Miracle-dz/UniFAR-FTUs huggingface dataset:
Murine Gammaherpesvirus 68 Efficiently Infects Myeloid Cells Resulting In An Atypical, Restricted Form Of Infection

The gammaherpesviruses (γHVs) establish a lifelong infection in their hosts, with the cellular outcome of infection intimately regulated by target cell type. Murine gammaherpesvirus 68 (MHV68), a small animal model of γHV infection, infects macrophages in vivo, resulting in a range of outcomes, from lytic replication to latent infection. Here, we have further investigated the nature of MHV68 macrophage infection using reductionist and primary in vivo infection studies. While MHV68 readily infected the J774 macrophage cell line, viral gene expression and replication were significantly impaired relative to a fully permissive fibroblast cell line. Lytic replication only occurred in a small subset of MHV68-infected J774 cells, despite the fact that these cells were fully competent to support lytic replication following pre-treatment with interleukin-4, a known potentiator of replication in macrophages. In parallel, we harvested virally-infected macrophages at 16 hours after MHV68 infection in vivo and analyzed gene expression by single cell RNA-sequencing. Among virally infected macrophages, only rare (0.25%) cells had lytic cycle gene expression, characterized by detection of multiple lytic cycle RNAs. In contrast, ∼50% of virally-infected macrophages were characterized by expression of ORF75A, ORF75B and/or ORF75C, in the absence of other detectable viral RNAs. Selective transcription of the ORF75 locus also occurred in MHV68-infected J774 cells. In total, these studies indicate that MHV68 efficiently infects macrophages, with the majority of cells characterized by an atypical state of restricted viral transcription, and only rare cells undergoing lytic replication. Importance The human gammaherpesviruses Epstein-Barr virus and Kaposi’s sarcoma associated herpesvirus are DNA viruses that cause lifelong infection and are associated with multiple diseases, especially in immunocompromised individuals. Murine gammaherpesvirus 68 (MHV68) is a powerful mouse model that permits close examination of these viruses. Previous studies of MHV68 identified that macrophages are an important in vivo target of infection; how infection within these cells is regulated remains incompletely understood. Here, we demonstrate that MHV68 infection of macrophages is characterized by two divergent outcomes across a population of infected cells: while a small subset of cells undergo lytic replication, to make new virus progeny, the majority of cells are characterized by an atypical, restricted form of infection characterized by a distinct viral gene transcription program not previously reported. These studies highlight important cell-type specific outcomes of gammaherpesvirus infection and identify a potential alternate program by which these viruses usurp macrophages.
An EGF-modified PLGA-lanthanide nanoplatform for combined NIR-II cancer imaging and targeted drug delivery

The use of multifunctional nanoplatforms for synergistic therapy and imaging is a promising approach in cancer treatment. In this study, we exploited the imaging properties of lanthanides by encapsulating CaF2:Y, Nd along with the chemotherapeutic drug doxorubicin (DOX) into poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to prepare a nanoplatform suitable for imaging in the second near-infrared (NIR-II) window and simultaneous anti-cancer therapy. To facilitate the accumulation of CaF2:Y, Nd+DOX@PLGA NPs in breast cancer cells, we modified the NPs with EGF. The diameter of the obtained CaF2:Y, Nd+DOX@PLGA/PEG/EGF NPs was approximately 150 nm, with a nearly round shape and homogeneous size distribution. In addition, analysis of the drug release behaviour showed that DOX was released more readily and had a longer release time in acidic environments. Accordingly, MTS results indicated that DOX-loaded NPs were significantly cytotoxic. Furthermore, fluorescence microscopy and flow cytometry studies revealed that CaF2:Y, Nd+DOX@PLGA/PEG and CaF2:Y, Nd+DOX@PLGA/PEG/EGF NPs were gradually taken up by 4T1 breast cancer cells over time, and EGF-coated Nd+DOX@PLGA NPs exhibited increased uptake rates after 72 h. Moreover, we found that EGF increased the solubility of Nd+DOX@PLGA NPs in water by comparing the aqueous solutions of the different NPs formulations. Finally, NIR imaging demonstrated strong fluorescence of PLGA NPs carrying CaF2:Y, Nd NPs at 900-1200 nm under 808 nm laser excitation. In conclusion, the developed CaF2:Y, Nd+DOX@PLGA/PEG/EGF NPs could be monitored for an extended period of time, and co-encapsulated DOX could be efficiently released to kill breast cancer cells.
Chemodiversity in flowers of Tanacetum vulgare has consequences on a florivorous beetle

