High-throughput arousing interconnected interfaces for excellent sodium storage chemistry.

Heterostructures endow electrochemical hybrids with promising energy storage properties owing to synergistic effects and interfacial interaction. However, developing a facile but effective approach to maximize interface effects is crucial but challenging. Herein, a bimetallic sulfide/carbon heterostructure is realized in a confined carbon network via a high-throughput template-assisted strategy to induce highly active and stable electrode architecture. The designed heterostructures not only yield abundant interconnected Co9S8/MoS2/N-doped carbon (Co9S8/MoS2/NC) heterojunctions with continuous channels for ion/electron transfer but maintain excellent conversion reversibility. Serving as anode for sodium storage, the Co9S8/MoS2/NC framework displayed excellent sodium storage properties (reversible capacity of 480 mAh/g after 100 cycles at 0.2 A/g and 286.2 mAh/g after 500 cycles at 2 A/g). Given this, this study can guide future design protocols for interface engineering by forming dynamic channels of conversion reaction kinetics for potential applications in high-performance electrodes.

Co3O4-Induced Na2CO3-Rich SEI Film on an FeNCN Electrode with Promoted Loading and High-Rate Na-Storage Performance.

Iron carbodiimide (FeNCN) often suffers from unstable interfacial structure with an unexpected failure of Na-ion storage performance. In this work, Co3O4 particles were deposited on the surface of FeNCN. This Co3O4 nanolayer led to the formation of a Na2CO3-rich inorganic component SEI film to enhance the stability of a promoted-loading FeNCN electrode interface with fast Na+ migration pathway. Benefitting from this strategy, the FeNCN electrode could present a capacity retention rate of 99.95% per cycle after 1500 cycles at 1 A g-1. The design of interfacial structure in a promoted-loading electrode could be a reference for stable and high-rate performance of carbodiimide-based materials.

A Mechanical Immune Checkpoint Inhibitor Stiffens Tumor Cells to Potentiate Antitumor Immunity.

Tumor progression is associated with tumor-cell softening. Improving the stiffness of the tumor cells can make them more vulnerable to lymphocyte-mediated attack. Tumor cell membranes typically exhibit higher cholesterol levels than normal cells, making tumor cells soft. Herein, we demonstrate a mechanical immune checkpoint inhibitor (MICI) formulated by cyclodextrin (CD) lipids and fusogenic lipids. Through fusing CD lipids into the tumor cell membrane using a fusogenic liposome formulation, the cholesterol in the plasma membrane is reduced due to the specific host-guest interactions between CD lipid and cholesterol. As a result, tumor cells are stiffened, and the activation of lymphocytes (including NK and cytotoxic effector T cells) is improved when contacting the stiffened tumor cells, characterized by robust degranulation and effector cytokine production. Notably, this treatment has negligible influence on the infiltration and proliferation of lymphocytes in tumor tissues, confirming that the enhanced antitumor efficacy should result from activating a specific number of lymphocytes caused by direct regulation of the tumor cell stiffness. The combination of MICIs and clinical immunotherapies enhances the lymphocyte-mediated antitumor effects in two tumor mouse models, including breast cancer and melanoma. Our research also reveals an unappreciated mechanical dimension to lymphocyte activation.

Downregulation of hsa_circ_0006620 inhibits the malignant progression of prostate cancer by regulation of the miR-502-3p/HK2 axis mediated by aerobic glycolysis.

