The regulation of chromatin configuration at AGAMOUS locus by LFR-SYD-containing complex is critical for reproductive organ development in Arabidopsis.

Switch defective/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes are evolutionarily conserved, multi-subunit machinery that play vital roles in the regulation of gene expression by controlling nucleosome positioning and occupancy. However, little is known about the subunit composition of SPLAYED (SYD)-containing SWI/SNF complexes in plants. Here, we show that the Arabidopsis thaliana Leaf and Flower Related (LFR) is a subunit of SYD-containing SWI/SNF complexes. LFR interacts directly with multiple SWI/SNF subunits, including the catalytic ATPase subunit SYD, in vitro and in vivo. Phenotypic analyses of lfr-2 mutant flowers revealed that LFR is important for proper filament and pistil development, resembling the function of SYD. Transcriptome profiling revealed that LFR and SYD shared a subset of co-regulated genes. We further demonstrate that the LFR and SYD interdependently activate the transcription of AGAMOUS (AG), a C-class floral organ identity gene, by regulating the occupation of nucleosome, chromatin loop, histone modification, and Pol II enrichment on the AG locus. Furthermore, the chromosome conformation capture (3C) assay revealed that the gene loop at AG locus is negatively correlated with the AG expression level, and LFR-SYD was functional to demolish the AG chromatin loop to promote its transcription. Collectively, these results provide insight into the molecular mechanism of the Arabidopsis SYD-SWI/SNF complex in the control of higher chromatin conformation of the floral identity gene essential to plant reproductive organ development.

Polymer-Dispersed Liquid Crystal Films on Flexible Substrates with Excellent Bending Resistance and Spacing Stability.

Polymer-dispersed liquid crystals (PDLCs) are very attractive due to their electrically switchable properties. However, current PDLC films still have problems such as high driving voltages, low contrast ratio (CR), and poor bending resistance and spacing stability. To solve these problems, a PDLC film with a system of coexisting polymer spacer columns and polymer network was proposed. First, based on the adhesive systems of IBMA and UV6301, the effects of IBMA concentration and LC content on the morphology of the polymer network and the electro-optical properties of PDLC were investigated, respectively. Then, the effects of the process conditions of mask polymerization such as temperature, time, and UV light intensity on the morphology and electro-optical properties of the polymer spacer columns were systematically investigated. It was found that PDLC films with the coexistence system exhibit both excellent electro-optical properties and outstanding bending resistance and spacing stability. Thus, it provides new practical possibilities for the preparation of high-performance PDLC films used in flexible devices.

TRPV1 activation mitigates hypoxic injury in mouse cardiomyocytes by inducing autophagy through the AMPK signaling pathway.

Autophagy is a highly conserved self-protection mechanism that plays a crucial role in cardiovascular diseases. Cardiomyocyte hypoxic injury promotes oxidative stress and pathological alterations in the heart, although the interplay between these effects remains elusive. The transient receptor potential vanilloid 1 (TRPV1) ion channel is a nonselective cation channel that is activated in response to a variety of exogenous and endogenous physical and chemical stimuli. Here, we investigated the effects and mechanisms of action of TRPV1 on autophagy in hypoxic cardiomyocytes. In this study, primary cardiomyocytes isolated from C57 mice were subjected to hypoxic stress, and their expression of TRPV1 and adenosine 5'-monophosphate-activated protein kinase (AMPK) was regulated. The autophagy flux was assessed by Western blotting and immunofluorescence staining, and the cell viability was determined through Cell counting kit-8 assay and Lactate dehydrogenase assays. In addition, the calcium influx after the upregulation of TRPV1 expression in cardiomyocytes was examined. The results showed that the number of autophagosomes in cardiomyocytes was higher under hypoxic stress and that the blockade of autophagy flux aggravated hypoxic damage to cardiomyocytes. Moreover, the expression of TRPV1 was induced under hypoxic stress, and its upregulation by capsaicin improved the autophagy flux and protected cardiomyocytes from hypoxic damage, whereas the silencing of TRPV1 significantly attenuated autophagy. Our observations also revealed that AMPK signaling was activated and involved in TRPV1-induced autophagy in cardiomyocytes under hypoxic stress. Overall, this study demonstrates that TRPV1 activation mitigates hypoxic injury in cardiomyocytes by improving autophagy flux through the AMPK signaling pathway and highlights TRPV1 as a novel therapeutic target for the treatment of hypoxic cardiac disease.

