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Sepsis is a systemic inflammatory response syndrome caused by infection, resulting in organ dysfunction. Sepsis‐induced acute kidney injury (AKI) is one of the most common potential complications. Increasing reports have shown that M1 and M2 macrophages both take part in the progress of AKI by influencing the level of inflammatory factors and the cell death, including pyroptosis. However, whether M1 and M2 macrophages regulate AKI by secreting exosome remains unknown. In the present study, we isolated the exosomes from M1 and M2 macrophages and used Western blot and enzyme‐linked immunosorbent assay (ELISA) to investigate the effect of M1 and M2 exosomes on cell pyroptosis. miRNA sequencing was used to identify the different miRNA in M1 and M2 exosomes. Luciferase reporter assay was used to verify the target gene of miRNA. We confirmed that exosomes excreted by macrophages regulated cell pyroptosis in vitro by using Western blot and ELISA. miRNA sequencing revealed the differentially expressed level of miRNAs in M1 and M2 exosomes, among which miR‐93‐5p was involved in the regulation of pyroptosis. By using bioinformatics predictions and luciferase reporter assay, we found that thioredoxin–interacting protein (TXNIP) was a direct target of miR‐93‐5p. Further in vitro and in vivo experiments indicated that exosomal miR‐93‐5p regulated the TXNIP directly to influence the pyroptosis in renal epithelial cells, which explained the functional difference between different phenotypes of macrophages. This study might provide new targets for the treatment of sepsis‐induced AKI.

Tumor metastasis is a hallmark of cancer. The communication between cancer-derived exosomes and stroma plays an irreplaceable role in facilitating pre-metastatic niche formation and cancer metastasis. However, the mechanisms underlying exosome-mediated pre-metastatic niche formation during colorectal cancer (CRC) liver metastasis remain incompletely understood. Here we identified HSPC111 was the leading upregulated gene in hepatic stellate cells (HSCs) incubated with CRC cell-derived exosomes. In xenograft mouse model, CRC cell-derived exosomal HSPC111 facilitated pre-metastatic niche formation and CRC liver metastases (CRLM). Consistently, CRC patients with liver metastasis had higher level of HSPC111 in serum exosomes, primary tumors and cancer-associated fibroblasts (CAFs) in liver metastasis than those without. Mechanistically, HSPC111 altered lipid metabolism of CAFs by phosphorylating ATP-citrate lyase (ACLY), which upregulated the level of acetyl-CoA. The accumulation of acetyl-CoA further promoted CXCL5 expression and secretion by increasing H3K27 acetylation in CAFs. Moreover, CXCL5-CXCR2 axis reinforced exosomal HSPC111 excretion from CRC cells and promoted liver metastasis. These results uncovered that CRC cell-derived exosomal HSPC111 promotes pre-metastatic niche formation and CRLM via reprogramming lipid metabolism in CAFs, and implicate HSPC111 may be a potential therapeutic target for preventing CRLM.

Quantum magnets provide the simplest example of strongly interacting quantum matter, yet they continue to resist a comprehensive understanding above one spatial dimension. We explore a promising framework in two dimensions, the Dirac spin liquid (DSL) — quantum electrodynamics (QED 3 ) with 4 Dirac fermions coupled to photons. Importantly, its excitations include magnetic monopoles that drive confinement. We address previously open key questions — the symmetry actions on monopoles on square, honeycomb, triangular and kagome lattices. The stability of the DSL is enhanced on triangular and kagome lattices compared to bipartite (square and honeycomb) lattices. We obtain the universal signatures of the DSL on triangular and kagome lattices, including those of monopole excitations, as a guide to numerics and experiments on existing materials. Even when unstable, the DSL helps unify and organize the plethora of ordered phases in correlated two-dimensional materials. The Dirac spin liquid is a candidate description for the strongly correlated behaviour of some quantum magnets. Song et al. study the symmetry dependence physics of monopole excitations and argue that the lattice-dependent consequences for magnetic ordering may provide a unifying picture for 2D quantum magnetism.

