Exosomal circRNAs in the plasma serve as novel biomarkers for IPF diagnosis and progression prediction.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a type of chronic interstitial pneumonia, often fatal, with elusive causes and a bleak prognosis. Its treatment options are limited and largely ineffective. Early detection and precise diagnosis are pivotal in managing the disease effectively and enhancing patient survival rates. Recently, the quest for trustworthy biomarkers for IPF has gained momentum. Notably, emerging studies indicate that circular RNAs (circRNAs) found in exosomes may hold significant potential as valuable diagnostic markers. METHODS: In this study, we initially explored the expression profile of circRNAs in exosomes sourced from the blood of IPF patients and healthy volunteers, employing a human circRNA microarray. We then utilized RT-qPCR to corroborate the dysregulated circRNAs identified by the microarray during the training phase. Next, the circRNAs that displayed a significant increase during the training phase were selected for further validation in a larger cohort encompassing 113 IPF patients and 76 healthy volunteers. Ultimately, the expression level and function of hsa_circ_0044226 were substantiated through a series of in vivo and in vitro experiments. RESULTS: Utilizing a human circRNA microarray, we identified 11 dysregulated circRNAs in the exosomes derived from the blood of IPF patients and control volunteers. Subsequent RT-qPCR analysis revealed significant increases in three circRNAs (hsa_circ_0044226, hsa_circ_0004099, hsa_circ_0008898) within the IPF patients. Notably, hsa_circ_0044226 was markedly elevated in patients experiencing acute exacerbation of IPF (AE-IPF) compared to those with stable IPF (S-IPF). Additionally, an upregulation of hsa_circ_0044226 was observed in the blood exosomes derived from a bleomycin-induced IPF mouse model. CONCLUSION: The expression levels of hsa_circ_0044226, hsa_circ_0004099, and hsa_circ_0008898 in plasma exosomes introduce a new paradigm of biomarkers for the diagnosis and progression of IPF.

The fungal quorum-sensing molecule, farnesol, regulates the immune response of vaginal epithelial cells against Candida albicans.

BACKGROUND: Farnesol is a Candida-secreted quorum-sensing molecule of great interest as a potential antifungal agent for serious and hardly curable infections-candidiasis, especially vulvovaginal candidiasis (VVC). METHODS: The effect of farnesol on cellular morphology and viability and evaluated the production of Th1 (IL-2), Th2 (IL-4), proinflammatory (IL-6), chemotactic (IL-8), and Th17 (IL-17) cytokines in the culture supernatants of vaginal epithelial cell line (VK2) were evaluated. Moreover, we tested the inhibitory effect of farnesol on C. albicans adhesion. Scanning electron microscopy was conducted to observe any VK2 cell ultrastructural changes. RESULTS: Only low concentrations (≤ 50 µmol/L) of farnesol did not affect the morphology and viability of the VK2 cells (P > 0.05). Farnesol reduced the adhesion of C. albicans to the VK2 cells. When treated with farnesol, statistical elevated levels of both IL-4 and IL-17 secreted by the infected VK2 cells were present in the culture supernatants (P < 0.05). CONCLUSIONS: Farnesol acts as a stimulator to up-regulate the Th17-type innate immune response, as well as Th2-type humoral immunity following C. albicans infection. Further research is required to select the optimal therapeutic dose to develop efficacious and safe mucosal immune adjuvant for treating VVCs.

ESM-1 Mediates Cell Progression in Clear Cell Renal Cell Carcinoma by Affecting Wnt/ß-Catenin Signalling Pathway.

BACKGROUND: Overexpressed endothelial cell specific molecule-1 (ESM-1) has been identified in various human malignancies, but its expression and function in clear cell renal cell carcinoma (ccRCC) progression are still uncovered. This study explored the critical roles as well as molecular mechanism of ESM-1 in ccRCC progression. METHODS: The ESM-1 expression in ccRCC tissues and cells was measured using Western blot assay. The function of ESM-1 knockdown in ccRCC cell viability, invasion as well as migration was analysed. Changes in specific proteins were also detected by Western blot analysis. RESULTS: The ESM-1 expression increased in ccRCC tissue samples and cells, which indicated poor prognosis. Moreover, ESM-1 silencing considerably inhibited ccRCC cell growth, invasion and migration in vitro. ESM-1 partially promoted ccRCC development through wingless-type mouse mammary tumour integration site family/beta-catenin (Wnt/ß-catenin signalling). CONCLUSIONS: ESM-1 acted as an oncogene by influencing the Wnt/ß-catenin pathway in ccRCC.

