A Macrophage-Pericyte Axis Directs Tissue Restoration via Amphiregulin-Induced Transforming Growth Factor Beta Activation.

The epidermal growth factor receptor ligand Amphiregulin has a well-documented role in the restoration of tissue homeostasis after injury; however, the mechanism by which Amphiregulin contributes to wound repair remains unknown. Here we show that Amphiregulin functioned by releasing bioactive transforming growth factor beta (TGF-ß) from latent complexes via integrin-αV activation. Using acute injury models in two different tissues, we found that by inducing TGF-ß activation on mesenchymal stromal cells (pericytes), Amphiregulin induced their differentiation into myofibroblasts, thereby selectively contributing to the restoration of vascular barrier function within injured tissue. Furthermore, we identified macrophages as a critical source of Amphiregulin, revealing a direct effector mechanism by which these cells contribute to tissue restoration after acute injury. Combined, these observations expose a so far under-appreciated mechanism of how cells of the immune system selectively control the differentiation of tissue progenitor cells during tissue repair and inflammation.

NK92 cells and peripheral blood NK cells respond oppositely upon dasatinib treatment.

Natural killer (NK) cell is a valuable tool for immunotherapy in cancer treatment, both the cultured cell line NK92 and primary NK cells are widely studied and used in research and clinical trials. Clinical observations witnessed the improvement of patients' NK cells in terms of cell counts and cytotoxic activity upon dasatinib treatment, an approved drug for chronic myeloid leukaemia and Ph+ acute lymphocytic leukaemia. Several studies supported the clinical observations, yet others argued a detrimental effect of dasatinib on NK cells. Due to the complex conditions in different studies, the definite influence of dasatinib on NK92 and primary NK cells remains to be settled. Here, we used a well-defined in vitro system to evaluate the effects of dasatinib on NK92 cells and peripheral blood (PB)-NK cells. By co-culturing NK cells with dasatinib to test the cell counts and target cell-killing activities, we surprisingly found that the chemical influenced oppositely on these two types of NK cells. While dasatinib suppressed NK92 cell proliferation and cytotoxic activity, it improved PB-NK-killing tumour cells. RNA sequencing analysis further supported this finding, uncovering several proliferating and cytotoxic pathways responding invertedly between them. Our results highlighted an intrinsic difference between NK92 and PB-NK cells and may build clues to understand how dasatinib interacts with NK cells in vivo.

Fetal monocytes possess increased metabolic capacity and replace primitive macrophages in tissue macrophage development.

Tissue-resident macrophages (MΦTR ) originate from at least two distinct waves of erythro-myeloid progenitors (EMP) arising in the yolk sac (YS) at E7.5 and E8.5 with the latter going through a liver monocyte intermediate. The relative potential of these precursors in determining development and functional capacity of MΦTR remains unclear. Here, we studied development of alveolar macrophages (AM) after single and competitive transplantation of different precursors from YS, fetal liver, and fetal lung into neonatal Csf2ra-/- mice, which lack endogenous AM. Fetal monocytes, promoted by Myb, outcompeted primitive MΦ (pMΦ) in empty AM niches and preferentially developed to mature AM, which is associated with enhanced mitochondrial respiratory and glycolytic capacity and repression of the transcription factors c-Maf and MafB. Interestingly, AM derived from pMΦ failed to efficiently clear alveolar proteinosis and protect from fatal lung failure following influenza virus infection. Thus, our data demonstrate superior developmental and functional capacity of fetal monocytes over pMΦ in AM development and underlying mechanisms explaining replacement of pMΦ in fetal tissues.

Two Birds with One Stone: Contemporaneously Enhancing OER Catalytic Activity and Stability for Dual-Phase Medium-Entropy Metal Sulfides.

