Analysis and Identification of Ferroptosis-Related Gene Signature for Acute Lung Injury.

BACKGROUND: Recent studies have shown that ferroptosis is involved in the evolution of acute lung injury (ALI), a serious respiratory pathological process leading to death. However, the regulatory mechanisms underlying ferroptosis in ALI remain largely unknown. The current study analyzed and identified a ferroptosis-related gene signature for ALI. METHODS: Key genes associated with ferroptosis in ALI were identified by bioinformatics analysis. GSE104214, GSE18341, and GSE17355 datasets were downloaded from the Gene Expression Omnibus database. The signature genes were screened by least absolute shrinkage and selection operator (LASSO) regression, and the key genes of ALI were screened by weighted correlation network analysis (WGCNA), followed by immune infiltration analysis and functional enrichment analysis. In addition, mRNA expression of key genes in the lungs of mice with hemorrhagic shock and sepsis was verified. RESULTS: A total of 2132 differential genes were identified by various analyses, and nine characteristic genes were detected using Lasso regression. We intersected nine signature genes with WGCNA module genes and finally determined four key genes (PROK2, IL6, TNF, SLC7A11). All four key genes were closely correlated with immune cells and regulatory genes of ALI, and the expression of the four genes was significantly different in the lung tissues of hemorrhagic shock and sepsis models. Besides, the ferroptosis related molecules GPX4 and ACSL4 showed remarkable difference in these models. CONCLUSION: These results indicate that PROK2, IL6, TNF, SLC7A11 may be key regulatory targets of ferroptosis during ALI. This study proved that ferroptosis is a common pathophysiological process in three ALI models.

Fluorination Enables Dual Ferroelectricity in Both Solid- and Liquid-Crystal Phases.

Ferroelectric materials are a special type of polar substances, including solids or liquid crystals. However, obtaining a material to be ferroelectric in both its solid crystal (SC) and liquid crystal (LC) phases is a great challenge. Moreover, although cholesteric LCs inherently possess the advantage of high fluidity, their ferroelectricity remains unknown. Here, through the reasonable H/F substitution on the fourth position of the phenyl group of the parent nonferroelectric dihydrocholesteryl benzoate, we designed ferroelectric dihydrocholesteryl 4-fluorobenzoate (4-F-BDC), which shows ferroelectricity in both SC and cholesteric LC phases. The fluorination induces a lower symmetric polar P1 space group and a new solid-to-solid phase transition in 4-F-BDC. Beneficial from fluorination, the SC and cholesteric LC phases of 4-F-BDC show clear ferroelectricity, as confirmed by well-shaped polarization-voltage hysteresis loops. The dual ferroelectricity in both SC and cholesteric LC phases of a single material was rarely found. This work offers a viable case for the exploration of the interplay between ferroelectric SC and LC phases and provides an efficient approach for designing ferroelectrics with dual ferroelectricity and cholesteric ferroelectric liquid crystals.

Solid-Liquid Crystal Biphasic Ferroelectrics with Tunable Biferroelectricity.

Ferroelectricity has been separately found in numerous solid and liquid crystal materials since its first discovery in 1920. However, a single material with biferroelectricity existing in both solid and liquid crystal phases is very rare, and the regulation of biferroelectricity has never been studied. Here, solid-liquid crystal biphasic ferroelectrics, cholestanyl 4-X-benzoate (4X-CB, X = Cl, Br, and I), which exhibits biferroelectricity in both the solid and liquid crystal phases, is presented. It is noted that the ferroelectric liquid crystal phase of 4X-CB is a cholesteric one, distinct from the ordinary chiral smectic ferroelectric liquid crystal phase. Moreover, 4X-CB shows solid-solid and solid-liquid crystal phase transitions, of which the transition temperatures gradually increase from Cl to Br to I substitution. The spontaneous polarization (Ps ) of 4X-CB in both solid and liquid crystal phases can also be regulated by different halogen substitutions, where the 4Br-CB has the optimal Ps because of the larger molecular dipole moment. To the authors' knowledge, 4X-CB is the first ferroelectric with tunable biferroelectricity, which offers a feasible case for the performance optimization of solid-liquid crystal biphasic ferroelectrics.