Inhibiting specificity protein 1 attenuated sevoflurane-induced mitochondrial stress and promoted autophagy in hippocampal neurons through PI3K/Akt/mTOR and α7-nAChR signaling.

Sevoflurane, a commonly used anesthetic in surgery, is considered as an inducer of neurodegenerative diseases and postoperative complications including postoperative cognitive dysfunction. Evidence showed that specificity protein 1 (SP1) participated in the regulation of various cellular processes. Also, SP1 was found to modulate sevoflurane-induced hippocampal inflammatory injury both in vitro and in vivo. Our study aimed to illustrate the role of SP1 in mediating mitochondrial stress and autophagy in neurons under sevoflurane exposure. SiRNA for SP1 was transfected in to hippocampus neurons for the loss-of-function assay before sevoflurane stimulation. Meanwhile, recilisib was utilized for PI3K/Akt/mTOR signaling activation, GTS-21 and MLA (methylycaconitine citrate) were used to activate or inactivate alpha 7 nicotinic acetylcholine receptor (α7-nAChR), respectively. Sevoflurane induced SP1 upregulation and autophagy suppression. Interfering SP1 dramatically depressed the promoted oxidative stress and mitochondrial dysfunction induced by sevoflurane. Additionally, SP1 silence blocked sevoflurane-induced activation of PI3K/Akt/mTOR signaling and inhibition of α7-nAChR. Restoring PI3K/Akt/mTOR signaling or depressing CAP significantly reversed the repressive effects of SP1 knockdown on mitochondrial stress and autophagy imbalance in hippocampal cells. In conclusions, our research indicated that SP1 regulated sevoflurane-induced oxidative stress dysregulation, mitochondrial function and cell autophagy in hippocampus via mediating the PI3K/Akt/mTOR and α7-nAChR pathways. Therefore, it might provide a novel sight for sevoflurane-induced hippocampus injury and POCD therapy.

Prediction of prognosis and immunotherapy response of amino acid metabolism genes in acute myeloid leukemia.

Background: Amino acid (AA) metabolism plays a crucial role in cancer. However, its role in acute myeloid leukemia (AML) is still unavailable. We screened out AA metabolic genes, which related to prognosis, and analyzed their correlation with tumor immune microenvironment in AML. Methods: We evaluated 472 amino acid metabolism-related genes in 132 AML patients. The predictive risk model was developed according to differentially expressed genes, univariate Cox and LASSO analyses. We validated the risk signature by survival analysis and independence tests. Single-sample gene set enrichment analysis (ssGSEA), tumor immune microenvironment (TME), tumor mutation burden (TMB), functional enrichment, and the IC50 of drugs were assessed to explore the correlations among the risk model, immunity, and drug sensitivity of AML. Results: Six amino acid metabolism-related genes were confirmed to develop the risk model, including TRH, HNMT, TFEB, SDSL, SLC43A2, and SFXN3. The high-risk subgroup had an immune "hot" phenotype and was related to a poor prognosis. The high-risk group was also associated with more activity of immune cells, such as Tregs, had higher expression of some immune checkpoints, including PD1 and CTLA4, and might be more susceptible to immunotherapy. Xenobiotic metabolism, the reactive oxygen species (ROS) pathway, fatty acid metabolism, JAK/STAT3, and the inflammatory response were active in the high-risk subgroup. Furthermore, the high-risk subgroup was sensitive to sorafenib, selumetinib, and entospletinib. ssGSEA discovered that the processes of glutamine, arginine, tryptophan, cysteine, histidine, L-serine, isoleucine, threonine, tyrosine, and L-phenylalanine metabolism were more active in the high-risk subgroup. Conclusion: This study revealed that AA metabolism-related genes were correlated with the immune microenvironment of AML patients and could predict the prognosis and immunotherapy response of AML patients.

