Overview of the interplay between m6A methylation modification and non-coding RNA and their impact on tumor cells.

N6-methyladenosine (m6A) is one of the most common internal modifications in eukaryotic RNA. The presence of m6A on transcripts can affect a series of fundamental cellular processes, including mRNA splicing, nuclear transportation, stability, and translation. The m6A modification is introduced by m6A methyltransferases (writers), removed by demethylases (erasers), and recognized by m6A-binding proteins (readers). Current research has demonstrated that m6A methylation is involved in the regulation of malignant phenotypes in tumors by controlling the expression of cancer-related genes. Non-coding RNAs (ncRNAs) are a diverse group of RNA molecules that do not encode proteins and are widely present in the human genome. This group includes microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and PIWI interaction RNAs (piRNAs). They function as oncogenes or tumor suppressors through various mechanisms, regulating the initiation and progression of cancer. Previous studies on m6A primarily focused on coding RNAs, but recent discoveries have revealed the significant regulatory role of m6A in ncRNAs. Simultaneously, ncRNAs also exert their influence by modulating the stability, splicing, translation, and other biological processes of m6A-related enzymes. The interplay between m6A and ncRNAs collectively contributes to the occurrence and progression of malignant tumors in humans. This review provides an overview of the interactions between m6A regulatory factors and ncRNAs and their impact on tumors.

Low Gilbert damping and high perpendicular magnetic anisotropy in an Ir-coupled L10-FePd-based synthetic antiferromagnet.

Thin ferromagnetic films possessing perpendicular magnetic anisotropy derived from the crystal lattice can deliver the requisite magnetocrystalline anisotropy density for thermally stable magnetic memory and logic devices at the single-digit-nm lateral size. Here, we demonstrate that an epitaxial synthetic antiferromagnet can be formed from L10 FePd, a candidate material with large magnetocrystalline anisotropy energy, through insertion of an ultrathin Ir spacer. Tuning of the Ir spacer thickness leads to synthetic antiferromagnetically coupled FePd layers, with an interlayer exchange field upwards of 0.6 T combined with a perpendicular magnetic anisotropy energy of 0.95 MJ/m3 and a low Gilbert damping of 0.01. Temperature-dependent ferromagnetic resonance measurements show that the Gilbert damping is mostly insensitive to temperature over a range of 20 K up to 300 K. In FePd|Ir|FePd trilayers with lower interlayer exchange coupling, optic and acoustic dynamic ferromagnetic resonance modes are explored as a function of temperature. The ability to engineer low damping and large interlayer exchange coupling in FePd|Ir|FePd synthetic antiferromagnets with high perpendicular magnetic anisotropy could prove useful for high performance spintronic devices.

Impact of anesthesia on micromagnetic stimulation (µMS) of the vagus nerve.

To treat diseases associated with vagal nerve control of peripheral organs, it is necessary to selectively activate efferent and afferent fibers in the vagus. As a result of the nerve's complex anatomy, fiber-specific activation proves challenging. Spatially selective neuromodulation using micromagnetic stimulation(µMS) is showing incredible promise. This neuromodulation technique uses microcoils(µcoils) to generate magnetic fields by powering them with a time-varying current. Following the principles of Faraday's law of induction, a highly directional electric field is induced in the nerve from the magnetic field. In this study on rodent cervical vagus, a solenoidalµcoil was oriented at an angle to left and right branches of the nerve. The aim of this study was to measure changes in the mean arterial pressure (MAP) and heart rate (HR) followingµMS of the vagus. Theµcoils were powered by a single-cycle sinusoidal current varying in pulse widths(PW = 100, 500, and 1000µsec) at a frequency of 20 Hz. Under the influence of isoflurane,µMS of the left vagus at 1000µsec PW led to an average drop in MAP of 16.75 mmHg(n = 7). In contrast,µMS of the right vagus under isoflurane resulted in an average drop of 11.93 mmHg in the MAP(n = 7). Surprisingly, there were no changes in HR to either right or left vagalµMS suggesting the drop in MAP associated with vagusµMS was the result of stimulation of afferent, but not efferent fibers. In urethane anesthetized rats, no changes in either MAP or HR were observed uponµMS of the right or left vagus(n = 3). These findings suggest the choice of anesthesia plays a key role in determining the efficacy ofµMS on the vagal nerve. Absence of HR modulation uponµMS could offer alternative treatment options using VNS with fewer heart-related side-effects.

