DTTZ suppresses ferroptosis and reverses mitochondrial dysfunction in normal tissues affected by chemotherapy.

Conventional antineoplastic therapies cause severe normal tissue damage and existing cytoprotectants with acute toxicities or potential tumor protection limit their clinical application. We evaluated the selective cytoprotection of 2,2-dimethylthiazolidine hydrochloride in this study, which could protect normal tissue toxicity without interfering antineoplastic therapies. By using diverse cell lines and A549 xenograft model, we discovered a synthetic aminothiol 2,2-dimethylthiazolidine hydrochloride selectively diminished normal cellular ferroptosis via SystemXc-/Glutathione Peroxidase 4 pathway upon antineoplastic therapies without interfering the anticancer efficacy. We revealed the malignant and non-malignant tissues presenting different energy metabolism patterns. And cisplatin induces disparate replicative stress, contributing to the distinguishable cytoprotection of 2,2-dimethylthiazolidine in normal and tumor cells. The compound pre-application could mitigate cisplatin-induced normal cellular mitochondrial oxidative phosphorylation (OXPHOS) dysfunction. Pharmacologic ablation of mitochondria reversed 2,2-dimethylthiazolidine chemoprotection against cisplatin in the normal cell line. Combined, these results provide a potential therapeutic adjuvant to selectively diminish normal tissue damages retaining antineoplastic efficacy.

Impact of dietary digestible aromatic amino acid levels and stachyose on growth, nutrient utilization, and cecal odorous compounds in broiler chickens.

This study evaluated the impact of dietary digestible aromatic amino acid (DAAA) levels and stachyose on growth, nutrient utilization and cecal odorous compounds in broiler chickens. A 3×2 two-factor factorial design: Three dietary DAAA levels (1.40, 1.54, 1.68%) supplemented with either 5 g/kg of stachyose or without any stachyose were used to create 6 experimental diets. Each diet was fed to 6 replicates of 10 birds from d 22 to 42. Findings revealed that broilers receiving a diet with 1.54% DAAA levels supplemented with 5 g/kg stachyose exhibited a significant boost in average daily gain and improved utilization of crude protein, ether extract, tryptophan, and methionine compared to other diet treatments (P < 0.05). As the dietary DAAA levels increased, there was a significant rise in the concentrations of indole, skatole, p-methylphenol, and butyric acid in the cecum of broilers (P < 0.05). The addition of stachyose to diets reduced concentrations of indole, skatole, phenol, p-methylphenol, acetic acid and propionic acid in the cecum (P < 0.05). The lowest concentrations of indole, phenol, p-methylphenol, volatile fatty acids and pH in cecum of broilers were observed in the treatment which diet DAAA level was 1.40% with stachyose (P < 0.05). In conclusion, dietary DAAA levels and stachyose had significant interactions on the growth, main nutrient utilization and cecal odorous compounds in broilers. The dietary DAAA level was 1.54% with 5 g/kg of stachyose can improve the growth performance, nutrient utilization. However, the dietary DAAA level was 1.40% with stachyose was more beneficial to decrease the cecal odor compound composition in broilers.

Targeting ferroptosis in the maintenance of mitochondrial homeostasis in the realm of septic cardiomyopathy.

Septic cardiomyopathy is one of the predominant culprit factors contributing to the rising mortality in patients with severe sepsis. Among various mechanisms responsible for the etiology of septic heart anomalies, disruption of mitochondrial homeostasis has gained much recent attention, resulting in myocardial inflammation and even cell death. Ferroptosis is a novel category of regulated cell death (RCD) provoked by iron-dependent phospholipid peroxidation through iron-mediated phospholipid (PL) peroxidation, enroute to the rupture of plasma membranes and eventually cell death. This review summarizes the recent progress of ferroptosis in mitochondrial homeostasis during septic cardiomyopathy. We will emphasize the role of mitochondrial iron transport channels and the antioxidant system in ferroptosis. Finally, we will summarize and discuss future research, which should help guide disease treatment.

