Excessive Polyamine Generation in Keratinocytes Promotes Self-RNA Sensing by Dendritic Cells in Psoriasis.

Psoriasis is a chronic inflammatory disease whose etiology is multifactorial. The contributions of cellular metabolism to psoriasis are unclear. Here, we report that interleukin-17 (IL-17) downregulated Protein Phosphatase 6 (PP6) in psoriatic keratinocytes, causing phosphorylation and activation of the transcription factor C/EBP-ß and subsequent generation of arginase-1. Mice lacking Pp6 in keratinocytes were predisposed to psoriasis-like skin inflammation. Accumulation of arginase-1 in Pp6-deficient keratinocytes drove polyamine production from the urea cycle. Polyamines protected self-RNA released by psoriatic keratinocytes from degradation and facilitated the endocytosis of self-RNA by myeloid dendritic cells to promote toll-like receptor-7 (TLR7)-dependent RNA sensing and IL-6 production. An arginase inhibitor improved skin inflammation in murine and non-human primate models of psoriasis. Our findings suggest that urea cycle hyperreactivity and excessive polyamine generation in psoriatic keratinocytes promote self-RNA sensation and PP6 deregulation in keratinocytes is a pivotal event that amplifies the inflammatory circuits in psoriasis.

A lncRNA Dleu2-encoded peptide relieves autoimmunity by facilitating Smad3-mediated Treg induction.

Micropeptides encoded by short open reading frames (sORFs) within long noncoding RNAs (lncRNAs) are beginning to be discovered and characterized as regulators of biological and pathological processes. Here, we find that lncRNA Dleu2 encodes a 17-amino-acid micropeptide, which we name Dleu2-17aa, that is abundantly expressed in T cells. Dleu2-17aa promotes inducible regulatory T (iTreg) cell generation by interacting with SMAD Family Member 3 (Smad3) and enhancing its binding to the Foxp3 conserved non-coding DNA sequence 1 (CNS1) region. Importantly, the genetic deletion of Dleu2-17aa in mice by start codon mutation impairs iTreg generation and worsens experimental autoimmune encephalomyelitis (EAE). Conversely, the exogenous supplementation of Dleu2-17aa relieves EAE. Our findings demonstrate an indispensable role of Dleu2-17aa in maintaining immune homeostasis and suggest therapeutic applications for this peptide in treating autoimmune diseases.

Single-Cell RNA Sequencing Identifies WARS1+ Mesenchymal Stem Cells with Enhanced Immunomodulatory Capacity and Improved Therapeutic Efficacy.

Psoriasis is a common inflammatory skin disorder with no cure. Mesenchymal stem cells (MSCs) have immunomodulatory properties for psoriasis, but the therapeutic efficacies varied, and the molecular mechanisms were unknown. In this study, we improved the efficacy by enhancing the immunomodulatory effects of umbilical cord-derived MSCs (UC-MSCs). UC-MSCs stimulated by TNF-α and IFN-γ exhibited a better therapeutic effect in a mouse model of psoriasis. Single-cell RNA sequencing revealed that the stimulated UC-MSCs overrepresented a subpopulation expressing high tryptophanyl-tRNA synthetase 1 (WARS1). WARS1-overexpressed UC-MSCs treat psoriasis-like skin inflammation more efficiently than control UC-MSCs by restraining the proinflammatory macrophages. Mechanistically, WARS1 maintained a RhoA-Akt axis and governed the immunomodulatory properties of UC-MSCs. Together, we identify WARS1 as a master regulator of UC-MSCs with enhanced immunomodulatory capacities, which paves the way for the directed modification of UC-MSCs for escalated therapeutic efficacy.

