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As placental mammals, the pregnant women and the fetus have intense and prolonged interactions during gestation. There is increasing evidence that multiple molecular as well as cellular components originating in pregnant women are transferred to the fetus. The transfer of maternal antibodies has long been recognized as a central component of newborn immunity against pathogens. More recent studies indicate that inflammatory mediators, micronutrients, microbial products and maternal cells are transferred in utero and influence the fetal immune system. Together, these multiple signals are likely to form a complex network of interactions that program the neonatal immune system and tune its homeostatic regulation. Maternal disorders, in particular infectious diseases, modify these signals and may thereby alter immunity in early life. Understanding maternal programming of the newborn immune system could provide a basis for interventions promoting child health.

Previously, it was widely documented that an overall decrease in surface solar radiation occurred in China at least until 2005, in contrast to the general background of 'global brightening'. Increased anthropogenic aerosol emissions were speculated to be the source of the reduction. In this study, we extend the trend analysis to the most recent decade from 2005-2015 and find that surface solar radiation has shifted from 'dimming' to 'brightening' over East China, with the largest increase over the northeast and southeast parts. Meanwhile, satellite and ground observation both indicate a reduction in aerosol optical depth (AOD) during the same period, whereas no significant trends in cloud amount show up. Detailed analysis using co-located radiation and aerosol observation at the XiangHe station in North China suggests that both AOD and single scattering albedo (SSA) changes contribute to the radiation trends. AOD reduction contributes to the increase of direct solar radiation, also decreasing the diffuse radiation, while the increase of SSA serves to increase the diffuse fraction. Simple calculations using a radiative transfer model confirm that the two effects combined explain changes in the global solar radiation and its components effectively. Our results have implications for potential climate effects with the reduction of China's aerosol emissions, and the necessity to monitor aerosol composition in addition to its loading.

Gamma-aminobutyric acid (GABA) can mediate plant stress tolerance. The objective of this study was to examine the effects of GABA on seed germination, seedling growth, ion elements, and carbohydrate and antioxidant metabolism in perennial ryegrass (Lolium perenne L.) cultivar ‘Inspire’ exposed to salinity stress. Seed germination percentage was significantly reduced by 175 mM NaCl, but 1 mM GABA added to the salinity treatment (GABA + NaCl) substantially improved germination (78%) compared to the NaCl treatment alone (46%). Compared to the non-stressed control, seedling length, shoot fresh weight, shoot dry weight, shoot carbon, and shoot nitrogen concentrations decreased under 175 mM NaCl, but such reductions were significantly lower in seedlings treated with GABA + NaCl. Salinity stress increased Na+ and did not alter K+ concentrations in the shoots, but GABA had no effect on both ions under the stress condition. The increased shoot glucose and fructose and unchanged sucrose concentrations were shown in the seedlings under the NaCl stress, and NaCl + GABA treatment had significantly higher glucose and lower sucrose but the same fructose concentrations, compared to the NaCl treatment alone. Salinity stress increased the activity of shoot superoxide dismutase (SOD) and decreased catalase (CAT) and ascorbate peroxidase (APX) activities, but higher CAT activity and unchanged SOD and APX activities were observed in the NaCl + GABA treatment, compared to the NaCl treatment alone. The results indicated that GABA ameliorated salinity tolerance by improving seed germination, seedling growth, and C and N status and altering carbohydrate and antioxidant metabolism.

This study systematically analyzed the color characteristics, microscopic inclusions (including fluid and mineral inclusions), spectral properties, and chemical composition of emerald samples from Kafubu, Zambia using infrared spectroscopy, UV–visible spectroscopy, Raman spectroscopy, and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The results were then compared with research data on emeralds from Afghanistan, Brazil, China, Colombia, Ethiopia, Madagascar, Russia, and the United States. The result establishes a global classification framework for emerald origins based on chromophores (Cr, V, Fe), categorizing deposits into two distinct groups: low-Fe regions and high-Fe regions. For high-Fe type IA emeralds, particularly those from Zambia and Madagascar exhibiting exceptionally similar Fe and Mg concentrations, a multi-element discrimination approach was developed. Using microscopic infrared testing to magnify and analyze the characteristic peaks related to OD in the range of 2550–2800 cm⁻1, it can be classified as HDO-dominant, and the high alkali metal element content in Zambian emeralds can be reflected by the absence of the HDO vOD absorption peak at 2685 cm⁻1. A further in-depth analysis of the trace elements in Zambian emeralds can provide a basis for inferring the possible rich ore geology for subsequent mining and provide more effective reference data for the identification of the origin of emeralds.

