[Research Advances in the Association Between Alzheimer's Disease and Double-Stranded RNA-Dependent Protein Kinase].

Alzheimer's disease (AD) is a severe threat to human health and one of the three major causes of human death.Double-stranded RNA-dependent protein kinase (PKR) is an interferon-induced protein kinase involved in innate immunity.In the occurrence and development of AD,PKR is upregulated and continuously activated.On the one hand,the activation of PKR triggers an integrated stress response in brain cells.On the other hand,it indirectly upregulates the expression of ß-site amyloid precursor protein cleaving enzyme 1 and facilitates the accumulation of amyloid-ß protein (Aß),which could activate PKR activator to further activate PKR,thus forming a sustained accumulation cycle of Aß.In addition,PKR can promote Tau phosphorylation,thereby reducing microtubule stability in nerve cells.Inflammation in brain tissue,neurotoxicity resulted from Aß accumulation,and disruption of microtubule stability led to the progression of AD and the declines of memory and cognitive function.Therefore,PKR is a key molecule in the development and progression of AD.Effective PKR detection can aid in the diagnosis and prediction of AD progression and provide opportunities for clinical treatment.The inhibitors targeting PKR are expected to control the activity of PKR,thereby controlling the progression of AD.Therefore,PKR could be a target for the development of therapeutic drugs for AD.

Enhanced photocatalytic U(VI) reduction via double internal electric field in CoWO4/covalent organic frameworks p-n heterojunction.

Photoreduction of highly toxic U(VI) to less toxic U(IV) is crucial for mitigating radioactive contamination. Herein, a CoWO4/TpDD p-n heterojunction is synthesized, with TpDD serving as the n-type semiconductor substrate and CoWO4 as the p-type semiconductor grown in situ on its surface. The Fermi energy difference between TpDD and CoWO4 provides the electrochemical potential for charge-hole separation. Moreover, the Coulombic forces from the distinct carrier types between the two materials synergistically facilitate the transfer of electrons and holes. Hence, an internal electric field directed from TpDD to CoWO4 is established. Under photoexcitation conditions, charges and holes migrate efficiently along the curved band and internal electric field, further enhancing charge-hole separation. As a result, the removal capacity of CoWO4/TpDD increases from 515.2 mg/g in the dark to 1754.6 mg/g under light conditions. Thus, constructing a p-n heterojunction proves to be an effective strategy for remediating uranium-contaminated environments.

Vibrio alginolyticus PEPCK Mediates Florfenicol Resistance through Lysine Succinylation Modification.

Protein succinylation modification is a common post-translational modification (PTM) that plays an important role in bacterial metabolic regulation. In this study, quantitative analysis was conducted on the succinylated proteome of wild-type and florfenicol-resistant Vibrio alginolyticus to investigate the mechanism of succinylation regulating antibiotic resistance. Bioinformatic analysis showed that the differentially succinylated proteins were mainly enriched in energy metabolism, and it was found that the succinylation level of phosphoenolpyruvate carboxyl kinase (PEPCK) was highly expressed in the florfenicol-resistant strain. Site-directed mutagenesis was used to mutate the lysine (K) at the succinylation site of PEPCK to glutamic acid (E) and arginine (R), respectively, to investigate the function of lysine succinylation of PEPCK in the florfenicol resistance of V. alginolyticus. The detection of site-directed mutagenesis strain viability under florfenicol revealed that the survival rate of the E mutant was significantly higher than that of the R mutant and wild type, indicating that succinylation modification of PEPCK protein may affect the resistance of V. alginolyticus to florfenicol. This study indicates the important role of PEPCK during V. alginolyticus antibiotic-resistance evolution and provides a theoretical basis for the prevention and control of vibriosis and the development of new antibiotics.

PANX1-mediated ATP release confers FAM3A's suppression effects on hepatic gluconeogenesis and lipogenesis.