CKBA suppresses mast cell activation via ERK signaling pathway in murine atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disorder. Mast cells play an important role in AD because they regulate allergic reactions and inflammatory responses. However, whether and how the modulation of mast cell activity affects AD has not been determined. In this study, we aimed to determine the effects and mechanisms of 3-O-cyclohexanecarbonyl-11-keto-ß-boswellic acid (CKBA). This natural compound derivative alleviates skin inflammation by inhibiting mast cell activation and maintaining skin barrier homeostasis in AD. CKBA markedly reduced serum IgE levels and alleviated skin inflammation in calcipotriol (MC903)-induced AD mouse model. CKBA also restrained mast cell degranulation both in vitro and in vivo. RNA-seq analysis revealed that CKBA downregulated the extracellular signal-regulated kinase (ERK) signaling in BM-derived mast cells activated by anti-2,4-dinitrophenol/2,4-dinitrophenol-human serum albumin. We proved that CKBA suppressed mast cell activation via ERK signaling using the ERK activator (t-butyl hydroquinone) and inhibitor (selumetinib; AZD6244) in AD. Thus, CKBA suppressed mast cell activation in AD via the ERK signaling pathway and could be a therapeutic candidate drug for AD.

A peptide encoded by pri-miRNA-31 represses autoimmunity by promoting Treg differentiation.

Recent evidence has revealed that small polypeptides (containing fewer than 100 amino acids) can be translated from noncoding RNAs (ncRNAs), which are usually defined as RNA molecules that do not encode proteins. However, studies on functional products translated from primary transcripts of microRNA (pri-miRNA) are quite limited. Here, we describe a peptide termed miPEP31 that is encoded by pri-miRNA-31. miPEP31 is highly expressed in Foxp3+ regulatory T cells (Tregs ) and significantly promotes the differentiation of Tregs without affecting their inhibitory ability. Our results show that miPEP31 is a cell-penetrating peptide both in vitro and in vivo. miPEP31 downregulates miR-31 expression, enhances peripheral Treg induction, and dramatically suppresses experimental autoimmune encephalomyelitis. Mechanistically, we show that miPEP31 acts as a transcriptional repressor inhibiting the expression of miRNA-31, a negative regulator of Tregs . Our results reveal an indispensable role of miPEP31 in maintaining immune homeostasis by promoting Treg differentiation and also present a potential therapeutic peptide for modulating miRNA expression and treating autoimmune diseases.

Enzyme-Triggered Transforming of Assembly Peptide-Modified Magnetic Resonance-Tuned Probe for Highly Sensitive Imaging of Bacterial Infection In Vivo.

Confirming bacterial infection at an early stage and distinguishing between sterile inflammation and bacterial infection is still highly needed for efficient treatment. Here, in situ highly sensitive magnetic resonance imaging (MRI) bacterial infection in vivo based on a peptide-modified magnetic resonance tuning (MRET) probe (MPD-1) that responds to matrix metallopeptidase 2 (MMP-2) highly expressed in bacteria-infected microenvironments is achieved. MPD-1 is an assembly of magnetic nanoparticle (MNP) bearing with gadolinium ion (Gd3+ ) modified MMP-2-cleavable self-assembled peptide (P1 ) and bacteria-targeting peptide (P), and it shows T2 -weighted signal due to the assemble of MNP and MRET ON phenomenon between MNP assembly and Gd3+ . Once MPD-1 accumulates at the bacterially infected site, P1 included in MPD-1 is cleaved explicitly by MMP-2, which triggers the T2 contrast agent of MPD-1 to disassemble into the monomer of MNP, leading the recovery of T1 -weighted signal. Simultaneously, Gd3+ detaches from MNP, further enhancing the T1 -weighted signal due to MRET OFF. The sensitive MRI of Staphylococcus aureus (low to 104 CFU) at the myositis site and accurate differentiation between sterile inflammation and bacterial infection based on the proposed MPD-1 probe suggests that this novel probe would be a promising candidate for efficiently detecting bacterial infection in vivo.

p53 downregulates PD-L1 expression via miR-34a to inhibit the growth of triple-negative breast cancer cells: a potential clinical immunotherapeutic target.