Circular RNAs (circRNA) are a class of covalently-closed, single-stranded RNAs that have been implicated in cancer progression due to their regulation of metabolism. However, the roles of circRNA in prostate cancer remain largely unknown. In this study, fluorescence in situ hybridization and RT-qPCR were used to investigate hsa_circ_0006620 expressions in both prostate cancer cells and tissues, after high-throughput sequencing. The luciferase reporter assay was used to identify hsa_circ_0006620 downstream targets. Transwell migration assays, 5-ethynyl-20-deoxyuridine assays, and Cell Counting Kit-8assays were used to investigate both proliferation and migration. In vivo tumorigenesis and metastasis assays were performed to investigate the role of hsa_circ_0006620 in prostate cancer. The results showed that hsa_circ_0006620 expression increased in prostate cancer cells and tissues. Hsa_circ_0006620 downregulation inhibited prostate cancer cell proliferation as well as in vivo and in vitro migrations. The luciferase results validated that miR-502-3p and hexokinase 2 (HK2) were hsa_circ_0006620 downstream targets. HK2 overexpression or miR-502-3p inhibition reversed prostate cancer cell migration after hsa_circ_0006620 silencing. The study also found that overexpression of HK2 or inhibition of prostate cancer reversed aerobic glycolysis after hsa_circ_0006620 silencing. In summary, the results showed thathsa_circ_0006620 downregulation inhibited prostate cancerby regulation of the miR-502-3p/HK2 axis mediated by aerobic glycolysis.

Recent Advances of Light/Hypoxia-Responsive Azobenzene in Nanomedicine Design.

Azobenzene (Azo) and its derivatives are versatile stimuli-responsive molecules. Their reversible photoisomerization and susceptibility to reduction-mediated cleavage make them valuable for various biomedical applications. Upon exposure to the UV light, Azo units undergo a thermodynamically stable trans-to-cis transition, which can be reversed by heating in the dark or irradiation with visible light. Additionally, the N=N bonds in azobenzenes can be cleaved under hypoxic conditions by azoreductase, making azobenzenes useful as hypoxia-responsive linkers. The integration of azobenzenes into nanomedicines holds promise for enhancing therapeutic efficacy, particularly in tumor targeting and controllable drug release. In this Concept paper, recent advances in the design and applications of azobenzene-based nanomedicines are updated, and future development opportunities are also summarized.

Identification of a novel intronic variant in COL4A2 gene associated with fetal severe cerebral encephalomalacia and subdural hemorrhage.

BACKGROUND: Genetic variants in COL4A2 are less common than those of COL4A1 and their fetal clinical phenotype has not been well described to date. We present a fetus from China with an intronic variant in COL4A2 associated with a prenatal diagnosis of severe cerebral encephalomalacia and subdural hemorrhage. METHODS: Whole exome sequencing (WES) was applied to screen potential genetic causes. Bioinformatic analysis was performed to predict the pathogenicity of the variant. In in vitro experiment, the minigene assays were performed to assess the variant's effect. RESULTS: In this proband, we observed ventriculomegaly, subdural hemorrhage, and extensive encephalomalacia that initially suggested cerebral hypoxic-ischemic and/or hemorrhagic lesions. WES identified a de novo heterozygous variant c.549 + 5G > A in COL4A2 gene. This novel variant leads to the skipping of exon 8, which induces the loss of 24 native amino acids, resulting in a shortened COL4A2 protein (p.Pro161_Gly184del). CONCLUSION: Our study demonstrated that c.549 + 5G > A in COL4A2 gene is a disease-causing variant by aberrant splicing. This finding enriches the variant spectrum of COL4A2 gene, which not only improves the understanding of the fetal neurological disorders associated with hypoxic-ischemic and hemorrhagic lesions from a clinical perspective but also provides guidance on genetic diagnosis and counseling.

Antibody-Calixarene Drug Conjugate: A General Drug Delivery Platform for Tumor-Targeted Therapy.