BACKGROUND: Extracellular adenosine triphosphate (ATP) is an important signal molecule. In previous studies, intensive research had revealed the crucial roles of family with sequence similarity 3 member A (FAM3A) in controlling hepatic glucolipid metabolism, islet ß cell function, adipocyte differentiation, blood pressure, and other biological and pathophysiological processes. Although mitochondrial protein FAM3A plays crucial roles in the regulation of glucolipid metabolism via stimulating ATP release to activate P2 receptor pathways, its mechanism in promoting ATP release in hepatocytes remains unrevealed. METHODS: db/db, high-fat diet (HFD)-fed, and global pannexin 1 (PANX1) knockout mice, as well as liver sections of individuals, were used in this study. Adenoviruses and adeno-associated viruses were utilized for in vivo gene overexpression or inhibition. To evaluate the metabolic status in mice, oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT), insulin tolerance test (ITT), and magnetic resonance imaging (MRI) were conducted. Protein-protein interactions were determined by coimmunoprecipitation with mass spectrometry (MS) assays. RESULTS: In livers of individuals and mice with steatosis, the expression of ATP-permeable channel PANX1 was increased (P < 0.01). Hepatic PANX1 overexpression ameliorated the dysregulated glucolipid metabolism in obese mice. Mice with hepatic PANX1 knockdown or global PANX1 knockout exhibited disturbed glucolipid metabolism. Restoration of hepatic PANX1 rescued the metabolic disorders of PANX1-deficient mice (P < 0.05). Mechanistically, ATP release is mediated by the PANX1-activated protein kinase B-forkhead box protein O1 (Akt-FOXO1) pathway to inhibit gluconeogenesis via P2Y receptors in hepatocytes. PANX1-mediated ATP release also activated calmodulin (CaM) (P < 0.01), which interacted with c-Jun N-terminal kinase (JNK) to inhibit its activity, thereby deactivating the transcription factor activator protein-1 (AP1) and repressing fatty acid synthase (FAS) expression and lipid synthesis (P < 0.05). FAM3A stimulated the expression of PANX1 via heat shock factor 1 (HSF1) in hepatocytes (P < 0.05). Notably, FAM3A overexpression failed to promote ATP release, inhibit the expression of gluconeogenic and lipogenic genes, and suppress gluconeogenesis and lipid deposition in PANX1-deficient hepatocytes and livers. CONCLUSIONS: PANX1-mediated release of ATP plays a crucial role in maintaining hepatic glucolipid homeostasis, and it confers FAM3A's suppressive effects on hepatic gluconeogenesis and lipogenesis.

SHG Assisted Mixed-Phases Anatomizing in a Molecular Ferroelectric.

Anatomizing mixed-phases, referring to analyzing the mixing profiles and quantifying the phases' proportions in a material, which is of great significance in the genuine applications. Here, by using second-harmonic generation (SHG) polarimetry and piezoresponse force microscopy (PFM) techniques, this work elucidates the contributions and distributions of two different symmetric phases mixed in an archetype monoaxial molecular ferroelectric, diisopropylammonium chloride (DIPACl). The two competing phases are preferred in thermodynamics or kinetic process respectively, and this work evidences the switching behavior between the two competing phases facilitated by an external electrical field as opposed to a heating process. This research contributes novel insights into phase engineering in the field of molecular ferroelectrics and is poised to serve as a potent analytical tool for subsequent applications.

Therapeutic effect of manual massage on early postpartum rectus abdominis separation and postpartum depression.

BACKGROUND: Rectus abdominis separation (DRA) affects pelvic stability and body image. No studies have explored the effects of manual massage on early postpartum DRA and postpartum depression. AIM: To analyze the curative effect of massage on early postpartum DRA and its impact on postpartum depression and thus its ability promote the overall psychosomatic rehabilitation of postpartum women. METHODS: Data were retrospectively collected on 70 primiparous women with postpartum DRA who underwent rehabilitation at the Postpartum Rehabilitation Center of Huzhou Maternal and Child Health Hospital from October 2022 to September 2023. The patients were divided into the Group S (35 cases, biomimetic electrical stimulation treatment) and Group L (35 cases, biomimetic electrical stimulation combined with manual massage treatment). Baseline data, the edinburgh postpartum depression scale (EPDS) score, and the visual analog scale (VAS) scores for rectus abdominis distance, waist circumference, and lower back pain before and after treatment were compared. RESULTS: No significant differences were found in the baseline data, rectus abdominis distance, waist circumference, and VAS and EPDS scores between the two groups before treatment (P > 0.05). After treatment, the distance between rectus abdominis and waist circumference in Group L were significantly smaller than those in Group S (P < 0.05). Furthermore, lower back pain (VAS score) and the EPDS score in Group L were significantly lower than those in Group S (P < 0.05). CONCLUSION: Manual massage can significantly reduce early postpartum DRA, waist circumference, and back pain and improve the patient's mental state and postpartum depression.

