Niche Tet maintains germline stem cells independently of dioxygenase activity.

Ten-eleven translocation (TET) proteins are dioxygenases that convert 5-methylcytosine (5mC) into 5-hydroxylmethylcytosine (5hmC) in DNA and RNA. However, their involvement in adult stem cell regulation remains unclear. Here, we identify a novel enzymatic activity-independent function of Tet in the Drosophila germline stem cell (GSC) niche. Tet activates the expression of Dpp, the fly homologue of BMP, in the ovary stem cell niche, thereby controlling GSC self-renewal. Depletion of Tet disrupts Dpp production, leading to premature GSC loss. Strikingly, both wild-type and enzyme-dead mutant Tet proteins rescue defective BMP signaling and GSC loss when expressed in the niche. Mechanistically, Tet interacts directly with Bap55 and Stat92E, facilitating recruitment of the Polybromo Brahma associated protein (PBAP) complex to the dpp enhancer and activating Dpp expression. Furthermore, human TET3 can effectively substitute for Drosophila Tet in the niche to support BMP signaling and GSC self-renewal. Our findings highlight a conserved novel catalytic activity-independent role of Tet as a scaffold protein in supporting niche signaling for adult stem cell self-renewal.

Gap junction-transported cAMP from the niche controls stem cell progeny differentiation.

The niche has been shown to control stem cell self-renewal in different tissue types and organisms. Recently, a separate niche has been proposed to control stem cell progeny differentiation, called the differentiation niche. However, it remains poorly understood whether and how the differentiation niche directly signals to stem cell progeny to control their differentiation. In the Drosophila ovary, inner germarial sheath (IGS) cells contribute to two separate niche compartments for controlling both germline stem cell (GSC) self-renewal and progeny differentiation. In this study, we show that IGS cells express Inx2 protein, which forms gap junctions (GJs) with germline-specific Zpg protein to control stepwise GSC lineage development, including GSC self-renewal, germline cyst formation, meiotic double-strand DNA break formation, and oocyte specification. Germline-specific Zpg and IGS-specific Inx2 knockdowns cause similar defects in stepwise GSC development. Additionally, secondary messenger cAMP is transported from IGS cells to GSCs and their progeny via GJs to activate PKA signaling for controlling stepwise GSC development. Therefore, this study demonstrates that the niche directly controls GSC progeny differentiation via the GJ-cAMP-PKA signaling axis, which provides important insights into niche control of stem cell differentiation and highlights the importance of GJ-transported cAMP in tissue regeneration. This may represent a general strategy for the niche to control adult stem cell development in various tissue types and organisms since GJs and cAMP are widely distributed.

Identification and functional analysis of the LEAFY gene in longan flower induction.

BACKGROUND: Flowering at the right time is a very important factor affecting the stable annual yield of longan. However, a lack of knowledge of the regulatory mechanism and key genes of longan flowering restricts healthy development of the longan industry. Therefore, identifying relevant genes and analysing their regulatory mechanism are essential for scientific research and longan industry development. RESULTS: DlLFY (Dimocarpus longan LEAFY) contains a 1167 bp open reading frame and encodes 388 amino acids. The amino acid sequence has a typical LFY/FLO family domain. DlLFY was expressed in all tissues tested, except for the leaf, pericarp, and pulp, with the highest expression occurring in flower buds. Expression of DlLFY was significantly upregulated at the early flower induction stage in "SX" ("Shixia"). The results of subcellular localization and transactivation analysis showed that DlLFY is a typical transcription factor acting as a transcriptional activator. Moreover, overexpression of DlLFY in Arabidopsis promoted early flowering and restrained growth, resulting in reduced plant height and rosette leaf number and area in transgenic plants. DNA affinity purification sequencing (DAP-Seq) analysis showed that 13 flower-related genes corresponding to five homologous genes of Arabidopsis may have binding sites and be putative target genes. Among these five flower-related genes, only AtTFL1 (terminal flower 1) was strongly inhibited in transgenic lines. CONCLUSION: Taken together, these results indicate that DlLFY plays a pivotal role in controlling longan flowering, possibly by interacting with TFL1.

