CYTOR-NFAT1 feedback loop regulates epithelial-mesenchymal transition of retinal pigment epithelial cells.

Epithelial mesenchymal transition (EMT) occurring in retinal pigment epithelial cells (RPE) is a crucial mechanism that contributes to the development of age-related macular degeneration (AMD), a pivotal factor leading to permanent vision impairment. Long non-coding RNAs (lncRNAs) have emerged as critical regulators orchestrating EMT in RPE cells. In this study, we explored the function of the lncRNA CYTOR (cytoskeleton regulator RNA) in EMT of RPE cells and its underlying mechanisms. Through weighted correlation network analysis, we identified CYTOR as an EMT-related lncRNA associated with AMD. Experimental validation revealed that CYTOR orchestrates TGF-ß1-induced EMT, as well as proliferation and migration of ARPE-19 cells. Further investigation demonstrated the involvement of CYTOR in regulating the WNT5A/NFAT1 pathway and NFAT1 intranuclear translocation in the ARPE-19 cell EMT model. Mechanistically, CHIP, EMSA and dual luciferase reporter assays confirmed NFAT1's direct binding to CYTOR's promoter, promoting transcription. Reciprocally, CYTOR overexpression promoted NFAT1 expression, while NFAT1 overexpression increased CYTOR transcription. These findings highlight a mutual promotion between CYTOR and NFAT1, forming a positive feedback loop that triggers the EMT phenotype in ARPE-19 cells. These discoveries provide valuable insights into the molecular mechanisms of EMT and its association with AMD, offering potential avenues for targeted therapies in EMT-related conditions, including AMD.

The role and mechanism of 5-HTDRN-BNST neural circuit in anxiety and fear lesions.

Central 5-hydroxytryptaminergic dorsal raphe nucleus (5-HTDRN)-bed nucleus of stria terminalis (BNST) neural circuit dysfunction is one of the important neurobiological basis of anxiety and fear disorders. Under stress, 5-hydroxytryptamine (5-HT) neurons act on BNST receptors to attenuate anxiety and fear responses or enhance anxiety and fear. In BNST, corticotropin releasing factor neurons play a role in regulating emotions by reversely regulating excitatory or inhibitory 5-HT neurons. The composition of 5-HTDRN-BNST neural circuit, the pathological changes of 5-HTDRN-BNST neural circuit function damage under stress, and the effects of 5-HTDRN-BNST neural circuit on anxiety disorder, panic disorder and post-traumatic stress disorder were analyzed and are summarized in this paper. The characteristics of functional changes of the neural circuit and its effects on brain functional activities provide a basis and ideas for the treatment of anxiety and fear disorders through the regulation of 5-HTDRN-BNST neural circuit, and they also provide a new perspective for understanding the pathological mechanism of such diseases.

Pharmacokinetics, pharmacodynamics, and safety of frunexian in healthy Chinese volunteer adults: A randomized dose-escalation phase I study.

The purpose of this study was to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of frunexian (formerly known as EP-7041 and HSK36273) injection, a small molecule inhibitor of activated coagulation factor XI (FXIa), in healthy Chinese adult volunteers. This study was a randomized, placebo- and positive-controlled, sequential, ascending-dose (0.3/0.6/1.0/1.5/2.25 mg/kg/h) study of 5-day continuous intravenous infusions of frunexian. Frunexian administration exhibited an acceptable safety profile with no bleeding events. Steady state was rapidly reached with a median time ranging from 1.02 to 1.50 h. The mean half-life ranged from 1.15 to 1.43 h. Frunexian plasma concentration at a steady state and area under the concentration-time curve exhibited dose-proportional increases. The dose-escalation study of frunexian demonstrated its progressively enhanced capacities to prolong activated partial thromboplastin time (aPTT) and inhibit FXIa activity. The correlations between PK and PD biomarkers (aPTT/baseline and FXI clotting activity/baseline) were described by the two Emax models, with the EC50 values of 8940 and 1300 ng/mL, respectively. Frunexian exhibits good safety and PK/PD properties, suggesting it is a promising candidate for anticoagulant drug.

Predictive Analysis of Linoleic Acid in Red Meat Employing Advanced Ensemble Models of Bayesian and CNN-Bi-LSTM Decision Layer Fusion Based Hyperspectral Imaging.