Autophagy is required for the directed motility of keratinocytes driven by electric fields.

Endogenous wound electric fields (EFs), an important and fundamental occurrence of wound healing, profoundly influence the directed migration of keratinocytes. Although numerous studies have unveiled the signals responsible for EF-biased direction, the mechanisms by which EFs promote keratinocyte motility remains to be elucidated. In our study, EFs enhanced the directed migratory speed of keratinocytes by inducing autophagic activity, thereby facilitating skin barrier restoration. Initially, we found that electrical signals directed keratinocytes to the cathode with enhanced motility parameters [ i.e., trajectory distance, trajectory speed, displacement distance, and displacement speed ( Td/ t)] and more efficient migration (directionality and Td/ t along the x axis, among others). Meanwhile, EFs induced a time-dependent increase in autophagic activity in keratinocytes, with constant autophagic flux, accompanied by increased transcription of numerous autophagy-related genes. Deficiency in Atg5, a key protein necessary for autophagosome formation, led to significant reduction of autophagy, which was accompanied by a substantial reduction in EF-stimulated directed motility. These results demonstrated a causal relationship between autophagy and EF-directed migratory speed. In addition, both cell migration under normal conditions and EF-biased directionality were autophagy independent. Thus, our findings define autophagy as an important functional regulator of electrically enhanced directed motility, adding to a growing understanding of EFs.-Yan, T., Jiang, X., Lin, G., Tang, D., Zhang, J., Guo, X., Zhang, D., Zhang, Q., Jia, J., Huang, Y. Autophagy is required for the directed motility of keratinocytes driven by electric fields.

Decreased α-tubulin acetylation induced by an acidic environment impairs autophagosome formation and leads to rat cardiomyocyte injury.

Extracellular pH strongly affects cellular metabolism and function. An acidic environment induced under pathological conditions leads to cardiomyocyte injury and dysfunction, but the underlying mechanisms are still poorly understood. Autophagy has been reported as a cytoprotective mechanism that maintains cellular metabolism and viability by removing misfolded proteins and damaged organelles. In our research, we found that acidic environments inhibit autophagosome formation in cardiomyocytes. Up-regulation of autophagic activity, however, ameliorates the cell injury induced by acidic treatments.We also found that acidic treatments reduce the level of α-tubulin acetylation, as detected by Western blot and immunofluorescence staining, and that the number of autophagosomes increase after up-regulating α-tubulin acetylation by Taxol, suggesting that α-tubulin acetylation may play an important role in acidic pH-induced changes in autophagy. Furthermore, an HDAC6 activity assay showed an increase in HDAC6 activity after acidic treatment and that inhibiting HDAC6 activity by tubastatin A or specific siRNA up-regulates α-tubulin acetylation and autophagosome formation. These data confirm that autophagy plays a protective role against acidic pH-induced cell injury and indicate that HDAC6-mediated α-tubulin acetylation is an important mechanism of acidic pH-dependent autophagy in cardiomyocytes.

microRNA-199a-5p suppresses glioma progression by inhibiting MAGT1.

microRNAs (miRNAs) can function as a tumor suppressor or oncogenic genes in human cancers. Alternation expression of miR-199a-5p has been revealed in several human cancers. However, its expression pattern and biological roles in glioma remain unclear. Expression levels of miR-199a-5p in glioma were evaluated at first. The effects of miR-199a-5p expression on cell proliferation, migration, and invasion were investigated using the MTT assay, wound-healing assay, and transwell invasion assay. The expression of miR-199a-5p was found to be reduced in glioma cell lines. Overexpression of miR-199a-5p inhibits glioma cell proliferation, migration, and invasion in vitro. Furthermore, the target of miR-199a-5p was predicted by TargetScan and validated by luciferase activity reporter assay. We found magnesium transporter 1 (MAGT1) was a direct target of miR-199a-5p. Overexpression of MAGT1 reversed the effects of miR-199a-5p on glioma cell behaviors. Taken together, our study revealed that miR-199a-5p and MAGT1 have the potential to be used as a biomarker for glioma.