The chemical composition of plant individuals can vary, leading to high intraspecific chemodiversity. Diversity of floral chemistry may impact the responses of flower-feeding insect visitors. Plants of Tanacetum vulgare vary significantly in their leaf terpenoid composition, resulting in distinct chemotypes. We investigated the composition of terpenoids and nutritents of flower heads and pollen in plants belonging to three chemotypes, dominated either by β-thujone (BThu), artemisia ketone (Keto) or a mixture of (Z)-myroxide, santolina triene and artemisyl acetate (Myrox). Moreover, we tested the effects of these differences on preferences, weight gain and performance of adults of the shining flower beetle, Olibrus aeneus. The terpenoid composition and diversity of flower heads and pollen significantly differed among individuals belonging to these chemotypes, while total concentrations of terpenoids, sugars, amino acids or lipids of the pollen did not differ. Beetles preferred the BThu over the Myrox chemotype in both olfactory and contact choice assays, while the Keto chemotype was marginally repellent in olfactory assays. The beetles gained the least weight within 48 h and their initial mortality was highest when feeding exclusively on floral tissues of the Myrox chemotype. Short-term weight gain and long-term performance were highest on the BThu chemotype. In conclusion, the beetles showed chemotype-specific responses towards different T. vulgare chemotypes, which may be attributed to the terpenoid composition in flower heads and pollen rather than to differences in nutrient profiles. Both richness and overall diversity are important factors when determining chemodiversity of individual plants and their consequences on interacting insects. SHORT SUMMARY We demonstrate that Tanacetum vulgare chemotypes distinguished by their leaf terpenoid profiles also show unique floral and pollen chemotypes based on terpenoid composition and diversity, which affect the preference and performance of a beetle florivore.
The satiety hormone cholecystokinin gates reproduction in fish by controlling gonadotropin secretion

Life histories of oviparous species dictate high metabolic investment in the process of gonadal development leading to ovulation. In vertebrates, these two distinct processes are controlled by the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH), respectively. While it was suggested that a common secretagogue, gonadotropin-releasing hormone (GnRH), oversees both functions, the generation of loss-of-function fish challenged this view. Here we reveal that the satiety hormone cholecystokinin (CCK) is the primary regulator of this axis in zebrafish. We found that FSH cells express a CCK receptor, and our findings demonstrate that mutating this receptor results in a severe hindrance to ovarian development. Additionally, it causes a complete shutdown of both gonadotropins secretion. Using in-vivo and ex-vivo calcium imaging of gonadotrophs, we show that GnRH predominantly activates LH cells, whereas FSH cells respond to CCK stimulation, designating CCK as the bona fide FSH secretagogue. These findings indicate that the control of gametogenesis in fish was placed under different neural circuits, that are gated by CCK.
The extension of mammalian pregnancy required taming inflammation; independent evolution of extended placentation in the tammar wallaby