Achieving High Performance of ZnSnO Thin-Film Transistor via Homojunction Strategy.

The zinc-tin-oxide (ZTO) thin-film transistor (TFT) is one of the most promising candidates for advanced display applications, though its popularity is limited by its performances. In this work, a heterojunction channel strategy was adopted to regulate the electron transport behaviors and the TFT performances by manipulating the concentration and the distribution of oxygen vacancies, and a reasonable physical model was proposed based on experimental and simulation results. It is difficult to mediate the contradiction between mobility and threshold voltage for the single channel. Via a heterojunction channel strategy, desirable TFT performances, with mobility of 12.5 cm2/Vs, threshold voltage of 1.2 V and Ion/Ioff of 3 × 109, are achieved when the oxygen-vacancy-enriched layer gets close to the gate insulator (GI). The enhanced performances can be mainly attributed to the formation of two-dimensional electron gas (2DEG), the insensitive potential barrier and the reasonable distribution of oxygen vacancy. On the contrary, when the oxygen-vacancy-enriched layer stays away from GI, all the main performances degenerate due to the vulnerable potential well. The findings may facilitate the development and application of heterojunction channels for improving the performances of electronic devices.

Aryl Hydrocarbon Receptor Activation Coordinates Mouse Small Intestinal Epithelial Cell Programming.

In the face of mechanical, chemical, microbial, and immunologic pressure, intestinal homeostasis is maintained through balanced cellular turnover, proliferation, differentiation, and self-renewal. Here, we present evidence supporting the role of the aryl hydrocarbon receptor (AHR) in the adaptive reprogramming of small intestinal gene expression, leading to altered proliferation, lineage commitment, and remodeling of the cellular repertoire that comprises the intestinal epithelium to promote intestinal resilience. Ahr gene/protein expression and transcriptional activity exhibit marked proximalHI to distalLO and cryptHI to villiLO gradients. Genetic ablation of Ahr impairs commitment/differentiation of the secretory Paneth and goblet cell lineages and associated mucin production, restricts expression of secretory/enterocyte differentiation markers, and increases crypt-associated proliferation and villi-associated enterocyte luminal exfoliation. Ahr-/- mice display a decrease in intestinal barrier function. Ahr+/+ mice that maintain a diet devoid of AHR ligands intestinally phenocopy Ahr-/- mice. In contrast, Ahr+/+ mice exposed to AHR ligands reverse these phenotypes. Ligand-induced AHR transcriptional activity positively correlates with gene expression (Math1, Klf4, Tff3) associated with differentiation of the goblet cell secretory lineage. Math1 was identified as a direct target gene of AHR, a transcription factor critical to the development of goblet cells. These data suggest that dietary cues, relayed through the transcriptional activity of AHR, can reshape the cellular repertoire of the gastrointestinal tract.

Ursolic acid inhibits human dermal fibroblasts hyperproliferation, migration, and collagen deposition induced by TGF-ß via regulating the Smad2/3 pathway.

Hypertrophic scar (HS) is a skin condition characterized by excessive fibrosis with disordered collagens from skin fibroblasts, which causes abnormal esthetic and even functional symptoms, thereby affecting millions of people. Ursolic acid (UA) is widely used in skincare and exerts anti-fibrotic effects. The present study aimed to delve into the impact of UA on HS and the mechanism. Fibroblasts (FBs) were incubated with TGF-ß to investigate physiological characteristics compared with FBs isolated from normal skin (NSFBs) and hyperplastic scars (HSFBs). TGF-ß-incubated FBs were subjected to treatment with UA (0-20 µM). The expressions of Vimentin, α-SMA, Collagen I, and Collagen III were examined using immunofluorescence, RT-qPCR, and western blot. Cell viability, proliferation, apoptosis, migration, and contractility were examined by CCK-8, EdU, Annexin V-FITC/PI, Transwell, and collagen gel contraction assays, respectively. The activation of Smad2/3 signaling was also determined by western blot. The binding sites for UA of TGF-ßR1 (ALK5) were predicted by the Autodock tool. Compared with NSFBs, the cell proliferation, migration, and contractility of both HSFBs and TGF-ß-incubated FBs were all significantly up-regulated. UA markedly impaired the TGF-ß-induced increase in cell proliferation, migration, and contractility, α-SMA, collagen I, and Collagen III expression of FBs. UA significantly inhibited the phosphorylation levels of Smad2/3 in TGF-ß-incubated FBs with no influence on TGF-ßR1 and TGF-ßR2 expressions, which might be because of the binding of UA to the catalytic domain of ALK5 protein. UA attenuated TGF-ß1-induced hyperproliferation, migration, and collagen deposition in FBs via regulating the Smad2/3 pathway.