Antibody-drug conjugates (ADCs), which combine the precise targeting capabilities of antibodies with the powerful cytotoxicity of small-molecule drugs, have evolved into a promising approach for tumor treatment. However, the traditional covalent coupling method requires the design of a specific linker tailored to the properties of the small-molecule drugs, which greatly limits the development of ADCs and the range of drugs that can be used. Herein, a novel type of antibody-calixarene drug conjugates (ACDCs) that function similarly to ADCs by delivering drugs to their targets using antibodies but without the requirement of covalent conjugation of the drugs with antibodies is presented. By replacement of conventional linkers with supramolecular linkers, the ACDCs can load various chemotherapeutic drugs through host-guest interactions. Furthermore, ACDCs are readily reduced upon reaching the hypoxic microenvironment, resulting in rapid release of the drugs. With this precise drug encapsulation and controlled release mechanism, ACDCs deliver drugs to tumor tissues effectively and achieve a significantly enhanced antitumor effect. Considering that the ACDCs can be easily prepared by combining antibody-calixarene conjugates derived from tumor-targeting antibodies with various small-molecule drugs, ACDCs may provide a promising platform technology to accelerate ADC development and thus improve the therapeutic efficacy of chemotherapy.

Associations between insomnia and cardiovascular diseases: a meta-review and meta-analysis of observational and Mendelian randomization studies.

STUDY OBJECTIVES: Observational studies suggest associations between insomnia and cardiovascular diseases (CVDs), but the causal mechanism remains unclear. We investigated the potential causal associations between insomnia and CVDs by a combined systematic meta-review and meta-analysis of observational and Mendelian randomization (MR) studies. METHODS: We searched PubMed, Web of Science, and Embase for English-language articles from inception to 7/11/2023. Two reviewers independently screened the articles to minimize potential bias. We summarized the current evidence on the associations of insomnia with coronary artery disease (CAD), atrial fibrillation (AF), heart failure (HF), myocardial infarction (MI), hypertension (HTN), and stroke risk by combining meta-analyses of observational and MR studies. RESULTS: Four meta-analyses of observational studies and 9 MR studies were included in the final data analysis. A systematic meta-review of observational studies provided strong evidence that insomnia is an independent risk factor for many CVDs, including AF, MI, and HTN. A meta-analysis of MR studies revealed that insomnia may be potentially causally related to CAD (odds ratio (OR)=1.14, 95% confidence interval (CI)=1.10-1.19, I2=97%), AF (OR=1.02, 95% CI=1.01-1.04, I2=94%), HF (OR=1.04, 95% CI=1.03-1.06, I2 =97%), HTN (OR=1.16, 95% CI=1.13-1.18, I2=28%), large artery stroke (OR=1.14, 95% CI=1.05-1.24, I2=0%), any ischemic stroke (OR=1.09, 95% CI=1.03-1.14, I2=60%), and primary intracranial hemorrhage (OR=1.16, 95% CI=1.05-1.27, I2=0%). No evidence suggested that insomnia is causally associated with cardioembolic or small vessel stroke. CONCLUSIONS: Our results provide strong evidence supporting a possible causal association between insomnia and CVD risk. Strategies to treat insomnia may be promising targets for preventing CVDs.

An 18-gene signature of recurrence-associated endothelial cells predicts tumor progression and castration resistance in prostate cancer.

BACKGROUND: The prognostic and therapeutic implications of endothelial cells (ECs) heterogeneity in prostate cancer (PCa) are poorly understood. METHODS: We investigated associations of EC heterogeneity with PCa recurrence and castration resistance in 8 bulk transcriptomic and 4 single-cell RNA-seq cohorts. A recurrence-associated EC (RAEC) signature was constructed by comparing 11 machine learning algorithms through nested cross-validation. Functional relevances of RAEC-specific genes were also tested. RESULTS: A subset of ECs was significantly associated with recurrence in primary PCa and named RAECs. RAECs were characteristic of tip and immature cells and were enriched in migration, angiogenesis, and collagen-related pathways. We then developed an 18-gene RAEC signature (RAECsig) representative of RAECs. Higher RAECsig scores independently predicted tumor recurrence and performed better or comparably compared to clinicopathological factors and commercial gene signatures in multiple PCa cohorts. Of the 18 RAECsig genes, FSCN1 was upregulated in ECs from PCa with higher Gleason scores; and the silencing of FSCN1, TMEME255B, or GABRD in ECs either attenuated tube formation or inhibited PCa cell proliferation. Finally, higher RAECsig scores predicted castration resistance in both primary and castration-resistant PCa. CONCLUSION: This study establishes an endothelial signature that links a subset of ECs to prostate cancer recurrence and castration resistance.

