric response of NPSTF. [ABSTRACT FROM AUTHOR]

The increasing anthropogenic aerosols (AAs) over East Asia have caused significant regional climate responses, but the role of urban land-use changes which occur simultaneously, in altering these AA-induced changes, is not well understood. Here, the modulation of the AAs' effect on the East Asian winter (November–January) climate by the urban cover in eastern China was investigated using the Community Atmosphere Model version 5.1 coupled with the Community Land Model version 4. Results show that the winter sulfate aerosol burden is higher from central eastern China to southern Japan in the case with the presence of urban cover than in the case without it, resulting from urban-induced circulation changes. Such aerosol changes markedly increase the cloud fraction and precipitation over northern China and the adjacent ocean to the east, especially convection activities around southern Japan. This leads to a cooling effect near the surface over northern China and in the mid-upper troposphere to the east due to aerosol direct and indirect effects. The resulting circulation responses act to shift the mid-tropospheric East Asian trough southward and the upper-level East Asian westerly jet-stream as well, further supporting the surface changes. These winter climate responses to the urban-modulated aerosols can largely offset or even reverse those to the AAs forcing without the urban cover in the model, especially in northern East Asia. This study highlights the need to consider the modulating role of urban land-use changes in assessing the AAs' climatic effect over East Asia and other regions. [ABSTRACT FROM AUTHOR]

Lymph nodes have functions in the adaptive immune response, and interferon-tau (IFNT), a primary pregnancy recognition signal in domestic ruminants has effects on immune regulation. It, however, is unclear whether early pregnancy induces an increase in the abundance of interferon-stimulated gene (ISG) mRNA transcripts and proteins in lymph nodes of sheep. In this study, lymph nodes were obtained on day 16 of the estrous cycle from non-pregnant ewes and days 13, 16 and 25 of gestation from pregnant ewes, and the abundance of ISG mRNA transcripts, including signal transducer and activator of transcription 1 (STAT1), phosphorylated STAT1 (p-STAT1), 2′,5′-oligoadenylate synthetase (OAS1), myxovirus resistance protein 1 (MX1) and C-X-C motif chemokine 10 (CXCL10), was analyzed using real-time quantitative PCR. Furthermore, Western blot and immunohistochemistry analysis was conducted to assess relative abundance of proteins encoded by these genes. The results indicated that there was a larger abundance of STAT1 mRNA transcript and protein, and p-STAT1 protein in the maternal lymph node at days 16 and 25 of gestation, and that abundances of OAS1, MX1 and CXCL10 mRNA transcripts and protein were greatest on day 16 of gestations. In addition, STAT1 protein was located in the subcapsular sinus, lymph sinuses, B cells and T cells. The larger relative abundances of STAT1, p-STAT1, OAS1, MX1 and CXCL10 mRNA transcripts and/or protein in the lymph nodes of ewes may be associated with maternal immunoregulation through blood circulation and lymph circulation during early pregnancy. [ABSTRACT FROM AUTHOR]

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]

Simple Summary: The thymus is a main organ of the immune system. Immune tolerance exists in maternal immune system during pregnancy. Helper T (Th)1 and Th2 cytokines regulate the functions of immune system. We found that early pregnancy affected the production of Th1 and Th2 cytokines in maternal thymus in sheep, which may be beneficial for normal pregnancy. There is an immune tolerance in maternal immune system during pregnancy, and thymus is a main organ of the immune system. Helper T (Th)1 and Th2 cytokines are involved in the regulation of immune system, but the modulation of Th cytokines in the thymus during early pregnancy is unclear in ewes. Thymuses were collected on day 16 of the estrous cycle, and on days 13, 16, and 25 of pregnancy in ewes. qRT-PCR, Western blot, and immunohistochemistry were used to analyze the expression of Th1 and Th2 cytokines in the thymuses. There was a peak in the expression of interferon-gamma (IFN-γ) on day 16 of pregnancy, an upregulation of tumor necrosis factor beta (TNF-β), and a sustained expression of interleukin-2 (IL-2) and IL-4. Furthermore, there was a peak in the expression of IL-6 on day 13 of pregnancy, no expression of IL-6 on day 16 of the estrous cycle and day 25 of pregnancy, and an upregulation of IL-5 and IL-10 in the thymuses during early pregnancy. The immunohistochemistry results revealed that the IFN-γ and IL-6 proteins were limited to the stromal cells, capillaries, and thymic corpuscles. In conclusion, early pregnancy influenced the production of Th1 and Th2 cytokines of maternal thymus in sheep. [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]