Performance improvement of aqueous zinc batteries by zinc oxide and Ketjen black co-modified glass fiber separators.

Rechargeable aqueous zinc-based batteries (AZBs) are intriguing candidates for next-generation energy storage batteries. However, the dendrites generated plagued their development during charging. To inhibit the dendrite generation, a novel modification method based on the separators was proposed in this study. The separators were co-modified by spraying sonicated Ketjen black (KB) and zinc oxide nanoparticles (ZnO) uniformly. The highly conductive KB homogenizes the anode interface's electric field. The deposited ions are deposited on ZnO preferentially rather than on the anode electrode, and the deposited particles can be refined. The ZnO in the uniform KB conductive network can provide sites for zinc deposition, and the by-products of the zinc anode electrode reduced. The Zn-symmetric cell with the modified separator (Zn//ZnO-KB//Zn) can cycle for 2218 h at 1 mA cm-2 stably (the unmodified Zn-symmetric cell (Zn//Zn) only can cycle for 206 h). With the modified separator, the impedance and polarization of Zn//MnO2 reduced, and the cell can charge/discharge 995 times at 0.3 A g-1. In conclusion, the electrochemical performance of AZBs can be improved effectively after separator modification by the synergistic effect of ZnO and KB.

Near-Ideal Top-Gate Controllability of InGaZnO Thin-Film Transistors by Suppressing Interface Defects with an Ultrathin Atomic Layer Deposited Gate Insulator.

An ultrathin atomic-layer-deposited (ALD) AlOx gate insulator (GI) was implemented for self-aligned top-gate (SATG) amorphous InGaZnO (a-IGZO) thin-film transistors (TFTs). Although the 4.0-nm thick AlOx exhibited ideal insulating properties, the interaction between ALD AlOx and predeposited a-IGZO caused a relatively defective interface, thus giving rise to hysteresis and bias stress instabilities. As analyzed using high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, and the Hall measurement, the chemical reaction between the ALD precursor and a-IGZO is revealed. This was effectively prevented by preoxidizing a-IGZO with nitrous oxide (N2O) plasma. With 4 nm-AlOx GI and low-defect interfaces, high performance and stability were simultaneously achieved on SATG a-IGZO TFTs, including a near-ideal record-low subthreshold swing of 60.8 mV/dec, a low operation voltage below 0.4 V, a moderate mobility of 13.3 cm2/V·s, a low off-current below 10-13 A, a large on/off ratio over 109, and negligible threshold-voltage shifts less than 0.04 V against various bias-temperature stresses. This work clarifies the vital interfacial reaction between top-gate high-k dielectrics and amorphous oxide semiconductors (AOSs) and further provides a feasible way to remove this obstacle to downscaling SATG AOS TFTs.

ROS-Responsive and pH-Sensitive Aminothiols Dual-Prodrug for Radiation Enteritis.