The relationship between proportions of carbohydrate and fat intake and hyperglycaemia risk in Chinese adults.

OBJECTIVE: To address the relationship between the proportions of carbohydrates and fat and hyperglycaemia in the Chinese population. DESIGN: A cross-section research involving data from the China Health and Nutrition Survey in 2009, and nutritional status and health indicators were mainly focused. SETTING: China. PARTICIPANTS: 8197 Chinese individuals aged over 16 years, including 1345 subjects who had a low-carbohydrate and high-fat diet, 3951 individuals who had a medium proportion of carbohydrate and fat diet, 2660 participants who had a high-carbohydrate and low-fat diet and 241 people who had a very-high-carbohydrate and low-fat diet. RESULTS: Subjects with the high-carbohydrate and low-fat diet were significantly associated with an increased risk of hyperglycaemia (OR: 1·142; 95 % CI: 1·022, 1·276) when compared with the individuals with the medium proportion of carbohydrate and fat diet. Meanwhile, people with a very-high-carbohydrate and low-fat diet had a higher risk of hyperglycaemia (OR: 1·829; 95 % CI: 1·377, 2·429). In contrast, the association between participants with a low-carbohydrate and high-fat diet and hyperglycaemia was NS (OR: 1·082; 95 % CI: 0·942, 1·243) with adjusting a series of confounding factors. Furthermore, people with a very-high-carbohydrate and low-fat diet were significantly associated with a higher risk of hyperglycaemia in the major energy levels and social characteristics subgroup. CONCLUSIONS: We found the high-carbohydrate and low-fat and very-high-carbohydrate and low-fat diets were significantly associated with a high risk of hyperglycaemia. And, the association between low-carbohydrate and high-fat diets and the risk of hyperglycaemia was NS.

Effects of Intranasal Insulin Pretreatment on Preoperative Sleep Quality and Postoperative Delirium in Patients Undergoing Valve Replacement for Rheumatic Heart Disease.

Background: Postoperative delirium (POD) is a common neurological complication associated with valve replacement. Preoperative sleep disturbance is a risk factor for POD development, and nasal insulin modulates the sleep-wake cycle. This study investigated the beneficial effects of intranasal insulin pretreatment on preoperative sleep quality and reducing POD in patients undergoing valve replacement for rheumatic heart disease. Patients and Methods: This prospective, single-center, randomized controlled trial (RCT) included 76 adult patients aged 18-65 years undergoing valve surgery with cardiopulmonary bypass who were randomly allocated to receive intranasal insulin or normal saline interventions two days before surgery. POD incidence was on postoperative days 1 (T3), 2 (T4), and 3 (T5). Before the first intervention (T0), 1 d before surgery (T1), and before anesthesia on the day of surgery (T2), sleep quality was assessed and serum cortisol concentrations were measured. At T1 and T2, sleep quality related indicators monitored by sleep monitoring watches from the previous night were recorded. Results: Compared with the normal saline group, 3 days after surgery, the insulin group showed a significantly reduced incidence of POD; significantly increased deep sleep, REM sleep, deep sleep continuity, and total sleep quality scores at T1 and T2; and significantly reduced serum cortisol concentration, PSQI scale, light sleep ratio, and wakefulness at T1 and T2. Conclusion: The administration of 20 U of intranasal insulin twice daily, from 2 days preoperatively until 10 minutes preanesthesia on the day of surgery, can improved preoperative sleep quality significantly and reduced POD incidence in patients with rheumatic heart disease undergoing valve replacement. Clinical Trial Registration: This study was registered with the Chinese Clinical Trial Registry (www.chictr.org.cn, with the unique identifier ChiCTR2100048515; July 9, 2021).

Interruption of KLF5 acetylation promotes PTEN-deficient prostate cancer progression by reprogramming cancer-associated fibroblasts.

