Miracle-dz/UniFAR-FTUs huggingface dataset:
Long noncoding RNA NEAT1 promotes the growth of gastric cancer cells by regulating miR-497-5p/PIK3R1 axis.

OBJECTIVE To investigate the molecular mechanisms of long noncoding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in gastric cancer (GC) development progress. MATERIALS AND METHODS Relative mRNA and protein expression levels were quantified by quantitative Reverse Transcription-PCR (qRT-PCR) or Western blot analysis. Cell proliferation and cell apoptosis were measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and flow cytometry, respectively. Binding sites of miR-497-5p on NEAT1 or phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) were determined by RNA pull-down assay or dual-luciferase reporter assay. Finally, the tumorigenic role of NEAT1 in GC was assessed using a xenograft model on nude mice. RESULTS NEAT1 was upregulated in GC tissues, promoted proliferation, and inhibited apoptosis of GC cells. NEAT1 could directly bind to and negatively regulate miR-497-5p expression. PIK3R1 was then identified as a downstream target of miR-497-5P. In GC cell models, PIK3R1 was found to be directly negatively regulated by miR-497-5p and indirectly positively regulated by NEAT1. Finally, NEAT1 knockdown inhibited tumor growth, increased miR-497-5p expression, and decreased PIK3R1 expression in xenograft model mice compared with the negative control. CONCLUSIONS Functioned as an oncogene, NEAT1 promoted cell growth in GC by regulating miR-497-5p/PIK3R1 axis. These results provided valuable insights into the underlying regulation signaling in gastric cancer development, shedding light on NEAT1 a promising therapeutic target from bench to clinic.
Targeting Antigens to CD180 but Not CD40 Programs Immature and Mature B Cell Subsets to Become Efficient APCs

Key Points CD180 Ag targeting facilitates Ag presentation by B cells to CD4+ T cells. Immature B cells are sufficient for TFH cell maturation. Compared with CD180, CD40 targeting induces slower and lower-affinity IgG responses. Targeting Ags to the CD180 receptor activates both B cells and dendritic cells (DCs) to become potent APCs. After inoculating mice with Ag conjugated to an anti-CD180 Ab, B cell receptors were rapidly internalized. Remarkably, all B cell subsets, including even transitional 1 B cells, were programed to process, present Ag, and stimulate Ag-specific CD4+ T cells. Within 24–48 hours, Ag-specific B cells were detectable at T–B borders in the spleen; there, they proliferated in a T cell–dependent manner and induced the maturation of T follicular helper (TFH) cells. Remarkably, immature B cells were sufficient for the maturation of TFH cells after CD180 targeting: TFH cells were induced in BAFFR−/− mice (with only transitional 1 B cells) and not in μMT mice (lacking all B cells) following CD180 targeting. Unlike CD180 targeting, CD40 targeting only induced DCs but not B cells to become APCs and thus failed to efficiently induce TFH cell maturation, resulting in slower and lower-affinity IgG Ab responses. CD180 targeting induces a unique program in Ag-specific B cells and to our knowledge, is a novel strategy to induce Ag presentation in both DCs and B cells, especially immature B cells and thus has the potential to produce a broad range of Ab specificities. This study highlights the ability of immature B cells to present Ag to and induce the maturation of cognate TFH cells, providing insights toward vaccination of mature B cell–deficient individuals and implications in treating autoimmune disorders.
Asymmetric and Reduced Xanthene Fluorophores: Synthesis, Photochemical Properties, and Application to Activatable Fluorescent Probes for Detection of Nitroreductase

Xanthene fluorophores, including fluorescein, rhodol, and rhodamines, are representative classes of fluorescent probes that have been applied in the detection and visualization of biomolecules. “Turn on” activatable fluorescent probes, that can be turned on in response to enzymatic reactions, have been developed and prepared to reduce the high background signal of “always-on” fluorescent probes. However, the development of activity-based fluorescent probes for biological applications, using simple xanthene dyes, is hampered by their inefficient synthetic methods and the difficulty of chemical modifications. We have, thus, developed a highly efficient, versatile synthetic route to developing chemically more stable reduced xanthene fluorophores, based on fluorescein, rhodol, and rhodamine via continuous Pd-catalyzed cross-coupling. Their fluorescent nature was evaluated by monitoring fluorescence with variation in the concentration, pH, and solvent. As an application to activatable fluorescent probe, nitroreductase (NTR)-responsive fluorescent probes were also developed using the reduced xanthene fluorophores, and their fluorogenic properties were evaluated.
Dietary Fatty Acids and Host–Microbial Crosstalk in Neonatal Enteric Infection