Radiation exposure can immediately trigger a burst of reactive oxygen species (ROS), which can induce severe cell death and long-term tissue damage. Therefore, instantaneous release of sufficient radioprotective drugs is vital to neutralize those accumulated ROS in IR-exposed areas. To achieve this goal, we designed, synthesized, and evaluated a novel oral ROS-responsive radioprotective compound (M1) with high biocompatibility and efficient ROS-scavenging ability to act as a promising oral drug for radiation protection. The compound is stably present in acidic environments and is hydrolyzed in the intestine to form active molecules rich in thiols. M1 can significantly remove cellular ROS and reduce DNA damage induced by γ-ray radiation. An in vivo experiment showed that oral administration of M1 effectively alleviates acute radiation-induced intestinal injury. Immunohistochemical staining showed that M1 improved cell proliferation, reduced cell apoptosis, and enhanced the epithelial integrity of intestinal crypts. This study provides a promising oral ROS-sensitive agent for acute intestinal radiation syndrome.

Zinc dendrite suppression by a novel additive combination for rechargeable aqueous zinc batteries.

With the advantages of low cost, good safety, and easy assembly, aqueous zinc batteries (AZBs) are expected to be a promising energy storage device. However, AZBs are compromised by Zn dendrites and the hydrogen evolution reaction. Herein, we use polyethylene glycol-200 (PEG-200) and benzylidene acetone (BDA) as additives in the electrolyte of AZBs in order to inhibit Zn dendrite growth and side reactions, thus improving the cycle performance of the Zn electrode. PEG-200 can be not only used as a co-solvent for BDA but also as a surfactant to achieve a uniform interfacial electric field. As a brightening agent, BDA forms a diffusion layer on the plating substrate, which increases the electrochemical polarization and nucleation overpotential, increases the number of active nucleation sites, and finally refines the grain size of the zinc deposit. The surface of the symmetric battery electrode with electrolyte containing PEG-200 additive is smooth after cycling, and dendrite formation is successfully suppressed. The Zn-Zn symmetric cell with additive-containing electrolyte has a higher nucleation overpotential and a cyclic stability for as long as 890 h (only 48 h for the unmodified symmetric cell). This is due to the adsorption of the additive on the negative electrode, which homogenizes the deposition interface and reduces the contact of the negative electrode with water.

Clinical application of transcranial magnetic stimulation in multiple sclerosis.

Multiple sclerosis (MS) is a common chronic, autoimmune-mediated inflammatory and neurodegenerative disease of the central nervous system. The treatment of MS has enormous progress with disease-modifying drugs, but the complexity of the disease course and the clinical symptoms of MS requires personalized treatment and disease management, including non-pharmacological treatment. Transcranial magnetic stimulation (TMS) is a painless and non-invasive brain stimulation technique, which has been widely used in neurological diseases. In this review, we mainly focus on the progress of physiological assessment and treatment of TMS in MS.

MST1/2 inhibitor XMU-MP-1 alleviates the injury induced by ionizing radiation in haematopoietic and intestinal system.

The Hippo signalling pathway has been considered as potential therapeutic target in self-renewal and differentiation of stem and progenitor cells. Thus, mammalian Ste20-like kinase 1/2 (MST1/2) as the core serine-threonine kinases in the Hippo signalling pathway has been investigated for its role in immunological disease. However, little information of MST1/2 function in bone marrow suppression induced by ionizing radiation was fully investigated. Here, we reported that MST1/2 inhibitor XMU-MP-1 could rescue the impaired haematopoietic stem cells (HSCs) and progenitor cells (HPCs) function under oxidative stress condition. Also, XMU-MP-1 pretreatment markedly alleviated the small intestinal system injury caused by the total body irradiation 9 Gy and extended the average survival days of the mice exposed to the lethal dose radiation. Therefore, irradiation exposure causes the serious pathological changes of haematopoietic and intestinal system, and XMU-MP-1 could prevent the ROS production, the haematopoietic cells impairment and the intestinal injury. These detrimental effects may be associated with regulating NOX/ROS/P38MARK pathway by MST1/2.

Differently PEGylated Polymer Nanoparticles for Pancreatic Cancer Delivery: Using a Novel Near-Infrared Emissive and Biodegradable Polymer as the Fluorescence Tracer.