Arming Amorphous NiMoO4 on Nickel Phosphide Enables Highly Stable Alkaline Seawater Oxidation.

Seawater electrolysis holds tremendous promise for the generation of green hydrogen (H2 ). However, the system of seawater-to-H2 faces significant hurdles, primarily due to the corrosive effects of chlorine compounds, which can cause severe anodic deterioration. Here, a nickel phosphide nanosheet array with amorphous NiMoO4 layer on Ni foam (Ni2 P@NiMoO4 /NF) is reported as a highly efficient and stable electrocatalyst for oxygen evolution reaction (OER) in alkaline seawater. Such Ni2 P@NiMoO4 /NF requires overpotentials of just 343 and 370 mV to achieve industrial-level current densities of 500 and 1000 mA cm-2 , respectively, surpassing that of Ni2 P/NF (470 and 555 mV). Furthermore, it maintains consistent electrolysis for over 500 h, a significant improvement compared to that of Ni2 P/NF (120 h) and Ni(OH)2 /NF (65 h). Electrochemical in situ Raman spectroscopy, stability testing, and chloride extraction analysis reveal that is situ formed MoO4 2- /PO4 3- from Ni2 P@NiMoO4 during the OER test to the electrode surface, thus effectively repelling Cl- and hindering the formation of harmful ClO- .

Characterization of a mouse-adapted strain of bat severe acute respiratory syndrome-related coronavirus.

Bats carry genetically diverse severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Some of them utilize human angiotensin-converting enzyme 2 (hACE2) as a receptor and cannot efficiently replicate in wild-type mice. Our previous study demonstrated that the bat SARSr-CoV rRsSHC014S induces respiratory infection and lung damage in hACE2 transgenic mice but not wild-type mice. In this study, we generated a mouse-adapted strain of rRsSHC014S, which we named SMA1901, by serial passaging of wild-type virus in BALB/c mice. SMA1901 showed increased infectivity in mouse lungs and induced interstitial lung pneumonia in both young and aged mice after intranasal inoculation. Genome sequencing revealed mutations in not only the spike protein but the whole genome, which may be responsible for the enhanced pathogenicity of SMA1901 in wild-type BALB/c mice. SMA1901 induced age-related mortality similar to that observed in SARS and COVID-19. Drug testing using antibodies and antiviral molecules indicated that this mouse-adapted virus strain can be used to test prophylactic and therapeutic drug candidates against SARSr-CoVs. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlights the importance of developing a powerful animal model to evaluate the antibodies and antiviral drugs. We acquired the mouse-adapted strain of a bat-origin coronavirus named SMA1901 by natural serial passaging of rRsSHC014S in BALB/c mice. The SMA1901 infection caused interstitial pneumonia and inflammatory immune responses in both young and aged BALB/c mice after intranasal inoculation. Our model exhibited age-related mortality similar to SARS and COVID-19. Therefore, our model will be of high value for investigating the pathogenesis of bat SARSr-CoVs and could serve as a prospective test platform for prophylactic and therapeutic candidates.

N-linked glycoproteins and host proteases are involved in swine acute diarrhea syndrome coronavirus entry.

IMPORTANCE: Gaining insight into the cell-entry mechanisms of swine acute diarrhea syndrome coronavirus (SADS-CoV) is critical for investigating potential cross-species infections. Here, we demonstrated that pretreatment of host cells with tunicamycin decreased SADS-CoV attachment efficiency, indicating that N-linked glycosylation of host cells was involved in SADS-CoV entry. Common N-linked sugars Neu5Gc and Neu5Ac did not interact with the SADS-CoV S1 protein, suggesting that these molecules were not involved in SADS-CoV entry. Additionally, various host proteases participated in SADS-CoV entry into diverse cells with different efficiencies. Our findings suggested that SADS-CoV may exploit multiple pathways to enter cells, providing insights into intervention strategies targeting the cell entry of this virus.