ESTROGEN ALLEVIATES POSTHEMORRHAGIC SHOCK MESENTERIC LYMPH-MEDIATED LUNG INJURY THROUGH AUTOPHAGY INHIBITION.

ABSTRACT: Background: Hemorrhagic shock-induced acute lung injury (ALI) is commonly associated with the posthemorrhagic shock mesenteric lymph (PHSML) return. Whether excessive autophagy is involved in PHSML-mediated ALI remains unclear. The relationship between estrogen treatment and PHSML or autophagy needs to verify. The current study will clarify the role of estrogen in reducing PHSML-mediated ALI through inhibition of autophagy. Methods: First, a hemorrhagic shock model in conscious rats was used to observe the effects of 17ß-estradiol (E2) on intestinal blood flow, pulmonary function, intestinal and pulmonary morphology, and expression of autophagy marker proteins. Meanwhile, the effect of PHSML and autophagy agonist during E2 treatment was also investigated. Secondly, rat primary pulmonary microvascular endothelial cells were used to observe the effect of PHSML, PHSML plus E2, and E2-PHSML (PHSML obtained from rats treated by E2) on the cell viability. Results: Hemorrhagic shock induced intestinal and pulmonary tissue damage and increased wet/dry ratio, reduced intestinal blood flow, along with pulmonary dysfunction characterized by increased functional residual capacity and lung resistance and decreased inspiratory capacity and peak expiratory flow. Hemorrhagic shock also enhanced the autophagy levels in intestinal and pulmonary tissue, which was characterized by increased expressions of LC3 II/I and Beclin-1 and decreased expression of p62. E2 treatment significantly attenuated these adverse changes after hemorrhagic shock, which was reversed by PHSML or rapamycin administration. Importantly, PHSML incubation decreased the viability of pulmonary microvascular endothelial cells, while E2 coincubation or E2-treated lymph counteracted the adverse roles of PHSML. Conclusions: The role of estrogen reducing PHSML-mediated ALI is associated with the inhibition of autophagy.

Biferroelectricity of a homochiral organic molecule in both solid crystal and liquid crystal phases.

Ferroelectricity, existing in either solid crystals or liquid crystals, gained widespread attention from science and industry for over a century. However, ferroelectricity has never been observed in both solid and liquid crystal phases of a material simultaneously. Inorganic ferroelectrics that dominate the market do not have liquid crystal phases because of their completely rigid structure caused by intrinsic chemical bonds. We report a ferroelectric homochiral cholesterol derivative, ß-sitosteryl 4-iodocinnamate, where both solid and liquid crystal phases can exhibit the behavior of polarization switching as determined by polarization-voltage hysteresis loops and piezoresponse force microscopy measurements. The unique long molecular chain, sterol structure, and homochirality of ß-sitosteryl 4-iodocinnamate molecules enable the formation of polar crystal structures with point group 2 in solid crystal phases, and promote the layered and helical structure in the liquid crystal phase with vertical polarization. Our findings demonstrate a compound that can show the biferroelectricity in both solid and liquid crystal phases, which would inspire further exploration of the interplay between solid and liquid crystal ferroelectric phases.

Highest-T c single-component homochiral organic ferroelectrics.

Organic single-component ferroelectrics with low molecular mass have drawn great attention for application in organic electronics. However, the discovery of high-T c single-component organic ferroelectrics has been very scarce. Herein, we report a pair of homochiral single-component organic ferroelectrics (R)-10-camphorsulfonylimine and (S)-10-camphorsulfonylimine under the guidance of ferroelectric chiral chemistry. They crystallize in the chiral-polar space group P21, and their mirror image relations have been identified using vibrational circular dichroism spectra. They both exhibit 422F2 multiaxial ferroelectricity with T c as high as 429 K. Besides, they possess superior acoustic impedance characteristics with a value of 2.45 × 106 kg s-1 m-2, lower than that of PVDF. To our knowledge, enantiomeric (R and S)-10-camphorsulfonylimine show the highest T c among the known organic single-component ferroelectrics and low acoustic impedance well matching with that of bodily tissues. This work promotes the development of high-performance organic single-component ferroelectrics and is of great inspiration to explore their application in next-generation flexible smart devices.