Inactivation of phosphatase and tensin homolog (PTEN) is prevalent in human prostate cancer and causes high-grade adenocarcinoma with a long latency. Cancer-associated fibroblasts (CAFs) play a pivotal role in tumor progression, but it remains elusive whether and how PTEN-deficient prostate cancers reprogram CAFs to overcome the barriers for tumor progression. Here, we report that PTEN deficiency induced Krüppel-like factor 5 (KLF5) acetylation and that interruption of KLF5 acetylation orchestrated intricate interactions between cancer cells and CAFs that enhance FGF receptor 1 (FGFR1) signaling and promote tumor growth. Deacetylated KLF5 promoted tumor cells to secrete TNF-α, which stimulated inflammatory CAFs to release FGF9. CX3CR1 inhibition blocked FGFR1 activation triggered by FGF9 and sensitized PTEN-deficient prostate cancer to the AKT inhibitor capivasertib. This study reveals the role of KLF5 acetylation in reprogramming CAFs and provides a rationale for combined therapies using inhibitors of AKT and CX3CR1.

Ferromagnetic Mn3+ Sawtooth Chains in A2(Mn2O)(SeO3)3 (A = K, Rb) Quaternary Selenites.

Two quaternary manganese selenites, A2(Mn2O)(SeO3)3 (A = K, Rb), have been synthesized by hydrothermal reactions. They both crystallize in a complex triclinic (P-1) structure built of Jahn-Teller (JT) distorted Mn3+O4+2 octahedra, connected into nearly isosceles [Mn3O14] triangles, themselves arranged into so-called "sawtooth (ST) chains". The K and Rb compounds show subtle variations in the orientations of the MnO4 planes inside the elementary triangles. The ST chains are structurally and magnetically isolated by SeO3 groups and alkali cations. In the ST chains, predominant ferromagnetic interactions were calculated and verified experimentally, which finally order antiferromagnetically between the chains around TN ≈ 22 K. The spin exchanges calculated by DFT + U and fitted by Monte Carlo simulations allow for the quantification of an effective "overall" model. The specific role of the µ3-O bridge on the ferromagnetic (FM) exchanges is discussed, together with spin reorientations observed in the ordered state. Magnetocrystalline anisotropy along the [110] direction stabilized by ∼50 meV per Mn by spin-orbit coupling (SOC) was found by DFT + U + SOC.

The role and transcriptomic mechanism of cell wall in the mutual antagonized effects between selenium nanoparticles and cadmium in wheat.

Selenium nanoparticles (SeNPs) has been reported as a beneficial role in alleviating cadmium (Cd) toxicity in plant. However, underlying molecular mechanisms about SeNPs reducing Cd accumulation and alleviating Cd toxicity in wheat are not well understood. A hydroponic culture was performed to evaluate Cd and Se accumulation, cell wall components, oxidative stress and antioxidative system, and transcriptomic response of wheat seedlings after SeNPs addition under Cd stress. Results showed that SeNPs application notably reduced Cd concentration in root and in shoot by 56.9% and 37.3%, respectively. Additionally, SeNPs prompted Cd distribution in root cell wall by 54.7%, and increased lignin, pectin and hemicellulose contents by regulating cell wall biosynthesis and metabolism-related genes. Further, SeNPs alleviated oxidative stress caused by Cd in wheat through signal transduction pathways. We also observed that Cd addition reduced Se accumulation by downregulating the expression level of aquaporin 7. These results indicated that SeNPs alleviated Cd toxicity and reduced Cd accumulation in wheat, which were associated with the synergetic regulation of cell wall biosynthesis pathway, uptake transporters, and antioxidative system via signaling pathways.

Photostabilities and anti-tumor effects of curcumin and curcumin-loaded polydopamine nanoparticles.