Controlling the helicity of light by electrical magnetization switching.

Controlling the intensity of emitted light and charge current is the basis of transferring and processing information1. By contrast, robust information storage and magnetic random-access memories are implemented using the spin of the carrier and the associated magnetization in ferromagnets2. The missing link between the respective disciplines of photonics, electronics and spintronics is to modulate the circular polarization of the emitted light, rather than its intensity, by electrically controlled magnetization. Here we demonstrate that this missing link is established at room temperature and zero applied magnetic field in light-emitting diodes2-7, through the transfer of angular momentum between photons, electrons and ferromagnets. With spin-orbit torque8-11, a charge current generates also a spin current to electrically switch the magnetization. This switching determines the spin orientation of injected carriers into semiconductors, in which the transfer of angular momentum from the electron spin to photon controls the circular polarization of the emitted light2. The spin-photon conversion with the nonvolatile control of magnetization opens paths to seamlessly integrate information transfer, processing and storage. Our results provide substantial advances towards electrically controlled ultrafast modulation of circular polarization and spin injection with magnetization dynamics for the next-generation information and communication technology12, including space-light data transfer. The same operating principle in scaled-down structures or using two-dimensional materials will enable transformative opportunities for quantum information processing with spin-controlled single-photon sources, as well as for implementing spin-dependent time-resolved spectroscopies.

Planar hyperbolic polaritons in 2D van der Waals materials.

Anisotropic planar polaritons - hybrid electromagnetic modes mediated by phonons, plasmons, or excitons - in biaxial two-dimensional (2D) van der Waals crystals have attracted significant attention due to their fundamental physics and potential nanophotonic applications. In this Perspective, we review the properties of planar hyperbolic polaritons and the variety of methods that can be used to experimentally tune them. We argue that such natural, planar hyperbolic media should be fairly common in biaxial and uniaxial 2D and 1D van der Waals crystals, and identify the untapped opportunities they could enable for functional (i.e. ferromagnetic, ferroelectric, and piezoelectric) polaritons. Lastly, we provide our perspectives on the technological applications of such planar hyperbolic polaritons.

Primary Surgery Followed by Selective Chemoradiotherapy Versus Preoperative Chemoradiotherapy Followed by Surgery for Locally Advanced Rectal Cancer: A Randomized Clinical Trial.

PURPOSE: The aim of this work was to determine whether locally advanced rectal cancer (LARC) with negative mesorectal fascia (MRF) predicted by magnetic resonance imaging (MRI) can be excluded from preoperative radiation therapy treatment. METHODS AND MATERIALS: This multicenter, open-label, non-inferiority, randomized clinical trial enrolled patients with LARC within 6 to 12 cm from the anal verge and with negative MRI-predicted MRF. Participants were randomized to the intervention group (primary surgery, in which the patients with positive pathologic [CRM] circumferential margins were subjected to chemoradiotherapy [CRT] and those with negative CRM underwent adjuvant chemotherapy according to pathologic staging) or the control group (preoperative CRT, in which all patients underwent subsequent surgery and adjuvant chemotherapy). The primary endpoint was 3-year disease-free survival (DFS). RESULTS: A total of 275 patients were randomly assigned to the intervention (n = 140) and control (n = 135) groups, in which 33.57% and 28.15% patients were at clinical T4 stage and 85.92% and 80.45% patients were at "bad" or "ugly" risk in the intervention and control groups, respectively. There were 2 patients (1.52%) and 1 patient (0.77%) with positive CRM in the intervention and control groups, respectively (P > .05). The non-adherence rates for the intervention and control groups were 3.6% and 23.7%, respectively. After a median follow-up of 34.6 months (IQR, 18.2-45.7), 43 patients had positive events (28 patients and 15 patients in the intervention and control groups, respectively). There were 6 patients (4.4%) with local recurrence in the intervention group and none in the control group, which led to the termination of the trial. The 3-year DFS rate was 81.82% in the intervention group (95% CI, 78.18%-85.46%) and 85.37% in the control group (95% CI, 81.75%-88.99%), with a difference of -3.55% (95% CI, -3.71% to -3.39%; hazard ratio, 1.76; 95% CI, 0.94-3.30). In the per-protocol data set, the difference between 3-year DFS rates was -5.44% (95% CI, -5.63% to -5.25%; hazard ratio, 2.02; 95% CI, 1.01-4.06). CONCLUSIONS: Based on the outcomes of this trial, in patients with LARC and MRI-negative MRF, primary surgery could negatively influence their DFS rates. Therefore, primary surgery was an inferior strategy compared with preoperative CRT followed by surgery and cannot be recommended for patients with LARC.