Rapid non-destructive testing technologies are effectively used to analyze and evaluate the linoleic acid content while processing fresh meat products. In current study, hyperspectral imaging (HSI) technology was combined with deep learning optimization algorithm to model and analyze the linoleic acid content in 252 mixed red meat samples. A comparative study was conducted by experimenting mixed sample data preprocessing methods and feature wavelength extraction methods depending on the distribution of linoleic acid content. Initially, convolutional neural network Bi-directional long short-term memory (CNN-Bi-LSTM) model was constructed to reduce the loss of the fully connected layer extracted feature information and optimize the prediction effect. In addition, the prediction process of overfitting phenomenon in the CNN-Bi-LSTM model was also targeted. The Bayesian-CNN-Bi-LSTM (Bayes-CNN-Bi-LSTM) model was proposed to improve the linoleic acid prediction in red meat through iterative optimization of Gaussian process acceleration function. Results showed that best preprocessing effect was achieved by using the detrending algorithm, while 11 feature wavelengths extracted by variable combination population analysis (VCPA) method effectively contained characteristic group information of linoleic acid. The Bi-directional LSTM (Bi-LSTM) model combined with the feature extraction data set of VCPA method predicted 0.860 Rp2 value of linoleic acid content in red meat. The CNN-Bi-LSTM model achieved an Rp2 of 0.889, and the optimized Bayes-CNN-Bi-LSTM model was constructed to achieve the best prediction with an Rp2 of 0.909. This study provided a reference for the rapid synchronous detection of mixed sample indicators, and a theoretical basis for the development of hyperspectral on-line detection equipment.

Dynamic changes in the water and volatile compounds of chicken breast during the frying process.

The influence of frying times (0, 2, 4, 6, 8, and 10 min) on the continuous changes in the water distribution and the concentrations of key volatile compounds in chicken breast during the frying process were studied. The fried chicken samples could be distinguished by PCA of E-nose and PLS-DA of GC-MS. A total of 40 volatile compounds were identified by GC-MS, and 28 compounds were verified to be the key compounds after further screening by OAVs. The T22 was increased first and then decreased, while the M22 and M23 in fried chicken were considerably decreased and increased with increasing frying time, respectively. The content of the water and the total peak area of LF-NMR in fried chicken samples during the frying process significantly decreased, and the water was transferred from high to low degrees of freedom. In addition, water content, T21, T22, M22 and L* value were positively correlated with most alcohols and aldehydes, and were negatively correlated with pyrazines, while a*, b*, M23 and all amino acids were positively correlated with pyrazines and were negatively correlated with most alcohols and aldehydes. The results may guide the production processes of fried chicken and help produce high-quality chicken products.

BatmanNet: bi-branch masked graph transformer autoencoder for molecular representation.

Although substantial efforts have been made using graph neural networks (GNNs) for artificial intelligence (AI)-driven drug discovery, effective molecular representation learning remains an open challenge, especially in the case of insufficient labeled molecules. Recent studies suggest that big GNN models pre-trained by self-supervised learning on unlabeled datasets enable better transfer performance in downstream molecular property prediction tasks. However, the approaches in these studies require multiple complex self-supervised tasks and large-scale datasets , which are time-consuming, computationally expensive and difficult to pre-train end-to-end. Here, we design a simple yet effective self-supervised strategy to simultaneously learn local and global information about molecules, and further propose a novel bi-branch masked graph transformer autoencoder (BatmanNet) to learn molecular representations. BatmanNet features two tailored complementary and asymmetric graph autoencoders to reconstruct the missing nodes and edges, respectively, from a masked molecular graph. With this design, BatmanNet can effectively capture the underlying structure and semantic information of molecules, thus improving the performance of molecular representation. BatmanNet achieves state-of-the-art results for multiple drug discovery tasks, including molecular properties prediction, drug-drug interaction and drug-target interaction, on 13 benchmark datasets, demonstrating its great potential and superiority in molecular representation learning.

Dynamic changes in the water distribution and key aroma compounds of roasted chicken during roasting.