Synthesis of three-dimensional Au-graphene quantum dots@Pt core-shell dendritic nanoparticles for enhanced methanol electro-oxidation.

Au-graphene quantum dots (GQDs)@Pt core-shell nanodendrites are synthesized through a two-step reduction approach, in which Au forms the core, GQDs form an intermediate layer and dendritic Pt forms the shell. Among the above synthesized catalysts, the GQDs can manipulate the binding of reaction intermediates on the Pt surface as well as assemble π-π * conjugate bonds, thus forming a dendritic Pt shell instead of a compact Pt shell. The obtained core-shell structure was characterized by transmission electron microscopy, energy-dispersive x-ray and x-ray photoelectron spectroscopy. The methanol electro-oxidation was investigated in alkaline media on the Au-GQDs@Pt modified electrode via cyclic voltammetry, chronoamperometry and electrochemical impedance spectroscopy analysis. In particular, we discovered that Au-Pt assembled with GQDs could dramatically improve the activity and stability of the catalysts, owing to the synergistic effect raised by the GQDs, which exhibit prominent electron conductivity and great chemical/physical stability. It was also found that the Pt/Au mole ratios could control the Pt shell thickness, which significantly affected the catalytic methanol oxidation activity of the Au-GQDs@Pt nanodendrites. The Au-GQDs@Pt nanodendrites with optimum Pt/Au mole ratios of 1.0 exhibited a 2.5 times increase in electrocatalytic activity toward methanol oxidation compared with the commercial catalyst (Pt/C), and its CO tolerance was also greatly improved. The above results show that the Au-GQDs@Pt nanocatalysts have potential application prospects in direct methanol fuel cells.

A novel FPCL model producing directional contraction through induction of fibroblast alignment by biphasic pulse direct current electric field.

Although parallel alignment of fibroblasts to the tension lines of scar has been evidenced in vivo, how scar contracture generates directional contraction remains largely unclear due to the lack of effective in vitro model. Fibroblast populated collagen lattice (FPCL), a widely used in vitro model, fails to mimic scar contracture since it produces concentric contraction with the random orientation of fibroblast. We hypothesized that a novel FPCL model with fibroblast alignment might produce directional contraction and then simulate scar contracture better. Here, we showed that although direct current electric fields (DCEFs) enabled fibroblasts aligned perpendicularly to the field vector, it also promoted electrotactic migration of fibroblast in FPCL. By contrast, biphasic pulse direct current electric fields (BPDCEFs), featured by reversal of the EF direction periodically, abolished the electrotactic migration, but induced fibroblast alignment in a pulse frequency dependent manner. Specifically, BPDCEF at a pulse frequency of 0.0002 Hz induced fibroblast alignment comparable to that induced by DCEF under the same field strength (300 mV/mm), leading to an enhanced contraction of FPCL along the direction of cell alignment. FPCL pretreated by BPDCEF showed an elliptical contraction whereas it was concentric in control FPCL. Further study revealed that F-actin redistributions acted as a key mechanism for the induction of fibroblasts alignment by BPDCEF. Cytochalasin D, an inhibitor of actin dynamics, abolished F-actins redistribution, and significantly suppressed the fibroblasts alignment and the directional contraction of FPCL. Importantly, BPDCEF significantly increased RhoA activity in fibroblasts, while this response was attenuated by C3 transferase pre-treatment, a potent inhibitor of RhoA, caused F-actin depolymerization and actin filament bundle randomly distributed. Taken together, our study suggests a crucial role for fibroblast orientation in scar contracture, and provides a novel FPCL model that may be feasible and effective for investigating scar contracture in vitro.

MicroRNA-335-5p suppresses lower extremity deep venous thrombosis by targeted inhibition of PAI-1 via the TLR4 signalingpathway.