BACKGROUND: Compared with other breast cancer subtypes, triple-negative breast cancer (TNBC) has poorer responses to therapy and lower overall survival rates. The use of an inhibitor of immune checkpoint programmed cell death ligand 1 (PD-L1) is a promising treatment strategy and is approved for malignant tumors, especially for TNBC. p53 regulates various biological processes, but the association between p53 and immune evasion remains unknown. miR-34a is a known tumor suppressor and p53-regulated miRNA that is downregulated in several cancers; however, it has not been reported in TNBC. Herein, we aimed to explore the regulatory signaling axis among p53, miR-34a and PD-L1 in TNBC cells in vivo and in tissue and to improve our understanding of immunotherapy for TNBC. METHODS AND RESULTS: p53-EGFP, p53-siRNA and miR-34a mimics were transfected into TNBC cell lines, and the interaction between miR-34a and PD-L1 was analyzed via dual-luciferase reporter assays. We found that p53 could inhibit the expression of PD-L1 via miR-34a and that miR-34a could inhibit both cell activity and migration and promoted apoptosis and cytotoxicity in TNBC. Furthermore, miR-34a agomir was injected into MDA-MB-231 tumors of nude mice. The results showed that miR-34a could inhibit tumor growth and downregulate the expression of PD-L1 in vivo. A total of 133 TNBC tissue samples were analyzed by immunochemistry; the proportion of positive expression of PD-L1 was 57.14% (76/133), and the proportion of samples with negative expression of PD-L1 was 42.86% (57/133). CONCLUSION: Our research may provide a novel potential target for TNBC.

Corilagin attenuates osteoclastic osteolysis by enhancing HO-1 and inhibiting ROS.

Chinese herbal medicine has well-established therapeutic effects in various diseases. Corilagin (Cor), a gallic acid tannin in Phyllanthus niruri L., has anti-inflammatory and antioxidant effects in many diseases. However, its role in osteoclast-related bone diseases has not been determined. In vitro, bone marrow macrophages (BMMs) were extracted and isolated to differentiate into osteoclasts. The effects of Cor on osteoclast formation, bone resorption, and reactive oxygen species (ROS) production were performed. In addition, quantitative real-time polymerase chain reaction and western blot analysis were used to evaluate the effect of Cor on oxidative stress-related pathways, which are nuclear factors-κB ligand-receptor activator (RANKL) stimulates important downstream pathways. Furthermore, microcomputed tomography and bone histomorphometry were performed to analyze the therapeutic effect of Cor in mouse models of lipopolysaccharide (LPS)-mediated bone defects in vivo. Cor influenced the nuclear factor of activated T cells 1 (NFATc1) signaling pathway and reduced ROS in RANKL-treated osteoclasts, thereby inhibiting osteoclast formation and bone resorption. Moreover, Cor protected against LPS-mediated skull defects in vivo. In sum, our results confirm that Cor can inhibit osteoclastogenesis and intracellular oxidative stress. In addition, the inflammatory bone defect induced by LPS was also attenuated by Cor. Accordingly, Cor is a new candidate therapeutic agent for osteoclast-mediated osteolytic diseases.

Precise Molecular Design Toward Organic-Inorganic Zinc Chloride ABX3 Ferroelectrics.

Organic-inorganic ABX3 (A, B = cations, X = anion) hybrids with perovskite structure have recently attracted tremendous interest due to their structural tunability and rich functional properties, such as ferroelectricity. However, ABX3 hybrid ferroelectrics with other structures have rarely been reported. Here, we successfully designed an ABX3 hybrid ferroelectric [(CH3)3NCH2F]ZnCl3 with a spontaneous polarization of 4.8 µC/cm2 by the molecular modification of [(CH3)4N]ZnCl3 through hydrogen/halogen substitution. It is the first zinc halide ABX3 ferroelectric, which contains one-dimensional [ZnCl3]-n chains of corner-sharing ZnCl4 tetrahedra, distinct from the anionic framework of corner-sharing or face-sharing BX6 octahedra in the ABX3 perovskites. From zero dimension to one dimension, the high symmetry of ZnCl4 tetrahedra is broken, and all of them align along one direction to form a polar [ZnCl3]-n chain, beneficial to the generation of ferroelectricity. This finding provides an efficient polar anionic framework for enriching the family of hybrid ferroelectrics by assembling with various cations and should inspire further exploration of new classes of organic-inorganic ABX3 ferroelectrics.