In this study, a chemically synthetic polymer, benzo[1,2-b:4,5-b']difuran(BDF)-based donor-acceptor copolymer PBDFDTBO, was individually coated by amphiphilic poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-PCL) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol) (DSPE-PEG or PEG-DSPE), to form stably fluorescent nanoparticles in the near-infrared (NIR) window. The physicochemical properties of the synthesized nanoparticles were characterized and compared, including their size, surface charge, and morphology. In addition, in vitro studies were also performed using two pancreatic cancer cell lines, assessing the cell viability of the PBDFDTBO-included PEGylated nanoparticles formulations. Moreover, in vivo studies were also conducted, using subcutaneous murine cancer models to investigate the polymeric nanoparticles' circulation time, tumor accumulation, and preferred organ biodistribution. The overall results demonstrated that even with the same PEGylated surface, the hydrophobic composition anchored on the encapsulated PBDFDTBO core strongly affected the biodistribution and tumor accumulation of the nanoparticles, to a degree possibly determined by the hydrophobic interactions between the hydrophobic segment of amphiphilic polymers (DSPE or PCL moiety) and the enwrapped PBDFDTBO. Both PEGylated nanoparticles were compared to obtain an optimized coating strategy for a desired biological feature in pancreatic cancer delivery.

How does industrial policy affect manufacturing carbon emission? Evidence from Chinese provincial sub-sectoral data.

Assessing the environmental impact of industrial policy is of great importance to China's industrial green transformation and high-quality development, while this topic receives little attention in the literature. Based on the panel data of 29 manufacturing industrial sectors in China's 30 provinces from 2006 to 2015, using a model that includes the year, province, and industry fixed-effect, this paper fills the gap by exploring whether and how industrial policy affects carbon emission in Chinese manufacturing. The result shows that industrial policy significantly increases carbon emission in supported industries by 10.3%, which is achieved by increasing industrial energy consumption, relaxing government environmental regulation, and encouraging enterprises to invest more in fixed assets. Further, the effects of industrial policy on carbon emission are heterogeneous in many aspects. In the central and western regions, technology-intensive industries, industries with stronger government intervention, industries with higher exports, industries supported by both central and local governments, and during the 12th Five-Year Plan, the industrial policy will increase carbon emissions more. Our findings for the first time indicate the negative impact of industrial policies on carbon emission reduction in the Chinese manufacturing industry, which implies that traditional selective industrial policies in developing countries like China need a paradigm shift to achieve green development.

Metal Reaction-Induced Bulk-Doping Effect in Forming Conductive Source-Drain Regions of Self-Aligned Top-Gate Amorphous InGaZnO Thin-Film Transistors.

In this paper, the aluminum (Al) treatment-induced doping effect on the formation of conductive source-drain (SD) regions of self-aligned top-gate (SATG) amorphous indium gallium zinc oxide (a-InGaZnO or a-IGZO) thin-film transistors (TFTs) is systematically investigated. Average carrier concentration over 1 × 1020 cm-3 and sheet resistance of around 500 Ω/sq result from the Al reaction doping. It is shown that the doping effect is of bulk despite the treatment at the surface. The doping process is disclosed to be a chemical oxidation-reduction reaction, that generates defects of oxygen vacancies and metal interstitials at the metal/a-IGZO interface. Both the generated oxygen vacancies and metal interstitials act as shallow donors, and the oxygen vacancies diffuse rapidly, leading to the bulk-doping effect. The fabricated SATG a-IGZO TFTs with the Al reaction-doped SD regions exhibit both high performance and excellent stability, featuring a low width-normalized SD resistance of about 10 Ω cm, a decent saturation mobility of 13 cm2/(V s), an off current below 1 × 10-13 A, a threshold voltage of 0.5 V, a slight hysteresis of -0.02 V, and a less than 0.1 V threshold voltage shift under 30 V gate bias stresses for 2000 s.

