Tomo-seq identifies NINJ1 as a potential target for anti-inflammatory strategy in thoracic aortic dissection.

BACKGROUND: Thoracic aortic dissection (TAD) is a life-threatening disease caused by an intimal tear in the aorta. The histological characteristics differ significantly between the tear area (TA) and the distant area. Previous studies have emphasized that certain specific genes tend to cluster at the TA. Obtaining a thorough understanding of the precise molecular signatures near the TA will assist in discovering therapeutic strategies for TAD. METHODS: We performed a paired comparison of the pathological patterns in the TA with that in the remote area (RA). We used Tomo-seq, genome-wide transcriptional profiling with spatial resolution, to obtain gene expression signatures spanning from the TA to the RA. Samples from multiple sporadic TAD patients and animal models were used to validate our findings. RESULTS: Pathological examination revealed that the TA of TAD exhibited more pronounced intimal hyperplasia, media degeneration, and inflammatory infiltration compared to the RA. The TA also had more apoptotic cells and CD31+α-SMA+ cells. Tomo-seq revealed four distinct gene expression patterns from the TA to the RA, which were inflammation, collagen catabolism, extracellular matrix remodeling, and cell stress, respectively. The spatial distribution of genes allowed us to identify genes that were potentially relevant with TAD. NINJ1 encoded the protein-mediated cytoplasmic membrane rupture, regulated tissue remodeling, showed high expression levels in the tear area, and co-expressed within the inflammatory pattern. The use of short hairpin RNA to reduce NINJ1 expression in the beta-aminopropionitrile-induced TAD model led to a significant decrease in TAD formation. Additionally, it resulted in reduced infiltration of inflammatory cells and a decrease in the number of CD31+α-SMA+ cells. The NINJ1-neutralizing antibody also demonstrated comparable therapeutic effects and can effectively impede the formation of TAD. CONCLUSIONS: Our study showed that Tomo-seq had the advantage of obtaining spatial expression information of TAD across the TA and the RA. We pointed out that NINJ1 may be involved in inflammation and tissue remodeling, which played an important role in the formation of TAD. NINJ1 may serve as a potential therapeutic target for TAD.

Unrevealing Temporal Mechanoluminescence Behaviors at High Frequency via Piezoelectric Actuation.

Mechanoluminescence (ML) materials present widespread applications. Empirically, modulation for a given ML material is achieved by application of programmed mechanical actuation with different amplitude, repetition velocity and frequency. However, to date modulation on the ML is very limited within several to a few hundred hertz low-frequency actuation range, due to the paucity of high-frequency mechanical excitation apparatus. The universality of temporal behavior and frequency response is an important aspect of ML phenomena, and serves as the impetus for much of its applications. Here, we push the study on ML into high-frequency range (∼250 kHz) by combining with piezoelectric actuators. Two representative ML ZnS:Mn and ZnS:Cu, Al phosphors were chosen as the research objects. Time-resolved ML of ZnS:Mn and ZnS:Cu, Al shows unrevealed frequency-dependent saturation and quenching, which is associated with the dynamic processes of traps. From the point of applications, this study sets the cut-off frequency for ML sensing. Moreover, by in-situ tuning the strain frequency, ZnS:Mn exhibits reversible frequency-induced broad red-shift into near-infrared range. These findings offer keen insight into the photophysics nature of ML and also broaden the physical modulation of ML by locally adjusting the excitation frequency.

Si-integrated lanthanide-doped ferroelectrics for a photomemory based on a photochromic reaction.

We describe a Si-integrated photochromic photomemory based on lanthanide-doped ferroelectric Na0.5Bi2.5Nb2O9:Er3+ (NBN:Er) thin films. We show that upconversion emission can be effectively modulated by up to 78% through the photochromic reaction. The coupling between lanthanide upconversion emission and the photochromic effect ensures rewritable and nondestructive readout characteristics. Moreover, integrating photochromic thin films with Si would benefit from its compatibility with the mature complementary metal-oxide semiconductor (CMOS) technique. These results demonstrate the opportunity to develop more compact photochromic photomemories and related photonic devices.