Transition metal-based sulfides exhibit remarkable potential as electrocatalysts for oxygen evolution reaction (OER) due to the unique intrinsic structure and physicochemical characteristics. Nevertheless, currently available sulfide catalysts based on transition metals face a bottleneck in large-scale commercial applications owing to their unsatisfactory stability. Here, the first fabrication of (FeCoNiMn2 )S2 dual-phase medium-entropy metal sulfide (dp-MEMS) is successfully achieved, which demonstrated the expected optimization of stability in the OER process. Benefiting from the "cell wall" -like structure and the synergistic effect in medium-entropy systems, (FeCoNiMn2 )S2 dp-MEMS delivers an exceptionally low overpotential of 169 and 232 mV at current densities of 10 and 100 mA cm-2 , respectively. The enhancement mechanism of catalytic activity and stability is further validated by density functional theory (DFT) calculations. Additionally, the rechargeable Zn-air batteries integrated with FeCoNiMn2 )S2 dp-MEMS exhibit remarkable performance outperforming the commercial catalyst (Pt/C+RuO2 ). This work demonstrates that the dual-phase medium-entropy metal sulfide-based catalysts have the potential to provide a greater application value for OER and related energy conversion systems.

MXene-Bimetallic Hybrids via Mixed Molten Salts Etching for Kinetics-Enhanced and Dendrite-Free Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries with high theoretical energy density (2600 Wh kg-1) are considered to be one of the most promising secondary batteries. However, the practical application of Li-S batteries is limited by the polysulfides shuttling and unstable lithium metal anodes. Herein, an asymmetric separator (CACNM@PP), composed of Co-Ni/MXene (CNM) on the cathode and Cu-Ag/MXene (CAM) on the anode for high-performance Li-S batteries is reported. For the cathode, CNM provides a synergistic effect by integrating Co, Ni, and MXene, resulting in strong chemical interactions and fast conversion kinetics for polysulfides. For the anode, CAM with abundant lithiophilicity active sites can lower the nucleation barrier of Li. Moreover, LiCl/LiF layers are generated in situ as an ion conductor layer during charging and discharging, inducing a uniform deposition of Li. Therefore, the assembled cells with the CACNM@PP separators harvest excellent electrochemical performance. This work provides novel insights into the development of commercially available high-energy density Li-S batteries with asymmetric separators.

SnS/SnS2 Heterostructures Embedded in Hierarchical Porous Carbon as Polysulfides Immobilizer for High-Performance Lithium-Sulfur Batteries.

Driven by the strong adsorptive and catalytic ability of metal sulfides for soluble polysulfides, it is considered as a potential mediator to resolve the problems of shuttle effect and slow reaction kinetics of polysulfides in lithium-sulfur (Li-S) batteries. However, their further development is limited by poor electrical conductivity and bad long-term durability. Herein, one type of new catalyst composed of SnS/SnS2 heterostructures on hierarchical porous carbon (denoted as SnS/SnS2-HPC) by a simple hydrothermal method is reported and used as an interlayer coating on the conventional separator for blocking polysulfides. The SnS/SnS2-HPC integrates the advantages of a porous conductive network for promoting the transport of electrons and an enhanced electrocatalyst for accelerating polysulfides conversion. As a result, such a cell coupled with a SnS/SnS2-HPC interlayer exhibits a long-term lifespan of 1200 cycles. This work provides a new cell configuration by using heterostructures with a built-in electric field formed from a p-n heterojunction to improve the performance of Li-S batteries.

NiO/RuO2 p-n Heterojunction Nanofoam as a High-Performance Electrocatalyst for Desulfurization and Concurrent Hydrogen Evolution.

The development of bifunctional electrocatalysts with excellent performance in both the hydrogen evolution reaction (HER) and sulfide oxidation reaction (SOR) remains a formidable challenge. Herein, we experimentally synthesize a NiO/RuO2 p-n heterojunction nanofoam that exhibits highly desirable electrocatalytic properties for both the HER and the SOR. We further design an electrolytic cell by pairing alkaline HER with SOR utilizing the NiO/RuO2 heterojunction nanofoam as both the anode and the cathode, which demands a low applied voltage of 0.846 V to achieve a current density of 10 mA cm-2. Density functional theory calculations confirm that the formation of the NiO/RuO2 p-n heterojunction nanofoam effectively regulates the electronic structure, thereby boosting the electrocatalytic performances for both HER and SOR. This work not only provides a novel strategy to prepare an efficient and stable nanofoam electrocatalyst for hydrogen production but also highlights the potential application of oxide heterojunction electrocatalysts in treating sulfur-containing waste liquid.