Currently, the photostability of photosensitizer curcumin is the main bottleneck limiting their application, reducing the bioavailability of curcumin. Studying the effect of different light sources on the photostabilities of curcumin and loading it onto polydopamine nanocarriers with better biocompatibility will help improve its light utilization efficiency. In this study, we investigated the photostabilities of curcumin and a polydopamine-based nanoparticle (polydopamine-curcumin composite nanoparticles, PDA-Cur NPs) loaded with curcumin through in vitro and in vivo experiments to achieve better antitumor effects. The results demonstrated that curcumin has good photostability in dark, but with significant photodegradation rates in both red and blue light. Blue light has a faster effect on the photodegradation of curcumin, with a degradation rate of 42.1% after 10 minutes, which is about 1.7 times that of the red light. Our study successfully synthesized PDA-Cur NPs, demonstrating its ability to stably load and release curcumin, with a loading percentage of 65.7% after 2 hours and 41.9% release in 8 hours (pH 6.0). Compared with single curcumin treatments, the photodegradation rates of PDA-Cur NPs in red and blue light treatments were reduced by 46% and 50%, respectively. Meanwhile, PDA-Cur NPs exhibited remarkable antitumor efficacy due to PDT and promote apoptosis in cancer cells, which both better than that of single curcumin treatments. Moreover, in MCF-7 tumor-bearing mice, the PDA-Cur NPs led to significant tumor growth inhibition effects, without causing evident systemic damage in vivo. The findings highlight the potential of PDA-Cur NPs as anticancer photosensitizer with greatly increased utilization of curcumin in PDT.

Corosolic acid delivered by exosomes from Eriobotrya japonica decreased pancreatic cancer cell proliferation and invasion by inducing SAT1-mediated ferroptosis.

BACKGROUND: In this study, we investigated whether Exo regulate the proliferation and invasion of PC. METHODS: In this study, we isolated the Eriobotrya japonica Exo using Ultra-high speed centrifugal method. Mass spectrum were used for Exo active components analysis. PC (Capan-1 and Bxpc-3) cells proliferation, migration, and apoptosis were detected using CCK8, ethynyldeoxyuridine, transwell, wound healing, and flow cytometry analyses. We also constructed a lung metastatic mouse model and subcutaneous tumor model to illustrate the regulation effect of Exo or active components. Proteomics were used to reveal the regulatory mechanism responsible for the observed effects. RESULTS: We isolated Eriobotrya japonica Exo and found that Exo treatment significantly suppressed cell migration and proliferation in both in vivo and in vitro using Capan-1. Mass spectrum for Exo active components analysis found that Exo contains high amounts of corosolic acid (CRA). The further study found that CRA treatment inhibit the proliferation, migration, and increased cell death of both Capan-1 and Bxpc-3 cells in a concentration-dependent manner. In vivo experiments confirmed that CRA inhibited pulmonary metastasis by decreasing the number of metastatic foci. Cell proteomics analysis showed that CRA treatment induced spermidine/spermine N1-acetyltransferase 1 (SAT1)-dependent ferroptosis. Treatment with the ferroptosis suppressor ferrostatin-1 significantly reversed CRA-induced cell apoptosis. CONCLUSION: The data suggested that corosolic acid delivered by exosomes from Eriobotrya japonica decreased pancreatic cancer cell proliferation and invasion by inducing SAT1-mediated ferroptosis.

Ginsenoside Rh2 shifts tumor metabolism from aerobic glycolysis to oxidative phosphorylation through regulating the HIF1-α/PDK4 axis in non-small cell lung cancer.