Mechanically induced enhancement and modulation of upconversion photoluminescence by bending lanthanide-doped perovskite oxides.

We report experimental studies of the bending strain impact on the upconversion processes in Yb3+, Er3+, and Mn2+ co-doped BaTiO3 (BTO) thin films with mica as the flexible substrate. Bending strain induces strong enhancement and modulation of the upconversion emission in doped BTO thin films. Because the unshielded 3d5 configuration of Mn2+ is more susceptible to crystal field changes, the introduction of an Mn2+ ion further promotes the strain-induced modulation effect. The upconversion intensity is amplified by six times at bending strain ε = 1.83% in BTO:Yb3+/Er3+/Mn2+ thin films. These results demonstrate the opportunity of rendering an upconversion emission through integrating lanthanide-doped ferroelectric films with flexible mica, especially by incorporating an Mn2+ ion.

Control of upconversion luminescence by tailoring energy migration in doped perovskite superlattices.

We describe an experimental investigation of photon upconversion (UC) in a series of perovskite BaTiO3/SrTiO3 superlattices doped with different lanthanide compositions. We show that UC emission can be effectively enhanced by precisely incorporating a set of lanthanide ions into separated layers rather than homogeneously distributing the dopant ions in the host lattice. The use of an inert layer in the superlattice can suppress deleterious energy cross-relaxation. Furthermore, UC emission can be rendered by controlling the energy migration mediated by the Yb-doped sublattice. These results demonstrate the opportunity to modulate energy migration and transfer processes through the rational design of superlattice structures.

Determination of Afatinib in Human Plasma by 2-Dimensional Liquid Chromatography.

INTRODUCTION: A simple, sensitive, rapid, and practical 2-dimensional liquid chromatography (2D-LC) method was developed and validated for the quantification of a 500-µL afatinib sample extracted from human plasma. METHODS: The plasma samples were pretreated with acetonitrile for protein precipitation. The mobile phase consisted of a first-dimensional mobile phase (acetonitrile, methanol, and 25 mmol/L ammonium phosphate in a ratio of 25:25:50, V/V/V) and a second-dimensional mobile phase (acetonitrile and 10 mmol/L ammonium phosphate in a ratio of 25:75, V/V). The average recovery of the plasma samples was stable and reproducible (98.56%-100.02%). RESULTS: The analyte was sufficiently stable for handling and analysis. The calibration curve was linear, ranging from 10.93 to 277.25 ng/mL with regression equation y = 804.60 x - 4,169.87 (R2 = 0.999). The relative standard deviations for accuracy and precision studies were within ±2.30% and <3.41%, respectively (intra- and interday). Finally, the validated method was successfully employed to determine the drug levels in plasma from the patients treated with afatinib. In clinical assessment, the patients with gastric cancer were orally administered with 30 or 40 mg per day of afatinib, which resulted in large plasma concentrations, ranging from 5.52 to 45.16 ng/mL. CONCLUSION: The results indicated that this method was useful for the therapeutic drug monitoring of afatinib and suitable for the assessment of the risks and benefits of chemotherapy in patients with non-small cell lung cancer.

A novel method for the quantification of anlotinib in human plasma using two-dimensional liquid chromatography.

A simple, efficient, and stable detection method of two-dimensional liquid chromatography (2D-LC) was established and validated to determine anlotinib in the human plasma. The 2D-LC system comprises a first-dimensional column (LC1), an intermediate transfer column, and a second-dimensional column (LC2). With simple protein precipitation treatment, the samples were processed directly for detection. The analysis cycle time was completed within 9.50 min. For the anlotinib concentrations, the calibration curve was linear over the 5.00-320.00 ng/mL range. The intra-day and inter-day precision ranges were 0.77-6.22% and 1.92-4.26%, respectively, for anlotinib concentrations. The recoveries were in the range of 97.85-102.50%. A total of 135 plasma samples from 94 patients were analyzed by our method. The plasma concentrations of patients were in the range of 5.17-106.38 ng/mL, in which the female had a higher plasma concentration (6.44-106.38 ng/mL). The simultaneous application of dexamethasone can increase the anlotinib concentration in the plasma. In our clinical application, we found that the factors that affect the plasma concentration include the time and dose of the medication, gender, and drug interactions. The method appears to be sensitive, precise, selective, and suitable for determining the concentration of anlotinib in the plasma sample.