In the first live bearing mammals, it is assumed that pregnancy was short and ended with a brief period of inflammatory maternal-fetal interaction. This mode of reproduction has been retained in many marsupials. While inflammation is key to successful implantation in eutherians, a key innovation in eutherians is the ability to switch off this inflammation after it has been initiated. This extended period, in which inflammation is suppressed, likely allowed for an extended period of placentation. One lineage of marsupials, the macropodids (wallabies and kangaroos), have extended placentation beyond the 2-4 days seen in other marsupial taxa, which allows us to test whether a moderated inflammation response after attachment is a general pattern associated with the extension of placentation in mammals. We show that during tammar wallaby pregnancy, some inflammatory genes are expressed at key time points of gestation, including IL6, before attachment, IL12A and LIF throughout the period of placentation and prostaglandins before birth. However, we did not see evidence of a complete inflammatory response at any time point. We argue that genes involved in a moderated inflammation reaction may have been co-opted into roles for placentation, facilitating the establishment and maintenance of extended fetal-maternal contact. Whilst the absence of other key mediators of inflammation may prevent prolonged damage to the uterus. We argue the moderation of inflammation following maternal-fetal contact is a convergently evolved key innovation that allowed for the extension of placentation in different mammalian lineages. Significance statement Our data suggest that moderation of the inflammatory reaction to embryo attachment allows for extension of pregnancy in mammals. The ancestor of all mammals likely experienced an ancestral inflammatory reaction in response to embryo attachment. In contrast, eutherians and some marsupials, such as macropodids, have an extended period of fetal-maternal contact. During this period of placentation many inflammatory genes are silenced while a few others are still expressed. This moderated expression of inflammatory genes suggests that some genes of inflammation were coopted into establishing and maintaining the placenta. This challenges the perspective of inflammation as being detrimental to pregnancy, instead suggesting that fetal-maternal interactions are based on a modified inflammation response necessary for maintaining pregnancy over an extensive period of time.
miR-252 targeting temperature receptor CcTRPM to mediate the transition from summer-form to winter-form of Cacopsylla chinensis

Temperature determines the geographical distribution of organisms and affects the outbreak and damage of pests. Insects seasonal polyphenism is a successful strategy adopted by some species to adapt the changeable external environment. Cacopsylla chinensis (Yang & Li) showed two seasonal morphotypes, summer-form and winter-form, with significant differences in morphological characteristics. Low temperature is the key environmental factor to induce its transition from summer-form to winter-form. However, the detailed molecular mechanism remains unknown. Here, we firstly confirmed that low temperature of 10°C induced the transition from summer-form to winter-form by affecting the cuticle thickness and chitin content. Subsequently, we demonstrated that CcTRPM functions as a temperature receptor to regulate this transition. In addition, miR-252 was identified to mediate the expression of CcTRPM to involve in this morphological transition. Finally, we found CcTre1 and CcCHS1, two rate-limiting enzymes of insect chitin biosyntheis, act as the critical down-stream signal of CcTRPM in mediating this behavioral transition. Taken together, our results revealed that a signal transduction cascade mediates the seasonal polyphenism in C. chinensis. These findings not only lay a solid foundation for fully clarifying the ecological adaptation mechanism of C. chinensis outbreak, but also broaden our understanding about insect polymorphism.
Oil palm boom: its socioeconomic use and abuse

Oil palm cultivation has experienced explosive expansion in recent decades. Although the oil palm boom has serious environmental and socioeconomic consequences, only environmental issues have garnered attention in public discussion and synthesis studies. In this study, we synthesize the literature on the socioeconomic impacts of oil palm expansion across various observation units and spatial and temporal scales, which is of significant relevance to policymakers, researchers, and the wider public. Our review demonstrates that oil palm expansion is a double-edged sword. On the one hand, it has significantly helped both producing and non-producing countries’ economies by facilitating the (re)export of crude palm oil and its byproducts and by creating employment opportunities. This has stimulated rural economies, led to rural poverty reduction, and improved food security and diets for rural households in producer countries. On the other hand, it has increased conflicts and tension between local communities and agro-industrial companies, worsened workers’ conditions, and widened domestic economic inequality between producing and non-producing areas within a given producer country. Monetary quantification of the costs of oil palm’s negative environmental and social impacts indicates that the loss of ecosystem services and social services far outweighs the benefits derived from the increased production of oil palm. The direct income benefits through harvest sales and employment are more evident in the Southeast Asia production frontier, where oil palm cultivation and marketing are relatively advanced and well-integrated into global value chains. The negative outcomes are observed in all oil palm production regions, with more negative effects on food security in the African production frontiers. We propose multiple actionable research and policy recommendations that may jointly lead to inclusive and sustainable socioeconomic (and environmental) outcomes in oil palm cultivation. The socioeconomic consequences of oil palm expansion at the global level, in the African and American production frontiers, and the role of gender in oil palm production systems remain understudied. Hence, studies should be conducted.
Seizures regulate the cation-Cl− cotransporter NKCC1 in a hamster model of epilepsy: implications for GABA neurotransmission