Human milk is the best nutritional choice for infants. However, in instances where breastfeeding is not possible, infant formulas are used as alternatives. While formula manufacturers attempt to mimic the performance of human breast milk, formula-fed babies consistently have higher incidences of infection from diarrheal diseases than those breastfed. Differences in disease susceptibility, progression and severity can be attributed, in part, to nutritional fatty acid differences between breast milk and formula. Despite advances in our understanding of breast milk properties, formulas still present major differences in their fatty acid composition when compared to human breast milk. In this review, we highlight the role of distinct types of dietary fatty acids in modulating host inflammation, both directly and through the microbiome-immune nexus. We present evidence that dietary fatty acids influence enteric disease susceptibility and therefore, altering the fatty acid composition in formula may be a potential strategy to improve infectious outcomes in formula-fed infants.
The default-mode network represents aesthetic appeal that generalizes across visual domains

Significance Despite being highly subjective, aesthetic experiences are powerful moments of interaction with one’s surroundings, shaping behavior, mood, beliefs, and even a sense of self. The default-mode network (DMN), which sits atop the cortical hierarchy and has been implicated in self-referential processing, is typically suppressed when a person engages with the external environment. Yet not only is the DMN surprisingly engaged when one finds a visual artwork aesthetically moving, here we present evidence that the DMN also represents aesthetic appeal in a manner that generalizes across visual aesthetic domains, such as artworks, landscapes, or architecture. This stands in contrast to ventral occipitotemporal cortex (VOT), which represents the content of what we see, but does not contain domain-general information about aesthetic appeal. Visual aesthetic evaluations, which impact decision-making and well-being, recruit the ventral visual pathway, subcortical reward circuitry, and parts of the medial prefrontal cortex overlapping with the default-mode network (DMN). However, it is unknown whether these networks represent aesthetic appeal in a domain-general fashion, independent of domain-specific representations of stimulus content (artworks versus architecture or natural landscapes). Using a classification approach, we tested whether the DMN or ventral occipitotemporal cortex (VOT) contains a domain-general representation of aesthetic appeal. Classifiers were trained on multivoxel functional MRI response patterns collected while observers made aesthetic judgments about images from one aesthetic domain. Classifier performance (high vs. low aesthetic appeal) was then tested on response patterns from held-out trials from the same domain to derive a measure of domain-specific coding, or from a different domain to derive a measure of domain-general coding. Activity patterns in category-selective VOT contained a degree of domain-specific information about aesthetic appeal, but did not generalize across domains. Activity patterns from the DMN, however, were predictive of aesthetic appeal across domains. Importantly, the ability to predict aesthetic appeal varied systematically; predictions were better for observers who gave more extreme ratings to images subsequently labeled as “high” or “low. ” These findings support a model of aesthetic appreciation whereby domain-specific representations of the content of visual experiences in VOT feed in to a “core” domain-general representation of visual aesthetic appeal in the DMN. Whole-brain “searchlight” analyses identified additional prefrontal regions containing information relevant for appreciation of cultural artifacts (artwork and architecture) but not landscapes.
Associations of VEGFA and KDR single-nucleotide polymorphisms and increased risk and aggressiveness of high-grade gliomas