The effects of roasting times (0, 2, 4, 6, 8, 10, 12, and 14 min) on the dynamic changes of the water distribution and key aroma compounds in roasted chicken during the electric roasting process were studied. In total, 36 volatile compounds were further determined by GC-MS and 11 compounds, including 1-octen-3-ol, 1-heptanol, hexanal, decanal, (E)-2-octenal, acetic acid hexyl ester, nonanal, 2-pentylfuran, heptanal, (E, E)-2,4-decadienal and octanal, were confirmed as key aroma compounds. The relaxation time of T22 and T23 was increased first and then decreased, while the M22 and M23 in roasted chicken were decreased and increased with increasing roasting time, respectively. The fluidity of the water in the chicken during the roasting process was decreased, and the water with a high degree of freedom migrated to the water with a low degree of freedom. In addition, the L*, a*, b*, M23 and all amino acids were positively correlated with all the key aroma compounds, while T22, M22 and moisture content were negatively correlated with all the key aroma compounds.

Overcoming Intensity Saturation in Nonlinear Multiple-Quantum-Well Metasurfaces for High-Efficiency Frequency Upconversion.

Engineered intersubband transitions in semiconductor heterostructures featuring multiple quantum wells (MQWs) are shown to support record-high second-order nonlinear susceptibilities. By integrating these materials in metasurfaces with tailored optical resonances, it is possible to further enhance photonic interactions, yielding giant nonlinear responses in ultrathin devices. These metasurfaces form a promising platform for efficient nonlinear processes, including frequency upconversion of low-intensity thermal infrared radiation and harmonic generation, free of phase-matching constraints intrinsic to bulk nonlinear crystals. However, nonlinear saturation at moderately large pump intensities due to the transfer of electron population into excited subbands facilitated by strongly enhanced light-matter interactions in metasurfaces fundamentally limits their overall efficiency for various nonlinear processes. Here, the saturation limits of nonlinear MQW-based metasurfaces for mid-infrared frequency upconversion are significantly extended by optimizing their designs for excitation with a strong pump coherently coupled with unpopulated upper electron subbands. This counterintuitive pumping scheme, combined with tailored material and photonic engineering of the metasurface, avoids saturation at practical levels of continuous-wave pump intensities, yielding significantly larger upconversion efficiencies than in conventional approaches. The present results open new opportunities for nonlinear metasurfaces, less limited by saturation mechanisms, with important implications for night-vision imaging and compact nonlinear wave mixing systems.

Evaluation of key aroma compounds and protein secondary structure in the roasted Tan mutton during the traditional charcoal process.

The traditional charcoal technique was used to determine the changes in the key aroma compounds of Tan mutton during the roasting process. The results showed that the samples at the different roasting time were distinguished using GC-MS in combination with PLS-DA. A total of 26 volatile compounds were identified, among which 14 compounds, including (E)-2-octenal, 1-heptanol, hexanal, 1-hexanol, heptanal, 1-octen-3-ol, 1-pentanol, (E)-2-nonenal, octanal, 2-undecenal, nonanal, pentanal, 2-pentylfuran and 2-methypyrazine, were confirmed as key aroma compounds through the odor activity values (OAV) and aroma recombination experiments. The OAV and contribution rate of the 14 key aroma compounds were maintained at high levels, and nonanal had the highest OAV (322.34) and contribution rate (27.74%) in the samples after roasting for 10 min. The content of α-helix significantly decreased (P < 0.05), while the ß-sheet content significantly increased (P < 0.05) during the roasting process. The content of random coils significantly increased in the samples roasted for 0-8 min (P < 0.05), and then no obvious change was observed. At the same time, ß-turn content had no obvious change. Correlation analysis showed that the 14 key aroma compounds were all positively correlated with the content of α-helix and negatively correlated with the contents of ß-sheet and random coil, and also positively correlated with the content of ß-turn, except hexanal and 2-methypyrazine. The results are helpful to promoting the industrialization of roasted Tan mutton.

Water distribution and key aroma compounds in the process of beef roasting.