Magnetic Nanoparticles: A Review on Synthesis, Characterization, Functionalization, and Biomedical Applications.

Nowadays, magnetic nanoparticles (MNPs) are applied in numerous fields, especially in biomedical applications. Since biofluidic samples and biological tissues are nonmagnetic, negligible background signals can interfere with the magnetic signals from MNPs in magnetic biosensing and imaging applications. In addition, the MNPs can be remotely controlled by magnetic fields, which make it possible for magnetic separation and targeted drug delivery. Furthermore, due to the unique dynamic magnetizations of MNPs when subjected to alternating magnetic fields, MNPs are also proposed as a key tool in cancer treatment, an example is magnetic hyperthermia therapy. Due to their distinct surface chemistry, good biocompatibility, and inducible magnetic moments, the material and morphological structure design of MNPs has attracted enormous interest from a variety of scientific domains. Herein, a thorough review of the chemical synthesis strategies of MNPs, the methodologies to modify the MNPs surface for better biocompatibility, the physicochemical characterization techniques for MNPs, as well as some representative applications of MNPs in disease diagnosis and treatment are provided. Further portions of the review go into the diagnostic and therapeutic uses of composite MNPs with core/shell structures as well as a deeper analysis of MNP properties to learn about potential biomedical applications.

Metabolomics analysis to interpret changes in physiological and metabolic responses to chronic heat stress in Pekin ducks.

Heat stress (HS) is a major environmental threat that affects duck production in subtropical and tropical regions, especially in summer. This study aimed to evaluate the physiological and metabolic responses of Pekin ducks to chronic HS conditions via liquid chromatography-mass spectrometry (LC-MS) using a paired-fed (PF) experimental design. On the basis of equivalent feed intake (HS vs. PF), HS significantly reduced growth performance and the percentage of leg and breast muscles, however, markedly increased the percentage of abdominal fat and breast skin fat. Serum metabolomics results revealed that heat-stressed ducks showed enhanced glycolysis and pentose phosphate pathways, as demonstrated by higher glucose 6-phosphate and 6-phogluconic acid levels in the PF vs. HS comparison. HS decreased hepatic mRNA levels of mitochondrial fatty acid ß-oxidation-related genes (MCAD and SCAD) compared to the PF group, resulting in acetylcarnitine accumulation in serum. Moreover, HS elevated the concentrations of serum amino acids and mRNA levels of ubiquitination-related genes (MuRF1 and MAFbx) in the skeletal muscle and amino acid transporter-related genes (SLC1A1 and SLC7A1) and gluconeogenesis-related genes (PCK1 and PCase) in the liver compared to the PF group. When compared to the normal control group (NC), HS further decreased growth performance, but it elevated the abdominal fat rate. However, increased mRNA levels of ubiquitination-related genes and serum amino acid accumulation were not observed in the HS group compared to the NC group, implying that reduced feed intake masked the effect of HS on skeletal muscle breakdown and is a form of protection for the organism. These results suggest that chronic HS induces protein degradation in the skeletal muscle to provide amino acids for hepatic gluconeogenesis to provide sufficient energy, as Pekin ducks under HS conditions failed to efficiently oxidise fatty acids and ketones in the mitochondria, leading to poor growth performance and slaughter characteristics.

Production of AmpC ß-Lactamase and Development of a Competitive Array for Discriminative Determination of Cephalosporins in Milk.