The reliability, validity and correlation of two observational gait scales assessed by video tape for Chinese subjects with hemiplegia.

To test the reliability of the Wisconsin Gait Scale (WGS) and the Gait Abnormality Rating Scale (GARS) for hemiplegic Chinese subjects, as well as to establish the concurrent validity of these two scales with clinical measurements. [Subjects] Twenty hemiplegic stroke subjects were recruited for this study. [Methods] The subjects walked along a 10-meter walkway and their gait was videotaped from 4 directions. Two physical therapists assessed the subjects' gait using the aforementioned scales by watching the video tape. The Intraclass Correlation Coefficient (ICC) was calculated for the two physiotherapists' scores for each category and the total scores to assess the reliability. Concurrent validity was tested by comparing the total scores to subjects' walking speed, the Fugl-Meyer assessment, the Motricity Index of the lower limb, and the Composite Spasticity Index of the lower limb. [Results] The ICC of WGS was 0.961 for intra-rater reliability, and 0.945 for inter-rater reliability. The ICC of GARS was 0.708 for intra-rater reliability and 0.875 for inter-rater reliability. The correlations of the two scales with walking speed, the Fugl-Meyer assessment and the Motricity Index were statistically significant. [Conclusion] Both the Wisconsin Gait Scale and the Gait Abnormality Rating Scale are reliable and valid protocols for measuring the hemiplegic gait of stroke patients.

Exquisitely constructing hierarchical carbon nanoarchitectures decorated with sulfides for high-performance Li-S batteries.

The sluggish reaction kinetics and notorious shuttle effect of polysulfides significantly hinder the practical application of lithium-sulfur batteries (LSBs). Therefore, polysulfides are anchored and their conversion reactions are catalyzed to enhance the performance of LSBs. Herein, an exquisite hierarchical carbon nanoarchitecture decorated with sulfides is designed and introduced into LSBs. Systematic experiments show that the nanoarchitecture not only enables rapid electron/ion migration but also functions as an active catalyst to increase polysulfide conversion, thus effectively reducing the shuttle effect. As a result, LSBs with the nanoarchitecture modified separator exhibited outstanding rate capacity (724.9 mA h g-1 at 5C), low self-discharge capacity loss (4.1% capacity loss after 72 h), and exceptional reversible capacity (1518.3 mA h g-1 at 0.1C and 25.6% capacity loss after 100 cycles). Through the design of a multifunctional separator, this study offers an effective way to minimize the shuttle effect and speed up redox conversion. The strategy of constructing nanoarchitectures provides an innovative route for hierarchical heterocatalyst design for LSBs.

Discovery of the new alpha-glucosidase inhibitor with therapeutic potential in type 2 diabetes mellitus by a novel high-throughput virtual screening and free energy evaluation.

Type 2 diabetes can cause a variety of complications, significantly affecting people's health. Given their ability to suppress carbohydrate digestion, alpha-glucosidase inhibitors are effective treatments for diabetes. However, the current approved glucosidase inhibitors' side effects of abdominal discomfort limit their use. We used the compound Pg3R from the natural fruit berry as a reference, screening against a large database of 22 million compounds to identify potential health-friendly alpha-glucosidase inhibitors. Ligand-based screening enables us to identify 3968 ligands that exhibit structural similarity compared to the natural compound. These lead hits were used for LeDock, and their binding free energies were evaluated by MM/GBSA. Among the top-scoring candidates, ZINC263584304 exhibited the strongest binding affinity to alpha-glucosidase, with a "low-fat" structural characteristic. Its recognition mechanism was further investigated by microsecond MD simulations and free energy landscapes, exhibiting novel conformational changes during the binding process. Our study provided a novel alpha-glucosidase inhibitor with the potential to treat type 2 diabetes.

Prognostic value of coagulation and fibrinolysis function indexes and NETs for sepsis patients.