The key aroma compounds and water distribution of the beef at different roasting times (0, 3, 6, 9, 12, 15, and 18 min) were identified and analyzed. The results showed that the L * value increased considerably before peaking and then decreased. On average, a * values decreased significantly first and then kept stable, while b * values increased first and then decreased. A total of 47 odorants were identified in all samples, including 14 alcohols, 18 aldehydes, 6 ketones, 1 ester, 3 acids, 4 heterocyclic compounds, and 1 other compound. Among them, 11 key aroma compounds were selected and aldehydes and alcohols predominantly contributed to the key aroma compounds. The fluidity of the water in the beef during the roasting process was decreased, and the water with a high degree of freedom migrated to the water with a low degree of freedom. The correlation analysis showed that water content and L * were negatively correlated with key aroma compounds of the samples, while M 21 was positively correlated with key aroma compounds.

Stabilization of Extra-Large-Pore Zeolite by Boron Substitution for the Production of Commercially Applicable Catalysts.

Stable extra-large-pore zeolites are desirable for industrial purposes due to their ability to accommodate bulky reactants and diffusion through channels. Although there are several extra-large pore zeolites reported, stable ones are rare. Thus, their stabilization is a feasible strategy for industrial applications. Here, an extra-large-pore zeolite EWT with boron substitution is presented, and the resulting zeolite B-RZM-3 increased the thermal stability from 600 °C in its silica form to 850 °C. The crystal structure, determined by combining continuous rotation electron diffraction (cRED) and powder X-ray diffraction (PXRD), shows that B atoms preferentially substitute the interrupted (HO)T(OT)3 (Q3 ) sites and are partially converted into 3-coordination to relax framework deformation upon heating. After Al-reinsertion post-treatment, Al-B-RZM-3 shows higher ethylbenzene selectivity and ethylene conversion rate per mol acid site than commercial ZSM-5 and Beta zeolite in benzene alkylation reaction. Synthesizing extra-large-pore zeolite in borosilicate form is a potential approach to stabilize interrupted zeolites for commercial applications.

Synthesis of [B,Al]-EWT-Type Zeolite and Its Catalytic Properties.

EWT zeolite belongs to ultra-large pore zeolite with the 10MR and 21MR channels, which has good thermal stability, certain acid strength and good application prospects in petroleum refining and petrochemical reactions. However, EWT zeolite has fewer medium/strong acid sites, especially Brönsted acid sites, which makes it difficult to apply to acid-catalyzed reactions. The regulation of acid amount and distribution was achieved by boron and aluminum substitution into the siliceous framework of EWT. The physico-chemical properties of the samples were characterized by XRD, SEM, N2 adsorption-desorption, XRF, ICP, Py-IR, NH3-TPD and 11B & 27Al & 29Si MAS NMR. The results show that quantities of boron and aluminum elements can occupy the framework of [B,Al]-EWT to increase the density of medium and strong acid centers, with more acidity and Brönsted acid centers than EWT zeolite. In the reaction of glycerol with cyclohexanone, the conversion of the sample (U-90-08-10/U-90-H-HCl) is significantly higher than that of the EWT sample, approaching or exceeding the Beta zeolite. A catalytic activity study revealed a direct correlation between the Brönsted acidic site concentration and the activity of the catalyst. The U-90-08-10-H catalyst was also considerably stable in the catalytic process. This work shows, for the first time, that extra-large pore zeolites can be used in industrial acid-catalytic conversion processes with excellent catalytic performance.

High freezing rate improves flavor fidelity effect of hand grab mutton after short-term frozen storage.

Taking the eutectic point as the final freezing temperature, the differences of flavor substances of in hand grab mutton (HGM) frozen at three rates of 0. 26 cm/h (-18°C), 0.56 cm/h (-40°C) and 2.00 cm/h (-80°C) were determined and analyzed. The results showed that the flavor of HGM decreased significantly after freezing. With the increase of freezing rate, the contents of aldehydes, alcohols, ketones, acids, esters, others, free amino acids and 5'-nucleotides were higher, and the content of specific substances was also generally increased. All samples from unfrozen and frozen HGM could be divided into four groups using an electronic nose based on different flavor characteristics. Seven common key aroma components were determined by relative odor activity value (ROAV), including hexanal, heptanal, octanal, nonanal, (E)-oct-2-enal, (2E,4E)-deca-2,4-dienal and oct-1-en-3-ol. The higher the freezing rate, the greater the ROAVs. Taste activity values calculated by all taste substances were far <1, and the direct contribution of the substances to the taste of HGM was not significant. The equivalent umami concentration of HGM frozen at -80°C was the highest. These findings indicated that higher freezing rate was more conducive to the retention of flavor substances in HGM, and the flavor fidelity effect of freezing at -80°C was particularly remarkable.