Angiogenesis, induced by the vascular endothelial growth factor A through its ligation to the vascular endothelial growth receptor 2, has been described as a crucial point in high-grade glioma development. The aim of this study was to evaluate the influence of VEGFA–2578C/A, −2489C/T, −1154G/A, −634G/C, and −460C/T, and KDR–604T/C, −271G/A, +1192G/A, and +1719A/T single-nucleotide polymorphisms on risk and clinicopathological aspects of high-grade glioma. This case–control study enrolled 205 high-grade glioma patients and 205 controls. Individuals with VEGFA–2578 CC or CA, VEGFA–1154 GG, VEGFA–634 GC or CC, and VEGFA–460 CT or TT genotypes were under 2.56, 1.53, 1.54, and 1.84 increased risks of high-grade glioma, compared to others, respectively. And 1.61, 2.66, 2.52, 2.53, and 2.02 increased risks of high-grade glioma were seen in individuals with VEGFA–2578 CC plus VEGFA–1154 GG, VEGFA–2578 CC or CA plus VEGFA–634 GC or CC, VEGFA–2578 CC or CA plus VEGFA–460 CT or TT, VEGFA–1154 GG or GA plus VEGFA–634 GC or CC, and VEGFA 634 GC or CC plus VEGFA–460 CT or TT combined genotypes, respectively, when compared to others. The “CAGT” haplotype of KDR single-nucleotide polymorphisms was more common in patients with grade IV than in those with grade III tumors, and individuals carrying this haplotype were at 1.76 increased risk of developing grade IV tumors than others. We present, for the first time, preliminary evidence that VEGFA–2578C/A and VEGFA–1154G/A single-nucleotide polymorphisms increases high-grade glioma risk, and “CAGT” haplotype of the KDR gene alters high-grade glioma aggressiveness and risk of grade IV tumors in Brazil.
Defective Pollen Wall 3 (DPW3), a novel alpha integrin-like protein, is required for pollen wall formation in rice.

•In flowering plants, pollen wall is a specialized extracellular cell wall matrix surrounding male gametophytes and acts as a natural protector of pollen grains against various environmental and biological stresses. The formation of pollen wall is a complex but well-regulated process, which involves the action of many different genes. However, genetic and molecular mechanisms underlying this process remain largely unknown. •In this study, we isolated and characterized a novel rice male sterile mutant, defective pollen wall3 (dpw3), which displays smaller and paler anthers with aborted pollen grains. DPW3 encodes a novel membrane-associated alpha integrin-like protein conserved in land plants. DPW3 is ubiquitously expressed in anther developmental stages and its protein is localized to plasma membrane, endoplasmic reticulum (ER) and Golgi. •dpw3 anthers exhibited unbalanced anther cuticular profile, abnormal Ubisch bodies, disrupted callose deposition, defective pollen wall formation such as abnormal microspore plasma membrane undulation, defective primexine formation, resulting in pollen abortion and complete male sterility. •Our findings revealed a novel and vital role of alpha integrin-like proteins, in plant male reproduction. This article is protected by copyright. All rights reserved.
Efficacy of Difluoromethylornithine and Aspirin for Treatment of Adenomas and Aberrant Crypt Foci in Patients with Prior Advanced Colorectal Neoplasms

Difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, was shown to act synergistically with a NSAID for chemoprevention of colorectal neoplasia. We determined the efficacy and safety of DFMO plus aspirin for prevention of colorectal adenomas and regression of rectal aberrant crypt foci (ACF) in patients with prior advanced adenomas or cancer. A double-blinded, placebo-controlled trial was performed in 104 subjects (age 46–83) randomized (1:1) to receive daily DFMO (500 mg orally) plus aspirin (325 mg) or matched placebos for one year. All polyps were removed at baseline. Adenoma number (primary endpoint) and rectal ACF (index cluster and total) were evaluated at a one year colonoscopy. ACF were identified by chromoendoscopy. Toxicity was monitored, including audiometry. Eighty-seven subjects were evaluable for adenomas or ACF modulation (n = 62). At one year of treatment, adenomas were detected in 16 (38.1%) subjects in the DFMO plus aspirin arm (n = 42) versus 18 (40.9%) in the placebo arm (n = 44; P = 0.790); advanced adenomas were similar (n = 3/arm). DFMO plus aspirin was associated with a statistically significant reduction in the median number of rectal ACF compared with placebo (P = 0.036). Total rectal ACF burden was also reduced in the treatment versus the placebo arm relative to baseline (74% vs. 45%, P = 0.020). No increase in adverse events, including ototoxicity, was observed in the treatment versus placebo arms. While adenoma recurrence was not significantly reduced by one year of DFMO plus aspirin, the drug combination significantly reduced rectal ACF number consistent with a chemopreventive effect.
Oil dispersant Corexit 9500 is weakly estrogenic, but does not skew the sex ratio in Alligator mississippiensis