A novel super thermal insulation material: bamboo-like polymer nanotubes.

One-dimensional nanomaterials have widely applied in the fields of energy conversion and storage due to their exceptional performance because of the nano-size effect. Herein, we synthesized bamboo-like polymer nanotubes based on cationic polymerization using immiscible initiator nanodroplets that results in a hollow structure. The suspended microelectrode is fabricated to measure the axial thermal conductivity of a single polymer nanotube, which demonstrates that this hollow structure can reduce its effective thermal conductivity. The experimental results show that its effective thermal conductivity is close to 0.03 W m-1 K-1, and decreases to 0.02 W m-1 K-1 with increasing temperature of the heating microelectrode, which may be due to the increasing lattice vibration and inelastic scattering between phonons. Its effective thermal conductivity is smaller than that of air, indicating that the synthetic method is an effective way to fabricate thermal insulating polymer nanotubes by significantly lowering the effective thermal conductivity. Hence, the method offers a new strategy in the fields of thermal insulation and protection.

Effects of glaucocalyxin A on human liver cancer cells as revealed by GC/MS- and LC/MS-based metabolic profiling.

Studies have documented the potential antitumor activities of glaucocalyxin A (GLA), an ent-kaurene diterpenoid isolated from Rabdosia japonica. However, the metabolic mechanism underlying the antitumor activity of GLA remains largely unknown. The effects of GLA on the metabolome of human liver cancer cells using GC/MS- and LC/MS-based metabolic profiling have been investigated. An untargeted metabolomics approach in conjunction with orthogonal projection to latent structures-discriminant analysis (OPLS-DA) has been developed to characterize the metabolic modifications induced by GLA treatment in human hepatoma cell line SMMC7721. Results demonstrated that cells cultured in the presence or absence of GLA displayed different metabolic profiles: the treatment induced an increased purine metabolism, pyrimidine metabolism, and sphingolipid metabolism and a decreased amino acid metabolism. At the same time, GLA treatment induced cell apoptosis and cell cycle arrested at G2/M phase in a dose-dependent manner. In addition, two representative apoptosis-inducing cytotoxic agents were selected as positive control drugs to validate the reasonableness and accuracy of our metabolomic investigation on GLA. The study displayed a systemic metabolic alteration induced by GLA treatment, showing the impaired physiological activity of SMMC7721 cells, which also indicated anti-proliferative and apoptotic effects of GLA. In the meantime, GC/MS- and LC/MS-based metabolomics applied to cell culture enhanced our current understanding of the metabolic response to GLA treatment and its mechanism; such an approach could be transferred to study the mechanism of other anticancer drugs. Graphical abstract A systemic metabolic alteration induced by glaucocalyxin A (GLA) treatment of SMMC-7721 cells.

Chemical constituents from the rhizome of Polygonum paleaceum and their antifungal activity.

A new compounds neopaleaceolactoside (1), along with nine known compounds phyllocoumarin (2), quercetin (3), quercitrin (4), quercetin-3-methyl ether (5), vincetoxicoside B (6), isoquercitrin (7), kaempferol (8), (-)-epicatechin (9), and chlorogenic acid (10), was isolated from Polygonum paleaceum Wall. Their chemical structures were established based on one-dimensional and two-dimensional nuclear magnetic resonance techniques, mass spectrometry and by comparison with spectroscopic data reported. Some selected compounds were screened for their antifungal activity. Quercetin (3), vincetoxicoside B (6), kaempferol (8), and (-)-epicatechin (9) showed synergistic antifungal activities with the FICI values <0.5. A preliminary structure-activity relationship could be observed that free 3-OH in the structure of flavonoids was important for synergistic antifungal activity.