Impacts of spatial symmetries on stimulated Brillouin scatterings in nanoscale silicon waveguides: a theoretical and numerical study considering material anisotropies.

Fully considering the mechanical and photoelastic anisotropies of monocrystalline silicon, the impacts of spatial symmetries on the stimulated Brillouin scatterings (SBSs) in nanoscale suspended silicon waveguides are studied theoretically and numerically based on group theory. First, starting from an assumption that the principal material coordinate system can be arbitrarily orientated in a waveguide with fixed geometry, the silicon waveguides are systematically classified into a number of point groups according to their spatial symmetry features. Thereafter, the symmetry characteristics of physical fields and SBS opto-mechanical coupling characteristics in the silicon waveguides belonging to different point groups are further examined, and the major new findings can be summarized as follows: The SBS opto-mechanical couplings in several kinds of silicon waveguides with certain nontrivial symmetry features exhibit relatively predictable behaviors in that the opto-mechanical coupling coefficients can be deterministically vanishing or nonvanishing under very few constraints, which can thus serve as general symmetry selection rules for SBSs in suspended silicon waveguides. The results obtained in the present study could be a useful theoretical reference for the design of novel SBS-active silicon photonic devices.

Interface Engineering of Substrate-Integrated Single-Crystal Perovskite Wafers for Sensitive X-Ray Detection.

Metal halide perovskite single crystals are emerging candidates for X-ray detection, however, it is challenging for growth of thickness-controlled single-crystal wafer on commercial backplanes, limiting their practical imaging application. Herein, integration of micrometer-thick methylammonium lead triiodide (MAPbI3) single-crystal wafer on indium tin oxide (ITO) substrates by methylamine (MA)-induced interface recrystallization is reported. Through selection of hole transport material with rich functional group, intimate interface contact with low trap density can be achieved, leading to superior carrier transport properties and homogeneous photoresponse. The as-fabricated X-ray detectors exhibit high sensitivity of 1.4 × 104 µC Gyair -1 cm-2 and low detection limit of 177 nGyair s-1, which are comparable to previous reports based on free-standing MAPbI3 bulk crystals. This work provides a feasible strategy for constructing substrate-integrated single-crystal perovskite wafers with controlled thickness, which may promote practical imaging application of perovskite X-ray detectors.

Unveiling the mechanism of high sugar diet induced advanced glycosylation end products damage skin structure via extracellular matrix-receptor interaction pathway.

BACKGROUND: AGEs accumulate in the skin as a result of a high-sugar diet and play an important role in the skin aging process. OBJECTIVES: The aim of this study was to characterize the mechanism underlying the effect of a high-sugar diet on skin aging damage at a holistic level. METHODS: We established a high-sugar diet mouse model to compare and analyze differences in physiological indexes. The effect of a high-sugar diet on skin aging damage was analyzed by means of a transcriptome study and staining of pathological sections. Furthermore, the differences in the protein expression of AGEs and ECM components between the HSD and control groups were further verified by immunohistochemistry. RESULTS: The skin in the HSD group mice tended toward a red, yellow, dark, and deep color. In addition, the epidermis was irregular with anomalous phenomena, the epidermis was thinned, and the dermis lost its normal structure and showed vacuolated changes. Transcriptomics results revealed significant downregulation of the ECM-receptor interaction pathway, significant upregulation of the expression of AGEs and significant downregulation of the expression levels of COLI, FN1, LM5, and TNC, among others ECM proteins and ECM receptors. CONCLUSIONS: High-sugar diets cause skin aging damage by inducing the accumulation of AGEs, disrupting the expression of ECM proteins and their receptors, and downregulating the ECM-receptor interaction pathway, which affects cellular behavioral functions such as cell proliferation, migration, and adhesion, as well as normal skin tissue structure.