OBJECTIVE: To clarify the role of coagulation and fibrinolysis as well as the level of neutrophil extracellular traps (NETs) in patients with sepsis, and to explore their clinical significance in identifying the disease and predicting the prognosis. METHODS: In this retrospective study, the clinical data from 120 patients with sepsis admitted to People's Hospital of Changshou from January 2019 to December 2021 were analyzed. The patients were divided into a survival group and a death group according to the survival of patients within 28 days of admission. Another 120 patients with common bacterial infection were selected as the bacterial group and 120 healthy subjects who underwent physical examination in our hospital during the same period were selected as the healthy group. NETs, coagulation and fibrinolysis indexes, prothrombin time (PT), fibrinogen (FIB), D-dimer level, International Normalized Ratio (INR), Acute Physiology and Chronic Health Evaluation (APACHE) II score, and sequential organ failure assessment (SOFA) score of the patients with sepsis were compared with those of bacterial group and healthy group. Correlations between these measures were analyzed, and the predictive value of NETs for survival in patients with sepsis was assessed. RESULTS: Compared with bacterial group and healthy group, the levels of serum NETs, PT, FIB, D-dimer, and INR value in sepsis patients were significantly increased. The level of NETs was positively associated with APACHE II score, SOFA score, PT, FIB, D-dimer, and INR. INR showed good performance in predicting death within 28 days after admission in sepsis patients. CONCLUSION: The NETs and coagulation indexes have high predictive value for the prognosis of patients with sepsis.

A pH-responsive magnetic resonance tuning probe for precise imaging of bacterial infection in vivo.

Accurate and sensitive detection of bacteria is essential for treating bacterial infections. Herein, a pH-responsive magnetic resonance tuning (MRET) probe, whose T1-weighted signal is activated in the bacteria-infected acid microenvironment, is developed for in situ accurately magnetic resonance imaging (MRI) of bacterial infection in vivo. The MRET probe (MDVG-1) is an assembly of paramagnetic enhancer (gadolinium-modified i-motif DNA3, abbreviated as Gd-DNA3-Gd) and the precursor of superparamagnetic quencher (DNA and vancomycin-modified magnetic nanoparticle, abbreviated as MDV). The T1-weighted signal of Gd-DNA3-Gd is quenched once the formation of MDVG-1 (MRET ON). Interestingly, the MDVG-1 probe was disassembled into the monomers of Gd-DNA3-Gd and MDV under the bacteria-infected acid microenvironment, resulting significantly enhanced T1-weighted signal at the infected site (MRET OFF). The pH-responsive MRET probe-based enhanced MRI signal and bacteria targeting significantly improve the distinction between bacterial infectious tissues and sterile inflamed tissues, which provides a promising approach for accurately detecting bacterial infection in vivo. STATEMENT OF SIGNIFICANCE: Detecting pathogenic bacteria in vivo based on magnetic resonance imaging (MRI) strategy has been exploring recently. Although various bacterial-targeted MRI probes have been developed to image bacteria in vivo, the MRI signal of these MRI probes is always "on", which inevitably generates nonspecific background MRI signals, affecting the accuracy of MRI to a certain extent. In the current study, based on the magnetic resonance tuning (MRET) phenomenon, we present a pH-responsive MRET probe (MDVG-1) with T2-weighted imaging to T1-weighted imaging switchable properties to achieve in situ precise imaging of bacterial infection in vivo.

Azo Reductase Activated Magnetic Resonance Tuning Probe with "Switch-On" Property for Specific and Sensitive Tumor Imaging in Vivo.