Comparative genomics reveals evolutionary drivers of the dietary shift in Hemiptera.

Hemiptera insects exhibit a close relationship to plants and demonstrate a diverse range of dietary preferences, encompassing phytophagy as the predominant feeding habit while a minority engages in carnivorous or haematophagous behaviour. To counteract the challenges posed by phytophagous insects, plants have developed an array of toxic compounds, causing significant evolutionary selection pressure on these insects. In this study, we employed a comparative genomics approach to analyse the expansion and contraction of gene families specific to phytophagous insect lineages, along with their adaptive evolutionary traits, utilising representative species from the Hemiptera order. Our investigation revealed substantial expansions of gene families within the phytophagous lineages, especially in the Pentatomomorpha branch represented by Oncopeltus fasciatus and Riptortus pedestris. Notably, these expansions of gene families encoding enzymes are potentially involved in hemipteran-plant interactions. Moreover, the adaptive evolutionary analysis of these lineages revealed a higher prevalence of adaptively evolved genes in the Pentatomomorpha branch. The observed branch-specific gene expansions and adaptive evolution likely contribute significantly to the diversification of species within Hemiptera. These results help enhance our understanding of the genomic characteristics of the evolution of different feeding habits in hemipteran insects.

Orco mediates olfactory behavior and oviposition in the whitefly Bemisia tabaci.

Chemical signals play a central role in mediating insect feeding and reproductive behavior, and serve as the primary drivers of the insect-plant interactions. The detection of chemical signals, particularly host plant volatiles, relies heavily on the insect's complex olfactory system. The Bemisia tabaci cryptic species complex is a group of globally important whitefly pests of agricultural and ornamental crops that have a wide range of host plants, but the molecular mechanism of their host plant recognition is not yet clear. In this study, the odorant coreceptor gene of the Whitefly MEAM1 cryptic species (BtOrco) was cloned. The coding sequence of BtOrco was 1413 bp in length, with seven transmembrane structural domains, and it was expressed primarily in the heads of both male and female adult whiteflies, rather than in other tissues. Knockdown of BtOrco using transgenic plant-mediated RNAi technology significantly inhibited the foraging behavior of whiteflies. This inhibition was manifested as a reduced percentage of whiteflies responding to the host plant and a prolonged foraging period. Moreover, there was a substantial suppression of egg-laying activity among adult female whiteflies. These results indicate that BtOrco has the potential to be used as a target for the design of novel active compounds for the development of environmentally friendly whitefly control strategies.

Abiotic Methane Production Driven by Ubiquitous Non-Fenton-Type Reactive Oxygen Species.

Abiotic CH4 production driven by Fenton-type reactive oxygen species (ROS) has been confirmed to be an indispensable component of the atmospheric CH4 budget. While the chemical reactions independent of Fenton chemistry to ROS are ubiquitous in nature, it remains unknown whether the produced ROS can drive abiotic CH4 production. Here, we first demonstrated the abiotic CH4 production at the soil-water interface under illumination. Leveraging this finding, polymeric carbon nitrides (CNx) as a typical analogue of natural geobattery material and dimethyl sulfoxide (DMSO) as a natural methyl donor were used to unravel the underlying mechanisms. We revealed that the ROS, photocatalytically produced by CNx, can oxidize DMSO into CH4 with a high selectivity of 91.5 %. Such an abiotic CH4 production process was further expanded to various non-Fenton-type reaction systems, such as electrocatalysis, pyrocatalysis and sonocatalysis. This work provides insights into the geochemical cycle of abiotic CH4, and offers a new route to CH4 production via integrated energy development.

A strategy for the rapid discovery and validation of active diterpenoids as quality markers in different habitats of Langdu using ultrahigh-performance liquid chromatography-tandem mass spectrometry with multivariate statistical analysis.