STING deficiency alleviates ferroptosis through FPN1 stabilization in diabetic kidney disease.

Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, has known as one of the most significant pathological processes involved in diabetic kidney disease (DKD). Stimulator of interferon genes (STING) has been demonstrated its potential in regulating ferroptosis, but the regulatory role in DKD mice and underlying mechanisms haven't been illustrated. To elucidate whether and how STING regulates ferroptosis in DKD, we detected the influence of STING on diabetic-related ferroptosis in a diabetic model and in erastin-induced renal tubular epithelial cells (RTECs). Our study demonstrated that STING was abnormally activated and promoted ferroptosis in DKD. STING deficiency alleviated renal pathologic damages and disfunction in diabetic mice via alleviating ferroptosis and reducing oxidative stress. Mechanismly, STING inhibition was shown to improve ferroptosis and reduce oxidative stress in erastin-induced RTECs. The disruption of ferroportin1 (FPN1) on the basis of STING inhibition abolished the improvements in ferroptosis and promoted reactive oxygen species (ROS) generation. Further, STING inhibition alleviated ferroptosis via stabilizing FPN1 protein level by decreasing ubiquitinated FPN1 for proteasomal degradation. In conclusion, STING deficiency protected against diabetic renal injury via alleviating ferroptosis through stabilizing FPN1 and reducing oxidative stress, providing a possible potential approach for the treatment of DKD.

Two cuticle-enriched chemosensory proteins confer multi-insecticide resistance in Spodoptera frugiperda.

Recent studies revealed that insect chemosensory proteins (CSPs) both play essential roles in insect olfaction and insect resistance. However, functional evidence supporting the crosslink between CSP and insecticide resistance remains unexplored. In the present study, 22 SfruCSP transcripts were identified from the fall armyworm (FAW) and SfruCSP1 and SfruCSP2 are enriched in the larval cuticle and could be induced by multiple insecticides. Both SfruCSP1 and SfruCSP2 are highly expressed in the larval inner endocuticle and outer epicuticle, and these two proteins exhibited high binding affinities with three insecticides (chlorfenapyr, chlorpyrifos and indoxacarb). The knockdown of SfruCSP1 and SfruCSP2 increased the susceptibility of FAW larvae to the above three insecticides, and significantly increased the penetration ratios of these insecticides. Our in vitro and in vivo evidence suggests that SfruCSP1 and SfruCSP2 are insecticide binding proteins and confer FAW larval resistance to chlorfenapyr, chlorpyrifos and indoxacarb by an insecticide sequestration mechanism. The study should aid in the exploration of larval cuticle-enriched CSPs for insect resistance management.

Far-Infrared Therapy Based on Graphene Ameliorates High-Fat Diet-Induced Anxiety-Like Behavior in Obese Mice via Alleviating Intestinal Barrier Damage and Neuroinflammation.

The consumption of a high-fat diet (HFD) has been implicated in the etiology of obesity and various neuropsychiatric disturbances, including anxiety and depression. Compelling evidence suggests that far-infrared ray (FIR) possesses beneficial effects on emotional disorders. However, the efficacy of FIR therapy in addressing HFD-induced anxiety and the underlying mechanisms remain to be elucidated. Here, we postulate that FIR emitted from a graphene-based therapeutic device may mitigate HFD-induced anxiety behaviors. The graphene-FIR modify the gut microbiota in HFD-mice, particularly by an enriched abundance of beneficial bacteria Clostridiaceae and Erysipelotrichaceae, coupled with a diminution of harmful bacteria Lachnospiraceae, Anaerovoracaceae, Holdemania and Marvinbryantia. Graphene-FIR also improved intestinal barrier function, as evidenced by the augmented expression of the tight junction protein occludin and G protein-coupled receptor 43 (GPR43). In serum level, we observed the decreased free fatty acids (FFA), lipopolysaccharides (LPS), diamine oxidase (DAO) and D-lactate, and increased the glucagon-like peptide-2 (GLP-2) levels in graphene-FIR mice. Simultaneously, inflammatory cytokines IL-6, IL-1ß, and TNF-α manifested a decrease subsequent to graphene-FIR treatment in both peripheral and central system. Notably, graphene-FIR inhibited over expression of astrocytes and microglia. We further noticed that the elevated the BDNF and decreased TLR4 and NF-κB expression in graphene-FIR group. Overall, our study reveals that graphene-FIR rescued HFD-induced anxiety via improving the intestine permeability and the integrity of blood-brain barrier, and reduced inflammatory response by down regulating TLR4/NF-κB inflammatory pathway.

