Explore the vast range of titles available.

Background Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) metastasis and chemoresistance have not been fully characterized. Methods CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1. Results CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/β-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients. Conclusions CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.

A quantum thermal machine is an open quantum system coupled to hot and cold thermal baths. Thus, its dynamics can be well understood using the concepts and tools from non-Hermitian quantum systems. A hallmark of non-Hermiticity is the existence of exceptional points where the eigenvalues of a non-Hermitian Hamiltonian or a Liouvillian superoperator and their associated eigenvectors coalesce. Here, we report the experimental realization of a single-ion heat engine and demonstrate the effect of Liouvillian exceptional points on the dynamics and the performance of a quantum heat engine. Our experiments have revealed that operating the engine in the exact- and broken-phases, separated by a Liouvillian exceptional point, respectively during the isochoric heating and cooling strokes of an Otto cycle produces more work and output power and achieves higher efficiency than executing the Otto cycle completely in the exact phase where the system has an oscillatory dynamics and higher coherence. This result opens interesting possibilities for the control of quantum heat engines and will be of interest to other research areas that are concerned with the role of coherence and exceptional points in quantum processes and in work extraction by thermal machines. Investigations of quantum thermal machines and Liouvillian exceptional points have rarely crossed each other. Here, the authors realize experimentally a quantum Otto engine using a single trapped ion, and show that crossing a Liouvillian exceptional point during the cycle increases the engine performance.

Radioresistance hampers success in the treatment of patients with advanced colorectal cancer (CRC). Improving our understanding of the underlying mechanisms of radioresistance could increase patients’ response to irradiation (IR). MicroRNAs are a class of small RNAs involved in tumor therapy response to radiation. Here we found that miR-214 was markedly decreased in CRC cell lines and blood of CRC patients after IR exposure. Meanwhile, autophagy was enhanced in irradiated CRC cells. Mechanically, ATG12 was predicted and identified as a direct target of miR-214 by dual luciferase assay, qPCR, and Western blot. In vitro and in vivo experiments showed that miR-214 promoted radiosensitivity by inhibiting IR-induced autophagy. Restoration of ATG12 attenuated miR-214-mediated inhibition of cell growth and survival in response to IR. Importantly, miR-214 was highly expressed in radiosensitive CRC specimens and negatively correlated with plasma level of CEA. Moreover, ATG12 and LC3 expressions were increased in radioresistant CRC specimens. Our study elucidates that miR-214 promotes radiosensitivity by inhibition of ATG12-mediated autophagy in CRC. Importantly, miR-214 is a determinant of CRC irradiation response and may serve as a potential therapeutic target in CRC treatment.

Sarcopenia is an age-related disease, which is characterized by a decline in muscle mass and function. It is one of the most important health issues in the elderly and often leads to a high rate and variety of adverse outcomes. To evaluate the screening accuracy of SARC-F for sarcopenia in the elderly. We conducted a meta-analysis using articles available in 6 databases including PubMed (Medline), Web of Science, Embase, Cochrane Controlled Register of Trials (CENTRAL), China Knowledge Resource Integrated Database (CNKI), and Wanfang databases from inception to May 2020. Participants: Adults aged 60 years and older. Sarcopenia was defined by EWGSOP2, EWGSOP, AWGS, FNIH and IWGS. Two authors independently extracted data based on predefined criteria. Where data were available we calculated pooled summary estimates of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and their 95% confidence interval (CI) based on different criteria using the hierarchical logistic regression modeling including bivariate modeling and hierarchical summary receiver operating characteristic (HSROC) modeling. We included 20 studies, with the prevalence of sarcopenia ranging from 6.42% to 21.56%. The number of the literatures using EWGSOP, EWGSOP2, AWGS, IWGS and FNIH as diagnostic criteria was 13, 4, 13, 8, 7, respectively. Bivariate analysis yielded a pooled sensitivity of 32% (95%CI: 19%–47%), 77% (95%CI: 49%–92%), 27% (95%CI: 16%–42%), 39% (95%CI: 27%–52%), 35% (95%CI: 23%–49%) and a pooled specificity of 86% (95%CI:77%–92%), 63% (95%CI: 43%–79%), 91% (95%CI: 85%–95%), 86% (95%CI: 76%–92%), 89% (95%CI: 81%–93%), respectively. The area under the HSROC curve were 0.68 (95%CI: 0.64–0.72), 0.75 (95%CI: 0.71–0.78), 0.73 (95%CI: 0.69–0.77), 0.67 (95%CI: 0.62–0.71), 0.70 (95%CI: 0.65–0.73), respectively. The screening accuracy of SARC-F was various based on different diagnostic criteria. There were some limitations for SARC-F, however, considering the higher practicability and specificity for screening sarcopenia in practice, SARC-F was still an effective screening tool for sarcopenia in the elderly. And the screening accuracy of SARC-F needs further exploration when EWGSOP2 is applied as diagnostic criteria and geriatric inpatients are the target participants.