During the Deepwater Horizon oil spill, vast quantities of a chemical dispersant Corexit 9500 were applied in remediation efforts. In addition to the acute toxicity, it is essential to evaluate Corexit further with a broader scope of long‐term sublethal endocrine endpoints. The American alligator (Alligator mississippiensis) is an excellent organism for such an endeavor. It exhibits temperature‐dependent sex determination, in which egg incubation temperatures during a thermosensitive period (TSP) in embryonic development determine the sex of embryos. Estrogen signals play a critical role in this process. For example, a single exposure to exogenous estrogen during the TSP overrides the effects of temperature and leads to skewed sex ratios. At a concentration of 100 ppm, Corexit significantly induced transcriptional activity of both alligator nuclear estrogen receptors 1 and 2 in vitro in reporter gene assays. To investigate the estrogenic effects of Corexit on gonadal development, alligator eggs were exposed to Corexit at environmentally relevant concentrations (0.25, 2.5 and 25 ppm) before the TSP in ovo. Exposure to Corexit at 0.25 and 25 ppm significantly delayed hatching and growth. Corexit exposure at any treatment level did not affect sex ratios or testicular mRNA abundance as measured at 1‐week post‐hatching, suggesting that the combination of Corexit components did not synergize enough to induce ovarian development in ovo. These results point to a need for further investigations on individual and combined components of Corexit to understand better their long‐term effects on the development and reproductive health of alligators and other coastal aquatic wildlife.
Biogenic Amines Formation Mechanism and Determination Strategies: Future Challenges and Limitations

Abstract The evolution in foodstuff-monitoring processes has increased the number of studies on biogenic amines (BAs), in recent years. This trend with future perspective needs to be assembled to address the associated health risks. Thus, this study aims to cover three main aspects of BAs: (i) occurrence, physiology, and toxicological effects, most probable formation mechanisms and factors controlling their growth; (ii) recent advances, strategies for determination, preconcentration steps, model technique, and nature of the matrix; and (iii) milestone, limitations with existing methodologies, future trends, and detailed expected developments for clinical use and on-site ultra-trace determination. The core of the ongoing review will discuss recent trends in pre-concentration toward miniaturization, automation, and possible coupling with electrochemical techniques, surface-enhanced Raman scattering, spectrofluorimetry, and lateral flow protocols to be exploited for the development of rapid, facile, and sensitive on-site determination strategies for BAs.
Structural analysis of Borrelia burgdorferi periplasmic lipoprotein BB0365 involved in Lyme disease infection

The periplasmic lipoprotein BB0365 of the Lyme disease agent Borrelia burgdorferi is expressed throughout mammalian infection and is essential for all phases of Lyme disease infection; its function, however, remains unknown. In the current study, our structural analysis of BB0365 revealed the same structural fold as that found in the NqrC and RnfG subunits of the NADH:quinone and ferredoxin:NAD+ sodium‐translocating oxidoreductase complexes, which points to a potential role for BB0365 as a component of the sodium pump. Additionally, BB0365 coordinated Zn2+ by the His51, His55, His140 residues, and the Zn2+‐binding site indicates that BB0365 could act as a potential metalloenzyme; therefore, this structure narrows down the potential functions of BB0365, an essential protein for B. burgdorferi to cause Lyme disease.
Secondary forest fragments offer important carbon and biodiversity cobenefits