Effect of inosine monophosphate dehydrogenase-1 gene polymorphisms on mycophenolate mofetil effectiveness in neuromyelitis optica spectrum disorder patients.

BACKGROUND: Inosine monophosphate dehydrogenase-1 is the target of mycophenolate mofetil. This research investigated the association between the gene polymorphism of inosine monophosphate dehydrogenase-1 and effectiveness of mycophenolate mofetil therapy in neuromyelitis optica spectrum disorder patients. METHODS: Fifty-nine neuromyelitis optica spectrum disorder patients accepted Mycophenolate Mofetil therapy for 1 year at least were divided into two groups: relapsing (n=21) and non-relapsing (n=38). Four single-nucleotide polymorphisms (SNPs: rs2228075, rs2278294, rs2288550, and rs3793165) in the inosine monophosphate dehydrogenase-1 gene were detected. Then we analyzed the allelic frequencies and the genotypes of SNPs in two groups. RESULTS: The allelic frequency of rs2278294 distributed differently between the relapse and non-relapsing patients (P=0.03), while no significant difference found in rs2228075, rs2288550 and rs3793165 between two groups. The genotypes C/C, C/T and T/T of rs2278294 (P = 0.031) also distributed differently between the two groups. Logistic regression analysis (adjusted by optic neuritis) showed that compared to the wild genotype C/C, C/T genotype had a 9-fold protection against relapse (OR=0.111 (0.022-0.548)), and T/T genotype had a 6.7-fold protection against relapse (OR=0.149 (0.026-0.854)). CONCLUSION: Our study provides preliminary evidence that the genotype of rs2278294 is associated with the response of neuromyelitis optica spectrum disorder patients to mycophenolate mofetil therapy. And compared to wild allelic C, the mutation to T tended to respond better to MMF.

Self-supported Cu3P nanowire electrode as an efficient electrocatalyst for the oxygen evolution reaction.

Hydrogen is an ideal energy carrier due to its abundant reserves and high energy density. Electrolyzing water is one of the carbon free technologies for hydrogen production, which is limited by the sluggish kinetics of the half reaction of the anode - the oxygen evolution reaction (OER). In this study, a self-supported Cu3P nanowire (Cu3P NWs/CF) electrode is prepared by electrodeposition of a Cu(OH)2 nanowire precursor on conductive Cu foam (Cu(OH)2 NWs/CF) with a subsequent phosphating procedure under a N2 atmosphere. When used as an OER working electrode in 1.0 M KOH solution at room temperature, Cu3P NWs/CF exhibits excellent catalytic performance with an overpotential of 327 mV that delivers a current density of 20 mA cm-2. Notably, it can run stably for 22 h at a current density of 20 mA cm-2 without obvious performance degradation. This highly efficient and stable OER catalytic performance is mainly attributed to the unique nanostructure and stable electrode construction. Interestingly, this synthesis strategy has been proved to be feasible to prepare large-area working electrodes (e.g. 40 cm-2) with unique nanowire structure. Therefore, this work has provided a good paradigm for the mass fabrication of self-supporting non-noble metal OER catalysts and effectively promoted the reaction kinetics of the anode of the electrolyzing water reaction.

Associations Among Diffusion Tensor Image Along the Perivascular Space (DTI-ALPS), Enlarged Perivascular Space (ePVS), and Cognitive Functions in Asymptomatic Patients With Carotid Plaque.