Integrating cfDNA liquid biopsy and organoid-based drug screening reveals PI3K signaling as a promising therapeutic target in colorectal cancer.

BACKGROUND: The current precision medicine relies on biomarkers, which are mainly obtained through next-generation sequencing (NGS). However, this model failed to find effective drugs for most cancer patients. This study tried to combine liquid biopsy with functional drug tests using organoid models to find potential drugs for cancer patients. METHODS: Colorectal cancer (CRC) patients were prospectively enrolled and blood samples were collected from patients before the start of treatment. Targeted deep sequencing of cfDNA samples was performed using a 14-gene panel. Gastrointestinal (GI) cancer organoids were established and PI3K and mTOR inhibitors were evaluated on organoid models. RESULTS: A total of 195 mutations were detected across 58 cfDNA samples. The most frequently mutated genes were KRAS, TP53, PIK3CA, and BRAF, all of which exhibited higher mutation rates than tissue biopsy. Although 81% of variants had an allele frequency of less than 1%, certain mutations in KRAS, TP53, and SMAD4 had high allele frequencies exceeding 10%. Notably, among the seven patients with high allele frequency mutations, six had metastatic tumors, indicating that a high allele frequency of ctDNA could potentially serve as a biomarker of later-stage cancer. A high rate of PIK3CA mutation (31 out of 67, or 46.3%) was discovered in CRC patients, suggesting possible tumor progression mechanisms and targeted therapy opportunities. To evaluate the value of anti PI3K strategy in GI cancer, different lines of GI cancer organoids were established. The organoids recapitulated the morphologies of the original tumors. Organoids were generally insensitive to PI3K inhibitors. However, CRC-3 and GC-4 showed response to mTOR inhibitor Everolimus, and GC-3 was sensitive to PI3Kδ inhibitor Idelalisib. The CRC organoid with a PIK3CA mutation showed greater sensitivity to the PI3K inhibitor Alpelisib than wildtype organoids, suggesting potential treatment options for the corresponding patients. CONCLUSION: Liquid biopsy holds significant promise for improving precision treatment and tumor prognosis in colorectal cancer patients. The combination of biomarker-based drug prediction with organoid-based functional drug sensitivity assay may lead to more effective cancer treatment.

Epidermal ET-1 signal induces activation of resting hair follicles by upregulating the PI3K/AKT pathway in the dermis.

The prevalence of alopecia has increased recently. Hair loss is often accompanied by the resting phase of hair follicles (HFs). Dermal papilla (DP) plays a crucial role in HF development, growth, and regeneration. Activating DP can revive resting HFs. Augmenting WNT/ß-catenin signaling stimulates HF growth. However, the factors responsible for activating resting HFs effectively are unclear. In this study, we investigated epidermal cytokines that can activate resting HFs effectively. We overexpressed ß-catenin in both in vivo and in vitro models to observe its effects on resting HFs. Then, we screened potential epidermal cytokines from GEO DATASETs and assessed their functions using mice models and skin-derived precursors (SKPs). Finally, we explored the molecular mechanism underlying the action of the identified cytokine. The results showed that activation of WNT/ß-catenin in the epidermis prompted telogen-anagen transition. Keratinocytes infected with Ctnnb1-overexpressing lentivirus enhanced SKP expansion. Subsequently, we identified endothelin 1 (ET-1) expressed higher in hair-growing epidermis and induced the proliferation of DP cells and activates telogen-phase HFs in vivo. Moreover, ET-1 promotes the proliferation and stemness of SKPs. Western blot analysis and in vivo experiments revealed that ET-1 induces the transition from telogen-to-anagen phase by upregulating the PI3K/AKT pathway. These findings highlight the potential of ET-1 as a promising cytokine for HF activation and the treatment of hair loss.