This study aims to investigate the effects of microRNA-335-5p (miR-335-5p) on lower-extremity deep vein thrombosis (LEDVT) by targeting PAI-1 through the TLR4 signaling pathway in rat models. siRNA, mimic, and inhibitor were used for transfection. The miR-335-5p expression was detected by in situ hybridization. CCK-8 assay and flow cytometry were adopted to detect proliferation, cell cycle, and apoptosis, respectively. Scratch test and Matrigel-based tube formation assay were used to detect the effect of miR-335-5p on cell migration ability and tube formation ability. A miR-335-5p lentivirus plasmid was constructed and injected into LEDVT rats. The length and weight of thrombus were measured, changes of thrombus recanalization were observed by CD34 immunohistochemistry, and levels of PAI-1 and inflammatory factors in femoral vein blood were detected by ELISA. LEDVT rats showed a higher AOD value of PAI-1, higher expression of PAI-1, NF-κB, Rac1, IL-1ß, and TLR4 and a lower miR-335-5p expression. PAI-1 and miR-335-5p were negatively correlated. Compared to the blank and siRNA-NC groups, the miR-335-5p mimic and siRNA-PAI-1 groups showed declined expression of PAI-1, TLR4, NF-κB, Rac1, and IL-1ß, increased proliferation and tube formation abilities, less cells in G0/G1 phase, and decreased apoptosis, decreased length and weight of thrombus, organized thrombus, increased new blood vessels, and decreased levels of PAI-1, IL-1, IL-6, and Tnf-a. miR-335-5p may suppress the occurrence and development of LEDVT in rats by repressing the activation of the TLR4 signaling pathway by targeted inhibition of PAI-1.

PI3K-AKT Pathway Protects Cardiomyocytes Against Hypoxia-Induced Apoptosis by MitoKATP-Mediated Mitochondrial Translocation of pAKT.

BACKGROUND/AIMS: The phosphatidylinositol-3-kinase -AKT (PI3K-AKT) is an important intracellular signal pathway in regulating cell proliferation, differentiation and apoptosis. In previous studies, we've demonstrated that PI3K-AKT pathway protects cardiomyocytes from ischemic and hypoxic apoptosis through mitochondrial function. However, the molecular mechanisms underlying hypoxia-induced cardiomyocyte apoptosis via PI3K-AKT pathway remain ill-defined. Here, we addressed this question. METHODS: Cardiomyocytes were exposed to hypoxia, with/without different inhibitors and then protein levels were assessed by Western blotting. RESULTS: We found that the PI3K-AKT pathway was activated in cardiomyocytes that were exposed to hypoxia. Moreover, the phospho-AKT (pAKT) translocated from cytosol to mitochondria via mitochondrial adenosine triphosphate-dependent potassium (mitoKATP), leading to an increase in cytochrome c oxidase (CcO) activity to suppress apoptosis. On the other hand, the mitoKATP specific blocker, 5-hydroxydecanote (5-HD), or suppression of CcO using siRNA, inhibited the pAKT mitochondrial translocation to maintain the CcO activity, resulting in mitochondrial dysfunction and cellular apoptosis induced by hypoxia. CONCLUSION: These findings suggest that the anti-apoptotic effect of the PI3K-AKT pathway through pAKT translocation to mitochondrial via mitoKATP may be conducted through modification of CcO activity.

FG-4592 Accelerates Cutaneous Wound Healing by Epidermal Stem Cell Activation via HIF-1α Stabilization.

BACKGROUND/AIMS: Regional hypoxia promptly develops after trauma because of microvascular injury and increased oxygen consumption. This acute hypoxia plays a positive role in early skin wound healing. One of the mechanisms underlying the beneficial effects of acute hypoxia on wound healing may be increased hypoxia-inducible factor-1 (HIF-1α) expression. HIF-1α may affect the wound-healing process through many aspects, including angiogenesis, metabolism, and extra-cellular matrix synthesis and remodelling. Epidermal stem cells (EpSCs) are important participants in wound repair; however, whether these cells are regulated by hypoxia is unclear. This study aimed to elucidate the regulatory mechanism by which hypoxia acts on EpSCs. METHODS: CCK8 assays, western blots and live cell station observation were employed to compare the viability, proliferation and motility of EpSCs cultured under normoxic conditions (21% O2) with those cultured under hypoxic conditions (2% O2). Moreover, we used FG-4592 (a prolyl hydroxylase inhibitor that stabilizes HIF-1α in normoxia), KC7F2 (a selective inhibitor of HIF-1α transcription) and siRNA against HIF-1α to regulate HIF-1α expression. RESULTS: Acute hypoxia caused EpSCs to switch from a quiescent state to an activated state with higher viability and motility, as well as an earlier proliferation peak. We demonstrated that the HIF-1 signalling pathway mediated hypoxia-induced activation of EpSCs. Finally, the in vivo experiments showed that exogenous FG-4592 effectively accelerates wound healing, shortens healing times and even induces epidermal hyperplasia. CONCLUSION: This study demonstrated that both hypoxia and exogenous FG-4592 improve EpSC proliferation and motility by stabilizing HIF-1α, and its results suggest that HIF-1α is an important target through which wound healing can be accelerated and that FG-4592 is a promising new drug for wound repair.