Hyperoside alleviates photoreceptor degeneration by preventing cell senescence through AMPK-ULK1 signaling.

Vision loss and blindness are frequently caused by photoreceptor degeneration, for example in age-related macular degeneration and retinitis pigmentosa. However, there is no effective medicine to treat these photoreceptor degeneration-related diseases. Cell senescence is a common phenotype in many diseases; however, few studies have reported whether it occurs in photoreceptor degeneration diseases. Herein, we identified that cell senescence is associated with photoreceptor degeneration induced by N-methyl-N-nitrosourea (MNU, a commonly used photoreceptor degeneration model), presented as increased senescence-associated ß-galactosidase activity, DNA damage, oxidative stress and inflammation-related cytokine Interleukin 6 (IL6), and upregulation of cyclin p21 or p16. These results suggested that visual function might be protected using anti-aging treatment. Furthermore, Hyperoside is reported to help prevent aging in various organs. In this study, we showed that Hyperoside, delivered intravitreally, alleviated photoreceptor cell senescence and ameliorated the functional and morphological degeneration of the retina in vivo and in vitro. Importantly, Hyperoside attenuated the MNU-induced injury and aging of photoreceptors via AMPK-ULK1 signaling inhibition. Taken together, our results demonstrated that Hyperoside can prevent MNU-induced photoreceptor degeneration by inhibiting cell senescence via the AMPK-ULK1 pathway.

Enhanced Stability and Catalytic Activity of a Nanocatalyst with Reusable Ionic Liquid Hydrogels for the Reduction of Organic Pollutants.

Nitroaromatic compounds have a wide range of applications. However, they pose a significant threat to both the environment and human health. Ionic liquid hydrogels (ILs-gels) have emerged as a cost-effective and environmentally friendly option for various applications. However, conventional ILs-gels are known to possess mechanical flaws or defects. The procedure utilized a facile synthesis route that involved the polymerization of acrylamide (AM) and ionic liquids (ILs) to create a novel candidate for nanoparticle absorption. This study resolved this issue by creating toughened hydrophobic combined hydrogels synthesized through the addition of SiO2@poly(butyl acrylate) core-shell inorganic-organic hybrid latex particles (SiO2@PBA) to the AM-ILs mixture. The SiO2@PBA particles were chosen to provide the hydrogels with exceptional stretchability (up to 4050% strain) and high mechanical properties (tensile strength of 126 kPa) by acting as both a nanotoughener and a cross-linking point for hydrophobic linkage. Additionally, the P(AM/ILs)-SiO2@PBA hydrogel served as a template for the in situ and stable formation of palladium (Pd) nanoparticles. By incorporation of these Pd nanoparticles as catalysts into P(AM/ILs)-SiO2@PBA hydrogel carriers, the resulting P(AM/ILs)-SiO2@PBA/Pd hydrogels exhibited the ability to catalyze the degradation of p-nitrophenol. Remarkably, even after 15 applications, the efficiency of the degradation process remained consistently above 90%. Thus, the innovative SiO2@PBA toughened ILs-hydrogel design strategy can be utilized to develop robust and stretchable hydrogel materials for catalytic use in the sewage disposal industry.

IgA nephropathy: gut microbiome regulates the production of hypoglycosilated IgA1via the TLR4 signaling pathway.