BACKGROUND: Ginsenoside Rh2 (G-Rh2), a steroidal compound extracted from roots of ginseng, has been extensively studied in tumor therapy. However, its specific regulatory mechanism in non-small cell lung cancer (NSCLC) is not well understood. Pyruvate dehydrogenase kinase 4 (PDK4), a central regulator of cellular energy metabolism, is highly expressed in various malignant tumors. We investigated the impact of G-Rh2 on the malignant progression of NSCLC and how it regulated PDK4 to influence tumor aerobic glycolysis and mitochondrial function. METHOD: We examined the inhibitory effect of G-Rh2 on NSCLC through I proliferation assay, migration assay and flow cytometry in vitro. Subsequently, we verified the ability of G-Rh2 to inhibit tumor growth and metastasis by constructing subcutaneous tumor and metastasis models in nude mice. Proteomics analysis was conducted to analyze the action pathways of G-Rh2. Additionally, we assessed glycolysis and mitochondrial function using seahorse, PET-CT, Western blot, and RT-qPCR. RESULT: Treatment with G-Rh2 significantly inhibited tumor proliferation and migration ability both in vitro and in vivo. Furthermore, G-Rh2 inhibited the tumor's aerobic glycolytic capacity, including glucose uptake and lactate production, through the HIF1-α/PDK4 pathway. Overexpression of PDK4 demonstrated that G-Rh2 targeted the inhibition of PDK4 expression, thereby restoring mitochondrial function, promoting reactive oxygen species (ROS) accumulation, and inducing apoptosis. When combined with sodium dichloroacetate, a PDK inhibitor, it complemented the inhibitory capacity of PDKs, acting synergistically as a detoxifier. CONCLUSION: G-Rh2 could target and down-regulate the expression of HIF-1α, resulting in decreased expression of glycolytic enzymes and inhibition of aerobic glycolysis in tumors. Additionally, by directly targeting mitochondrial PDK, it elevated mitochondrial oxidative phosphorylation and enhanced ROS accumulation, thereby promoting tumor cells to undergo normal apoptotic processes.

Puerarin attenuates remifentanil­induced postoperative hyperalgesia via targeting PAX6 to regulate the transcription of TRPV1.

Remifentanil­induced hyperalgesia (RIH) is characterized by the emergence of stimulation­induced pain, including phenomena such as allodynia and thermal hyperalgesia following remifentanil infusion. As a sequence­specific DNA binding transcription factor, PAX6 positively and negatively regulates transcription and is expressed in multiple cell types in the developing and adult central nervous system. It was hypothesized that puerarin could relieve RIH via targeting PAX6 to regulate transcription of transient receptor potential cation channel subfamily V Member 1 (TRPV1). A total of 32 rats were randomly divided into five groups, namely control group, RI group, RI + 10 mg/kg puerarin group (RI + puerarin10), RI + 20 mg/kg puerarin group (RI + puerarin20), and RI + 40 mg/kg puerarin group (RI + puerarin40). Mechanical and thermal hyperalgesia were tested at ­24, 2, 6, 24 and 48 h after remifentanil infusion. Following the sacrifice of rats after the last behavioral test, western blot was used to detect the expression levels of TRPV1 in the tissues; Immunofluorescence staining and western blotting were used to detect the expression of PAX6 in the spinal cord. PharmMapper and JASPAR were used to predict the binding sites of puerarin/PAX6/TRPV1. Chromatin immunoprecipitation­PCR and dual luciferase reporter assay were used to verify the targeting relationship between PAX6 and TRPV1. Immunofluorescence was used to detect the expression levels of TRPV1 and p­NR2B. The results revealed that puerarin (10, 20, 40 mg/kg) dose­dependently reduced thermal and mechanical hyperalgesia from 2 to 48 h after remifentanil infusion. Remifentanil infusion remarkably stimulated the expression of phosphorylated (p­)NR2B. Nevertheless, the increased amount of p­NR2B by RIH was dose­dependently suppressed by puerarin in rats. In conclusion, puerarin was revealed to attenuate postoperative RIH via targeting PAX6 to regulate the transcription of TRPV1.

Oncogenic circ-SLC16A1 promotes progression of non-small cell lung cancer via regulation of the miR-1287-5p/profilin 2 axis.