Cancer remains a threat to human health. However, if tumors can be detected in the early stage, then the effectiveness of cancer treatment could be significantly improved. Therefore, it is worthwhile to develop more sensitive and accurate cancer diagnostic methods. Herein, we demonstrated an azo reductase (AzoR)-activated magnetic resonance tuning (MRET) probe with a "switch-on" property for specific and sensitive tumor imaging in vivo. Specifically, Gd-labeled DNA1 (DNA1-Gd) and cyclodextrin-coated magnetic nanoparticles (MNP-CD) were employed as enhancer and quencher of MRET, respectively, while DNA2, an azobenzene (Azo) group-modified aptamer (AS1411), served as a linker between enhancer and quencher to construct the MRET probe of MNP@DNA(1-2)-Gd. In tumor tissues with high-level AzoR, the T1-weighted magnetic resonance signal of the MRET probe could be restored by intelligently regulating the switch from "OFF" to "ON" after activation with AzoR, thus accurately indicating the location of the tumor accurately. Moreover, the tumor with a 4 times smaller size than that of the normal tumor model could be imaged based on the proposed MRET probe. The as-proposed MRET-based magnetic resonance imaging strategy not only achieves tumor imaging accurately but also shows promise for early diagnosis of tumors, which might improve patients' survival rates and provide an opportunity for image-guided biomedical applications in the future.

The microprotein encoded by exosomal lncAKR1C2 promotes gastric cancer lymph node metastasis by regulating fatty acid metabolism.

Lymph node metastasis (LNM) is the prominent route of gastric cancer dissemination, and usually leads to tumor progression and a dismal prognosis of gastric cancer. Although exosomal lncRNAs have been reported to be involved in tumor development, whether secreted lncRNAs can encode peptides in recipient cells remains unknown. Here, we identified an exosomal lncRNA (lncAKR1C2) that was clinically correlated with lymph node metastasis in gastric cancer in a VEGFC-independent manner. Exo-lncAKR1C2 secreted from gastric cancer cells was demonstrated to enhance tube formation and migration of lymphatic endothelial cells, and facilitate lymphangiogenesis and lymphatic metastasis in vivo. By comparing the metabolic characteristics of LN metastases and primary focuses, we found that LN metastases of gastric cancer displayed higher lipid metabolic activity. Moreover, exo-lncAKR1C2 encodes a microprotein (pep-AKR1C2) in lymphatic endothelial cells and promotes CPT1A expression by regulating YAP phosphorylation, leading to enhanced fatty acid oxidation (FAO) and ATP production. These findings highlight a novel mechanism of LNM and suggest that the microprotein encoded by exosomal lncAKR1C2 serves as a therapeutic target for advanced gastric cancer.

Tenascin C+ papillary fibroblasts facilitate neuro-immune interaction in a mouse model of psoriasis.

Dermal fibroblasts and cutaneous nerves are important players in skin diseases, while their reciprocal roles during skin inflammation have not been characterized. Here we identify an inflammation-induced subset of papillary fibroblasts that promotes aberrant neurite outgrowth and psoriasiform skin inflammation by secreting the extracellular matrix protein tenascin-C (TNC). Single-cell analysis of fibroblast lineages reveals a Tnc+ papillary fibroblast subset with pro-axonogenesis and neuro-regulation transcriptomic hallmarks. TNC overexpression in fibroblasts boosts neurite outgrowth in co-cultured neurons, while fibroblast-specific TNC ablation suppresses hyperinnervation and alleviates skin inflammation in male mice modeling psoriasis. Dermal γδT cells, the main producers of type 17 pathogenic cytokines, frequently contact nerve fibers in mouse psoriasiform lesions and are likely modulated by postsynaptic signals. Overall, our results highlight the role of an inflammation-responsive fibroblast subset in facilitating neuro-immune synapse formation and suggest potential avenues for future therapeutic research.

Vertical GaN Power MOSFET with Integrated Fin-Shaped Diode for Reverse Conduction.

A vertical GaN power MOSFET featuring an integrated fin-shaped non-junction diode (FDMOS) is proposed to improve reverse conduction and switching characteristics. Its static and dynamic characteristics are studied and analyzed by Sentaurus TCAD simulation. Compared with the conventional MOSFET (Con. MOS) with a body diode as a freewheeling diode (FWD), the FDMOS uses the integrated fin-shaped diode to reverse conduction, and thus, a low reverse turn-on voltage VON of 0.66 V is achieved, with a decreasing of 77.9%. Moreover, the Qrr of the FDMOS is reduced to 1.36 µC from 1.64 µC of the Con. MOS, without the minority carrier injection. The gate charge (QGD) of the FDMOS is significantly reduced because the fin structure reduces the gate area and transforms some part of CGD to CGS, and thus, a low switching loss is realized. The QGD, the turn-on loss (Eon) and the turn-off loss (Eoff) of the FDMOS are decreased by 56.8%, 33.8% and 53.8%, respectively, compared with those of the Con. MOS. In addition, the FDMOS is beneficial to reduce the parasitic inductance and the total chip area compared with the conventional method of using an externally connected Schottky diode as an FWD.