In this study, AmpC ß-lactamase of Escherichia coli was expressed, and its intermolecular interaction mechanisms with 15 cephalosporins (CPs) were studied by using a molecular docking technique. Results showed that this enzyme mainly interacted with the ß-lactam ring of these CPs, and the key contacting amino acids were Ser80 and Ser228. The AmpC ß-lactamase was combined with 5 horseradish peroxidase-labeled conjugates to develop a direct competitive array on a microplate for determination of 15 drugs in milk. Due to the use of principal component analysis method to analyze the data, this method could discriminate the 15 drugs at the concentration as low as 10 ng/mL. The detection results for the unknown milk samples were consistent with those obtained by the liquid chromatography-mass spectrometry method. As a general comparison, this method is better than the previous antibody-based and receptor-based detection methods for CPs. This is the first paper reporting a competitive array for discriminative determination of a class of small-molecule substances.

Development of a Progesterone-Receptor-Based Pseudo-immunoassay for Multi-detection of Progestins in Milk and Studying Its Recognition Mechanism.

The residues of progestins in milk are dangerous to consumers, but an immunoassay capable of multi-determining progestins in milk has not been reported thus far. In this study, the ligand binding domain of the human progesterone receptor was expressed and its intermolecular interactions with the commonly used steroid hormones were studied. The docking results showed that the receptor fragment only recognized progestins and did not recognize other steroid hormones. Then, it was used as recognition material to develop a pseudo-direct competitive enzyme-linked immunosorbent assay for multi-determination of five progestins in milk. Because biotinylated horseradish peroxidase was combined with streptavidinated horseradish peroxidase to enhance the signal, the sensitivities for the five progestins (IC50 of 0.029-0.097 ng/mL) were improved 96-143-fold in comparison to the use of the conventional horseradish peroxidase signal system (IC50 of 3.0-12.5 ng/mL). This method showed negligible cross-reactivities to other steroid hormones, consistent with the docking results. This was the first paper developing a progesterone-receptor-based method for detection of progestins, and this method exhibited generally better performance than all of the previously reported immunoassays for progestins.

Development of a receptor based signal amplified fluorescence polarization assay for multi-detection of 35 sulfonamides in pork.

With the increasing focus on food security, a screening method with high-throughput, ultra-sensitivity, and user-friendly operation is urgently needed for monitoring of sulfonamides residues in animal-derived foods. In this study, the sulfonamides' receptor dihydropteroate synthase of Staphylococcus aureus was subjected to saturate mutation, and a mutant with higher affinities for sulfonamides was obtained. The mutant was then used as recognition material to establish a fluorescence polarization assay for determination of 35 sulfonamides in pork. Due to the use of an enhanced fluorescent tracer containing two fluorophore molecules, the sensitivities for the 35 sulfonamides were improved for 2.8-8.6 folds (LODs 0.03-1.16 ng/mL) in comparison with using conventional fluorescent tracer. The present method outperformed all previous fluorescence polarization (immuno)assays for sulfonamides due to its broader spectrum, higher sensitivity, and shorter assay time. Furthermore, this is the first study reporting an enhanced fluorescence polarization assay for determination of small molecule substance.

Determination of niclosamide and its two metabolites in fish by molecularly imprinted microsphere-based pseudo-ELISA.

Niclosamide is usually used for the treatment of parasite infections in animals. However, niclosamide and one of its metabolites 2-chloro-4-nitroaniline are mutagenic substances, and their residues in animal-derived foods are potential risks to consumers. As far as we know, there has been no immunoassay or pseudo immunoassay reported to determine niclosamide and its metabolites in animal-derived foods. In this study, a molecularly imprinted microsphere for niclosamide was first synthesized, and a streptavidin-horseradish peroxidase labelled conjugate was also synthesized. The two reagents were used to develop a pseudo enzyme-linked immunosorbent assay on conventional microplates for the determination of niclosamide and its two metabolites (2-chloro-4-nitroaniline and 5-chlorosalicylic acid) in fish. Because biotinylated horseradish peroxidase was used to amplify the signal, the method sensitivities for the three analytes were increased fivefold to 27.5-fold (limits of detection of 0.004-0.03 ng/mL) in comparison with the use of single horseradish peroxidase labelled conjugate (limits of detection of 0.11-0.16 ng/mL). Their recoveries from the standards fortified blank fish samples were in the range of 70.6-95.5%. This is the first study reporting a molecularly imprinted polymer-based pseudo immunoassay for screening of niclosamide and its metabolites in food sample.