Tropical forests store large amounts of carbon and high biodiversity, but are being degraded at alarming rates. The emerging global Forest and Landscape Restoration (FLR) agenda seeks to limit global climate change by removing carbon dioxide from the atmosphere through the growth of trees. In doing so, it may also protect biodiversity as a free cobenefit, which is vital given the massive shortfall in funding for biodiversity conservation. We investigated whether natural forest regeneration on abandoned pastureland offers such cobenefits, focusing for the first time on the recovery of taxonomic diversity (TD), phylogenetic diversity (PD) and functional diversity (FD) of trees, including the recovery of threatened and endemic species richness, within isolated secondary forest (SF) fragments. We focused on the globally threatened Brazilian Atlantic Forest, where commitments have been made to restore 1 million hectares under FLR. Three decades after land abandonment, regenerating forests had recovered ~20% (72 Mg/ha) of the above‐ground carbon stocks of a primary forest (PF), with cattle pasture containing just 3% of stocks relative to PFs. Over this period, SF recovered ~76% of TD, 84% of PD and 96% of FD found within PFs. In addition, SFs had on average recovered 65% of threatened and ~30% of endemic species richness of primary Atlantic forest. Finally, we find positive relationships between carbon stock and tree diversity recovery. Our results emphasize that SF fragments offer cobenefits under FLR and other carbon‐based payments for ecosystem service schemes (e.g. carbon enhancements under REDD+). They also indicate that even isolated patches of SF could help to mitigate climate change and the biodiversity extinction crisis by recovering species of high conservation concern and improving landscape connectivity.
Modulating Electron Transfer in an Organic Reaction via Chemical Group Modification of the Photocatalyst.

Tuning electron transfer (ET) rates from catalysts to substrates is important for modulating photocatalytic organic reactions. In this work, we have taken pyrene-based photocatalysts (Py) for photocatalytic hydrodefluorination of polyfluoroarenes (FA) as model systems, and conducted a first-principle study on modulating ET rates from Py to FA via chemical modification of Py with different electron donating/withdrawing groups (EDGs/EWGs). The computed spatial distributions of frontier Kohn-Sham orbitals suggest that ET is energetically more favorable for Py-EDGs than for Py-EWGs. The estimated ET rates by a simplified Marcus model show that they are appreciably enhanced by EDGs substitution and weakened by EWGs substitution. Noticeably, the associated Gibbs free energy change plays a dominant role. Our findings of tuning ET rates for Py-FA complexes via chemical group modifications cast new insight into the rational design of metal-free photocatalysts for organic transformations.
Drivers of productivity and its temporal stability in a tropical tree diversity experiment

There is increasing evidence that mixed‐species forests can provide multiple ecosystem services at a higher level than their monospecific counterparts. However, most studies concerning tree diversity and ecosystem functioning relationships use data from forest inventories (under noncontrolled conditions) or from very young plantation experiments. Here, we investigated temporal dynamics of diversity–productivity relationships and diversity–stability relationships in the oldest tropical tree diversity experiment. Sardinilla was established in Panama in 2001, with 22 plots that form a gradient in native tree species richness of one‐, two‐, three‐ and five‐species communities. Using annual data describing tree diameters and heights, we calculated basal area increment as the proxy of tree productivity. We combined tree neighbourhood‐ and community‐level analyses and tested the effects of both species diversity and structural diversity on productivity and its temporal stability. General patterns were consistent across both scales indicating that tree–tree interactions in neighbourhoods drive observed diversity effects. From 2006 to 2016, mean overyielding (higher productivity in mixtures than in monocultures) was 25%–30% in two‐ and three‐species mixtures and 50% in five‐species stands. Tree neighbourhood diversity enhanced community productivity but the effect of species diversity was stronger and increased over time, whereas the effect of structural diversity declined. Temporal stability of community productivity increased with species diversity via two principle mechanisms: asynchronous responses of species to environmental variability and overyielding. Overyielding in mixtures was highest during a strong El Niño‐related drought. Overall, positive diversity–productivity and diversity–stability relationships predominated, with the highest productivity and stability at the highest levels of diversity. These results provide new insights into mixing effects in diverse, tropical plantations and highlight the importance of analyses of temporal dynamics for our understanding of the complex relationships between diversity, productivity and stability. Under climate change, mixed‐species forests may provide both high levels and high stability of production.