Methane is the second largest anthropogenic greenhouse gas, and changes in atmospheric methane concentrations can reflect the dynamic balance between its emissions and sinks. Therefore, the monitoring of CH 4 concentration changes and the assessment of underlying driving factors can provide scientific basis for the government's policy making and evaluation. China is the world's largest emitter of anthropogenic methane. However, due to the lack of ground-based observation sites, little work has been done on the spatial-temporal variations for the past decades and influencing factors in China, especially for areas with high anthropogenic emissions as Central and Eastern China. Here to quantify atmospheric CH 4 enhancements trends and its driving factors in Central and Eastern China, we combined the most up-to-date TROPOMI satellite-based column CH 4 (xCH 4) concentration from 2018 to 2022, anthropogenic and natural emissions, and a random forest-based machine learning approach, to simulate atmospheric xCH 4 enhancements from 2001 to 2018. The results showed that (1) the random forest model was able to accurately establish the relationship between emission sources and xCH 4 enhancement with a correlation coefficient (R²) of 0.89 and a root mean-square error (RMSE) of 11.98 ppb; (2)The xCH 4 enhancement only increased from 48.21±2.02 ppb to 49.79±1.87 ppb from the year of 2001 to 2018, with a relative change of 3.27%±0.13%; (3) The simulation results showed that the energy activities and waste treatment were the main contributors to the increase in xCH 4 enhancement, contributing 68.00% and 31.21%, respectively, and the decrease of animal ruminants contributed -6.70% of its enhancement trend. [Display omitted] [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]

This study has discovered a significant linear relationship between the Southern Hemisphere (SH) annular mode (SAM) and the mid‐latitude Northern Hemisphere (NH) circulation in February using two reanalysis data sets. Significant positive height anomalies corresponding to the positive SAM appear over the mid‐latitude region of the NH, and significant positive surface air temperature anomalies prevail over Western Europe and Northeast Asia. The realistic vorticity forcing associated with the SAM is applied in a dry linear baroclinic model, and the results demonstrate that the SAM in February can induce height anomalies with the same sign at 300 hPa over the mid‐latitudes of the NH and that these anomalies have amplitudes as large as 22% of their counterparts in the SH. Further numerical experiments show that the positive height response over the mid‐latitudes of the NH mainly comes from the influence of the realistic positive vorticity over the mid‐latitudes of the SH and that the vorticity forcing over the southern Indian Ocean seems to be the most effective at exciting the NH circulation anomalies. The numerical experiments also demonstrate that the transient eddy feedback forcing contributes to the formation of mid‐latitude NH circulation anomalies, especially over Northeast Asia. The maintenance of the negative vorticity anomalies over Europe is further diagnosed through vorticity budget analysis. In December, however, the significant vorticity anomalies associated with the SAM are not limited to the middle and high latitudes of the SH but also appear over the subtropics of the SH (approximately 30°S). The numerical experiments show that cancellation occurs between the responses to the subtropical vorticity forcing and the mid‐latitude vorticity forcing, thereby accounting for the independence of the NH circulation from the December SAM variability. Simultaneous regression coefficients of the geopotential height at 300 hPa (a) and the surface air temperature (b) at 2 m on the Southern Hemisphere annular mode index in February. The contour intervals are 15 gpm for h300. For T2m, contours are drawn at every −2.5, −1.5, −0.5, 0.5, 1.5 and 2.5°C. In all of the panels, the red solid contours and the blue dashed contours denote positive and negative values, respectively. The zero lines are omitted. Shading denotes the statistically significant region at the 0.05 significance level. [ABSTRACT FROM AUTHOR]

Abstract S100B, a member of the multigene family of Ca2+-binding proteins, is overexpressed by most malignant gliomas but its biological role in gliomagenesis is unclear. Recently, we demonstrated that low concentrations of S100B attenuated microglia activation through the induction of STAT3. Furthermore, S100B downregulation in a murine glioma model inhibited macrophage trafficking and tumor growth. Based on these observations, we hypothesized that S100B inhibitors may have antiglioma properties through modulation of tumor microenvironment. To discover novel S100B inhibitors, we developed a high-throughput screening cell-based S100B promoter-driven luciferase reporter assay. Initial screening of 768 compounds in the NIH library identified 36 hits with >85% S100B inhibitory activity. Duloxetine (Dul, an SNRI) was selected for the initial proof-of-concept studies. At low concentrations (1–5 μM) Dul inhibited S100B and CCL2 production in mouse GL261 glioma cells, but had minimal cytotoxic activity in vitro. In vivo , however, Dul (30 mg/kg/14 days) inhibited S100B production, altered the polarization and trafficking of tumor-associated myeloid-derived cells, and inhibited the growth of intracranial GL261 gliomas. Dul therapeutic efficacy, however, was not observed in the K-Luc glioma model that expresses low levels of S100B. These findings affirm the role of S100B in gliomagenesis and justify the development of more potent S100B inhibitors for glioma therapy. Graphical abstract Image 1 Highlights • S100B is overexpressed by most malignant gliomas but its biological role in gliomagenesis is unclear. • S100B downregulation in a murine glioma model inhibits macrophage trafficking and tumor growth. • High-throughput screening assay was developed to discover novel S100B inhibitors. • Duloxetine, a serotonin-norepinephrine reuptake inhibitor, was identified as an inhibitor of S100B. • In a murine glioma model, duloxetine inhibited S100B production and tumor growth, and altered polarization of macrophages. [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]