Multichannel Control of Multiferroicity in Single-Component Homochiral Organic Crystals.

A ferroelectric/ferroelastic is a material whose spontaneous polarization/strain can be switched by applying an external electric field/mechanical stress. However, the optical control of spontaneous polarization/strain remains relatively unexplored in crystalline materials, although photoirradiation stands out as a nondestructive, noncontact, and remote-controlled stimulus beyond stress or electric field. Here, we present two new organic single-component homochiral photochromic multiferroics, (R)- and (S)-N-3,5-di-tert-butylsalicylidene-1-4-bromophenylethylamine (SA-Ph-Br(R) and SA-Ph-Br(S)), which show a full ferroelectric/ferroelastic phase transition of 222F2 type at 336 K. Under photoirradiation, their spontaneous polarization/strain can be switched quickly within seconds and reversibly between two ferroelectric/ferroelastic phases with the respective enol and trans-keto forms triggered by structural photoisomerizations. In addition, they possess a superior acoustic impedance characteristic with a value of ∼2.42 × 106 kg·s-1·m-2, lower than that of polyvinylidene fluoride (PVDF, (3.69-4.25) × 106 kg·s-1·m-2), which can better match human tissues. This work realizes for the first time that multiple ferroic orders in single-component organic crystals with ultralow acoustic impedance can be simultaneously controlled and coupled by three physical channels (electric, stress, light fields), suggesting their great potential in multichannel data storage, optoelectronics, and related applications compatible with all-organic electronics and human tissues.

Coexistence of magnetic and electric orderings in a divalent Cr2+-based multiaxial molecular ferroelectric.

Multiferroic materials have attracted great interest because of their underlying new science and promising applications in data storage and mutual control devices. However, they are still very rare and highly imperative to be developed. Here, we report an organic-inorganic hybrid perovskite trimethylchloromethylammonium chromium chloride (TMCM-CrCl3), showing the coexistence of magnetic and electric orderings. It displays a paraelectric-ferroelectric phase transition at 397 K with an Aizu notation of 6/mFm, and spin-canted antiferromagnetic ordering with a Néel temperature of 4.8 K. The ferroelectricity originates from the orientational ordering of TMCM cations, and the magnetism is from the [CrCl3]- framework. Remarkably, TMCM-CrCl3 is the first experimentally confirmed divalent Cr2+-based multiferroic material as far as we know. A new category of hybrid multiferroic materials is pointed out in this work, and more Cr2+-based multiferroic materials will be expectedly developed in the future.

Optical Control of Polarization Switching in a Single-Component Organic Ferroelectric Crystal.

The optical control of polarization switching is attracting tremendous interest because photoirradiation stands out as a nondestructive, noncontact, and remote-control means beyond an electric or strain field. The current research mainly uses various photoexcited electronic effects to achieve the photocontrol polarization, such as a light-driven flexoelectric effect and a photovoltaic effect. However, since photochromism was discovered in 1867, the structural phase transition caused by photoisomerization has never been associated with ferroelectricity. Here, we successfully synthesized an organic photochromic ferroelectric with polar space group Pna21, 3,4,5-trifluoro-N-(3,5-di-tert-butylsalicylidene)aniline, whose color can change between yellow and orange via laser illumination. Its dielectric permittivity and spontaneous polarization can be switched reversibly with a photoinduced phase transition triggered by structural photoisomerization between the enol form and the trans-keto form. To our knowledge, this is the first photoswitchable ferroelectric crystal to achieve polarization switching through a structural phase transition triggered by photoisomerization. This finding paves the way toward photocontrol of smart materials and biomechanical applications in the future.

Salicylideneaniline is a Photoswitchable Ferroelectric Crystal.

Since the discovery of the first ferroelectric Rochelle salt, most ferroelectrics have been investigated showing thermally triggered symmetry-breaking phase transition. Although photochromism arising from geometrical isomerization was reported as early as 1867, such photoswitchable ferroelectric crystals have scarcely been developed to date. Herein, we report that salicylideneaniline is a photochromic ferroelectric crystal. Upon photoirradiation, the dielectric constant shows obvious switching between high and low dielectric states, and more importantly, the ferroelectric polarization demonstrates quick and reversible switching. This work opens the gate to developing photoswitchable ferroelectrics, which holds great potential for applications in optically controlled smart devices.