Sevoflurane induces inflammation of microglia in hippocampus of neonatal rats by inhibiting Wnt/ß-Catenin/CaMKIV pathway.

OBJECTIVE: To investigate the effect of sevoflurane on inflammation of microglia in hippocampus of neonatal rats, and to investigate whether the related mechanism is related to Wnt/ß-Catenin/CaMKIV pathway. METHODS: Neonatal rats were anesthetized with 2% or 3% sevoflurane for 4 h a day for 3 consecutive days. Water maze test was used to detect the effect of sevoflurane anesthesia on memory function of neonatal rats. H&E and Nissl staining were used to observe the pathological damage of hippocampal area of neonatal rats induced by sevoflurane anesthesia. The expression of microglial marker Iba-1 was detected by Immunofluorescence. Immunofluorescence and WB were used to detect the expression CD32b, CD86, TNF-α, IL-6, Wnt3a, ß-Catenin and CaMKIV in hippocampus. To further explore the related mechanism, Wnt-3α inhibitor and activator was treated to study the effect of sevoflurane on microglial inflammation in hippocampus of neonatal rats. RESULTS: Sevoflurane anesthesia significantly increased escape latency time, reduced platform crossing times, and damaged the learning and memory ability of neonatal rats. H&E and Nissl staining results showed that sevoflurane anesthesia caused obvious damage to the hippocampus of neonatal rats. Sevoflurane anesthesia promoted the expression of Iba-1 and activated microglia. Sevoflurane anesthesia not only significantly increased the positive expression of CD32b, CD86, TNF-α and IL-6, but also decreased the expression of Wnt3a, ß-Catenin and CaMKIV. These results suggested that sevoflurane inhibited Wnt/ß-Catenin/CaMKIV pathway. CONCLUSION: Sevoflurane induces inflammation of microglia in hippocampus of neonatal rats by inhibiting Wnt/ß-Catenin/CaMKIV pathway.

Identification of immune-related genes with prognostic significance in the microenvironment of cutaneous melanoma.

Cutaneous melanoma is one of the most aggressive cancers characterized by increasing incidence and mortality. In recent years, the emergence of immunotherapy has greatly raised the survival rate of patients suffering from cutaneous melanoma, yet some sufferers remain to have poor outcomes after treatment mainly due to the tumor microenvironment (TME). In this study, cutaneous melanoma-associated TME was systematically analyzed using the ESTIMATE algorithm based on the gene transcriptome data obtained from the TCGA database. Totally, 471 patients were included and 553 TME-related genes were screened. Afterwards, a 3-gene signature-based model (CLEC4A, GBP4, KIR2DL4) was constructed via univariate Cox, LASSO, and multivariate Cox regression analyses. To validate the validity of this model, ROC analysis was conducted, and the model was further validated to be an independent prognostic biomarker through univariate and multivariate regression analyses. Finally, the three genes in the model were studied by GSEA and GSVA for their biological significance. We found that the three genes could promote cancer immune response predominantly through affecting immune-related pathways such as antigen processing and presentation, and they may help tumor cells in escaping from surveillance of the immune system when their expression levels were decreased. Additionally, we as well discovered that the expression of the three genes was significantly and positively correlated with the infiltration of related immune cells, but negatively associated with tumor purity. Overall, this study comprehensively analyzed the TME of cutaneous melanoma, identified related biomarkers, and discovered their association with immune system.

ZFAS1 Promotes Cisplatin Resistance via Suppressing miR-421 Expression in Oral Squamous Cell Carcinoma.