Trachelogenin, a novel inhibitor of hepatitis C virus entry through CD81.

Although much progress has been made in antiviral agents against hepatitis C virus (HCV) in recent years, novel HCV inhibitors with improved efficacy, optimized treatment duration and more affordable prices are still urgently needed. Here, we report the identification of a natural plant-derived lignan, trachelogenin (TGN), as a potent entry inhibitor of HCV without genotype specificity, and with low cytotoxicity. TGN was extracted and purified from Caulis trachelospermi, a traditional Chinese herb with anti-inflammatory and analgesic effects. A crucial function of TGN was the inhibition of HCV entry during a post-binding step without affecting virus replication, translation, assembly and release. TGN blocked virus infection by interfering with the normal interactions between HCV glycoprotein E2 and the host entry factor CD81, which are key processes for valid virus entry. In addition, TGN diminished HCV cell-to-cell spread and exhibited additional synergistic effects when combined with IFN or telaprevir. In conclusion, this study highlights the effect of a novel HCV entry inhibitor, TGN, which has a target that differs from those of the current antiviral agents. Therefore, TGN is a potential candidate for future cocktail therapies to treat HCV-infected patients.

Constituents from the Roots of Actinidia chinensis and Their Cytochrome P450 Enzyme Inhibitory Activities.

A newly discovered triterpenoid, (2α,3ß)-2,3,23-trihydroxyurs-13(18)-en-28-oic acid (1), along with twelve known compounds (2 - 13), were isolated from the roots of Actinidia chinensis Planch (Actinidiaceae). Their chemical structures were determined by 1D- and 2D-NMR spectra and mass spectrometry (MS). The crude extracts and six main constituents (8 - 13) were tested for cytochrome P450 (CYPs) enzyme inhibitory activity. The results showed that, except for compound 8, compounds 9 - 13 had different inhibitory effects on the cytochrome P450 (CYPs) enzyme, and compound 9 significantly inhibited the catalytic activities of CYP3A4 to < 10% of its control activities.

[Chemical Constituents from Polygonum paleaceum].

Objective: To isolate and identify the chemical constituents from Polygonum paleaceum. Methods: Chemical constituents were isolated and purified by column chromatography on silica gel,Sephadex HL-20 and macroporous resin etc. The chemical structures were identified by MS,NMR and spectral analysis. Results: Ten compounds were isolated and their structures were elucidated as ethyl chlorogenate( 1),methyl chlorogenate( 2), kaempferol-3-O-α-L-rhamnopyranoside( 3), (-)-epicatechin( 4), paleaceolactoside( 5), protocatechuic acid( 6), kaempferol( 7), gallic acid( 8), chlorogenic acid( 9) and isoquercitrin( 10). Conclusion: Compounds 1,3,6,7 and 10 are isolated from this plant for the first time.

Symmetry in thermal cycles and processes.

Symmetry analysis is a cutting-edge research approach in physics, yet its application in macroscopic energy systems remains limited. This study demonstrates its potential to provide valuable insights for a deeper understanding and development of thermodynamic cycles. This article first studies the symmetry of the proposed C-P diagrams and finds rich symmetries including reflection symmetry, translation symmetry, and rotational symmetry within Carnot cycles. Then, it emphasizes that one can use symmetry alone to prove that the highest efficiency for any cycle operating in a certain temperature range is the Carnot efficiency, without relying on the entropy concept in the second law of thermodynamics. Lastly, it is found that this symmetry analysis framework can also be used for thermal cycles with phase transitions, as exemplified by applying in Rankine cycles. This research not only contributes groundbreaking insights into unraveling the symmetry inherent in thermodynamic cycles, but also promotes symmetry analysis to be an alternative analysis mean.

Derived energy storage systems from Brayton cycle.