BACKGROUND: IgA nephropathy (IgAN) is a major cause of primary glomerulonephritis characterized by mesangial deposits of galactose-deficient IgA1 (Gd-IgA1). Toll-like receptors (TLRs), particularly TLR4 are involved in the pathogenesis of IgAN. The role of gut microbiota on IgAN patients was recently investigated. However, whether gut microbial modifications of Gd-IgA1 through TLR4 play a role in IgAN remains unclear. METHODS: We recruited subjects into four groups, including 48 patients with untreated IgAN, 22 treated IgAN patients (IgANIT), 22 primary membranous nephropathy (MN), and 31 healthy controls (HCs). Fecal samples were collected to analyze changes in gut microbiome. Gd-IgA1 levels, expression of TLR4, B-cell stimulators, and intestinal barrier function were evaluated in all subjects. C57BL/6 mice were treated with a broad-spectrum antibiotic cocktail to deplete the gut microbiota and then gavaged with fecal microbiota transplanted fromclinical subjects of every group. Gd-IgA1 and TLR4 pathway were detected in peripheral blood mononuclear cells (PBMCs) from IgAN and HCs co-incubated with Lipopolysaccharide (LPS) and TLR4 inhibitor. RESULTS: Compared with other three groups, different compositions and decreased diversity demonstrated gut dysbiosis in un-treated IgAN, especially the enrichment of Escherichia -Shigella. Elevated Gd-IgA1 levels were found in un-treated IgAN patients and correlated with gut dysbiosis, TLR4, B-cell stimulators, indexes of intestinal barrier damage, and proinflammatory cytokines. In vivo, mice colonized with gut microbiota from IgAN and IgANIT patients, copied the IgAN phenotype with the activation of TLR4/MyD88/NF-κB pathway, B-cell stimulators in the intestine, and complied with enhanced proinflammatory cytokines. In vitro, LPS activated TLR4/MyD88/NF-κB pathway, B-cell stimulators and proinflammatory cytokines in the PBMCs from IgAN patients, which resulted in overproduction of Gd-IgA1 and inhibited by TLR4 inhibitor. CONCLUSIONS: Our results illustrated that gut-kidney axis was involved in the pathogenesis of IgAN. Gut dysbiosis could stimulate the overproduction of Gd-IgA1 by TLR4 signaling pathway production and B-cell stimulators.

Significant Isotope Effects from the Nonadiabatic Couplings in the Cl(2P) + HD(v = 0, j = 0) Reaction.

The impact of non-Born-Oppenheimer couplings on the isotopic effects in the reaction of the Cl(2P) atom with the HD (v = 0, j = 0) molecule is investigated with our recently developed nonadiabatic time-independent quantum scattering methods, where the full open-shell characteristics are included in the six-state model, and also with the recently developed two-state model solving by time-independent methods, where part of the open-shell characteristic is included. The same reaction is also calculated with the simple adiabatic model using the lowest adiabatic potential energy surface. Compared with the results from different models, it is found that the reactivity of the Cl + HD → HCl + D channel is significantly overestimated in the adiabatic model. In contrast, the reactivity of the other channel agrees well with the nonadiabatic models. This is due to the van der Waals well in the reactant channel being changed a lot by including the nonadiabatic couplings. These quantum dynamics calculations suggest that sometimes the adiabatic model should be used with caution; otherwise, it may result in significant deviations for some reactions.

Could emergency admission plasma D-dimer level predict first pass effect of stent retriever thrombectomy in acute ischemic stroke?

BACKGROUND: Evidence on plasma biomarkers to identify first pass effect (FPE) in patients with acute ischemic stroke (AIS) with large vessel occlusion (LVO) treated with thrombectomy is limited. PURPOSE: To evaluate whether plasma D-dimer could predict FPE. MATERIAL AND METHODS: Consecutive patients with LVO who underwent first-line stent retriever thrombectomy at our center between January 2018 and August 2021 were enrolled. Patients were classified into the FPE (modified Thrombolysis in Cerebral Infarction [mTICI] ≥2c) group or non-FPE (mTICI 0-2b) group based on angiographic outcomes. Logistic regression analysis was performed to determine the predictors of FPE. The overall ability of D-dimer levels in predicting FPE was evaluated using receiver operating characteristic (ROC) curves. RESULTS: In total, 313 patients were included; 88 (28.1%) patients achieved FPE. Compared to those with non-FPE, patients with FPE had more diabetes mellitus history, lower D-dimer levels, higher clot burden score, a higher proportion of M1 middle cerebral artery, and a higher proportion of main stem occlusion pattern (P <0.05). After adjusting for potential variables, D-dimer levels (OR=0.81, 95% CI=0.52-0.96), clot burden score (OR=1.76, 95% CI=1.38-2.87), and main stem occlusion pattern (OR=1.85, 95% CI=1.19-2.62) remained independently associated with FPE. Based on the ROC analysis, the D-dimer as a predictor for predicting FPE presented with a specificity of 79%, a negative predictive value of 87%, and an area under the curve of 0.761. CONCLUSION: Low emergency admission plasma D-dimer level is an independent predictor of FPE in patients with AIS treated with stent retriever thrombectomy.