M1 polarization of macrophages promotes stress-induced hair loss via interleukin-18 and interleukin-1ß.

Stress-induced hair loss is a prevalent health concern, with mechanisms that remain unclear, and effective treatment options are not yet available. In this study, we investigated whether stress-induced hair loss was related to an imbalanced immune microenvironment. Screening the skin-infiltrated immune cells in a stressed mouse model, we discovered a significant increase in macrophages upon stress induction. Clearance of macrophages rescues mice from stress-induced hair shedding and depletion of hair follicle stem cells (HFSCs) in the skin, demonstrating the role of macrophages in triggering hair loss in response to stress. Further flow cytometry analysis revealed a significant increase in M1 phenotype macrophages in mice under stressed conditions. In searching for humoral factors mediating stress-induced macrophage polarization, we found that the hormone Norepinephrine (NE) was elevated in the blood of stressed mice. In addition, in-vivo and in-vitro studies confirm that NE can induce macrophage polarization toward M1 through the ß-adrenergic receptor, Adrb2. Transcriptome, enzyme-linked immunosorbent assay (ELISA), and western blot analyses reveal that the NLRP3/caspase-1 inflammasome signaling and its downstream effector interleukin 18 (IL-18) and interleukin 1 beta (IL-1ß) were significantly upregulated in the NE-treated macrophages. However, inhibition of the NE receptor Adrb2 with ICI118551 reversed the upregulation of NLRP3/caspase-1, IL-18, and IL-1ß. Indeed, IL-18 and IL-1ß treatments lead to apoptosis of HFSCs. More importantly, blocking IL-18 and IL-1ß signals reversed HFSCs depletion in skin organoid models and attenuated stress-induced hair shedding in mice. Taken together, this study demonstrates the role of the neural (stress)-endocrine (NE)-immune (M1 macrophages) axis in stress-induced hair shedding and suggestes that IL-18 or IL-1ß may be promising therapeutic targets.

N6-Methyladenosine Reader YTHDF1 Promotes Stemness and Therapeutic Resistance in Hepatocellular Carcinoma by Enhancing NOTCH1 Expression.

N6-methyladenosine (m6A) RNA modification is the most common and conserved epigenetic modification in mRNA and has been shown to play important roles in cancer biology. As the m6A reader YTHDF1 has been reported to promote progression of hepatocellular carcinoma (HCC), it represents a potential therapeutic target. In this study, we evaluated the clinical significance of YTHDF1 using human HCC samples and found that YTHDF1 was significantly upregulated in HCCs with high stemness scores and was positively associated with recurrence and poor prognosis. Analysis of HCC spheroids revealed that YTHDF1 was highly expressed in liver cancer stem cells (CSC). Stem cell-specific conditional Ythdf1 knockin (CKI) mice treated with diethylnitrosamine showed elevated tumor burden as compared with wild-type mice. YTHDF1 promoted CSCs renewal and resistance to the multiple tyrosine kinase inhibitors lenvatinib and sorafenib in patient-derived organoids and HCC cell lines, which could be abolished by catalytically inactive mutant YTHDF1. Multiomic analysis, including RNA immunoprecipitation sequencing, m6A methylated RNA immunoprecipitation sequencing, ribosome profiling, and RNA sequencing identified NOTCH1 as a direct downstream of YTHDF1. YTHDF1 bound to m6A modified NOTCH1 mRNA to enhance its stability and translation, which led to increased NOTCH1 target genes expression. NOTCH1 overexpression rescued HCC stemness in YTHDF1-deficient cells in vitro and in vivo. Lipid nanoparticles targeting YTHDF1 significantly enhanced the efficacy of lenvatinib and sorafenib in HCC in vivo. Taken together, YTHDF1 drives HCC stemness and drug resistance through an YTHDF1-m6A-NOTCH1 epitranscriptomic axis, and YTHDF1 is a potential therapeutic target for treating HCC. SIGNIFICANCE: Inhibition of YTHDF1 expression suppresses stemness of hepatocellular carcinoma cells and enhances sensitivity to targeted therapies, indicating that targeting YTHDF1 may be a promising therapeutic strategy for liver cancer.