Background and Aim: Carotid atherosclerosis (CAS) is a common pathogenesis of cerebrovascular disease closely related to stroke and silent cerebrovascular disease (SCD), while the insufficient brain perfusion mechanism cannot quite explain the mechanism. The purpose of this study was to utilize diffusion tensor image analysis along the perivascular space (DTI-ALPS) to evaluate the glymphatic system activity and correlated DTI-ALPS with enlarged perivascular spaces (ePVS), carotid intima-media thickening (CIMT), mini-mental state examination (MMSE), and serological indicator in individuals with carotid plaque. Methods: Routine MRI and diffusion tensor images scan of the brain, carotid ultrasound, and blood examination were conducted on 74 individuals (52 carotid plaque subjects, 22 non-carotid plaque subjects), whose demographic and clinical characteristics were also recorded. DTI-ALPS index between patients with carotid plaque and normal controls were acquired and the correlations with other variables were analyzed. Results: The values of ALPS-index in the carotid plaque group was significantly lower compared to normal controls (2.12 ± 0.39, 1.95 ± 0.28, respectively, p = 0.034). The ALPS-index was negatively correlated with the basal ganglia (BG)-ePVS score (r = -0.242, p = 0.038) while there was no significant difference in the centrum semiovale (CSO)-ePVS score. Further analysis showed that there are more high-grade ePVS in the BG compared to the carotid plaque group than in the non-carotid plaque group (84.6% vs. 40.9%, p = 0.001). Conclusions: ALPS-index reflects the glymphatic system of the brain, which is associated with early high-risk cerebrovascular diseases. There may be damage in the function of the glymphatic system which induces the expansion of the perivascular space (PVS) in the BG in individuals with carotid plaque.

The Relationship Between Serum Cytokine Levels and the Degree of Psychosis and Cognitive Impairment in Patients With Methamphetamine-Associated Psychosis in Chinese Patients.

Background: Cytokine levels can be changed in methamphetamine (METH) use disorders (MUDs) and primary psychosis. The present study assessed serum levels of some kinds of interleukins (ILs) in METH-associated psychosis (MAP) and their relationships with psychotic symptoms and cognitive dysfunction. Methods: Serum IL-2R, IL-6, IL-8, and IL-10 levels were examined by chemiluminescence assays in MAP patients (n = 119) and healthy controls (n = 108). The Positive and Negative Syndrome Scale (PANSS) and Montreal Cognitive Assessment (MOCA) were administered. Results: Serum levels of IL-6 and IL-8 were significantly increased in MAP patients (all p < 0.05). There was a negative relationship between IL-2R levels and PANSS positive (P) subscale scores (r = -0.193, p = 0.035). IL-6, IL-8 and IL-10 levels were all negatively correlated with the naming, delayed recall and orientation subscores on the MOCA (r = -0.209, p = 0.022; r = -0.245, p = 0.007; r = -0.505, p < 0.001, respectively). Conclusions: Our results indicate that immune disturbances are related to MAP and that IL-2R, IL-6, IL-8, and IL-10 are associated with the severity of psychotic symptoms and cognitive function impairment.

ß-Naphthoflavone Activation of the Ah Receptor Alleviates Irradiation-Induced Intestinal Injury in Mice.

Radiotherapy induced gastrointestinal syndrome results from the acute damage of intestinal stem cells, impaired crypts reconstruction, and subsequent breakdown of the mucosal barrier. The toxicity of ionizing radiation is associated with oxidative stress in the intestinal epithelial cells (IECs). Moreover, the rapid proliferation of IECs is a risk factor for radiation damage. ß-naphthoflavone (BNF) is an agonist of the aryl hydrocarbon receptor (AhR) and possesses potential antioxidative activity. We investigated BNF radioprotection in IECs experiencing γ-ray exposure, contributed to mitigation of radiation enteritis. BNF significantly enhanced cell viability and suppressed cell apoptosis in an AhR activation-dependent manner. The mechanism of BNF reducing the IECs radiosensitivity was associated with cell cycle arrest and suppression of cell proliferation. In contrast, AhR antagonist CH-223191 significantly blocked BNF-induced cell cycle arrest. Cyp1a1 mRNA levels are induced after irradiation in a dose-dependent manner, and CYP1A1 protein expression increased in the irradiated intestinal tract as well. BNF also reduces DNA strand breaks induced by irradiation. These studies demonstrate that BNF pretreatment prolonged median survival time of mice upon exposure to a lethal dose of radiation and alleviated irradiation-induced toxicity within the bowel.