SLC-30A9 is required for Zn2+ homeostasis, Zn2+ mobilization, and mitochondrial health.

The trace element zinc is essential for many aspects of physiology. The mitochondrion is a major Zn2+ store, and excessive mitochondrial Zn2+ is linked to neurodegeneration. How mitochondria maintain their Zn2+ homeostasis is unknown. Here, we find that the SLC-30A9 transporter localizes on mitochondria and is required for export of Zn2+ from mitochondria in both Caenorhabditis elegans and human cells. Loss of slc-30a9 leads to elevated Zn2+ levels in mitochondria, a severely swollen mitochondrial matrix in many tissues, compromised mitochondrial metabolic function, reductive stress, and induction of the mitochondrial stress response. SLC-30A9 is also essential for organismal fertility and sperm activation in C. elegans, during which Zn2+ exits from mitochondria and acts as an activation signal. In slc-30a9-deficient neurons, misshapen mitochondria show reduced distribution in axons and dendrites, providing a potential mechanism for the Birk-Landau-Perez cerebrorenal syndrome where an SLC30A9 mutation was found.

The Effects of Bivalirudin and Ordinary Heparin on the Incidence of Bleeding Events and the Level of Inflammation after Interventional Therapy for Acute Myocardial Infarction.

Objective: To evaluate and compare the efficacy, bleeding events, and inflammation levels of optimized bivalirudin versus ordinary heparin in the context of percutaneous coronary intervention (PCI) for patients with acute myocardial infarction. This approach will underscore the comprehensive scope of the study, addressing multiple dimensions of clinical outcomes. Methods: This study involved 120 acute myocardial infarction patients treated from January 2022 to January 2023, randomly allocated into two groups: the control group received ordinary heparin, and the observation group received bivalirudin. Both groups underwent percutaneous coronary intervention (PCI). The study specifically measured coagulation indexes such as prothrombin time (PT) and activated partial thromboplastin time (aPTT), and inflammatory markers including C-reactive protein (CRP) and interleukin-6 (IL-6). Additionally, the incidence of bleeding events and major adverse cardiovascular events (MACE) within 30 days post-PCI were recorded, with bleeding events categorized according to the Bleeding Academic Research Consortium (BARC) criteria and MACE defined by the occurrence of death, non-fatal myocardial infarction, or stroke. Results: No significant differences were observed in coagulation indexes and pre-operation inflammation levels between the two groups (P > .05). However, at 7 days post-operation, despite both groups showing reduced inflammation-NLR decreased by 25%, hs-CRP by 30%, and IL-10 increased by 20%-the bivalirudin group exhibited notably lower incidence rates of various bleeding events (mucosal 2% vs 6%, gingival 1% vs 4%, puncture site 3% vs 8%, and hematuria 1% vs 5%) within 30 days post-PCI compared to the heparin group. TIMI blood flow grades 3 (indicating normal flow) were achieved in 85% of the bivalirudin group compared to 70% in the heparin group. The incidence of MACE was comparable between groups with both reporting a 5% occurrence rate (P > .05). Conclusion: The study reveals that while both bivalirudin and ordinary heparin effectively prevent MACE post-acute myocardial infarction intervention, bivalirudin significantly reduces postoperative bleeding events and maintains comparable anti-inflammatory effects. This suggests its preferable use in clinical settings, particularly in patient populations at high risk for bleeding. Future research could further explore the specific patient characteristics that optimize bivalirudin's benefits over heparin, enhancing tailored therapeutic approaches. This could potentially include randomized trials focusing on patients with different baseline bleeding risks.