Formation of volatile flavor compounds, maillard reaction products and potentially hazard substance in China stir-frying beef sao zi.

The effects of stir-frying stages on the formation of flavor volatile compounds, Maillard reaction products (MRPs) and potentially hazardous substances with time in stir-fried beef sao zi were investigated. A total of 122 volatile compounds were identified in beef sao zi after stir-frying. Most of the volatile compounds were produced in the stir-frying fat (SFF) process of beef sao zi. Furosine, fluorescence intensity, Nε-(1-Carboxymethyl)-L-lysine (CML), Nε-(1-Carboxyethyl)-L-lysine (CEL) polyaromatic hydrocarbons (PAHs), heterocyclic aromatic amines (HAAs) and acrylamides (AA) are mainly presented in stir-fried beef sao zi. The furosine peaked at MSF 120 s as the Maillard reaction progressed. The fluorescent compound gradually increased with time during the stir-frying process. The CML and CEL peaked at MSF 120 s. AA reached its maximum in MSF 90 s and then decreased. The quantities and content of HAAs and PAHs were increased by prolonging the stir-frying time, but ended up far lower than the maximum permissible value specified by the Commission of the European Communities. The extended stir-frying promoted MRPs and some hazardous substances, but the content of potentially hazardous substances was still within the safety range for stir-frying beef sao zi.

Effect of Traditional Stir-Frying on the Characteristics and Quality of Mutton Sao Zi.

The effects of stir-frying stage and time on the formation of Maillard reaction products (MRP) and potentially hazardous substances with time in stir-fried mutton sao zi were investigated. Furosine, fluorescence intensity, Nε-(1-carboxymethyl)-L-lysine (CML), Nε-(1-carboxyethyl)-L-lysine (CEL), polyaromatic hydrocarbons PAHs), heterocyclic aromatic amines (HAAs), and acrylamides (AA) mainly presented were of stir-fried mutton sao zi. The furosine decreased after mixed stir-frying (MSF) 160 s due to its degradation as the Maillard reaction (MR) progressed. The fluorescent compound gradually increased with time during the stir-frying process. The CML and CEL peaked in MSF at 200 s. AA reached its maximum at MSF 120 s and then decreased. All the 5 HAAs were detected after MSF 200 s, suggesting that stir-frying mutton sao zi was at its best before MSF for 200 s. When stir-frying exceeded the optimal processing time of (MSF 160 s) 200 s, the benzo[a]pyrene peaked at 0.82 µg/kg, far lower than the maximum permissible value specified by the Commission of the European Communities. Extended stir-frying promoted MRP and some hazardous substances, but the content of potentially hazardous substances was still within the safety range for food.

Characterization of flavor volatile compounds in industrial stir-frying mutton sao zi by GC-MS, E-nose, and physicochemical analysis.

This study aims to investigate the flavor changes of industrial stir-frying mutton sao zi, a mutton product popular in the northwest of China, at different stir-frying stages. Electronic nose (E-nose) was used to recognize mutton sao zi odors at different processing time points, and the individual volatile compounds were further identified by the solid-phase microextraction (SPME) combined with gas chromatography-mass spectrometry (GC-MS). A total of 105 volatile compounds were detected by GC-MS, of which 51 were major volatile compounds. Additionally, GC-MS and E-nose data of the samples were also correlated with the fatty acids, crude composition (moisture, fat, protein), and amino acids. The stir-frying time and temperature may be the critical contributors to different flavors of industrial stir-frying mutton sao zi. The signal intensities of W1S, W1W, W2S, W2W, and W3S sensors positively correlate with protein, fat, and 18 amino acids, but negatively with SFA and moisture. Hence, this study explored the flavor changes of industrial stir-frying mutton sao zi by E-nose and SPME-GC-MS for the first time, providing an insight into the industrial production and flavor control stir-frying machine of stir-frying mutton products with household flavor.

Effect of H2SiF6 modification of IM-5 on catalytic performance in benzene alkylation with ethylene.