Background The balance between the activity of the Na+/K+/Cl− cotransporter (NKCC1) that introduces Cl− into the cell and the K+/Cl− cotransporter (KCC2) that transports Cl− outside the cell is critical in determining the inhibitory or excitatory outcome of GABA release. Mounting evidence suggests that the impairment of GABAergic inhibitory neurotransmission plays a crucial role in the pathophysiology of epilepsy, both in patients and animal models. Previous studies indicate that decreased KCC2 expression is linked to audiogenic seizures in GASH/Sal hamsters, highlighting that Cl− imbalance can cause neuronal hyperexcitability. In this study, we aimed to investigate whether the Na+/K+/Cl− cotransporter NKCC1 is also affected by audiogenic seizures and could, therefore, play a role in neuronal hyperexcitability within the GASH/Sal epilepsy model. Methods NKCC1 protein expression in both the GASH/Sal strain and wild type hamsters was analyzed by immunohistochemistry and Western blotting techniques. Brain regions examined included cortex, hippocampus, hypothalamus, inferior colliculus and pons-medulla oblongata, which were evaluated both at rest and after sound-inducing seizures in GASH/Sal hamsters. A complementary analysis of NKCC1 gene slc12a2 expression was conducted by real-time PCR. Finally, protein and mRNA levels of glutamate decarboxylase GAD67 were measured as an indicator of GABA release. Results The induction of seizures caused significant changes in NKCC1 expression in epileptic GASH/Sal hamsters, despite the similar brain expression pattern of NKCC1 in GASH/Sal and wild type hamsters in the absence of seizures. Interestingly, the regulation of brain NKCC1 by seizures demonstrated regional specificity, as protein levels exclusively increased in the hippocampus and hypothalamus. Complementary real-time PCR analysis revealed that NKCC1 regulation was post-transcriptional only in the hypothalamus. In addition, seizures also modulated GAD67 mRNA levels in a brain region-specific manner. The increased GAD67 expression in the hippocampus and hypothalamus of the epileptic hamster brain suggests that NKCC1 upregulation overlaps with GABA release in these regions during seizures. Conclusions Our results indicate that seizure induction causes dysregulation of NKCC1 expression in GASH/Sal animals, which overlaps with changes in GABA release. These observations provide evidence for the critical role of NKCC1 in how seizures affect neuronal excitability, and support NKCC1 contribution to the development of secondary foci of epileptogenic activity.
Rice-Magnaporthe transcriptomics reveals host defense activation induced by red seaweed-biostimulant in rice plants