Langdu, known as a traditional Chinese medicine, was identified as the roots of species of Euphorbia ebracteolata Hayata and Euphorbia fischeriana Steud, displaying anti-tuberculosis activity. To clarify the potent quality markers of Langdu, this research first developed a fast and sensitive ultrahigh-performance liquid chromatography-tandem mass spectrometry method for the quantification of 13 diterpenoids in Langdu. The developed method was further applied in the analyses of 12 authentic E. ebracteolata and E. fischeriana samples collected in northern and southeastern China. Then, the anti-tuberculosis evaluation of 12 batches of Langdu samples was performed in vitro. Finally, partial least squares discrimination analysis was used in the discrimination of E. ebracteolata and E. fischeriana from different origins and processing methods. Jolkinolide A (1), jolkinolide E (3), yuexiandajisu D (6), and ebractenone A (11) were identified as key, potent diterpenoids for the quality control of E. ebracteolata Hayata and E. fischeriana Steud. The present study established a qualitative chemical analysis method for Langdu (E. ebracteolata and E. fischeriana) and suggested the key bioactive components that will improve qualitative control methodology for this important medicine.

GM-CSF instigates a dendritic cell-T-cell inflammatory circuit that drives chronic asthma development.

BACKGROUND: Steroid-resistant asthma is often characterized by high levels of neutrophils and mixed TH2/TH17 immune profiles. Indeed, neutrophils are key drivers of chronic lung inflammation in multiple respiratory diseases. Their numbers correlate strongly with disease severity, and their presence is often associated with exacerbation of chronic lung inflammation. OBJECTIVE: What factors drive development of neutrophil-mediated chronic lung disease remains largely unknown, and we sought to study the role of GM-CSF as a potential regulator in chronic asthma. METHODS: Different experimental animal models of chronic asthma were used in combination with alveolar macrophage-reconstitution of global GM-CSF receptor knockout mice as well as cell-type-specific knockout animals to elucidate the role of GM-CSF signaling in chronic airway inflammation. RESULTS: We identify GM-CSF signaling as a critical factor regulating pulmonary accumulation of neutrophils. We show that although being not required for intrinsically regulating neutrophil migration, GM-CSF controls lung dendritic cell function, which in turn promotes T-cell-dependent recruitment of neutrophils to the airways. We demonstrate that GM-CSF regulates lung dendritic cell antigen uptake, transport, and TH2/TH17 cell priming in an intrinsic fashion, which in turn drives pulmonary granulocyte recruitment and contributes to development of airway hyperresponsiveness in chronic disease. CONCLUSIONS: We identify GM-CSF as a potentially novel therapeutic target in chronic lung inflammation, describing a GM-CSF-dependent lung conventional dendritic cell-T-cell-neutrophil axis that drives chronic lung disease.

Metabolomics Profiling and AKR Characterization During Paurometabolous Development of Corythucha ciliata (Hemiptera: Tingidae).

The sycamore lace bug, Corythucha ciliata (Say) is an invasive pest infesting trees of the genus Platanus. Both adults and nymphs damage the foliage of sycamore trees. Nymphs cannot survive in low temperatures; however, the sycamore lace bug overwinters as adults. In this study, we analyzed the metabolite profiles of this pest to determine significantly regulated metabolites during paurometabolous development from nymphs to adults. The identification of metabolites is essential to convert analytical data into meaningful biological knowledge. A total of 62 metabolites were identified using GC-MS. Among them, 29 different metabolites showed differences in content among nymphs, adult females (AF), and adult males (AM). Five of the 29 metabolites, including caffeic acid, D-glucose, D-mannose, glycerol and aminooxyacetic acid, were significantly increased and nine of them were significantly decreased during the developmental stages from nymph to adult. In addition, we identified three novel aldo-keto reductase (AKR) genes that may play a significant role in the control of glycerol biosynthesis. Moreover, the characteristics and expression levels of these genes were analyzed. This study will provide us with the necessary information to improve our understanding of the changes in metabolites in C. ciliata during paurometabolous development.

Changes in Gene Expression and Metabolite Profiles in Platanus acerifolia Leaves in Response to Feeding Damage Caused by Corythucha ciliata.