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: 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]

This study categorized blocking high (BH) episodes during the boreal summer in northeast Asia (40°-70°N, 100°-150°E) into four types according to their wave-breaking features at the dynamic tropopause on the initial day: anticyclonic warm, cyclonic warm, anticyclonic cold, and cyclonic cold. Based on the results of a statistical analysis, it was shown that 1) the anticyclonic-warm type tended to occur in eastern Russia (55°-70°N, 127.5°-142.5°E), whereas the other three types preferentially occurred in the vicinity of Lake Baikal; 2) the two cold types generally were more common than the two warm types; and 3) the average life spans of the two anticyclonic types were longer than those of the two cyclonic types. According to a composite analysis, the four BH types were preceded by different wave train-like anomalies over the Eurasian continent over approximately one week. Correspondingly, each BH type was characterized by distinct Rossby wave propagation features. Interestingly, a northeastward propagation of the Rossby waves around the BHs was evident in the two cyclonic types. This feature differs from the quasi-meridional propagation of Rossby waves originating from suppressed convection activity over subtropical regions documented in previous studies. This study also found that every BH type was accompanied by distinct precipitation anomaly patterns over East Asia, highlighting the necessity of classifying BHs. [ABSTRACT FROM AUTHOR]

• Pregnancy increased expression of PI3K, AKT1, FoxO1, SREBP-1 and PTEN in maternal liver. • Pregnancy increased expression of p-mTOR in maternal liver on days 16 and 25. • Pregnancy increased expression of PPARα in maternal liver, and PI3K in maternal duodenum on day 13. • Pregnancy decreased expression of FXR in maternal liver and duodenum on days 13 and 16, and FoxO1, SREBP-1 and PTEN in maternal duodenum. • Pregnancy increased expression of AKT1 and p-mTOR on day 16, and PPARα in maternal duodenum on day 25. The liver and intestine play a critical role in nutrient absorption, storage, and metabolism. The aim of this study was to evaluate expression pattern of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR) signaling pathway that included PI3K, AKT1, mTOR, FoxO1, SREBP-1, PPARα, PTEN and FXR in the maternal liver and duodenum. Ovine livers and duodenums were sampled at day 16 of the estrous cycle, and at days 13, 16 and 25 of gestation, and RT-qPCR, western blot and immunohistochemistry analysis were used to detect mRNA and protein expression. The results showed that expression of PI3K, AKT1, p-mTOR, FoxO1, SREBP-1 and PTEN upregulated in the maternal liver, and PPARα upregulated in the duodenum. However, expression of FoxO1, SREBP-1 and PTEN in the duodenum downregulated during early pregnancy. In addition, expression levels of SREBP-1, PTEN and PPARα in the maternal liver, and PI3K in the duodenum peaked at day 13 of pregnancy. In addition, expression levels of PI3K, p-mTOR and FoxO1 in the liver, and AKT1 and p-mTOR in the duodenum peaked at day 16 of pregnancy. Nevertheless, expression levels of FXR both in the maternal liver duodenum downregulated at days 13 and 16 of pregnancy. In conclusion, early pregnancy regulated expression pattern of PI3K/AKT/mTOR signaling pathway in the ovine liver and duodenum in a pregnancy stage-specific and tissue-specific manner, which may be necessary for the adaptations in maternal hepatic nutrient metabolism and intestinal nutrient absorption early pregnancy. [ABSTRACT FROM AUTHOR]

There is a pregnant maternal immunological tolerance that protects the fetus and promotes its growth, and nuclear factor kappa B (NF-κB) family participates in the regulation of innate immune and adaptive immune responses. The thymus is related to establishing central tolerance, and early pregnancy has effects on expression of a good number of genes and proteins in the maternal thymus in sheep. However, it is unclear whether early pregnancy changes expression of NF-κB subunits in the ovine thymus. In this study, the thymic samples were collected from day 16 of non-pregnant ewes, and days 13, 16 and 25 of pregnant ewes, and the expression of NF-κB members (NF-κB1, NF-κB2, RelA, RelB and c-Rel) was analyzed through real-time quantitative PCR, Western blot and immunohistochemical analysis. The results showed that c-Rel mRNA and protein upregulated at day 25 of pregnancy, and NF-κB1 mRNA and proteins increased at days 16 and 25 of pregnancy, and RelB mRNA and proteins enhanced during early pregnancy. However, expression levels of NF-κB2 and RelA were decreased during early pregnancy, but upregulated from day 13 to 25 of pregnancy. In addition, the RelA protein was located in the epithelial reticular cells, capillaries and thymic corpuscles. This paper reported for the first time that early pregnancy induced expression of NF-κB1, RelB and c-Rel, but inhibited expression of NF-κB2 and RelA in the maternal thymus during early pregnancy, which is involved in the central immune tolerance, and helpful for successful pregnancy in sheep. [ABSTRACT FROM AUTHOR]