Potassium transporter OsHAK9 regulates seed germination under salt stress by preventing gibberellin degradation through mediating OsGA2ox7 in rice.

Soil salinity has a major impact on rice seed germination, severely limiting rice production. Herein, a rice germination defective mutant under salt stress (gdss) was identified by using chemical mutagenesis. The GDSS gene was detected via MutMap and shown to encode potassium transporter OsHAK9. Phenotypic analysis of complementation and mutant lines demonstrated that OsHAK9 was an essential regulator responsible for seed germination under salt stress. OsHAK9 is highly expressed in germinating seed embryos. Ion contents and non-invasive micro-test technology results showed that OsHAK9 restricted K+ efflux in salt-exposed germinating seeds for the balance of K+/Na+. Disruption of OsHAK9 significantly reduced gibberellin 4 (GA4) levels, and the germination defective phenotype of oshak9a was partly rescued by exogenous GA3 treatment under salt stress. RNA sequencing (RNA-seq) and real-time quantitative polymerase chain reaction analysis demonstrated that the disruption of OsHAK9 improved the GA-deactivated gene OsGA2ox7 expression in germinating seeds under salt stress, and the expression of OsGA2ox7 was significantly inhibited by salt stress. Null mutants of OsGA2ox7 created using clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 approach displayed a dramatically increased seed germination ability under salt stress. Overall, our results highlight that OsHAK9 regulates seed germination performance under salt stress involving preventing GA degradation by mediating OsGA2ox7, which provides a novel clue about the relationship between GA and OsHAKs in rice.

[Impact of different angles of pulmonary surfactant administration on bronchopulmonaryplasia and intracranial hemorrhage in preterm infants: a prospective randomized controlled study]. / ä¸åŒè§’åº¦æ³¨å ¥è‚ºè¡¨é¢æ´»æ€§ç‰©è´¨å¯¹æ—©äº§å„¿æ”¯æ°”ç®¡è‚ºå‘è‚²ä¸è‰¯å’Œé¢ å† å‡ºè¡€çš„å½±å“ï¼šä¸€é¡¹å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To investigate the effects of different angles of pulmonary surfactant (PS) administration on the incidence of bronchopulmonary dysplasia and intracranial hemorrhage in preterm infants. METHODS: A prospective study was conducted on 146 preterm infants (gestational age <32 weeks) admitted to the Department of Neonatology, Provincial Hospital Affiliated to Anhui Medical University from January 2019 to May 2023. The infants were randomly assigned to different angles for injection of pulmonary surfactant groups: 0° group (34 cases), 30° group (36 cases), 45° group (38 cases), and 60° group (38 cases). Clinical indicators and outcomes were compared among the groups. RESULTS: The oxygenation index was lower in the 60° group compared with the other three groups, with shorter invasive ventilation time and oxygen use time, and a lower incidence of bronchopulmonary dysplasia than the other three groups (P<0.05). The incidence of intracranial hemorrhage was lower in the 60° group compared to the 0° group (P<0.05). The cure rate in the 60° group was higher than that in the 0° group and the 30° group (P<0.05). CONCLUSIONS: The clinical efficacy of injection of pulmonary surfactant at a 60° angle is higher than other angles, reducing the incidence of intracranial hemorrhage and bronchopulmonary dysplasia in preterm infants.

Enhancing Stability and Albumin Binding Efficiency of α-Conotoxin GI through Fatty Acid Modification.