Various energy storage systems (ESS) can be derived from the Brayton cycle, with the most representative being compressed air energy storage and pumped thermal electricity storage systems. Although some important studies on above ESS are reported, the topological structure behind those systems (i.e., derivations of the Brayton cycle) has not been studied, and the underlying thermodynamic ideas still need to be further explored. This paper first introduces the topological structure and the symmetry of ESS and their based Brayton cycles. The formation method of ESS based on paths and separation points is specified. It is found that round-trip path can form ESS directly. Then various ESS formed are compared. Finally, the synergistic effect and gain principle of thermal cycle and ESS are revealed. This work helps to reveal the intrinsic relationship between thermal cycles and ESS, understand the general laws behind ESS, and guide the combination of thermal cycles and ESS.

Negative Photoconductivity of Fe3GeTe2 Crystal with Native Heterostructure for Ultraviolet to Terahertz Ultra-Broadband Photodetection.

Gaining insight into the photoelectric behavior of ferromagnetic materials is significant for comprehensively grasping their intrinsic properties and broadening future application fields. Here, through a specially designed Fe3GeTe2/O-Fe3GeTe2 heterostructure, first, the broad-spectrum negative photoconductivity phenomenon of ferromagnetic nodal line semimetal Fe3GeTe2 is reported that covers UV-vis-infrared-terahertz bands (355 nm to 3000 µm), promising to compensate for the inadequacies of traditional optoelectronic devices. The significant suppression of photoexcitation conductivity is revealed to arise from the semimetal/oxidation (sMO) interface-assisted dual-response mechanism, in which the electron excitation origins from the semiconductor photoconductivity effect in high-energy photon region, and semimetal topological band-transition in low-energy photon region. High responsivities ranging from 103 to 100 mA W-1 are acquired within ultraviolet-terahertz bands under ±0.1 V bias voltage at room temperature. Notably, the responsivity of 2.572 A W-1 at 3000 µm (0.1 THz) and the low noise equivalent power of 26 pW Hz-1/2 surpass most state-of-the-art mainstream terahertz detectors. This research provides a new perspective for revealing the photoelectric conversion properties of Fe3GeTe2 crystal and paves the way for the development of spin-optoelectronic devices.

Distributed fiber strain and vibration sensor based on Brillouin optical time-domain reflectometry and polarization optical time-domain reflectometry.

A distributed fiber strain and vibration sensor which effectively combines Brillouin optical time-domain reflectometry and polarization optical time-domain reflectometry is proposed. Two reference beams with orthogonal polarization states are, respectively, used to perform the measurement. By using the signal obtained from either reference beam, the vibration of fiber can be measured from the polarization effect. After combining the signals obtained by both reference beams, the strain can be measured from the Brillouin effect. In the experiment, 10 m spatial resolution, 0.6 kHz frequency measurement range, 2.5 Hz frequency resolution, and 0.2 MHz uncertainty of Brillouin frequency measurement are realized for a 4 km sensing distance.

Business credit network characteristics and impact on green economy efficiency: Evidence from the Greater Bay Area around Hangzhou Bay of China.

In regions where the development of formal finance is relatively lagging behind, commercial credit has partially replaced the role of formal finance and facilitated the development of the private economy and even the country, thus making commercial credit an important entry point for understanding and promoting sustainable economic development. Taking the Hangzhou Bay Greater Bay Area as a case study, based on the City Business Credit Environment Index (CEI) from 2015 to 2019, we examine the characteristics of business credit networks using social network analysis and discuss the impact of business credit on urban green economy efficiency heterogeneity by drawing on spatial econometrics. The study confirms that the structure of business credit networks in the Hangzhou Bay Greater Bay Area tends to be dense, the network density and number of connections show growth, the spatial network structure is taking shape, and the strength of spatial connections among cities has increased. Hangzhou, Shaoxing, Jiaxing and Shanghai are at the centre of the network and play a radiation-driven role. The business credit network in the Hangzhou Bay Greater Bay Area is characterised by self-stability and has evolved from a multi-centre to a single centre. Business credit is negatively correlated with the efficiency of the green economy in the Hangzhou Bay Area, which is a departure from the Chinese "financial development paradox". In terms of heterogeneity, the relationship remains consistent for port cities and open coastal cities in general, while the effect is less pronounced for cities above sub-provincial level. The study concludes that, with the high-quality economic development of the Hangzhou Bay Greater Bay Area, the Chinese "financial development paradox" does not exist in the region at this stage, which also highlights the need to accelerate the construction of a Chinese-style modernisation theory and practice system.