There is a pregnant maternal immunological tolerance that protects the fetus and promotes its growth, and nuclear factor kappa B (NF-κB) family participates in the regulation of innate immune and adaptive immune responses. The thymus is related to establishing central tolerance, and early pregnancy has effects on expression of a good number of genes and proteins in the maternal thymus in sheep. However, it is unclear whether early pregnancy changes expression of NF-κB subunits in the ovine thymus. In this study, the thymic samples were collected from day 16 of non-pregnant ewes, and days 13, 16 and 25 of pregnant ewes, and the expression of NF-κB members (NF-κB1, NF-κB2, RelA, RelB and c-Rel) was analyzed through real-time quantitative PCR, Western blot and immunohistochemical analysis. The results showed that c-Rel mRNA and protein upregulated at day 25 of pregnancy, and NF-κB1 mRNA and proteins increased at days 16 and 25 of pregnancy, and RelB mRNA and proteins enhanced during early pregnancy. However, expression levels of NF-κB2 and RelA were decreased during early pregnancy, but upregulated from day 13 to 25 of pregnancy. In addition, the RelA protein was located in the epithelial reticular cells, capillaries and thymic corpuscles. This paper reported for the first time that early pregnancy induced expression of NF-κB1, RelB and c-Rel, but inhibited expression of NF-κB2 and RelA in the maternal thymus during early pregnancy, which is involved in the central immune tolerance, and helpful for successful pregnancy in sheep. [ABSTRACT FROM AUTHOR]

The most of embryo losses occur before the day 16 after artificial insemination, but there is no low cost and easy operation that can detect pregnancy with high accuracy within three weeks post-insemination in cattle. In this study, blood samples were collected at day 18 of the estrous cycle, and days 18, 25 and 35 of pregnancy, and relative levels of interferon stimulated genes (ISGs), Toll-like receptor (TLRs), complement components, early pregnancy factor (EPF) and pregnancy-associated plasma protein A (PAPPA) proteins were analyzed through Western blot. In addition, a colloidal gold immunochromatographic test strip was developed using the selected antibody, and the test was used for early pregnancy diagnosis. The results showed that there were changes in relative levels of plasma ISGs, TLRs, complement components, EPF and PAPPA proteins during early pregnancy in cattle, and complement component 1q (C1q) could be used as an ideal marker to develop a colloidal gold immunochromatographic test strip for early pregnancy diagnosis. In addition, the accuracy of pregnancy diagnosis by this test strip was 91.67% (11/12) for pregnant cows and 80% (8/10) nonpregnant cows at day 18 after insemination. In conclusion, the changes in plasma ISGs, TLRs, complement components, EPF and PAPPA proteins may be related to the maternal systemic immune modulation during early pregnancy, and a colloidal gold immunochromatographic test strip was developed for early pregnancy diagnosis using C1q as the ideal marker in cows. However, this colloidal gold immunochromatographic test strip needs further studies to improve the accuracy. • Early pregnancy induces changes in plasma ISGs, TLRs, complement components. • C1q can be used as an ideal marker for early pregnancy diagnosis in cows. • Development of an immunochromatographic test strip for early pregnancy diagnosis. [ABSTRACT FROM AUTHOR]

Abstract: Carbon nantotubes (CNTs) are emerging as a new family of nanovectors for drug and gene delivery into biological systems. To evaluate potential application of this technology for brain tumor therapy, we studied uptake and toxicity of multi-walled CNTs (MWCNTs) in the GL261 murine intracranial glioma model. Within 24 h of a single intratumoral injection of labeled MWCNTs (5 µg), nearly 10–20% of total cells demonstrated CNT internalization. Most CNT uptake, however, occurred by tumor-associated macrophages (MP), which accounted for most (75%) MWCNT-positive cells. Within 24 h of injection, nearly 30% of tumor MP became MWCNT-positive. Despite a transient increase in inflammatory cell infiltration into both normal and tumor-bearing brains following MWCNT injection, no significant toxicity was noted in mice, and minor changes in tumor cytokine expression were observed. This study suggests that MWCNTs could potentially be used as a novel and non-toxic vehicle for targeting MP in brain tumors. [Copyright &y& Elsevier]

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]