The antiferromagnetic spin-1/2 Heisenberg model on a kagome lattice is one of the most paradigmatic models in the context of spin liquids, yet the precise nature of its ground state is not understood. We use large-scale density matrix renormalization group simulations (DMRG) on infinitely long cylinders and find indications for the formation of a gapless Dirac spin liquid. First, we use adiabatic flux insertion to demonstrate that the spin gap is much smaller than estimated from previous DMRG simulation. Second, we find that the momentum-dependent excitation spectrum, as extracted from the DMRG transfer matrix, exhibits Dirac cones that match those of a π -flux free-fermion model [the parton mean-field ansatz of a U(1) Dirac spin liquid].

Air pollution is inevitably the result of human civilization, industrialization, and globalization. It is composed of a mixture of gases and particles at harmful levels. Particulate matter (PM), nitrogen oxides (NOx), and carbon dioxides (CO2) are mainly generated from vehicle emissions and fuel consumption and are the main materials causing outdoor air pollution. Exposure to polluted outdoor air has been proven to be harmful to human eyes. On the other hand, indoor air pollution from environmental tobacco smoking, heating, cooking, or poor indoor ventilation is also related to several eye diseases, including conjunctivitis, glaucoma, cataracts, and age-related macular degeneration (AMD). In the past 30 years, no updated review has provided an overview of the impact of air pollution on the eye. We reviewed reports on air pollution and eye diseases in the last three decades in the PubMed database, Medline databases, and Google Scholar and discussed the effect of various outdoor and indoor pollutants on human eyes.

BackgroundTertiary lymphoid structures (TLSs) have been proposed to assess the prognosis of patients with cancer. Here, we investigated the prognostic value and relevant mechanisms of TLSs in colorectal cancer liver metastases (CRCLM).Methods603 patients with CRCLM treated by surgical resection from three cancer centers were included. The TLSs were categorized according to their anatomic subregions and quantified, and a TLS scoring system was established for intratumor region (T score) and peritumor region (P score). Differences in relapse-free survival (RFS) and overall survival (OS) between groups were determined. Multiplex immunohistochemical staining (mIHC) was used to determine the cellular composition of TLSs in 40 CRCLM patients.ResultsT score positively correlated with superior prognosis, while P score negatively associated with poor survival (all p<0.05). Meanwhile, T score was positively associated with specific mutation subtype of KRAS. Furthermore, TLSs enrichment gene expression was significantly associated with survival and transcriptomic subtypes of CRCLM. Subsequently, mIHC showed that the densities of Treg cells, M2 macrophages and Tfh cells were significantly higher in intratumor TLSs than in peritumor TLSs (p=0.029, p=0.047 and p=0.041, respectively), and the frequencies of Treg cells and M2 macrophages were positively correlated with P score, while the frequencies of Tfh cells were positively associated with T scores in intratumor TLSs (all p<0.05). Next, based on the distribution and abundance of TLSs, an Immune Score combining T score and P score was established which categorized CRCLM patients into four immune classes with different prognosis (all p<0.05). Among them, patients with higher immune class have more favorable prognoses. The C-index of Immune Class for RFS and OS was higher than Clinical Risk Score statistically. These results were also confirmed by the other two validation cohorts.ConclusionsThe distribution and abundance of TLSs is significantly associated with RFS and OS of CRCLM patients, and a novel immune class was proposed for predicting the prognosis of CRCLM patients.

A bstract Recently it was proposed that the theory space of effective field theories with consistent UV completions can be described as a positive geometry, termed the EFThedron. In this paper we demonstrate that at the core, the geometry is given by the convex hull of the product of two moment curves. This makes contact with the well studied bi-variate moment problem, which in various instances has known solutions, generalizing the Hankel matrices of couplings into moment matrices. We extend these solutions to hold for more general bi-variate problem, and are thus able to obtain analytic expressions for bounds, which closely match (and in some cases exactly match) numerical results from semi-definite programing methods. Furthermore, we demonstrate that crossing symmetry in the IR imposes non-trivial constraints on the UV spectrum. In particular, permutation invariance for identical scalar scattering requires that any UV completion beyond the scalar sector must contain arbitrarily high spins, including at least all even spins ℓ ≤ 28, with the ratio of spinning spectral functions bounded from above, exhibiting large spin suppression. The spinning spectrum must also include at least one state satisfying a bound m J 2 < M h 2 J 2 − 12 J 4 − 32 J 2 + 204 8 150 − 43 J 2 + 2 J 4 , where J 2 = ℓ ( ℓ +1), and M h is the mass of the heaviest spin 2 state in the spectrum.