The sycamore lace bug, Corythucha ciliata (Say) is a highly invasive pest insect that feeds on sycamore trees (Platanus spp.) worldwide. The interaction between Platanus species and this insect pest has not yet been studied at the molecular level. Therefore, a recent study was conducted to compare the gene expression and metabolite profiles of Platanus acerifolia leaves in response to C. ciliata feeding damage after 24 and 48 h. We employed high throughput RNA sequencing (RNA- seq) to identify a total of 2,828 significantly differentially expressed genes (DEGs) after C. ciliata feeding. In addition, 303 unigenes were found to be up-regulated at both time points. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that monoterpenoid biosynthesis, the linoleic acid metabolism pathway, and alpha- linolenic acid metabolism were the most prominent pathways among the DEGs. Further analysis of the metabolite profiles showed that nine metabolites were significantly different before and after C. ciliata damage. In addition, we analyzed DEGs detected in the P. acerifolia and C. ciliata interaction using Mapman. The terpene synthase gene family was also identified. We suggest that the results obtained from DEGs and metabolite analysis can provide important information for the identification of genes involved in the P. acerifolia-C. ciliata interaction, which might be necessary for controlling C. ciliata efficiently.

Expression of lima bean terpene synthases in rice enhances recruitment of a beneficial enemy of a major rice pest.

Volatile terpenoids play a key role in plant defence against herbivory by attracting parasitic wasps. We identified seven terpene synthase genes from lima bean, Phaseolus lunatus L. following treatment with either the elicitor alamethicin or spider mites, Tetranychus cinnabarinus. Four of the genes (Pltps2, Pltps3, Pltps4 and Pltps5) were up-regulated with their derived proteins phylogenetically clustered in the TPS-g subfamily and PlTPS3 positioned at the base of this cluster. Recombinant PlTPS3 was able to convert geranyl diphosphate and farnesyl diphosphate to linalool and (E)-nerolidol, the latter being precursor of the homoterpene (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT). Recombinant PlTPS4 showed a different substrate specificity and produced linalool and (E)-nerolidol, as well as (E,E)-geranyllinalool from geranylgeranyl diphosphate. Transgenic rice expressing Pltps3 emitted significantly more (S)-linalool and DMNT than wild-type plants, whereas transgenic rice expressing Pltps4 produced (S)-linalool, DMNT and (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene (TMTT). In laboratory bioassays, female Cotesia chilonis, the natural enemy of the striped rice stemborer, Chilo suppressalis, were significantly attracted to the transgenic plants and their volatiles. We further confirmed this with synthetic blends mimicking natural rice volatile composition. Our study demonstrates that the transformation of rice to produce volatile terpenoids has the potential to enhance plant indirect defence through natural enemy recruitment.

The maize transcription factor EREB58 mediates the jasmonate-induced production of sesquiterpene volatiles.

Over the past two decades, Zea mays (maize) has been established as a model system for the study of indirect plant defense against herbivores. When attacked by lepidopteran larvae, maize leaves emit a complex blend of volatiles, mainly composed of sesquiterpenes, to attract the natural enemies of the herbivores. This is associated with a swift transcriptional induction of terpene synthases such as TPS10; however, the molecular components controlling the complex transcriptional reprogramming in this process are still obscure. Here, by exploiting the finding that the maize TPS10 promoter retained its full responsiveness to herbivory in Arabidopsis, we identified the region from -300 to -200 of the TPS10 promoter as both necessary and sufficient for its herbivore inducibility through 5' deletion mapping. A high-throughput screening of an Arabidopsis transcription factor library using this promoter region as the bait identified seven AP2/ERF family transcription factors. Among their close homologs in maize, EREB58 was the only gene responsive to herbivory, with a spatiotemporal expression pattern highly similar to that of TPS10. Meanwhile, EREB58 was also responsive to Jasmonate. In vivo and in vitro assays indicated that EREB58 promotes TPS10 expression by directly binding to the GCC-box within the region from -300 to -200 of the TPS10 promoter. Transgenic maize plants overexpressing EREB58 constitutively over-accumulate TPS10 transcript, and also (E)-ß-farnesene and (E)-α-bergamotene, two major sesquiterpenes produced by TPS10. In contrast, jasmonate induction of TPS10 and its volatiles was abolished in EREB58-RNAi transgenic lines. In sum, these results demonstrate that EREB58 is a positive regulator of sesquiterpene production by directly promoting TPS10 expression.

Klebsiella pneumoniae alleviates influenza-induced acute lung injury via limiting NK cell expansion.