• Two daily patterns of winter circulation responses to aerosols are identified. • Daily patterns are linked to tropical rainfall and extratropical transient eddies. • Seasonal mean changes can arise from certain daily response patterns. Anthropogenic aerosols (AA) have significantly caused anomalous winter mean atmospheric circulation over the Northern Hemisphere, but the main daily patterns of winter large-scale circulation change are not well understood. Here a self-organizing map analysis is applied to identify the leading patterns in AA-induced winter daily geopotential height (Z) anomaly fields simulated by three atmospheric general circulation models, with a focus on fast adjustments. Two winter daily circulation response patterns with a synoptic time scale are found: one pattern shows concurring Z anomalies over North America and North Asia with the same sign and the Bering Sea seeing the opposite, resembling the Asia–Bering–North American teleconnection; while the other is the Arctic Oscillation-like pattern with similar Z anomalies over North Pacific and North Atlantic and the opposite over the Arctic region. The AA-induced anomalous precipitation over the tropics and anomalous synoptic eddy activities over the extratropical oceans concur to support and maintain these circulation anomaly patterns. The winter-mean climate responses to AA can be understood as a result of these daily anomaly patterns, especially over the higher latitudes. Specifically, the associated changes in surface air temperature (SAT) over the mid-high latitudes are caused by the AA-driven meridional movements of polar (cold and dry) airmass and midlatitude (warm and moist) airmass in the regions, mainly through the relevant surface downward longwave radiation. This study highlights the role of AA in altering daily weather patterns, which is not sufficiently captured by seasonal mean responses. [ABSTRACT FROM AUTHOR]

Using the ensemble hindcasts of the European Centre for Medium-Range Weather Forecasts (ECMWF) coupled model for the period of 1980–2005, spatiotemporal evolution in the covariability of sea surface temperature (SST) and low-level winds in the ensemble mean and spread over the tropical Atlantic is investigated with the month-reliant singular value decomposition (SVD) method, which treats the variables in a given monthly sequence as one time step. The leading mode of the ensemble mean represents a coevolution of SST and winds over the tropical Atlantic associated with a phase transition of El Niño from the peak to decay phase, while the second mode is related to a phase transition from El Niño to La Niña, indicating a precursory role of the north tropical Atlantic (NTA) SST warming in La Niña development. The leading mode of ensemble spread in SST and winds further illustrates that an NTA SST anomaly acts as a precursor for El Niño–Southern Oscillation (ENSO). A north-tropical pathway for the delayed effect of the NTA SST anomaly on the subsequent ENSO event is identified; the NTA SST warming induces the subtropical northeast Pacific SST cooling through the modulation of a zonal–vertical circulation, setting off a North Pacific meridional mode (NPMM). The coupled SST–wind anomalies migrate southwestward to the central equatorial Pacific and eventually amplify into a La Niña event in the following months due to the equatorial Bjerknes feedback. Ensemble spread greatly increases the sample size and affords insights into the interbasin interactions between the tropical Atlantic and Pacific, as demonstrated here in the NTA SST impact on ENSO. [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]

Simple Summary: Interferon-tau is a maternal recognition factor in ruminants, and spleen plays an essential role in regulating innate and adaptive immune responses. We found that interferon-tau derived from conceptus induces expression of STAT1, OAS1, and CXCL10 in ovine maternal spleen, which may be helpful for maternal immune regulation. Interferon-tau is a maternal recognition factor in ruminant species, and spleen plays an essential role in regulating innate and adaptive immune responses. However, it is not fully understood that early pregnancy induces expression of interferon stimulated genes (ISGs) in the spleen during early pregnancy in ewes. In this study, spleens were collected from ewes at day 16 of the estrous cycle, and on days 13, 16, and 25 of gestation (n = 6 for each group), and RT-qPCR, western blot and immunohistochemistry analysis were used to detect the expression of signal transducer and activator of transcription 1 (STAT1), 2′,5′-oligoadenylate synthetase 1 (OAS1), myxovirusresistance protein 1 (Mx1) and C-X-C motif chemokine 10 (CXCL10). The results revealed that STAT1, OAS1 and CXCL10 mRNA and proteins were upregulated in the spleens during early pregnancy, and STAT1 protein was located in connective tissue cells in the capsule and trabeculae, and blood cells and lymphocytes in the red pulp. However, early pregnancy had no significant effects on expression of MX1 mRNA and protein. In conclusion, early pregnancy induces expression of STAT1, OAS1 and CXCL10 in maternal spleen, suggesting that maternal spleen is involved in immune regulation of pregnancy in sheep. [ABSTRACT FROM AUTHOR]