Mitochondrial Dynamics in Rat Heart Induced by 5-Fluorouracil.

BACKGROUND Patients treated with 5-FU can develop rare but potentially severe cardiac effects, including cardiomyopathy, angina pectoris, ventricular tachycardia, heart failure, acute myocardial infarction, and cardiogenic shock. The specific pathologies and mechanisms are not fully understood. Research found that mitochondrial dynamics are widely detected in many angiocardiopathies. Therefore, in the present study we studied the mitochondrial damage and explored the role of mitochondrial fusion/fission proteins on myocardium of rats treated with 5-fluorouracil (5-FU). MATERIAL AND METHODS Thirty male SD rats were randomly divided into 3 groups with 10 rats in each group: (1) control group, (2) low 5-FU group (25 mg/kg), (3) high 5-FU group (50 mg/kg). The animals received intraperitoneal injection for 5 consecutive days. We assessed alterations in mitochondrial morphology, ATP content, mitochondrial membrane potential, and mitochondria fusion/fission proteins expression in hearts of rats receiving intraperitoneal injection with different doses of 5-FU. RESULTS 5-FU intraperitoneal injection induced ultra-structural damage in hearts, such as mitochondrial swelling, cristae disorder, and vacuolization. These changes were accompanied by decreases of mitochondrial membrane potential. The low dose of 5-FU led to a slight increase in ATP content. However, the high 5-FU dose caused a more significant reduction compared with the control group. Furthermore, 5-FU intraperitoneal injection significantly increased specific mitochondrial fission proteins (Drp1 and Fis1) and decreased mitochondrial fusion proteins (Opa1, Mfn1, and Mfn2) in rat hearts. However, no changes in cardiac structure and function were detected by echocardiogram. The high dose caused more damage to mitochondrial function than the low dose. CONCLUSIONS Mitochondrial damage is a potentially important mechanism and early indicator for 5-FU-induced cardiovascular disease.

BNIP3 promotes the motility and migration of keratinocyte under hypoxia.

The migration of keratinocytes from wound margins plays a critical role in the re-epithelialization of skin wounds. Hypoxia occurs immediately after injury and acts as an early stimulus to initiate the healing processes. Although our previous studies have revealed that hypoxia promotes keratinocyte migration, the precise mechanisms involved remain unclear. Here, we found that BNIP3 expression was upregulated in hypoxic keratinocytes, and BNIP3 silencing suppressed hypoxia-induced cell migration. Additionally, hypoxia activated the focal adhesion kinase (FAK) pathway through upregulation of BNIP3, while FAK inhibition attenuated hypoxic keratinocyte migration. Here, we conclusively demonstrate a novel role for BNIP3 in hypoxia-induced keratinocyte migration. Furthermore, we provide a new perspective on the molecular mechanisms of wound healing and identify BNIP3 as a potential new molecular target for clinical treatments to enhance wound healing.

[Three-dimensional tooth model reconstruction based on fusion of dental computed tomography images and laser-scanned images].

Complete three-dimensional(3D) tooth model provides essential information to assist orthodontists for diagnosis and treatment planning. Currently, 3D tooth model is mainly obtained by segmentation and reconstruction from dental computed tomography(CT) images. However, the accuracy of 3D tooth model reconstructed from dental CT images is low and not applicable for invisalign design. And another serious problem also occurs, i.e. frequentative dental CT scan during different intervals of orthodontic treatment often leads to radiation to the patients. Hence, this paper proposed a method to reconstruct tooth model based on fusion of dental CT images and laser-scanned images. A complete3 D tooth model was reconstructed with the registration and fusion between the root reconstructed from dental CT images and the crown reconstructed from laser-scanned images. The crown of the complete 3D tooth model reconstructed with the proposed method has higher accuracy. Moreover, in order to reconstruct complete 3D tooth model of each orthodontic treatment interval, only one pre-treatment CT scan is needed and in the orthodontic treatment process only the laser-scan is required. Therefore, radiation to the patients can be reduced significantly.