PURPOSE: Oral squamous cell carcinoma (OSCC), with high incidence and mortality, represents one of the main reasons for head and neck malignant tumors. We want to investigate the effect of ZFAS1 on DDP resistance in oral squamous cell carcinoma. METHODS: The proliferation and migration of cells was detected by CCK-8 and Transwell assay. The apoptosis was measured by flow cytometry and Western blot. The interaction of ZFAS1, miR-421, and MEIS2 was verified by luciferase reporter assay. The role of ZFAS1 in DDP resistance in vivo was tested by the nude mice model. The expression of ZFAS1 in exosomes from cisplatin-resistant patients was also determined. RESULTS: ZFAS1 overexpression improved OSCC cell growth and inhibited OSCC cell susceptibility to DDP. In addition, the silencing of ZFAS1 promoted DDP-induced apoptosis. ZFAS1 directly bound to miR-421, which was verified by luciferase reporter assay. Inhibition of miR-421 reversed the effect of si-ZFAS1, which promoted the cell viability and decreased the sensitivity of DDP in DDP-resistant cells. The in vivo experiment showed the role of ZFAS1 in increasing the DDP resistance in OSCC tumor. Importantly, this study also showed upregulated ZFAS1 in serum exosomes derived from cisplatin-resistant patients. CONCLUSION: ZFAS1 promotes chemoresistance of oral squamous cell carcinoma to cisplatin and might become a latent therapeutic target for treating OSCC.

miR-146a promotes proliferation, invasion, and epithelial-to-mesenchymal transition in oral squamous carcinoma cells.

Epithelial-to-mesenchymal transition (EMT) is key to invasion and metastasis by oral squamous carcinoma (OSCC) cells. MicroRNAs (miRNAs) such as miRNA-146a are known to be upregulated in OSCC. However, it is unclear whether they are involved in driving EMT. Here, we investigated the effect of miR-146a overexpression on proliferation, migration, and EMT in OSCC cells. OSCC cells were transfected with a plasmid expressing miR-146a precursor. Cell lines that stably overexpressed miRNA-146a were assessed for proliferation, colony formation, and invasiveness in vitro. Expression of markers and regulators of EMT, cell motility, and invasion were measured by qRT-PCR and western blot. Potential miRNA-146a binding sites in the 3'UTR of ST8SIA4 were identified by bioinformatic analysis. To confirm that miRNA-146a binds to and regulates ST8SIA4, we transfected OSCC cell lines with miRNA-146a mimics and a luciferase reporter construct containing either the wild type or mutant 3'UTR of ST8SIA4. OSCC cell lines that overexpressed miR-146a displayed higher proliferation, colony formation, invasion, and MMP-2 activity than cells transfected with a control vector. Overexpression of miR-146a also decreased expression of the epithelial cell marker E-cadherin and increased expression of Twist1, a transcription factor that promotes EMT, as well as markers associated with mesenchymal cells (vimentin and N-cadherin) and tumor invasion (p-paxillin and p-cortactin). Luciferase expression was lower in OSCC cells transfected with miRNA-146a mimics or with luciferase constructs carrying the wild type, but not mutant, 3'UTR of ST8SIA4. Overexpression of miR-146a promotes EMT phenotypes and may drive tumorigenesis and progression in OSCC, making it a useful target for future OSCC treatments.

Ultrasound and Clinical Characteristics of False-negative Results in Mammography Screening of Dense Breasts.

OBJECTIVE: We analyzed the clinical and ultrasound characteristics associated with false-negative mammography results in women with dense breasts. MATERIALS AND METHODS: The present study included 191 women (mean age, 54.47 ± 11.61 years; range, 31-75 years) who had presented from July 2015 to June 2018 with pathologically confirmed breast cancer. The mammography, conventional ultrasound, and elastography imaging results of these patients were reviewed. Breast density and screening cancer probability from mammography and conventional ultrasound imaging were scored using the Breast Imaging Reporting and Data System. Multivariate logistic regression analysis was performed to identify the factors independently associated with the false-negative results on breast mammographic screening. RESULTS: Of 191 confirmed breast cancer cases, 55 (28.8%) were assigned to category ≤ 3, and 136 (71.2%) were assigned to category ≥ 4a according to the mammography findings. All the breasts were graded mammographically as dense. A rougher margin (odds ratio [OR], 8.123; 95% confidence interval [CI], 1.731-38.127) was the strongest independent factor associated with negative results, followed by a lower stiffness ratio (OR, 7.773; 95% CI, 2.574-23.473), negative axillary lymph node status (OR, 5.066; 95% CI, 1.028-24.955), and softer lesions (OR, 1.037; 95% CI, 1.001-1.075). CONCLUSION: Women with dense breasts, a lower lesion/glandular tissue stiffness ratio, and softer cancer can easily lead to a misdiagnosis using mammography. By giving sufficient attention to the margin, earlier stage cancer with negative lymph node status are more likely to benefit from supplemental ultrasound imaging.