The spleen combines the innate and adaptive immune systems, and the early conceptus must regulate the maternal intrauterine immune and systemic immune response during early pregnancy in sheep. However, it is unclear whether early pregnancy exerts its effects on the characterization of the T helper (Th) cytokines profile in the spleen during early pregnancy in ewes. In this study, spleens were obtained at day 16 of the oestrous cycle and at days 13, 16 and 25 of pregnancy (n = 6 for each group) from ewes, and qRT-PCR, western blot and immunohistochemistry analysis were used to analyze the Th cytokines profile of the spleens. Our results showed that there was down-regulation of IFN-γ at days 13 and 16 of pregnancy, but there was upregulation of IL-2, IL-5 and IL-6 at day 25 of pregnancy, TNF-β at days 16 and 25 of pregnancy, and IL-4 and IL-10 in all pregnant groups. Immunohistochemistry results showed that the IL-6 protein was limited to the capsule, trabeculae and splenic cords. This paper reported, for the first time, that characterization of the Th cytokines profile varied in the maternal spleen during early pregnancy, which may be essential for successful pregnancy in sheep. [ABSTRACT FROM AUTHOR]

In this study, we use the long-term satellite data to investigate seasonal and interannual variation of low-cloud fraction (LCF) and the associated controlling factors over the eastern and western North Pacific. On the seasonal time scale, the enhanced LCF over the eastern North Pacific in summer is actively coupled with strong estimated inversion strength (EIS) and 700-hPa relative humidity, and the LCF over the western North Pacific in winter is large and mainly caused by increased sensible heat flux and tropospheric low-level cold advection. On the interannual time scale, the increased LCF over the eastern North Pacific in summer is associated with increased EIS and decreased sea surface temperatures, in which the El Niño plays an important role; the enhanced LCF over the western North Pacific in spring and winter has a positive correlation with enhanced sensible heat flux (SHF) and tropospheric low-level cold advection, which can be partly explained by the subpolar frontal zone (SPFZ) intensity. [ABSTRACT FROM AUTHOR]

Thymus is a primary lymphoid organ, must adapt to the presence of fetal alloantigens. Prostaglandins (PGs) have diverse effects to activate or inhibit the immune response, but effects of early pregnancy on the expression of PG synthases in ovine maternal thymus are unclear. In this study, ovine thymic samples were obtained at day 16 of the estrous cycle, and days 13, 16 and 25 of pregnancy. The expression of PG synthases, including cyclooxygenase 1 (COX-1), COX-2, PGE2 synthase (PTGES), and a prostaglandin F2α synthase (Aldo-keto reductase family 1, member B1, AKR1B1), was evaluated using quantitative real-time PCR, Western blot and immunohistochemistry analysis. In addition, the thymus/body ratio was also calculated. Our results showed that the expression of COX-2 mRNA and protein, AKR1B1 mRNA and dimer were up-regulated on day 25 of pregnancy (P < 0.05), and expression of COX-1, PTGES mRNA and protein, AKR1B1 monomer and thymus/body ratio were similar at different stages of pregnancy and the estrous cycle. The immunohistochemistry results showed that the COX-2 and AKR1B1 proteins were located in the stromal cells, capillaries and thymic corpuscles. This is the first study to report that expression of COX-2 and AKR1B1 dimer is up-regulated in the maternal thymus during early pregnancy, suggesting that early pregnancy exerts its effects on maternal thymus, which is involved in immunomodulation during early pregnancy in sheep. • Up-regulation expression of COX-2 mRNA and protein in the thymus on day 25 of pregnancy. • Up-regulation expression of AKR1B1 mRNA and dimer in the thymus on day 25 of pregnancy. • COX-2 and AKR1B1 proteins were limited to the stromal cells, capillaries and thymic corpuscles in the thymus. [ABSTRACT FROM AUTHOR]

Abstract As a fetal allograft to the mother, early conceptus regulates the intrauterine immune and systemic immune responses during early pregnancy in sheep. However, expression of T helper 1 (Th1) and Th2 cytokines in maternal lymph nodes is unclear during early pregnancy in sheep. In this study, inguinal lymph nodes were obtained on day 16 of the estrous cycle and on days 13, 16 and 25 of pregnancy (n = 4 for each group) in ewes, and qRT-PCR, western blot and immunohistochemistry were used to compare the expression of Th1 and Th2 cytokines in the lymph nodes. Our results showed that there were the highest levels of Th1 cytokines (IFN-γ, TNF-β and IL-2) and Th2 cytokines (IL-4, IL-5, IL-6 and IL-10) in the lymph nodes on day 13 or 16 of pregnancy. Furthermore, there were a downregulation of TNF-β and IL-2 and an upregulation of IL-5 and IL-10 on day 25 of pregnancy compared with that in nonpregnancy, with no significant difference in the expression of IFN-γ, IL-4, and IL-6 between the ewes on day 25 of pregnancy and nonpregnancy. The immunohistochemistry results showed that the IL-2 and IL-10 proteins were limited to the subcapsular sinus and trabeculae in the cortex, lymph sinus. In conclusion, early pregnancy exerted its effects on the lymph node and induced a Th2-biased response, which was essential for a normal pregnancy in sheep. Highlights • Downregulation of tumor necrosis factor beta and IL-2 in the lymph node. • Upregulation of IL-5 and IL-10 in the lymph node. • IL-2 and IL-10 were localized in the subcapsular sinus and trabeculae in the cortex, medullary sinuses. [ABSTRACT FROM AUTHOR]