The First High-Temperature Supramolecular Radical Ferroics.

Organic radical ferroics such as TEMPO have attracted widespread interest. However, the relatively low Curie temperature of 287 K and melting point of 311 K severely hinder its application potential. Despite extensive interest, high-temperature radical ferroics have not yet been found. Here, taking advantage of chemical design and supramolecular radical chemistry, we designed two high-temperature organic supramolecular radical ferroics [(NH3 -TEMPO)([18]crown-6)](ReO4 ) (1) and [(NH3 -TEMPO)([18]crown-6)](ClO4 ) (2), which can retain ferroelectricity up to 413 K and 450 K, respectively. To our knowledge, they are both the first supramolecular radical ferroics and unprecedented high-temperature radical ferroics, where the supramolecular component is vital for the stabilization of the radical and extending the working temperature window. Both also have paramagnetism, non-interacting spin moments, and excellent piezoelectric and electrostrictive behaviors comparable to that of LiNbO3 .

Homochiral anionic modification toward the chemical design of organic enantiomeric ferroelectrics.

The well-developed design strategy of molecular modification for assembling molecular ferroelectrics mainly focuses on the cations. Herein, by homochiral anionic modification of the non-ferroelectric (quinuclidinium)(HSO4), we designed high-temperature multiaxial organic enantiomeric ferroelectrics, (quinuclidinium)(l- and d-camphorsulfonate). This work paves a new road for precisely constructing excellent molecular ferroelectrics.

Interaction of Estradiol and Endoplasmic Reticulum Stress in the Development of Esophageal Carcinoma.

Gender differences in esophageal cancer patients indicate that estradiol may have antitumor effects on esophageal cancer. The initiation of endoplasmic reticulum stress (ERS) can induce apoptosis in esophageal cancer cells. However, it is still unknown whether estradiol inhibits the development of esophageal cancer by activating ERS pathway. In this study, the gender difference in the development of esophageal cancer was observed by analyzing clinical data and the experimental tumor xenografts in mice. Meanwhile, we investigated the mechanism of ERS in estradiol-mediated inhibition of esophageal cancer using esophageal squamous cell carcinoma cell line EC109. The proportion of male patients with esophageal cancer was significantly higher than female patients. Meanwhile, male patients were prone to have adventitial invasion. The weight of transplanted tumors in female mice was significantly smaller than that in male mice. In vitro experiments showed estradiol inhibits the viability and migration of EC109 cells by increasing the expression of ERS-related proteins, whereas ERS inhibitor 4-PBA abolished the effects of estradiol. In conclusion, our data demonstrate that sex difference exists in the occurrence of esophageal cancer. Estradiol can inhibit the viability and migration of esophageal cancer cells through the activation of ERS, providing a novel insight for esophageal cancer development, treatment, and prevention.

Record Enhancement of Phase Transition Temperature Realized by H/F Substitution.

A high transition temperature (Tc ) is essential for the practical application of ferroelectrics as electronic devices under extreme thermal conditions in the aerospace, automotive, and energy industries. In recent decades, the isotope effect and strain engineering are found to effectively modulate Tc ; however, these strategies are limited to certain systems. Developing simple, universal, and practical methods to improve Tc has become an imminent challenge for expanding the applications of ferroelectrics. Here, by adopting a molecular design strategy involving H/F substitution on an organic-inorganic hybrid perovskite (1-azabicyclo[2.2.1]heptane)CdCl3 at a Tc of 190 K, the successful synthesis of a multiaxial, ferroelectric hybrid perovskite (4-fluoro-1-azabicyclo[2.2.1]heptane)CdCl3 is reported, which demonstrates a large spontaneous polarization of 11.2 µC cm-2 (greater than that of polyvinylidene difluoride) and a Tc of 419 K (greater than that of BaTiO3 ). This temperature enhancement (229 K) is the largest reported for molecular ferroelectrics, far exceeding the reported enhancements induced by the isotope effect and other techniques. This pioneering technique provides an effective and universal method for improving Tc in ferroelectrics and represents an important step toward the development of high-performance ferroelectric technology.

A Molecular Thermochromic Ferroelectric.