HSP27 phosphorylation protects against endothelial barrier dysfunction under burn serum challenge.

F-actin rearrangement is an early event in burn-induced endothelial barrier dysfunction. HSP27, a target of p38 MAPK/MK2 pathway, plays an important role in actin dynamics through phosphorylation. The question of whether HSP27 participates in burn-related endothelial barrier dysfunction has not been identified yet. Here, we showed that burn serum induced a temporal appearance of central F-actin stress fibers followed by a formation of irregular dense peripheral F-actin in pulmonary endothelial monolayer, concomitant with a transient increase of HSP27 phosphorylation that conflicted with the persistent activation of p38 MAPK/MK2 unexpectedly. The appearance of F-actin stress fibers and transient increase of HSP27 phosphorylation occurred prior to the burn serum-induced endothelial hyperpermeability. Overexpressing phospho-mimicking HSP27 (HSP27(Asp)) reversed the burn serum-induced peripheral F-actin rearrangement with the augmentation of central F-actin stress fibers, and more importantly, attenuated the burn serum-induced endothelial hyperpermeability; such effects were not observed by HSP27(Ala), a non-phosphorylated mutant of HSP27. HSP27(Asp) overexpression also rendered the monolayer more resistant to barrier disruption caused by Cytochalasin D, a chemical reagent that depolymerizes F-actin specifically. Further study showed that phosphatases and sumoylation-inhibited MK2 activity contributed to the blunting of HSP27 phosphorylation during the burn serum-induced endothelial hyperpermeability. Our study identifies HSP27 phosphorylation as a protective response against burn serum-induced endothelial barrier dysfunction, and suggests that targeting HSP27 wound be a promising therapeutic strategy in ameliorating burn-induced lung edema and shock development.

Pigment epithelium-derived factor regulates microvascular permeability through adipose triglyceride lipase in sepsis.

The integrity of the vascular barrier, which is essential to blood vessel homoeostasis, can be disrupted by a variety of soluble permeability factors during sepsis. Pigment epithelium-derived factor (PEDF), a potent endogenous anti-angiogenic molecule, is significantly increased in sepsis, but its role in endothelial dysfunction has not been defined. To assess the role of PEDF in the vasculature, we evaluated the effects of exogenous PEDF in vivo using a mouse model of cecal ligation and puncture (CLP)-induced sepsis and in vitro using human dermal microvascular endothelial cells (HDMECs). In addition, PEDF was inhibited using a PEDF-monoclonal antibody (PEDF-mAb) or recombinant lentivirus vectors targeting PEDF receptors, including adipose triglyceride lipase (ATGL) and laminin receptor (LR). Our results showed that exogenous PEDF induced vascular hyperpermeability, as measured by extravasation of Evan's Blue (EB), dextran and microspheres in the skin, blood, trachea and cremaster muscle, both in a normal state and under conditions of sepsis. In control and LR-shRNA-treated HDMECs, PEDF alone or in combination with inflammatory mediators resulted in activation of RhoA, which was accompanied by actin rearrangement and disassembly of intercellular junctions, impairing endothelial barrier function. But in ATGL-shRNA-treated HDMECs, PEDF failed to induce the aforementioned alterations, suggesting that PEDF-induced hyperpermeability was mediated through the ATGL receptor. These results reveal a novel role for PEDF as a potential vasoactive substance in septic vascular hyperpermeability. Furthermore, our results suggest that PEDF and ATGL may serve as therapeutic targets for managing vascular hyperpermeability in sepsis.

A novel system of galangin-potassium permanganate-polyphosphoric acid for the determination of tryptophan and its chemiluminescence mechanism.