Quantum lock-in detection (QLID) is a powerful technique for extracting weak oscillating signals within noise. While entanglement may enhance measurement precision beyond the standard quantum limit (SQL), its integration with QLID is still an experimental challenge. Here we report the first experimental realization of entanglement-enhanced QLID using two trapped 40 Ca + ions. We prepare a Greenberger-Horne-Zeilinger (GHZ) state using a M ϕ lmer-S ϕ rensen gate and then apply periodic multipulse sequences to execute QLID. Using the GHZ state, the measurement precision approaches the Heisenberg limit ( Δ ω  ∝  N −1 ), surpassing the SQL ( Δ ω  ∝  N −1/2 ) achievable with non-entangled states. Notably, QLID achieves a superior inverse-quadratic temporal scaling ( Δ ω  ∝  T −2 ), exceeding the conventional inverse-linear scaling ( Δ ω  ∝  T −1 ), regardless of entanglement. We further optimize pulse sequences for enhanced robustness against experimental errors. This work establishes a powerful pathway to Heisenberg-limited quantum sensing of weak oscillating signals within noise. Quantum lock-in detection (QLID) is crucial for extracting oscillating signals from noise, while quantum entanglement is vital to surpass the standard of quantum limit in precision measurement. Here, the authors experimentally realise entanglement-enhanced QLID using two trapped ions, achieving frequency measurement precision at the Heisenberg limit and demonstrating an improved inverse-quadratic temporal scaling.

To ward off a wide variety of pathogens, the human adaptive immune system harbors a vast array of T-cell receptors (TCRs) and B-cell receptors (BCRs), collectively referred to as the immune repertoire. High-throughput sequencing (HTS) of TCR/BCR genes allows in-depth molecular analysis of T/B-cell clones, providing an unprecedented level of detail when examining the T/B-cell repertoire of individuals. It can evaluate TCR/BCR complementarity-determining region 3 (CDR3) diversity and assess the clonal composition, including the size of the repertoire; similarities between repertoires; V(D)J segment use; nucleotide insertions and deletions; CDR3 lengths; and amino acid distributions along the CDR3s at sequence-level resolution. Deep sequencing of B-cell and T-cell repertoires offers the potential for a quantitative understanding of the adaptive immune system in healthy and disease states. Recently, paired sequencing strategies have also been developed, which can provide information about the identity of immune receptor pairs encoded by individual T or B lymphocytes. HTS technology provides a previously unimaginable amount of sequence data, accompanied, however, by numerous challenges associated with error correction and interpretation that remain to be solved. The review details some of the technologies and some of the recent achievements in this field.

It is a huge challenge in both classical and quantum physics to solve analytically the equation of motion in a strongly anharmonic confinement. For an isolated nanoring, we propose a continuous and bounded potential model, which patches up the disadvantages of the usual square-well and parabolic potentials. A fully nonlinear and nonperturbative approach is developed to solve analytically the equation of motion, from which various frequency shifts and dynamic displacements are exactly derived by an order-by-order self-consistent method. A series of new energy levels and new energy states are found, indicating an alternative magnetic response mechanism. In nominally identical rings, especially, we observe a diamagnetic-paramagnetic transition in the period-halving Φ 0 /2-current with Φ 0 the flux quantum and a large increase in the Φ 0 -current at least one order of magnitude, which explain well the experimental observations. This work opens a new way to solve the strong or weak nonlinear problems.