Ethylbenzene (EB) is an important bulk chemical intermediate. The vapor-phase process is considered to be more efficient than the liquid-phase process when using dilute ethylene (e.g. FCC or DCC off-gas) as the feed due to its high ethylene space velocity. However, realizing a balance between reducing the xylene formation and enhancing the EB selectivity is still a challenge due to the poor performance of ZSM-5 at low reaction temperature. This study concerns an IM-5 zeolite (IMF topology) modified by H2SiF6, with 89% ethylbenzene selectivity, 98.6% total EB + DEB selectivity and only 540 ppm of xylene at 330 °C. IM-5 zeolites with different Si/Al2 ratios (40-170) were prepared by H2SiF6 modification and their catalytic performance in vapor phase alkylation of benzene with ethylene was investigated. There was an obvious decrease in the acid sites and acid strength of IM-5 in the H2SiF6 treatment process, which led to a slight decrease in ethylbenzene selectivity and a significant decline in xylene yield. Under the conditions of complete ethylene conversion, the selectivity to EB + DEB increased from 96.1% to 98.6% in the parent I-40 and modified IM-5. Compared with ZSM-5 that has a similar acidity, the slightly bigger channel opening makes IM-5 more conductive to the formation and diffusion of DEB while xylene may present adverse effects. The 120 hour-lifetime test showed that IM-5 (I-110) has superior activity, equivalent stability, higher DEB selectivity and a much lower xylene selectivity in comparison with ZSM-5. The catalytic performance of the IM-5 zeolite in the vapor phase process provides a new choice for the production of ethylbenzene.

Frequency combs induced by phase turbulence.

Wave instability-the process that gives rise to turbulence in hydrodynamics1-represents the mechanism by which a small disturbance in a wave grows in amplitude owing to nonlinear interactions. In photonics, wave instabilities result in modulated light waveforms that can become periodic in the presence of coherent locking mechanisms. These periodic optical waveforms are known as optical frequency combs2-4. In ring microresonator combs5,6, an injected monochromatic wave becomes destabilized by the interplay between the resonator dispersion and the Kerr nonlinearity of the constituent crystal. By contrast, in ring lasers instabilities are considered to occur only under extreme pumping conditions7,8. Here we show that, despite this notion, semiconductor ring lasers with ultrafast gain recovery9,10 can enter frequency comb regimes at low pumping levels owing to phase turbulence11-an instability known to occur in hydrodynamics, superconductors and Bose-Einstein condensates. This instability arises from the phase-amplitude coupling of the laser field provided by linewidth enhancement12, which produces the needed interplay of dispersive and nonlinear effects. We formulate the instability condition in the framework of the Ginzburg-Landau formalism11. The localized structures that we observe share several properties with dissipative Kerr solitons, providing a first step towards connecting semiconductor ring lasers and microresonator frequency combs13.

Retraction Note: Diagnostic and prognostic value of plasma microRNA-195 in patients with non-small cell lung cancer.

This article [1] is retracted at the request of Editor-in-Chief due to overlap with articles [2-5].None of the authors have responded to any correspondence from the editor or publisher about this retraction.

Frequency-Modulated Combs Obey a Variational Principle.

Laser dynamics encompasses universal phenomena that can be encountered in many areas of physics, such as bifurcation and chaos, mode competition, resonant nonlinearities, and synchronization-or locking-of oscillators. When a locking process occurs in a multimode laser, an optical frequency comb is produced, which is an optical spectrum consisting of equidistant modes with a fixed phase relationship. Describing the formation of self-starting frequency combs in terms of fundamental laser equations governing the field inside the cavity does not allow one, in general, to grasp how the laser synchronizes its modes. Our finding is that, in a particular class of lasers where the output is frequency modulated with small or negligible intensity modulation, a greatly simplified description of self-locking exists. We show that in quantum cascade lasers-solid-state representatives of these lasers characterized by an ultrashort carrier relaxation time-the frequency comb formation obeys a simple variational principle, which was postulated over 50 years ago and relies on the maximization of the laser output power. The conditions for the breakdown of this principle are also experimentally identified, shedding light on the behavior of many different types of lasers, such as dye, diode, and other cascade lasers. This discovery reveals that the formation of frequency-modulated combs is an elegant example of an optimization problem solved by a physical system.