Injectable versatile liquid-solid transformation implants alliance checkpoint blockade for magnetothermal dynamic-immunotherapy.

The ongoing circulating energy loss, low reactive oxygen species (ROS) accumulation and poor immunogenicity of tumors make it difficult to induce sufficient immunogenic cell death (ICD) in the tumor immunosuppressive microenvironment (TIME), resulting in unsatisfactory immunotherapy efficacy. Furthermore, for highly malignant tumors, simply enhancing ICD is insufficient for exhaustively eliminating the tumor and inhibiting metastasis. Herein, we propose a unique magnetothermal-dynamic immunotherapy strategy based on liquid-solid transformation porous versatile implants (Fe3O4/AIPH@PLGA) that takes advantage of less energy loss and avoids ongoing circulating losses by minimally invasive injection into tumors. In addition, the magnetothermal effect regresses and eliminates tumors that are not limited by penetration to simultaneously trigger 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) decomposition and generate a large amount of oxygen-irrelevant free radicals and heat shock protein (HSP) accumulation by heating, evoking both intracellular oxidative stress and endoplasmic reticulum (ER) stress to induce large-scale ICD and enhance tumor immunogenicity. More importantly, in orthotopic bilateral breast tumor models, a significant therapeutic effect was obtained after combining amplified ICD with CTLA4 checkpoint blockade. The 21-day primary and distant tumor inhibition rates reached 90%, and the underlying mechanism of the effective synergetic strategy of inducing the T-cell-related response, the immune memory effect and TIME reprogramming in vivo was verified by immune cell analyses. This remarkable therapeutic effect provides a new direction for antitumor immunotherapy based on magnetothermally controlled oxygen-independent free radical release.

Spectroscopic characterization of soil dissolved organic matter during dielectric barrier discharge (DBD) plasma treatment: Effects of discharge power, atmosphere and soil moisture content.

Non-thermal plasma (NTP) technology is an emerging advanced oxidation process, which has shown excellent performances in soil organic pollution remediation. Dissolved organic matter (DOM) is one of the most important components in soil, however, investigations on the structural and compositional changes of DOM during NTP process are lacking. Therefore, in the present study, we systematically investigated the soil DOM changes under different discharge voltages, atmospheres or soils with different moisture contents. The results indicated that after NTP treatment, substantial soil organic matters were released and dissolved in water. For instance, the DOC value of DOM increased dramatically from 21.1 to 197.3 mg L-1 after being discharged for 120 min under the discharge voltage of 80 V. The UV-Vis characterization results indicated the significant increase of hydrophilicity, and decreases of aromaticity and molecular weight for soil DOM during the initial discharge period. However, long time discharge resulted in slight recovery of aromaticity and hydrophobicity, possibly due to the dehydration and re-condensation of small molecules. EEM-FRI results indicated that the total fluorescence intensity of DOM decreased obviously, indicating the destruction of fluorescent dissolved organic matter (FDOM). While the proportions of humic-like and microbial byproduct-like substances increased, indicating that those substances were more recalcitrant under NTP treatment compared with fulvic acid-like and aromatic protein-like substances. Four fluorescence components were identified by PARAFAC, and microbial and terrestrial humic-like substances were more difficult to degrade compared to other humic-like substances and fulvic acid-like substances. Additionally, discharge voltage and atmosphere had great influences on DOM changes, while the impact of soil moisture content was not significant. Overall, this study provided insights into the DOM changes during NTP process, which is valuable for more comprehensive evaluation of the NTP technique application in practical soil remediation.