A protective effect induced by bacterial preinfection upon a subsequent lethal influenza virus infection has been observed, but the underlying immune mechanisms have not yet been fully elucidated. In this study, we used a mouse model of Klebsiella pneumoniae preinfection to gain insight into how bacterial preinfection influences the subsequent lethal influenza virus infection. We found that K. pneumoniae preinfection significantly attenuated lung immune injury and decreased mortality during influenza virus infection, but K. pneumoniae-specific immunity was not involved in this cross-protection against influenza virus. K. pneumoniae preinfection limited NK cell expansion, which was involved in influenza-induced immune injury and death. Furthermore, K. pneumoniae preinfection could not control NK cell expansion and death during influenza virus infection in Rag1(-/-) mice, but adoptive transfer of T cells from wild-type mice was able to restore this protective effect. Our data suggest that the adaptive immune response activated by bacterial infection limits the excessive innate immune response induced by a subsequent influenza infection, ultimately protecting mice from death.

Transcriptome Sequencing of Lima Bean (Phaseolus lunatus) to Identify Putative Positive Selection in Phaseolus and Legumes.

The identification of genes under positive selection is a central goal of evolutionary biology. Many legume species, including Phaseolus vulgaris (common bean) and Phaseolus lunatus (lima bean), have important ecological and economic value. In this study, we sequenced and assembled the transcriptome of one Phaseolus species, lima bean. A comparison with the genomes of six other legume species, including the common bean, Medicago, lotus, soybean, chickpea, and pigeonpea, revealed 15 and 4 orthologous groups with signatures of positive selection among the two Phaseolus species and among the seven legume species, respectively. Characterization of these positively selected genes using Non redundant (nr) annotation, gene ontology (GO) classification, GO term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that these genes are mostly involved in thylakoids, photosynthesis and metabolism. This study identified genes that may be related to the divergence of the Phaseolus and legume species. These detected genes are particularly good candidates for subsequent functional studies.

[Diagnostic Value of Combining Permeability with T1 Perfusion Parameters in Quantitative Dynamic Contrast-enhanced Magnetic Resonance Imaging for Glioma Grading].

UNLABELLED: OBJECTIVE To investigate the diagnostic value of combining permeability with T1 perfusion parameters in quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in glioma grading. METHODS: Magnetic resonance imaging was performed in 16 patients with high grade gliomas (HGG) and 12 patients with low grade gliomas(LGG) confirmed by pathology. The permeability was quantitatively analyzed and the T1 perfusion parameters of the tumor were calculated by the pharmacokinetic model,including volume transfer constant (K(trans)),volume fraction of extravascular extracellular space (ve),reflux constant (kep),fractional plasma volume (vp),cerebral blood flow (CBF),cerebral blood volume (CBV),and mean transit time (MTT). A t-test was used to calculate the statistical significance of quantitative analysis parameters between HGG and LGG. The receiver operating characteristic curve analysis was also performed for evaluating the sensitivity,specificity,and area under curve (AUC) of the permeability parameters and perfusion parameters and the combination of these parameters. RESULTS: The differences of the K(trans),ve,CBF,and CBV values [(0.276<0.164)/min vs. (0.084<0.044)/min;0.486<0.191 vs. 0.274<0.132;(1.755<1.164)ml/(g·min) vs. (0.761<0.625) ml/(g·min);(0.204<0.101) ml/g vs. (0.115<0.097)ml/g] were statistically significant (t=3.934,3.293,2.672,2.338,P<0.05) between HGG and LGG. The differences of the kep,vp, and MTT value [(1.632<1.204)/min vs. (1.537<1.194)/min;0.114<0.107 vs. 0.055<0.039;(0.128<0.070)min vs. (0.145<0.066)min] were not statistically significant (t=0.208,1.823,0.688,P>0.05). When the K(trans) value was 0.105/min,the AUC was the largest (0.919) by the single parameter in glioma grading,and meanwhile the sensitivity and specificity were 87.5% and 83.3%,respectively. When the ve-CBF value was 0.631,the AUC was the largest (0.974) by the multiple parameter,and meanwhile the sensitivity and specificity were 93.7% and 100.0%,respectively. CONCLUSION: Combining permeability with perfusion parameters in quantitative DCE-MRI can improve the accuracy of the glioma grading.