BACKGROUND: Circular RNAs (circRNAs) are single-stranded RNAs with covalently closed structures that have been implicated in cancer progression. However, the regulatory mechanisms remain largely unclear. So, the aim of this study was to reveal the role and regulatory mechanisms of circ-SLC16A1. METHODS: In this study, next-generation sequencing was used to identify abnormally expressed circRNAs between cancerous and para-carcinoma tissues. Fluorescence in situ hybridization and quantitative reverse transcription polymerase chain reaction were performed to assess the expression patterns of circ-solute carrier family 16 member 1 (SLC16A1) in non-small cell lung cancer (NSCLC) cells and tissue specimens. The dual-luciferase reporter assay was utilized to identify downstream targets of circ-SLC16A1. Transwell migration, wound healing, 5-ethynyl-2'-deoxyuridine incorporation, cell counting, and colony formation assays were conducted to assess the proliferation and migration of NSCLC cells. A mouse tumor xenograft model was employed to determine the roles of circ-SLC16A1 in NSCLC progression and metastasis in vivo. RESULTS: The results found that circ-SLC16A1 was upregulated in NSCLC cells and tissues. Downregulation of circ-SLC16A1 inhibited tumor growth by reducing proliferation, lung metastasis, and lymphatic metastasis of NSCLC cells, and arrested the cell cycle in the G1 phase. Also, silencing of circ-SLC16A1 promoted apoptosis of NSCLC cells. The results of bioinformatics analysis and the dual-luciferase reporter assay confirmed that microRNA (miR)-1287-5p and profilin 2 (PFN2) are downstream targets of circ-SLC16A1. PFN2 overexpression or circ-SLC16A1 inhibition restored proliferation and migration of NSCLC cells after silencing of circ-SLC16A1. PFN2 overexpression restored migration and proliferation of NSCLC cells post miR-1287-5p overexpression. CONCLUSIONS: Collectively, these findings show that miR-1287-5p/PFN2 signaling was associated with downregulation of circ-SLC16A1 and reduced invasion and proliferation of NSCLC cells. So, circ-SLC16A1 is identified as a mediator of multiple pro-oncogenic signaling pathways in NSCLC and can be targeted to suppress tumor progression.

Inhibitory effects of Pseudomonas sp. W112 on cadmium accumulation in wheat grains: Reduced the bioavailability in soil and enhanced the interception by plant organs.

Microorganisms play an important role in heavy metal bioremediation and soil fertility. The effects of soil inoculation with Pseudomonas sp. W112 on Cd accumulation in wheat were investigated by analyzing the transport, subcellular distribution and speciation of Cd in the soil and plants. Pseudomonas sp. W112 application significantly decreased Cd content in the roots, internode and grains by 10.2%, 29.5% and 33.0%, respectively, and decreased Cd transfer from the basal nodes to internodes by 63.5%. Treatment with strain W112 decreased the inorganic and water-soluble Cd content in the roots and increased the proportion of residual Cd in both the roots and basal nodes. At the subcellular level, the Cd content in the root cell wall and basal node cytosol increased by 19.6% and 61.8%, respectively, indicating that strain W112 improved the ability of the root cell wall and basal node cytosol to fix Cd. In the rhizosphere soil, strain W112 effectively colonized and significantly decreased the exchangeable Cd, carbonate-bound Cd and iron-manganese oxide-bound Cd content by 43.5%, 27.3% and 17.6%, respectively, while it increased the proportion of residual Cd by up to 65.2%. Moreover, a 3.1% and 23.5% increase in the pH and inorganic nitrogen content in the rhizosphere soil, respectively, was recorded. Similarly, soil bacterial community sequencing revealed that inoculating with strain W112 increased the abundance of Pseudomonas, Thauera and Azoarcus, which are associated with inorganic nitrogen metabolism, and decreased that of Acidobacteria, which is indicative of soil alkalinization. Hence, root application of Pseudomonas sp. W112 improved soil nitrogen availability and inhibited Cd accumulation in the wheat grains in a two-stage process: by reducing the Cd availability in the rhizosphere soil and by improving Cd interception and fixation in the wheat roots and basal nodes. Pseudomonas sp. W112 may be a suitable bioremediation agent for restoring Cd-contaminated wheat fields.