Molecular ferroelectrics have attracted considerable interests because of their easy and environmentally friendly processing, low acoustical impedance and mechanical flexibility. Herein, a molecular thermochromic ferroelectric, N,N'-dimethyl-1,4-diazoniabicyclo[2.2.2]octonium tetrachlorocuprate(II) ([DMe-DABCO]CuCl4 ) is reported, which shows both excellent ferroelectricity and intriguing thermochromism. [DMe-DABCO]CuCl4 undergoes a ferroelectric phase transition from Pca21 to Pbcm at a significantly high Curie temperature of 413 K, accompanied by a color change from yellow to red that is due to the remarkable deformation of [CuCl4 ]2- tetrahedron, where the ferroelectric and paraelectric phases correspond to yellow and red, respectively. Combined with multiple bistable physical properties, [DMe-DABCO]CuCl4 would be a promising candidate for next-generation smart devices, and should inspire further exploration of multifunctional molecular ferroelectrics.

MiR-101 relates to chronic peripheral neuropathic pain through targeting KPNB1 and regulating NF-κB signaling.

Accumulating evidences indicates that chronic neuropathic pain is a kind of neuro-immune disorder with enhanced activation of the immune system. Although the prevalence is very high, neuropathic pain remains extremely difficult to cure. miRNAs are a group of short nonprotein coding RNAs, regulating target genes expression via targeting 3'-untranslated region. More and more research indicates that altered miRNAs expression profile relates to the pathogenesis of neuropathic pain. In this study, we firstly detected the expression of six candidate miRNAs in the plasma samples from 23 patients with neuropathic pain and 10 healthy controls. Subsequently, the level of miR-132 and miR-101 was detected in the sural nerve biopsies. We found miR-101 level was significantly repressed in both the plasma samples and sural nerve biopsies from neuropathic pain patients. Predicted by bioinformatics tools and confirmed by dual luciferase assay and immunoblotting, we identified that KPNB1 is a direct target of miR-101. The negative correlation between miR-101 and KPNB1 was also confirmed in the sural nerve biopsies, and miR-101 reduction relates to the activation of NF-κB signaling in vivo and in vitro which contributes to the pathogenesis of neuropathic pain.

In vitro effect of Porphyromonas gingivalis combined with influenza A virus on respiratory epithelial cells.

OBJECTIVE: Respiratory epithelial cells are the first natural barrier against bacteria and viruses; hence, the interactions among epithelial cells, bacteria, and viruses are associated with disease occurrence and development. The effect of co-infection by P. gingivalis and influenza A virus (IAV) on respiratory epithelial cells remains unknown. The aim of this study was to analyze in vitro cell viability and apoptosis rates in respiratory epithelial A549 cells infected with P. gingivalis or IAV alone, or a combination of both pathogens. DESIGN: A549 cells were first divided into a control group, a P. gingivalis group, an IAV group, and a P. gingivalis + IAV group, to examine cell viability and apoptosis rates, the levels of microtubule associated protein 1 light chain 3 B (LC3-II), microtubule associated protein 1 light chain 3A (LC3-I), and sequestosome 1 (P62), and the formation of autophagosomes. The autophagy inhibitor, 3-methyladenine (3MA), was used to assess autophagy and apoptosis in A549 cells infected with P. gingivalis or IAV. RESULTS: An MTT assay revealed that cell viability was significantly lower in the IAV group than in the P. gingivalis + IAV group (P < 0.05). Flow cytometry indicated that the apoptosis rate was significantly higher in the IAV group than in the P. gingivalis + IAV group (P < 0.05). The fluorescence levels of GFP-LC3 increased significantly, the LC3-II/LC3-I ratio was significantly higher, and the P62 protein levels were statistically lower in the P. gingivalis + IAV group compared with the IAV group (all P < 0.05). Western blotting revealed that the LC3- II/LC3-I ratio was significantly lower, and caspase-3 levels were significantly higher in the 3MA + P. gingivalis + IAV group compared to the P. gingivalis + IAV group (all P < 0.05). CONCLUSION: In vitro studies showed that infection by P. gingivalis combined with IAV temporarily inhibited apoptosis in respiratory epithelial cells, and this may be related to the initiation of autophagy.