The spleen is a unique lymphoid organ that plays a key role in immune regulation. Interferon‐tau induces upregulation of interferon‐stimulated gene 15‐kDa protein (ISG15) in the uterus during early pregnancy in sheep. Prostaglandins (PGs) have important effects in both the activation and the inhibition of immune response through an autocrine and paracrine manner. In this study, splenic samples were obtained at Day 16 of the estrous cycle, and Days 13, 16, and 25 of pregnancy from ewes, and the expression of ISG15 and PG synthases, including cyclooxygenase 1 (COX‐1), COX‐2, PGE synthase (PTGES), and PGF synthase (aldo‐keto reductase family 1, member B1, AKR1B1), was detected through quantitative real‐time PCR, western blot, and immunohistochemistry analysis. Our results showed that there was upregulation of COX‐2 mRNA and protein at Day 25 of pregnancy, and ISG15 mRNA and conjugated proteins, and AKR1B1 mRNA and dimer at Days 16 and 25 of pregnancy. COX‐2 and AKR1B1 proteins were limited to the capsule, trabeculae, and splenic cords. However, the expression of COX‐1 and PTGES was not affected by early pregnancy. In conclusion, ISG15‐conjugated proteins, COX‐2 and AKR1B1 upregulated in maternal spleen during early pregnancy, which may be beneficial for the placentation in sheep. [ABSTRACT FROM AUTHOR]

S100B, a member of the multigene family of Ca2+-binding proteins, is overexpressed by most malignant gliomas but its biological role in gliomagenesis is unclear. Recently, we demonstrated that low concentrations of S100B attenuated microglia activation through the induction of STAT3. Furthermore, S100B downregulation in a murine glioma model inhibited macrophage trafficking and tumor growth. Based on these observations, we hypothesized that S100B inhibitors may have antiglioma properties through modulation of tumor microenvironment. To discover novel S100B inhibitors, we developed a high-throughput screening cell-based S100B promoter-driven luciferase reporter assay. Initial screening of 768 compounds in the NIH library identified 36 hits with >85% S100B inhibitory activity. Duloxetine (Dul, an SNRI) was selected for the initial proof-of-concept studies. At low concentrations (1-5 μM) Dul inhibited S100B and CCL2 production in mouse GL261 glioma cells, but had minimal cytotoxic activity in vitro. In vivo, however, Dul (30 mg/kg/14 days) inhibited S100B production, altered the polarization and trafficking of tumor-associated myeloid-derived cells, and inhibited the growth of intracranial GL261 gliomas. Dul therapeutic efficacy, however, was not observed in the K-Luc glioma model that expresses low levels of S100B. These findings affirm the role of S100B in gliomagenesis and justify the development of more potent S100B inhibitors for glioma therapy. [ABSTRACT FROM AUTHOR]

The spleen plays a key role in immune regulation. Progesterone (P4) exhibits different immunological effects through binding to different types of receptor. In the present study, splenic samples were obtained at day 16 of non-pregnancy and days 13, 16, and 25 of pregnancy to study the expression of P4 receptor (PGR) and P4-induced blocking factor (PIBF) in ewes through quantitative real-time PCR, Western blot and immunohistochemistry analysis. Our results showed that the relative expression levels of PGR and PIBF mRNA increased from day 13–16 in pregnant ewes, but decreased from day 16–25, and the 26 kDa isoform of PGR and the 22 kDa variant of PIBF were down-regulated in the spleens at day 25 of pregnancy compared with expression at day 16 of the oestrous cycle and days 13 and 16 of pregnancy. The immunohistochemistry test results confirmed that PGR and PIBF proteins were localized in the cytoplasm of cells in the capsule, trabeculae and splenic cords. This paper reports for the first time that the 26 kDa isoform of PGR and the 22 kDa variant of PIBF were down-regulated during early pregnancy, which may be essential for normal pregnancy in ewes. [ABSTRACT FROM AUTHOR]