Volume-Confined Fabrication of Large-Scale Single-Crystalline Molecular Ferroelectric Thin Films and Their Applications in 2D Materials.

With outstanding advantages of chemical synthesis, structural diversity, and mechanical flexibility, molecular ferroelectrics have attracted increasing attention, demonstrating themselves as promising candidates for next-generation wearable electronics and flexible devices in the film form. However, it remains a challenge to grow high-quality thin films of molecular ferroelectrics. To address the above issue, a volume-confined method is utilized to achieve ultrasmooth single-crystal molecular ferroelectric thin films at the sub-centimeter scale, with the thickness controlled in the range of 100-1000 nm. More importantly, the preparation method is applicable to most molecular ferroelectrics and has no dependency on substrates, showing excellent reproducibility and universality. To demonstrate the application potential, two-dimensional (2D) transitional metal dichalcogenide semiconductor/molecular ferroelectric heterostructures are prepared and investigated by optical spectroscopic method, proving the possibility of integrating molecular ferroelectrics with 2D layered materials. These results may unlock the potential for preparing and developing high-performance devices based on molecular ferroelectric thin films.

Astaxanthin suppresses LPS-induced myocardial apoptosis by regulating PTP1B/JNK pathway in vitro.

PURPOSE: Myocardial injury induced by sepsis can increase the patient's mortality, which is an important complication of sepsis. Myocardial apoptosis plays a key role in septic myocardial injury. Here we explored the potential mechanism of astaxanthin (ATX) inhibiting myocardial apoptosis induced by lipopolysaccharide (LPS) in vitro. METHODS: The H9C2 cell experiment was conducted in three parts. In the first part, we set up three groups: control group, LPS group (10 µg/ml), a model of septic myocardial injury, and LPS + ATX (5, 10, 30 µM); In the second part, we set up four groups: control group, LPS group, LPS + PTP1B-IN-1, a protein tyrosine phosphatase 1B (PTP1B) inhibitor, and LPS + PTP1B-IN-1 + ATX; In the third part, we set up four groups: control group, LPS group, LPS + Anisomycin, a c-Jun N-terminal kinase (JNK) activator, and LPS + Anisomycin + ATX. We assessed H9C2 cell viability using the Cell Counting Kit-8 (CCK-8) assay. We observed cell apoptosis using flow cytometry analysis. We tested the mitochondrial membrane potential (ΔΨm) using JC-1 staining. To identify the molecular targets of ATX, Astaxanthin targets were predicted through the SwissTargetPrediction database. We verified the binding affinity of ATX and its targets using microscale thermophoresis (MST). We investigated the p-JNK expression using immunofluorescence staining. Finally, Western blot was used to evaluate PTP1B, JNK, p-JNK and the mitochondrial apoptosis-associated protein expression. RESULTS: LPS inhibited H9C2 cell viability in a time-dependent manner and ATX treatment enhances H9C2 cell viability in a concentration dependent manner after LPS administration. ATX inhibited the LPS-induced apoptosis and loss of mitochondrial membrane potential in H9C2 cells. As predicted by the SwissTargetPrediction database, PTP1B was a potential target of ATX, and the interaction between ATX and PTP1B was further verified by MST. ATX attenuated the LPS-induced protein expression of PTP1B and p-JNK, regardless of PTP1B inhibition. Both immunofluorescence staining and Western blotting showed that ATX suppressed the LPS-induced p-JNK expression in H9C2 cells, regardless of Anisomycin administration. In addition, by adding Anisomycin to overexpress JNK, ATX inhibited the LPS-induced apoptosis, loss of mitochondrial membrane potential and upregulation of mitochondrial apoptosis-associated proteins in H9C2 cells via JNK signaling. CONCLUSION: ATX inhibited LPS-induced mitochondrial apoptosis of H9C2 cells by PTP1B/JNK pathway and PTP1B was the target of ATX.