Bronchopulmonary dysplasia (BPD) is a severe complication of preterm infants characterized by increased alveolarization and inflammation. Premature exposure to hyperoxia is believed to be a key contributor to the pathogenesis of BPD. No effective preventive or therapeutic agents have been created. Stimulator of interferon gene (STING) is associated with inflammation and apoptosis in various lung diseases. Long non‐coding RNA MALAT1 has been reported to be involved in BPD. However, how MALAT1 regulates STING expression remains unknown. In this study, we assessed that STING and MALAT1 were up‐regulated in the lung tissue from BPD neonates, hyperoxia‐based rat models and lung epithelial cell lines. Then, using the flow cytometry and cell proliferation assay, we found that down‐regulating of STING or MALAT1 inhibited the apoptosis and promoted the proliferation of hyperoxia‐treated cells. Subsequently, qRT‐PCR, Western blotting and dual‐luciferase reporter assays showed that suppressing MALAT1 decreased the expression and promoter activity of STING. Moreover, transcription factor CREB showed its regulatory role in the transcription of STING via a chromatin immunoprecipitation. In conclusion, MALAT1 interacts with CREB to regulate STING transcription in BPD neonates. STING, CREB and MALAT1 may be promising therapeutic targets in the prevention and treatment of BPD.

Defects in conformal field theory (CFT) are of significant theoretical and experimental importance. The presence of defects theoretically enriches the structure of the CFT, but at the same time, it makes it more challenging to study, especially in dimensions higher than two. Here, we demonstrate that the recently-developed theoretical scheme, fuzzy (non-commutative) sphere regularization , provides a powerful lens through which one can dissect the defect of 3D CFTs in a transparent way. As a notable example, we study the magnetic line defect of 3D Ising CFT and clearly demonstrate that it flows to a conformal defect fixed point. We have identified 6 low-lying defect primary operators, including the displacement operator, and accurately extract their scaling dimensions through the state-operator correspondence. Moreover, we also compute one-point bulk correlators and two-point bulk-defect correlators, which show great agreement with predictions of defect conformal symmetry, and from which we extract various bulk-defect operator product expansion coefficients. Our work demonstrates that the fuzzy sphere offers a powerful tool for exploring the rich physics in 3D defect CFTs. The study of defects and boundaries in the context of conformal field theory is important but challenging in dimensions higher than two. Here the authors use the recently developed fuzzy sphere regularization approach to perform non-perturbative analysis of defect conformal field theory in 3D

Microalgal lipid is one of the most promising feedstocks for biodiesel production. Chlorella appears to be a particularly good option, and nitrogen (N) starvation is an efficient environmental pressure used to increase lipid accumulation in Chlorella cells. The effects of N starvation of an oil-producing wild microalga, Chlorella sorokiniana C3, on lipid accumulation were investigated using thin layer chromatography (TLC), confocal laser scanning microscopy (CLSM) and flow cytometry (FCM). The results showed that N starvation resulted in lipid accumulation in C. sorokiniana C3 cells, oil droplet (OD) formation and significant lipid accumulation in cells were detected after 2 d and 8 d of N starvation, respectively. During OD formation, reduced photosynthetic rate, respiration rate and photochemistry efficiency accompanied by increased damage to PSII were observed, demonstrated by chlorophyll (Chl) fluorescence, 77K fluorescence and oxygen evolution tests. In the mean time the rate of cyclic electron transportation increased correspondingly to produce more ATP for triacylglycerols (TAGs) synthesis. And 0.5 d was found to be the turning point for the early stress response and acclimation of cells to N starvation. Increased level of membrane peroxidation was also observed during OD formation, and superoxide dismutase (SOD), peroxide dismutase (POD) and catalase (CAT) enzyme activity assays suggested impaired reactive oxygen species (ROS) scavenging ability. Significant neutral lipid accumulation was also observed by artificial oxidative stress induced by H2O2 treatment. These results suggested coupled neutral lipid accumulation and oxidative stress during N starvation in C. sorokiniana C3.