Lysosomes as a therapeutic target.

Lysosomes are membrane-bound organelles with roles in processes involved in degrading and recycling cellular waste, cellular signalling and energy metabolism. Defects in genes encoding lysosomal proteins cause lysosomal storage disorders, in which enzyme replacement therapy has proved successful. Growing evidence also implicates roles for lysosomal dysfunction in more common diseases including inflammatory and autoimmune disorders, neurodegenerative diseases, cancer and metabolic disorders. With a focus on lysosomal dysfunction in autoimmune disorders and neurodegenerative diseases - including lupus, rheumatoid arthritis, multiple sclerosis, Alzheimer disease and Parkinson disease - this Review critically analyses progress and opportunities for therapeutically targeting lysosomal proteins and processes, particularly with small molecules and peptide drugs.

Knock-down of JAK2 and PTEN on pain behavior in rat model of trigeminal neuropathic pain.

Trigeminal neuropathic pain is seen as a huge clinical challenge. Although numerous drugs have been developed to treat the condition, some patients have shown intolerance to the drugs and thus continue to suffer. In the present study, a rat model of trigeminal neuropathic pain was established using incorrectly positioned dental implants, which had various manifestations that were similar to human trigeminal neuropathic pain. Using this model, we investigated the differential regulation of JAK2 and PTEN. Firstly, we examined the expression of JAK2 and PTEN in the medullary dorsal horn. After inhibiting JAK2/PTEN, we evaluated nociception-related behavioral alterations. The rat models were established by replacing the left lower second molar with a mini dental implant. Immunoblot assay and immunofluorescence experiments indicated high expression of JAK2 and PTEN in medullary dorsal horn after the nerve injury, which attained plateau levels on post-operative day (POD) 5-10 and 10-20. Administration of adenovirus-shRNA-JAK2 on POD 1 reduced mechanical allodynia and downstream STAT activation. Meanwhile, the administration of adenovirus-shRNA-PTEN on POD 1 attenuated mechanical allodynia while upregulating AKT. In addition to postoperative JAK2 and PTEN activation, dexmedetomidine treatment (10 mg/kg) also modulated the downstream sensors of these signaling molecules. These data suggest that JAK2 and PTEN are pivotal to the development of trigeminal neuropathic pain, and that JAK2 and PTEN suppression alleviates the neuropathic pain.

Effect of Inhibitor on Adsorption Behavior and Mechanism of Micro-Zone Corrosion on Carbon Steel.

A new type of inhibitor is studied in this paper. Inhibition efficiency and adsorption behavior of an inhibitor film on the steel surface is tested via the electrochemical method and theoretical calculation to establish the adsorption model. Test results confirm that inhibition efficiency is improved with the addition of an inhibitor, and the inhibitor film is formed firmly by comparing the characteristic peaks of S and N. Moreover, the micro-zone corrosion progress of Fe in 3.5% invasive NaCl-simulated seawater environment is studied. The results further show that corrosion is initiated under the zone without the inhibitor film, while it is prevented under the protection of the film. By the experiments, it is shown that inhibitor can be adsorbed on the surface of steel stably and has excellent protection performance for reinforced rebar, which can be widely used in concrete structure.

Blocking nuclear export of HSPA8 after heat shock stress severely alters cell survival.