Evolution of a natural TetR protein and development of a Fe3O4 assisted semi-homogeneous fluorescent method for determination of tetracyclines in milk.

Compared with antibody, the recognition spectrum of a receptor is broader, and its recognition ability can be improved using simple mutagenesis technique. Compared with conventional immunoassay, the magnetic bead based immunoassay is simpler and can be recycled. Compared with colorimetric and luminescent immunoassays, fluoroimmunoassay is simpler because it does not require a substrate. So a method combines these merits is desirable. In this study, two amino acids in the binding pocket of a natural Escherichia coli TetR protein were mutated to produce a mutant, and the molecular docking showed the binding energies and the numbers of contact acid for 10 tetracyclines all increased. The mutant was coupled with Fe3O4 to synthesize a magnetic complex, and a fluorescent tracer was synthesized by coupling quantum dot and minocycline with bovine serum albumin. Under the assistance of 96-well bottom magnet, a semi-homogeneous method based on the two materials was developed on conventional microplate for determination of the 10 tetracyclines in milk. Results showed once assay was finished within 20 min, the limits of detection (drug concentration showing 10% inhibition) for the 10 drugs were in the range of 0.32-0.94 ng/mL, and the magnetic complex could be regenerated for 6 times. Furthermore, the sensitivities were improved for 4-6 folds in comparison with the use of natural TetR. Therefore, this method is simple, sensitive, time-saving and recyclable, and it can be used for routine screening of the 10 tetracyclines in milk.

Room Temperature Spin-to-Charge Conversion in Amorphous Topological Insulating Gd-Alloyed BixSe1-x/CoFeB Bilayers.

Disordered topological insulator (TI) films have gained intense interest by benefiting from both the TI's exotic transport properties and the advantage of mass production by sputtering. Here, we report on the clear evidence of spin-charge conversion (SCC) in amorphous Gd-alloyed BixSe1-x (BSG)/CoFeB bilayers fabricated by sputtering, which could be related to the amorphous TI surface states. Two methods have been employed to study SCC in BSG (tBSG = 6-16 nm)/CoFeB(5 nm) bilayers with different BSG thicknesses. First, spin pumping is used to generate a spin current in CoFeB and detect SCC by the inverse Edelstein effect (IEE). The maximum SCC efficiency (SCE) is measured to be as large as 0.035 nm (IEE length λIEE) in a 6 nm thick BSG sample, which shows a strong decay when tBSG increases due to the increase of BSG surface roughness. The second method is THz time-domain spectroscopy, which reveals a small tBSG dependence of SCE, validating the occurrence of a pure interface state-related SCC. Furthermore, our angle-resolved photoemission spectroscopy data show dispersive two-dimensional surface states that cross the bulk gap until the Fermi level, strengthening the possibility of SCC due to the amorphous TI states. Our studies provide a new experimental direction toward the search for topological systems in amorphous solids.

Structural Anisotropy-Driven Atomic Mechanisms of Phase Transformations in the Pt-Sn System.

Using in situ atomic-resolution scanning transmission electron microscopy, atomic movements and rearrangements associated with diffusive solid to solid phase transformations in the Pt-Sn system are captured to reveal details of the underlying atomistic mechanisms that drive these transformations. In the PtSn4 to PtSn2 phase transformation, a periodic superlattice substructure and a unique intermediate structure precede the nucleation and growth of the PtSn2 phase. At the atomic level, all stages of the transformation are templated by the anisotropic crystal structure of the parent PtSn4 phase. In the case of the PtSn2 to Pt2Sn3 transformation, the anisotropy in the structure of product Pt2Sn3 dictates the path of transformation. Analysis of atomic configurations at the transformation front elucidates the diffusion pathways and lattice distortions required for these phase transformations. Comparison of multiple Pt-Sn phase transformations reveals the structural parameters governing solid to solid phase transformations in this technologically interesting intermetallic system.