Background Breast cancer exhibits high incidence and mortality among women, with distant metastasis, especially bone metastasis, being the leading cause of death. Despite advances in adjuvant therapies, bone metastasis remains a challenge for patient survival and quality of life. Exosomes, small vesicles capable of mediating intercellular communication, play a crucial role in tumor metastasis. Results This study investigated the role of tumor-derived exosomal long noncoding RNA (lncRNA)-MIR193BHG in breast cancer bone metastasis. LncRNA-MIR193BHG was delivered to osteoclasts via exosomes and promoted osteoclast formation and activity by targeting the miR-489-3p/DNA methyltransferase 3A (DNMT3A) signaling axis, thereby accelerating breast cancer-induced osteolysis. Knockdown experiments demonstrated that reducing the levels of exosomal lncRNA-MIR193BHG significantly inhibited osteoclast differentiation and bone resorption, which was confirmed both in vitro and in vivo. Additionally, mechanistic studies revealed that lncRNA-MIR193BHG acted as a competitive endogenous RNA (ceRNA) interacting with miR-489-3p, regulating DNMT3A expression and subsequently affecting osteoclast differentiation. Conclusions These findings suggest that lncRNA-MIR193BHG plays a critical regulatory role in breast cancer bone metastasis, and the lncRNA-MIR193BHG/miR-489-3p/DNMT3A signaling axis could be a potential target for the treatment of breast cancer bone metastasis. Future studies should further explore the broader applicability of this mechanism and its clinical feasibility.

Adjuvant trastuzumab therapy has yielded conflicting results for overall survival, concerns about central nervous system (CNS) metastasis, and questions about optimal schedule. Therefore, we carried out a meta-analysis to assess the benefits of concurrent or sequential trastuzumab with adjuvant chemotherapy for early breast cancer patients with HER2-positive tumors. Computerized and manual searches were performed to identify randomized clinical trials comparing adjuvant chemotherapy with or without trastuzumab in HER2-positive early breast cancer patients. Odds ratios were used to estimate the association between the addition of trastuzumab to adjuvant chemotherapy and various survival outcomes. The fixed-effects or random-effects model was used to combine data. With six eligible studies identified, this analysis demonstrated that patients with HER2-positive breast cancer derived benefit in disease-free survival, overall survival, locoregional recurrence and distant recurrence (all P<0.001) from the addition of trastuzumab to adjuvant chemotherapy, whereas trastuzumab did worse in CNS recurrence as compared to the control group (P = 0.018). Furthermore, concomitant use of trastuzumab significantly lowered the hazard of death (P<0.001) but bore a higher incidence of CNS recurrence (P = 0.010), while statistical significance failed to be discerned for either overall survival (P = 0.069) or CNS metastasis (P = 0.374) between the sequential and observation arms. This analysis verifies the efficacy of trastuzumab in the adjuvant setting. Additionally, our findings indirectly corroborate the superiority of concurrent trastuzumab to sequential use and also illuminate that prolonged survival is the possible reason for the higher incidence of CNS with trastuzumab versus observation.

Topologically associating domains (TADs) are essential units of genome architecture, influencing transcriptional regulation and diseases. Despite numerous methods proposed for TAD identification, it remains challenging due to complex background and nested TAD structures. We introduce HTAD, a human-in-the-loop TAD caller that combines machine learning with human supervision to achieve high accuracy. HTAD begins with feature extraction for potential TAD border pairs, followed by an interactive labeling process through active learning. Performance assessments using public curation and synthetic datasets demonstrate HTAD’s superiority over other state-of-the-art methods and reveal highly hierarchical TAD structures, offering a human-in-the-loop solution for detecting complex genomic patterns.