The nuclear translocation of endogenous heat shock cognate protein HSPA8 is a requisite for cell survival during oxidative and heat shock stress. Upon these events, cytoplasmic HSPA8 is thought to concentrate within the nucleus and nucleolus. When the situation returns to normal, HSPA8 is released from its nuclear/nucleolar anchors and redistributes into the cytoplasm. By using different stress conditions and a 21-mer phosphopeptide tool called P140, which binds HSPA8 and hampers its chaperone properties, we deciphered the cellular and molecular effects arising during this vital cytoplasmic-nuclear-cytoplasmic shuttling process. Using the non-metastatic fibroblastoid cell line MRL/N-1 derived from a MRL/MpTn-gld/gld lupus-prone mouse, we discovered that P140 treatment neutralized the egress of HSPA8 from nucleus to cytoplasm in the cell recovery phase. This lack of relocation of HSPA8 into the cytoplasm of heat-shocked MRL/N-1 cells altered the ability of these cells to survive when a second mild oxidative stress mimicking inflammatory conditions was applied. Crosslinking experiments followed by proteomics studies showed that P140 binds regions close to nuclear import and export signal sequences encompassed within the HSPA8 structure. These data are consistent with HSPA8 having a crucial cell protective role against reactive oxygen species (ROS) production by mitochondria during inflammatory conditions.

Autophagy: A new concept in autoimmunity regulation and a novel therapeutic option.

Nowadays, pharmacologic treatments of autoinflammatory diseases are largely palliative rather than curative. Most of them result in non-specific immunosuppression, which can be associated with broad disruption of natural and induced immunity with significant and sometimes serious unwanted injuries. Among the novel strategies that are under development, tools that modulate the immune system to restore normal tolerance mechanisms are central. In these approaches, peptide therapeutics constitute a class of agents that display many physicochemical advantages. Within this class of potent drugs, the phosphopeptide P140 is very promising for treating patients with lupus, and likely also patients with other chronic inflammatory diseases. We discovered that P140 targets autophagy, a finely orchestrated catabolic process, involved in the regulation of inflammation and in the biology of immune cells. In vitro, P140 acts directly on a particular form of autophagy called chaperone-mediated autophagy, which seems to be hyperactivated in certain subsets of lymphocytes in lupus and in other autoinflammatory settings. In lupus, the "correcting" effect of P140 on autophagy results in a weaker signaling of autoreactive T cells, leading to a significant improvement of pathophysiological status of treated mice. These findings also demonstrated ex vivo in human cells, open novel avenues of therapeutic intervention in pathological conditions, in which specific and not general targeting is highly pursued in the context of the new action plans for personalized medicines.

Lysosome-dependent cell death and deregulated autophagy induced by amine-modified polystyrene nanoparticles.

Nanoparticles (NPs) typically accumulate in lysosomes. However, their impact on lysosomal function, as well as autophagy, a lysosomal degradative pathway, is still not well known. We have previously reported in the 1321N1 cell line that amine-modified polystyrene (NH2-PS) NPs induce apoptosis through damage initiated in the lysosomes leading ultimately to release of lysosomal content in the cytosol, followed by apoptosis. Here, by using a combination of biochemical and cell biological approaches, we have characterized in a mouse embryonic fibroblast cell line that the lysosomal alterations induced by NH2-PS NPs is progressive, initiating from mild lysosomal membrane permeabilization (LMP), to expansion of lysosomal volume and intensive LMP before the summit of cell death. Though the cells initially seem to induce autophagy as a surviving mechanism, the damage of NH2-PS NPs to lysosomes probably results in lysosomal dysfunctions, leading to blockage of autophagic flux at the level of lysosomes and the eventual cell death.

Rescue of autophagy and lysosome defects in salivary glands of MRL/lpr mice by a therapeutic phosphopeptide.

Sjögren's syndrome is a multifactorial systemic autoimmune disorder characterized by lymphocytic infiltrates in exocrine organs. Patients present with sicca symptoms, such as extensive dry eyes and dry mouth, and parotid enlargement. Other serious complications include profound fatigue, chronic pain, major organ involvement, neuropathies and lymphomas. Current treatments only focus on relieving symptoms and do not target the origin of the disease, which is largely unknown. The question we addressed here was whether some defects exist in autophagy processes in Sjögren's syndrome and if they can be corrected or minimized using an appropriate mechanism-driven treatment targeting this central survival pathway. Using a recognized murine model of secondary Sjögren's syndrome, we identified molecular alterations of autophagy occurring in the salivary glands of MRL/lpr mice, and discovered that opposite (up- or down-regulated) autophagy events can arise in distinct organs of the same mouse strain, here in lymphoid organs and salivary glands. We showed further that the therapeutic P140 peptide, known to directly act on chaperone-mediated autophagy, rescued MRL/lpr mice from cellular infiltration and autophagy defects occurring in salivary glands. Our findings provide a proof-of-concept that targeting autophagy might represent a promising therapeutic strategy for treating patients with Sjögren's syndrome.