α-Conotoxin GI is a competitive blocker of muscle-type acetylcholine receptors and holds the potential for being developed as a molecular probe or a lead compound for drug discovery. In this study, four fatty acid-modified α-conotoxin GI analogues of different lengths were synthesized by using a fatty acid modification strategy. Then, we performed a series of in vitro stability assays, albumin binding assays, and pharmacological activity assays to evaluate these modified mutants. The experimental results showed that the presence of fatty acids significantly enhanced the in vitro stability and albumin binding ability of α-conotoxin GI and that this effect was proportional to the length of the fatty acids used. Pharmacological activity tests showed that the modified mutants maintained a good acetylcholine receptor antagonistic activity. The present study shows that fatty acid modification can be an effective strategy to significantly improve conotoxin stability and albumin binding efficiency while maintaining the original targeting ion channel activity.

Astrocytic aryl hydrocarbon receptor mediates chronic kidney disease-associated mental disorders involving GLT1 hypofunction and neuronal activity enhancement in the mouse brain.

Chronic kidney disease (CKD)-associated mental disorders have been attributed to the excessive accumulation of hemodialysis-resistant indoxyl-3-sulfate (I3S) in the brain. I3S not only induces oxidative stress but is also a potent endogenous agonist of the aryl hydrocarbon receptor (AhR). Here, we investigated the role of AhR in CKD-induced brain disorders using a 5/6 nephrectomy-induced CKD mouse model, which showed increased I3S concentration in both blood and brain, anxiety and impaired novelty recognition, and AhR activation in the anterior cortex. GFAP+ reactive astrocytes were increased accompanied with the reduction of glutamate transporter 1 (GLT1) on perineuronal astrocytic processes (PAPs) in the anterior cingulate cortex (ACC) in CKD mice, and these alterations were attenuated in both neural lineage-specific and astrocyte-specific Ahr conditional knockout mice (nAhrCKO and aAhrCKO). By using chronic I3S treatment in primary astrocytes and glia-neuron (GN) mix cultures to mimic the CKD brain microenvironment, we also found significant reduction of GLT1 expression and activity in an AhR-dependent manner. Chronic I3S treatment induced AhR-dependent pro-oxidant Nox1 and AhR-independent anti-oxidant HO-1 expressions. Notably, AhR mediates chronic I3S-induced neuronal activity enhancement and synaptotoxicity in GN mix, not neuron-enriched cortical culture. In CKD mice, neuronal activity enhancement was observed in ACC and hippocampal CA1, and these responses were abrogated by both nAhrCKO and aAhrCKO. Finally, intranasal AhR antagonist CH-223191 administration significantly ameliorated the GLT1/PAPs reduction, increase in c-Fos+ neurons, and memory impairment in the CKD mice. Thus, astrocytic AhR plays a crucial role in the CKD-induced disturbance of neuron-astrocyte interaction and mental disorders.

Single-Cell Landscape of Lungs Reveals Key Role of Neutrophil-Mediated Immunopathology during Lethal SARS-CoV-2 Infection.

Due to the limitation of human studies with respect to individual difference or the accessibility of fresh tissue samples, how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in pathological complications in lung, the main site of infection, is still incompletely understood. Therefore, physiologically relevant animal models under realistic SARS-CoV-2 infection conditions would be helpful to our understanding of dysregulated inflammation response in lung in the context of targeted therapeutics. Here, we characterized the single-cell landscape in lung and spleen upon SARS-CoV-2 infection in an acute severe disease mouse model that replicates human symptoms, including severe lung pathology and lymphopenia. We showed a reduction of lymphocyte populations and an increase of neutrophils in lung and then demonstrated the key role of neutrophil-mediated lung immunopathology in both mice and humans. Under severe conditions, neutrophils recruited by a chemokine-driven positive feedback produced elevated "fatal signature" proinflammatory genes and pathways related to neutrophil activation or releasing of granular content. In addition, we identified a new Cd177high cluster that is undergoing respiratory burst and Stfahigh cluster cells that may dampen antigen presentation upon infection. We also revealed the devastating effect of overactivated neutrophil by showing the highly enriched neutrophil extracellular traps in lung and a dampened B-cell function in either lung or spleen that may be attributed to arginine consumption by neutrophil. The current study helped our understanding of SARS-CoV-2-induced pneumonia and warranted the concept of neutrophil-targeting therapeutics in COVID-19 treatment. IMPORTANCE We demonstrated the single-cell landscape in lung and spleen upon SARS-CoV-2 infection in an acute severe disease mouse model that replicated human symptoms, including severe lung pathology and lymphopenia. Our comprehensive study revealed the key role of neutrophil-mediated lung immunopathology in SARS-CoV-2-induced severe pneumonia, which not only helped our understanding of COVID-19 but also warranted the concept of neutrophil targeting therapeutics in COVID-19 treatment.