Red seaweed extracts have been shown to trigger the biotic stress tolerance in several crops. However, reports on transcriptional modifications in plants treated with seaweed biostimulant are limited. To understand the specific response of rice to blast disease in seaweed-biostimulant-primed and non-primed plants, transcriptomics of a susceptible rice cultivar IR-64 was carried out at zero and 48 h post inoculation with Magnaporthe oryzae (strain MG-01). A total of 3498 differentially expressed genes (DEGs) were identified; 1116 DEGs were explicitly regulated in pathogen-inoculated treatments. Functional analysis showed that most DEGs were involved in metabolism, transport, signaling, and defense. In a glass house, artificial inoculation of MG-01 on seaweed-primed plants resulted in the restricted spread of the pathogen leading to the confined blast disease lesions, primarily attributed to reactive oxygen species (ROS) accumulation. The DEGs in the primed plants were defense-related transcription factors, kinases, pathogenesis-related genes, peroxidases, and growth-related genes. The beta-D-xylosidase, a putative gene that helps in secondary cell wall reinforcement, was downregulated in non-primed plants, whereas it upregulated in the primed plants indicating its role in the host defense. Additionally, Phenylalanine ammonia-lyase, pathogenesis-related Bet-v-I family protein, chalcone synthase, chitinases, WRKY, AP2/ERF, and MYB families were upregulated in seaweed and challenge inoculated rice plants. Thus, our study shows that priming rice plants with seaweed bio-stimulants resulted in the induction of the defense in rice against blast disease. This phenomenon is contributed to early protection through ROS, protein kinase, accumulation of secondary metabolites, and cell wall strengthening.
ERP evidence for Slavic and German word stress cue sensitivity in English

Word stress is demanding for non-native learners of English, partly because speakers from different backgrounds weight perceptual cues to stress like pitch, intensity, and duration differently. Slavic learners of English and particularly those with a fixed stress language background like Czech and Polish have been shown to be less sensitive to stress in their native and non-native languages. In contrast, German English learners are rarely discussed in a word stress context. A comparison of these varieties can reveal differences in the foreign language processing of speakers from two language families. We use electroencephalography (EEG) to explore group differences in word stress cue perception between Slavic and German learners of English. Slavic and German advanced English speakers were examined in passive multi-feature oddball experiments, where they were exposed to the word impact as an unstressed standard and as deviants stressed on the first or second syllable through higher pitch, intensity, or duration. The results revealed a robust Mismatch Negativity (MMN) component of the event-related potential (ERP) in both language groups in response to all conditions, demonstrating sensitivity to stress changes in a non-native language. While both groups showed higher MMN responses to stress changes to the second than the first syllable, this effect was more pronounced for German than for Slavic participants. Such group differences in non-native English word stress perception from the current and previous studies are argued to speak in favor of customizable language technologies and diversified English curricula compensating for non-native perceptual variation.
The prognostic index PRIMA-PI combined with Ki67 as a better predictor of progression of disease within 24 months in follicular lymphoma

Background Progression of disease within 24 months (POD24) is a risk factor for poor survival in follicular lymphoma (FL), and there is currently no optimal prognostic model to accurately predict patients with early disease progression. How to combine traditional prognostic models with new indicators to establish a new prediction system, to predict the early progression of FL patients more accurately is a future research direction. Methods This study retrospectively analyzed patients with newly diagnosed FL patients in Shanxi Provincial Cancer Hospital from January 2015 to December 2020. Data from patients undergoing immunohistochemical detection (IHC) were analyzed using χ2 test and multivariate Logistic regression. Also, we built a nomogram model based on the results of LASSO regression analysis of POD24, which was validated in both the training set and validation set, and additional external validation was performed using a dataset (n = 74) from another center, Tianjin Cancer Hospital. Results The multivariate Logistic regression results suggest that high-risk PRIMA-PI group, Ki-67 high expression represent risk factors for POD24 (P<0.05). Next, PRIMA-PI and Ki67 were combined to build a new model, namely, PRIMA-PIC to reclassify high and low-risk groups. The result showed that the new clinical prediction model constructed by PRIMA-PI with ki67 has a high sensitivity to the prediction of POD24. Compared to PRIMA-PI, PRIMA-PIC also has better discrimination in predicting patient’s progression-free survival (PFS) and overall survival (OS). In addition, we built nomogram models based on the results of LASSO regression (histological grading, NK cell percentage, PRIMA-PIC risk group) in the training set, which were validated using internal validation set and external validation set, we found that C-index and calibration curve showed good performance. Conclusion As such, the new predictive model-based nomogram established by PRIMA-PI and Ki67 could well predict the risk of POD24 in FL patients, which boasts clinical practical value.