Robust negative longitudinal magnetoresistance and spin-orbit torque in sputtered Pt3Sn and Pt3SnxFe1-x topological semimetal.

Contrary to topological insulators, topological semimetals possess a nontrivial chiral anomaly that leads to negative magnetoresistance and are hosts to both conductive bulk states and topological surface states with intriguing transport properties for spintronics. Here, we fabricate highly-ordered metallic Pt3Sn and Pt3SnxFe1-x thin films via sputtering technology. Systematic angular dependence (both in-plane and out-of-plane) study of magnetoresistance presents surprisingly robust quadratic and linear negative longitudinal magnetoresistance features for Pt3Sn and Pt3SnxFe1-x, respectively. We attribute the anomalous negative longitudinal magnetoresistance to the type-II Dirac semimetal phase (pristine Pt3Sn) and/or the formation of tunable Weyl semimetal phases through symmetry breaking processes, such as magnetic-atom doping, as confirmed by first-principles calculations. Furthermore, Pt3Sn and Pt3SnxFe1-x show the promising performance for facilitating the development of advanced spin-orbit torque devices. These results extend our understanding of chiral anomaly of topological semimetals and can pave the way for exploring novel topological materials for spintronic devices.

[Effect of Sparganii Rhizoma-Curcumae Rhizoma-medicated serum on proliferation, apoptosis, and migration of human ectopic endometrial stromal cells: based on JAK2/STAT3 signaling pathway].

Based on the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signaling pathway, this study investigated the effect of medicated serum of Sparganii Rhizoma(SR) and Curcumae Rhizoma(CR) on the proliferation, apoptosis, migration, and secretion of inflammatory factors of ectopic endometrial stromal cells(ESCs). Specifically, human ESCs were primary-cultured. The effect of different concentration(5%, 10%, 20%) of SR-, CR-, and SR-CR combination-medicated serum, and AG490 solution(50 µmol·L~(-1)) on the proliferation of ESCs was detected by methyl thiazolyl tetrazolium(MTT) assay, and the optimal dose was selected accordingly for further experiment. The cells were classified into normal serum(NS) group, SR group(10%), CR group(10%), combination(CM) group(10%), and AG490 group. The apoptosis level of ESCs was detected by flow cytometry, and the migration ability was examined by wound healing assay. The secretion of interleukin(IL)-1ß, IL-6, and tumor necrosis factor(TNF)-α was determined by enzyme-linked immunosorbent assay(ELISA). The protein levels of cysteinyl aspartate specific protei-nase-3(caspase-3), B-cell lymphoma(Bcl-2), and Bcl-2-associated X protein(Bax) and the levels of phosphorylated(p)-JAK2 and p-STAT3 were detected by Western blot. The results showed that the viability of ESCs cells was lowered in the administration groups compared with the blank serum group(P<0.01), especially the 10% drug-medicated serum, which was selected for further experiment. The 10% SR-medicated serum, 10% CR-medicated serum, and 10% CM-medicated serum could increase the apoptosis rate(P<0.01), up-regulate the protein expression of caspase-3 and Bax in cells(P<0.05 or P<0.01), down-regulate the expression of Bcl-2(P<0.01), decrease the cell migration rate(P<0.05 or P<0.01), and reduce the secretion levels of IL-1ß, IL-6, and TNF-α(P<0.05 or P<0.01), and levels of p-JAK2 and p-STAT3(P<0.05 or P<0.01). Compared with the SR and CR groups, CM group showed low cell viability(P<0.01), high protein expression of caspase-3 and Bax(P<0.05 or P<0.01), and low protein expression of Bcl-2 and p-JAK2(P<0.05). After incubation with CM, the apoptosis rate was higher(P<0.05) and the migration rate was lower(P<0.01) than that of the CR group. The p-STAT3 protein level of CM group was lower than that of the RS group(P<0.05). The mechanism of SR, CR, and the combination underlying the improvement of endometriosis may be that they blocked JAK2/STAT3 signaling pathway, inhibited ESC proliferation, promoted apoptosis, weakened cell migration, and reduced the secretion of inflammatory factors. The effect of the combination was better than that of RS alone and CR alone.