Expression and significance of ASPP2 in squamous carcinoma of esophagus.

To study the significance of apoptosis stimulating protein of P53 2 (ASPP2) expression in esophageal squamous cell carcinoma (ESCC), immunohistochemistry S-P method was used to examine the expression of ASPP2 in 136 cases of ESCC, 35 cases of high grade intraepithelial neoplasia (HGIN), 29 cases of low grade intraepithelial neoplasia (LGIN) and 37 cases of normal esophageal epithelium (NEE). The associations of ASPP2 expression with clinicopathological data and overall survival (OS) were also analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate ASPP2 expression in a total of 20 matched human ESCC tumor tissues and normal adjacent tissues (NAT). In addition, EC109 cells were treated with cisplatin (CDDP) in vitro for 24 h (the intervention group) and the control group was set up at the same time. Western blot was used to examine the expression of ASPP2 protein between the two groups. The expression of ASPP2 decreased progressively from NEE to LGIN, to HGIN, and to ESCC, and it was related to TNM stage, histological differentiation and lymph node metastasis in ESCC (P < 0.05). ASPP2 was a protective factor of patients with ESCC (P = 0.008). The relative expression of ASPP2 mRNA was markedly downregulated in ESCC compared with the paired NAT (P < 0.01). Western blot results showed that cells in the intervention group could express ASPP2 while there was no expression of ASPP2 in the control group. Taken together, these results indicate that the abnormal expression of ASPP2 may play an important role for development and metastasis in ESCC.

Directly-coupled-column ultra-fast liquid chromatography with diode array detection method for the rapid quantification of allergenic disperse dyes in water preconcentrated by magnetic solid-phase extraction.

A directly-coupled-column ultra-fast liquid chromatography coupled with diode array detection method for the determination of 12 allergenic disperse dyes in river water at sub-ppb levels has been developed and successfully validated. The analytical method is based on the use of two different reversed-phased columns connected through a two-position switching valve. A baseline separation was achieved by proper selection of stationary phases, mobile phases, and the use of a gradient elution in both dimensions. Furthermore, an easy-to-handle magnetic solid-phase extraction procedure was developed for the preconcentration of 12 allergenic disperse dyes from river water. An enrichment factor of 100 times was obtained. The results showed excellent performance in terms of trueness (76.8-99.0%), precision (intraday: 2.2-8.0%, interday: 3.3-8.2%), and sensitivity (limits of determination, 0.027-1.46 µg/L). Twenty real samples collected from the outfalls in the Yaojiang, Yongjiang and Fenghuajiang estuary were analyzed, and three of the studied compounds were found in one collected sample (12.6 µg/L for disperse blue 7, 11.6 µg/L for disperse blue 106, and 0.22 µg/L for disperse blue 3).

Fast throughput determination of 21 allergenic disperse dyes from river water using reusable three-dimensional interconnected magnetic chemically modified graphene oxide followed by liquid chromatography-tandem quadrupole mass spectrometry.

We report the template-free fabrication of three-dimensional hierarchical nanostructures, i.e., three-dimensional interconnected magnetic chemically modified graphene oxide (3D-Mag-CMGO), through a simple and low-cost self-assembly process using one-pot reaction based on solvothermal method. The excellent properties of the 3D-Mag-CMGO are characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), vibrating sample magnetometer (VSM), FTIR, elementary analyzer (EA) and X-ray photoelectron spectroscopy (XPS). The easiness-to-handle of the magnetic dispersive solid phase extraction (Mag-dSPE) procedure is developed for preconcentration of 21 allergenic disperse dyes from river water. The obtained results show the higher extraction capacity of 3D-Mag-CMGO with recoveries between 80.0-112.0%. Furthermore, an ultra-fast liquid chromatography-tandem quadrupole mass spectrometry (UFLC-MS/MS) method for determination of 21 allergenic disperse dyes in river at sub-ppt levels has been developed with pretreatment of the samples by Mag-dSPE. The limits of quantification (LOQs) for the allergenic disperse dyes are between 0.57-34.05ng/L. Validation results on linearity, specificity, trueness and precision, as well as on application to the analysis of 21 allergenic disperse dyes in fifty real samples demonstrate the applicability to environment monitoring analysis.