Does the history of opening ports and trading influence the long-term business credit environment of cities? Evidence from the Yangtze River Delta region of China.

Based on the China City Commercial Credit Environment Index (CEI), a more scientific spatial DID model was used to examine the long-term impact of the opening of ports and trading in the late Qing Dynasty on the urban commercial credit environment, taking cities above the prefecture level in the Yangtze River Delta as a sample. The study confirms that: (1) the opening of ports and commerce in the late Qing Dynasty had a significant contribution to the urban commercial credit environment, which was conducive to the transformation of production methods and interpersonal relationships from traditional to modern, and to the improvement of the urban commercial credit environment. (2) Before the signing of the Treaty of Shimonoseki, the local forces of the late Qing Dynasty were resistant to the economic aggression of the Great Powers, and the positive impact of the opening of ports and trading on the commercial credit environment of port cities was more significant, but the impact was not obvious after the signing of the Treaty of Shimonoseki. (3) From the history of the opening of ports for trade in the late Qing Dynasty, the economic aggression of the Western powers against the non-patronage areas by means of the buying class objectively strengthened the concept of rule of law and credit awareness in the local market and exerted a long-term influence on the commercial credit environment of the cities, but the impact of the opening of ports for trade on the commercial credit environment of the patronage areas was not prominent. (4) Cities located in the sphere of influence of the common law powers had a more pronounced impact on the commercial credit environment as their institutions and concepts were more easily transplanted, while the impact of the opening of ports and trading on the commercial credit environment of cities in the sphere of influence of the civil law powers was not significant. Policy Insights: (1) Enhance the ability to negotiate with foreign countries on economic and trade matters from a level-headed world perspective, and be bold and adept at fighting unreasonable rules, standards and requirements in order to better optimise the business credit environment; (2) Regulate the use of administrative resources and avoid undue administrative intervention, which is an important prerequisite for improving the basic system of the market economy to enhance the business credit environment; (3) Emphasise both connotative development to follow a Chinese style modernisation path, and (3) emphasising selective cooperation to promote outward development, promoting the interaction, convergence and matching of domestic and foreign regulations, and continuously improving the regional commercial credit environment.

CircTFF1 Promotes Proliferation, Migration and Invasion of Lung Cancer Cells by Facilitating Methylation of BCL6B Promoter via miR-29c-3p/DNMT3A Axis.

Lung cancer exists as a major risk of cancer-related death worldwide. As a novel circular RNA (circRNA), circTFF1 has not been explored in lung cancer thoroughly. This study aims to probe into the function and mechanism of circTFF1 in lung cancer. RT-qPCR and western blot were used to detect expression of RNAs and proteins. The influence of circTFF1 and BCL6B on cells behavior was explored via CCK-8 assay, colony formation assay, wound healing assay and transwell assay. Methylation of BCL6B was detected via MSP assay. Bioinformatics analysis and mechanism assays were conducted for investigating the interaction among genes. CircTFF1 was found to be upregulated in lung cancer cell lines used in this study. Functional experiments revealed circTFF1 facilitated cell proliferation, migration and invasion. BCL6B was downregulated in lung cancer cell lines used in this study, and the downregulation of BCL6B was mainly mediated by methylation. Additionally, BCL6B exerted suppressive impacts on lung cancer cell line malignant behavior. Moreover, circTFF1 acted as the miR-29c-3p sponge to upregulate DNMT3A, which facilitated the methylation of BCL6B. In all, circTFF1 promoted proliferation, migration and invasion of lung cancer cell lines by facilitating methylation of BCL6B promoter via miR-29c-3p/DNMT3A axis.