Prognostic significance of circulating Epstein-Barr virus DNA in pulmonary lymphoepithelioma-like carcinoma: A meta-analysis and validation study.

In small-scale studies, circulating Epstein-Barr virus (EBV) DNA levels have prognostic value in patients with pulmonary lymphoepithelioma-like carcinoma (LELC). Therefore, we performed a comprehensive meta-analysis to evaluate the prognostic significance of circulating EBV DNA levels in patients with pulmonary LELC. Studies that discussed the prognostic significance of circulating EBV DNA detection in pulmonary LELC were eligible for inclusion in this study. The overall survival (OS) and progression-free survival (PFS) were the primary outcomes. Pooled hazard ratio (HR), 95% confidence intervals (CIs), and p value were calculated to estimate the prognostic significance of EBV DNA levels. Additionally, we conducted a further observation using an independent cohort. The pooled HR and 95% CI of pretreatment EBV DNA levels for OS and PFS were 3.63 (95% CI: 2.90-4.55) and 2.88 (95% CI: 1.90-4.38), respectively. The pooled HR and 95% CI for Posttreatment EBV DNA levels for OS and PFS were 3.77 (95% CI: 2.96-4.80) and 3.52 (95% CI: 1.91-6.51, p < 0.001), respectively. The independent cohort showed similar results that patients with high pretreatment EBV DNA or positive posttreatment EBV DNA had significantly inferior PFS. Circulating EBV DNA levels provide prognostic values of survival and treatment response in pulmonary LELC patients.

Identification of a key locus, qNL3.1, associated with seed germination under salt stress via a genome-wide association study in rice.

KEY MESSAGE: Two causal OsTTL and OsSAPK1 genes of the key locus qNL3.1 significantly associated with seed germination under salt stress were identified via a genome-wide association study, which could improve rice seed germination under salt stress. Rice is a salt-sensitive crop, and its seed germination determines subsequent seedling establishment and yields. In this study, 168 accessions were investigated for the genetic control of seed germination under salt stress based on the germination rate (GR), germination index (GI), time at which 50% germination was achieved (T50) and mean level (ML). Extensive natural variation in seed germination was observed among accessions under salt stress. Correlation analysis showed significantly positive correlations among GR, GI and ML and a negative correlation with T50 during seed germination under salt stress. Forty-nine loci significantly associated with seed germination under salt stress were identified, and seven of these were identified in both years. By comparison, 16 loci were colocated with the previous QTLs, and the remaining 33 loci might be novel. qNL3.1, colocated with qLTG-3, was simultaneously identified with the four indices in two years and might be a key locus for seed germination under salt stress. Analysis of candidate genes showed that two genes, the similar to transthyretin-like protein OsTTL and the serine/threonine protein kinase OsSAPK1, were the causal genes of qNL3.1. Germination tests indicated that both Osttl and Ossapk1 mutants significantly reduced seed germination under salt stress compared to the wild type. Haplotype analysis showed that Hap.1 of OsTTL and Hap.1 of OsSAPK1 genes were excellent alleles, and their combination resulted in high seed germination under salt stress. Eight accessions with elite performance of seed germination under salt stress were identified, which could improve rice seed germination under salt stress.