Intermittent time-set technique controlling the temperature of magnetic-hyperthermia-ablation for tumor therapy.

Magnetic-hyperthermia-ablation is considered as an effective and minimally invasive technology for tumor therapy. However, inappropriate temperature control could induce an excessively high temperature which brings potential safety problems and limits clinical transformation of this technique. Herein, aiming to control the temperature during magnetic hyperthermia ablation, we develop an intermittent time-set technique for temperature control in magnetic hyperthermia ablation of tumors using a polylactic-co-glycolic acid (PLGA)-Fe3O4 implant. In vitro, the intermittent time is set as follows: tubes are continuously heated for 110 seconds. Then the heating process is paused for 20 seconds, and then the tubes are reheated for 10 seconds, followed by repeating the last two processes. The temperature elevation profile upon magnetic hyperthermia interestingly also demonstrates good controllability despite some differences in time-setting between in vitro and in vivo. The in vivo results show the temperature fluctuates within the range of 6.45 ± 1.34 °C after reaching the target temperature. Furthermore, we observe the deformation of an implant employing three-dimensional (3D) ultrasound to better understand the temperature change. The results show no significant deformation of the implant after being heated. The microscopic images prove that this simple technique can successfully cause tumor regression. This temperature control technique provides great benefits for hyperthermia ablation against tumors, advancing the magnetic hyperthermal ablation technology in clinical translation.

A pH and magnetic dual-response hydrogel for synergistic chemo-magnetic hyperthermia tumor therapy.

To overcome the toxicity of chemotherapy, increasing attention has been paid to local drug delivery systems (DDSs). pH-Sensitive hydrogels have emerged as promising DDS materials in the biomedical field due to their remarkable characteristics. However, the pH environment in tumor varies from person to person, which makes the applicability of systems based on pH challenging. In this study, we developed a contractible hydroxypropyl methyl cellulose (HPMC)/Fe3O4 hydrogel with dual-response pH and magnetic properties aiming to overcome the limitations of pH-sensitive hydrogel drug delivery systems and further increase their efficiency in tumor therapy. The HPMC/Fe3O4 hydrogel could act as a drug delivery system that combines pH-sensitive triggering and magnetic dual-response drug release for synergistic chemo-magnetic hyperthermia therapy. The drug delivery profile of the HPMC/Fe3O4/doxorubicin hydrochloride (DOX) hydrogel was determined in vitro and revealed a remarkable pH-sensitive performance. After synergistic chemo-magnetic hyperthermia treatment, mice with 4T1 breast cancer xenografts recovered without any recurrence or metastasis, demonstrating the synergistic effect of chemotherapy and magnetic hyperthermia therapy. Meanwhile, reduced toxicity and superior anticancer effects were achieved due to the combined effect of the pH and magnetic hyperthermia response properties. This study demonstrated the high efficacy and low toxicity of the improved design of HPMC/Fe3O4 for drug delivery, which may provide a promising approach for the application of chemo-magnetic hyperthermia cancer therapy.

Molecule adsorption and corrosion mechanism of steel under protection of inhibitor in a simulated concrete solution with 3.5% NaCl.

Herein, the protective performance of a new triazole inhibitor for carbon steel was studied by electrochemical methods. Potentiodynamic polarization curves showed that the anti-corrosion efficiency improved with increasing concentrations of the inhibitor and the results show that it is 22 times corrosion resistance efficiency for inhibitor compared to bare aggressive solution. X-ray photoelectron spectroscopy showed that the film adsorbed well on the carbon steel surface. The scanning vibrating electrode technique demonstrated the corrosion process of carbon steel with and without the protection of inhibitor. Thus, a mechanism for the corrosion process was proposed and the behavior of carbon steel under the protection of the inhibitor was discussed.