Lymph nodes are the sites where the immune reaction or suppression takes place. Progesterone (P4) exerts an essential effect of the immunomodulation on the maternal uterus during early pregnancy in ruminants. At present study, the inguinal lymph nodes were obtained at day 16 of non-pregnancy, days 13, 16 and 25 of pregnancy (n = 3 for each group) in ewes, and RT-PCR assay, western blot and immunohistochemistry analysis were used to analyze to the effect of early pregnancy on the expression of P4 receptor (PGR) and progesterone-induced blocking factor (PIBF) in the lymph nodes. Our results showed that the PGR and PIBF mRNA were up-regulated in the lymph nodes in pregnant ewes, and the PGR isoform (60 kDa) and the PIBF variant (75 kDa) were expressed constantly in the lymph nodes. However, there was no expression of the PGR isoform (40 kDa) and the PIBF variant (48 kDa) at day 16 of the estrous cycle. The immunohistochemistry results confirmed that the PGR and PIBF proteins were limited to the subcapsular sinus and trabeculae in the cortex, medullary sinuses, and were localized in the cytoplasm of the specific cells. This paper reports for the first time that early pregnancy exerts its effect on the specific cells in the lymph nodes through P4, which results in the up-regulated expression of the PGR mRNA and 40 kDa isoform, the PIBF mRNA and 48 kDa variant, and is involved in the immunoregulation of the lymph nodes through a cytosolic pathway in ewes. [ABSTRACT FROM AUTHOR]

Microglia (MG) and macrophages (MPs) represent a significant component of the inflammatory response to gliomas. When activated, MG/MP release a variety of pro-inflammatory cytokines, however, they also secrete anti-inflammatory factors that limit their cytotoxic function. The balance between pro and anti-inflammatory functions dictates their antitumor activity. To evaluate potential variations in MG and MP function in gliomas, we isolated these cells (and other Gr1+ cells) from intracranial GL261 murine gliomas by FACS and evaluated their gene expression profiles by microarray analysis. As expected, arginase 1 (Arg1, M2 marker) was highly expressed by tumor-associated Gr1+, MG and MP. However, in contrast to MP and Gr1+ cells that expressed Arg1 shortly after tumor trafficking, Arg1 expression in MG was delayed and occurred in larger tumors. Interestingly, depletion of MPs in tumors did not prevent MG polarization, suggesting direct influence of tumor-specific factors on MG Arg1 upregulation. Finally, Arg1 expression was confirmed in human GBM samples, but most Arg1+ cells were neutrophils and not MPs. These findings confirm variations in tumor MG and MP polarization states and its dependency on tumor microenvironmental factors. [ABSTRACT FROM AUTHOR]

Even when treated with aggressive current therapies, most patients with glioblastoma survive less than two years. Rapid tumor growth, an invasive nature, and the blood-brain barrier, which limits the penetration of large molecules into the brain, all contribute to the poor tumor response associated with conventional therapies. Immunotherapy has emerged as a therapeutic approach that may overcome these challenges. We recently reported that single-walled carbon nanotubes (SWCNTs) can be used to dramatically increase the immunotherapeutic efficacy of CpG oligonucleotides in a mouse model of glioma. Following implantation in the mouse brain, the tumor cell line used in these previous studies (GL261) tends to form a spherical tumor with limited invasion into healthy brain. In order to evaluate SWCNT/CpG therapy under more clinically-relevant conditions, here we report the treatment of a more invasive mouse glioma model (K-Luc) that better recapitulates human disease. In addition, a CpG sequence previously tested in humans was used to formulate the SWCNT/CpG which was combined with temozolomide, the standard of care chemotherapy for glioblastoma patients. We found that, following two intracranial administrations, SWCNT/CpG is well-tolerated and improves the survival of mice bearing invasive gliomas. Interestingly, the efficacy of SWCNT/CpG was enhanced when combined with temozolomide. This enhanced anti-tumor efficacy was correlated to an increase of tumor-specific cytotoxic activity in splenocytes. These results reinforce the emerging understanding that immunotherapy can be enhanced by combining it with chemotherapy and support the continued development of SWCNT/CpG. [ABSTRACT FROM AUTHOR]

Factors released by glioma-associated microglia/macrophages (GAMs) play an important role in the growth and infiltration of tumors. We have previously demonstrated that the co-chaperone stress-inducible protein 1 (STI1) secreted by microglia promotes proliferation and migration of human glioblastoma (GBM) cell lines in vitro . In the present study, in order to investigate the role of STI1 in a physiological context, we used a glioma model to evaluate STI1 expression in vivo . Here, we demonstrate that STI1 expression in both the tumor and in the infiltrating GAMs and lymphocytes significantly increased with tumor progression. Interestingly, high expression of STI1 was observed in macrophages and lymphocytes that infiltrated brain tumors, whereas STI1 expression in the circulating blood monocytes and lymphocytes remained unchanged. Our results correlate, for the first time, the expression of STI1 and glioma progression, and suggest that STI1 expression in GAMs and infiltrating lymphocytes is modulated by the brain tumor microenvironment. [ABSTRACT FROM AUTHOR]