Plant growth regulators can mediate plant response to stress. The objective of this study was to investigate hormone alterations associated with plant growth and heat tolerance in perennial ryegrass (Lolium perenne). The heat tolerant accession PI265351 and sensitive accession PI225825 were exposed to 35°C/30°C at 7-, 14-, and 21-days in a growth chamber. Heat stress decreased plant height (HT) and leaf water content (LWC) in both accessions, but reductions in HT and LWC delayed one week in PI265351. Chlorophyll fluorescence remained unchanged in PI265351 but decreased in PI225825 under heat stress, compared to their controls. Heat stress increased leaf trans-zeatin and abscisic acid (ABA) and decreased gibberellin (GA3) concentrations, occurring at 14- and 21-days for PI265351 and during the entire stress period for PI225825, respectively, compared to the unstressed controls. Both accessions showed similar trends in kinetin with an increased concentration at 14- and 21-days. An elevated level of indole-3-acetic acid (IAA) was observed in PI265351 at 21 days of heat stress, while indole-3-butyric acid (IBA) increased at 14- and 21-days for PI265351 and only at 14 days for PI225825. Heat stress increased salicylic acid (SA) concentration at 14 days for PI265351 but caused reductions in SA during the stress period for PI225825. The results indicated that the maintenance of IAA, IBA, and SA, delayed increases in ABA, and delayed reductions of GA3 could contribute to heat tolerance of perennial ryegrass.

Breast cancer (BrCa) is the malignant tumor that most seriously threatens female health; however, the molecular mechanism underlying its progression remains unclear. Here, we found that conditional deletion of hypermethylated in cancer 1 (HIC1) in the mouse mammary gland might contribute to premalignant transformation in the early stage of tumor formation. Moreover, the chemokine (C-X-C motif) ligand 14 (CXCL14) secreted by HIC1-deleted BrCa cells bound to its cognate receptor GPR85 on mammary fibroblasts in the microenvironment and was responsible for activating these fibroblasts via the ERK1/2, Akt, and neddylation pathways, whereas the activated fibroblasts promoted BrCa progression via the induction of epithelial-mesenchymal transition (EMT) by the C-C chemokine ligand 17 (CCL17)/CC chemokine receptor 4 (CCR4) axis. Finally, we confirmed that the HIC1-CXCL14-CCL17 loop was associated with the malignant progression of BrCa. Therefore, the crosstalk between HIC1-deleted BrCa cells and mammary fibroblasts might play a critical role in BrCa development. Exploring the progression of BrCa from the perspective of microenvironment will be beneficial for identifying the potential prognostic markers of breast tumor and providing more effective treatment strategies.

Hydrocephalus is a common and serious neuropathological condition characterized by disrupted cerebrospinal fluid (CSF) circulation, which lacks effective pharmacotherapy. Here, we demonstrate that adenosine A 2A receptor (A 2A R) signaling in the choroid plexus (ChP) is a trigger of hydrocephalus. Adenosine levels are increased in the CSF of hydrocephalus patients and mice, together with elevated ChP-A 2A R density. Accordingly, continued infusion of adenosine for 14 days or transgenic ChP-A 2A R overexpression is sufficient to drive CSF hypersecretion and ventriculomegaly. Conversely, selective knockdown of ChP-A 2A R reduces CSF production and ameliorates CSF hypersecretion and ventriculomegaly induced by autologous blood and kaolin. Furthermore, we unveil ChP-A 2A R signaling as a molecular mechanism linking brain insults with CSF hypersecretion through parallel PI3K/Akt-dependent activation of SPAK phosphorylation and NF-κB-dependent transcriptional regulation of ATP1A2. Lastly, the A 2A R antagonist KW6002 protects against hydrocephalus induced by autologous blood and kaolin, offering a novel treatment for hydrocephalus by repurposing the FDA-approved A 2A R antagonist istradefylline. This study identifies adenosine A 2A receptor (A 2A R) signaling in the choroid plexus as a key driver of cerebrospinal fluid hypersecretion and ventriculomegaly in hydrocephalus. Pharmacological or genetic inhibition of choroid plexus A 2A R mitigates disease pathology, highlighting A 2A R antagonism as a promising therapeutic strategy for hydrocephalus.