The development of high-performance ultraelastic metals with superb strength, a large elastic strain limit and temperature-insensitive elastic modulus (Elinvar effect) are important for various industrial applications, from actuators and medical devices to high-precision instruments 1 , 2 . The elastic strain limit of bulk crystalline metals is usually less than 1 per cent, owing to dislocation easy gliding. Shape memory alloys 3 —including gum metals 4 , 5 and strain glass alloys 6 , 7 —may attain an elastic strain limit up to several per cent, although this is the result of pseudo-elasticity and is accompanied by large energy dissipation 3 . Recently, chemically complex alloys, such as ‘high-entropy’ alloys 8 , have attracted tremendous research interest owing to their promising properties 9 – 15 . In this work we report on a chemically complex alloy with a large atomic size misfit usually unaffordable in conventional alloys. The alloy exhibits a high elastic strain limit (approximately 2 per cent) and a very low internal friction (less than 2 × 10 −4 ) at room temperature. More interestingly, this alloy exhibits an extraordinary Elinvar effect, maintaining near-constant elastic modulus between room temperature and 627 degrees Celsius (900 kelvin), which is, to our knowledge, unmatched by the existing alloys hitherto reported. A chemically complex alloy that exhibits a high elastic strain limit and low internal friction is described; it also has an Elinvar effect (invariant elastic modulus) over a large temperature range, up to 627 °C.

Atomoxetine (ATX), a drug for treatment of depression and ADHD, has a high affinity for the norepinephrine transporter (NET); however, our previous study showed it had a blocking effect similar to fluoxetine on binding of [11C]DASB, a selective serotonin transporter (SERT) ligand. Whether the therapeutic effects of ATX are due to inhibition of either or both transporters is not known. Here we report our comparative PET imaging studies with [11C]MRB (a NET ligand) and [11C]AFM (a SERT ligand) to evaluate in vivo IC50 values of ATX in monkeys. Rhesus monkeys were scanned up to four times with each tracer with up to four doses of ATX. ATX or saline (placebo) infusion began 2h before each PET scan, lasting until the end of the 2-h scan. The final infusion rates were 0.01–0.12mg/kg/h and 0.045–1.054mg/kg/h for the NET and SERT studies, respectively. ATX plasma levels and metabolite-corrected arterial input functions were measured. Distribution volumes (VT) and IC50 values were estimated. ATX displayed dose-dependent occupancy on both NET and SERT, with a higher occupancy on NET: IC50 of 31±10 and 99±21ng/mL plasma for NET and SERT, respectively. At a clinically relevant dose (1.0–1.8mg/kg, approx. 300–600ng/mL plasma), ATX would occupy >90% of NET and >85% of SERT. This extrapolation assumes comparable free fraction of ATX in humans and non-human primates. Our data suggests that ATX at clinically relevant doses greatly occupies both NET and SERT. Thus, therapeutic modes of ATX action for treatment of depression and ADHD may be more complex than selective blockade of NET. •We examine the in vivo selectivity of atomoxetine (ATX) with PET.•[11C]MRB and [11C]AFM were used to evaluate ATX IC50 values for NET & SERT.•ATX at clinically relevant doses greatly occupies both NET and SERT.•ATX for treatment of depression and ADHD may be more complex than current thinking.•The implications on the therapeutic mechanisms of ATX are discussed.

Since the advent in 2004, high-entropy alloys (HEAs) have been attracting a great deal of research interest worldwide. Being deemed as a major paradigmatic shift, the design of HEAs without base elements poses challenges to the existing thermodynamic models and theories that were long established for traditional alloys, one of which is related to the thermodynamic mechanisms for the formation of random solid solution in a concentrated multicomponent alloy. In this article, we discuss the design of HEAs from the perspective of correlated mixing (nonideal mixing of atoms with interatomic correlations). In a quantitative manner, we can show that the formation of a random solid solution in HEAs depends not only on the number of constituent elements but also on the alloy’s melting/processing temperature and on various interatomic correlations. Through the correlated mixing rule, we further demonstrate a strategy to screen out equiatomic alloys with the thermodynamic characteristics close to those of random solid solutions from an expanded library of 20 candidate elements.