A novel galangin-potassium permanganate (KMnO4)-polyphosphoric acid (PPA) system was found to have an outstanding response to tryptophan (Trp). Trp determination using this KMnO4 -PPA system was enhanced significantly in the presence of galangin. A highly sensitive flow-injection chemiluminescence (CL) method to determine Trp was developed based on the CL reaction of galangin-KMnO4 -Trp in PPA media. The presence of galangin, a member of the flavonol class of flavonoid complexes, greatly increased the luminous intensity of Trp in KMnO4 -PPA systems. Under optimized conditions, Trp was determined in the 0.05-10 µg/mL range, with a detection limit (3σ) of 5.0 × 10(-3) µg/mL. The relative standard deviation (RSD) was 1.0% for 11 replicate determinations of 1.0 µg/mL Trp. Two synthetic samples were determined selectively with recoveries of 98.4-100.1% in the presence of other amino acids. The possible mechanism is summarized as follows: excited states of Mn(II)(*) and Mn(III(*) types are the main means of generating chemical luminescent species, and Trp concentration and luminescence intensity have a linear relationship, which enables quantitative analysis.

Model prediction of radioactivity levels in the environment and food around the world's first AP 1000 nuclear power unit.

Objectives: Model prediction of radioactivity levels around nuclear facilities is a useful tool for assessing human health risks and environmental impacts. We aim to develop a model for forecasting radioactivity levels in the environment and food around the world's first AP 1000 nuclear power unit. Methods: In this work, we report a pilot study using time-series radioactivity monitoring data to establish Autoregressive Integrated Moving Average (ARIMA) models for predicting radioactivity levels. The models were screened by Bayesian Information Criterion (BIC), and the model accuracy was evaluated by mean absolute percentage error (MAPE). Results: The optimal models, ARIMA (0, 0, 0) × (0, 1, 1)4, and ARIMA (4, 0, 1) were used to predict activity concentrations of 90Sr in food and cumulative ambient dose (CAD), respectively. From the first quarter (Q1) to the fourth quarter (Q4) of 2023, the predicted values of 90Sr in food and CAD were 0.067-0.77 Bq/kg, and 0.055-0.133 mSv, respectively. The model prediction results were in good agreement with the observation values, with MAPEs of 21.4 and 22.4%, respectively. From Q1 to Q4 of 2024, the predicted values of 90Sr in food and CAD were 0.067-0.77 Bq/kg and 0.067-0.129 mSv, respectively, which were comparable to values reported elsewhere. Conclusion: The ARIMA models developed in this study showed good short-term predictability, and can be used for dynamic analysis and prediction of radioactivity levels in environment and food around Sanmen Nuclear Power Plant.

PAI-1 and IFN-γ in the regulation of innate immune homeostasis during sublethal yersiniosis.

Plasminogen activator inhibitor type 1 (PAI-l), a key part of the fibrinolytic system, plays a critical host protective role during the acute phase of infection by regulating interferon(IFN)-γ release. IFN-γ regulates PAI-1 expression, which suggests an intricate interplay between PAI-1 and IFN-γ. Here, using the notion of a feedback loop, we report the complicated regulatory relationship between PAI-1 and IFN-γ. Mice were inoculated intravenously with 1×10(3) colony forming units of Yersinia enterocolitica; PAI-1 deficiency enhanced lethality (p<0.0001) and increased bacterial growth and dissemination (p=0.08 on day 3, p=0.004 on day 5, respectively). PAI-1 significantly increased the levels IFN-γ mRNA (p<0.005), which may increase survival and decrease bacterial burden. Simultaneously, we showed that IFN-γ increased PAI-1 mRNA levels in vivo (p<0.05). Next, we investigated the transduction signal pathway. After mice were inoculated intraperitoneally with 50µg lipopolysaccharide (LPS), both levels of IFN-γ mRNA (p=0.05) and levels of PAI-1 mRNA (p<0.0001) decreased in MyD88-deficient mice. The same trend was also found in mice treated with 1000µg LPS. As a result of correlations of IFN-γ and PAI-1 in wild-type mice, we delineated the transduction signal pathway, namely MyD88-IFN-γ-PAI-1. The in vivo LPS-injected animal model further confirmed that PAI-1 feedback controlled IFN-γ in a direct or indirect manner. New perspectives of the relationship between PAI-1 and IFN-γ should help in understanding the complex and often conflicting results that have been reported in different infection models. Thus, the feedback loop between PAI-1 and IFN-γ is part of the dynamic equilibrium of coagulation and inflammation that helps maintain innate immune homeostasis.

CXCL12/CXCR4 axis promotes mesenchymal stem cell mobilization to burn wounds and contributes to wound repair.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BM-MSCs) play a crucial role in tissue repair. Their role in thermal burn wound regeneration and the relevant mechanism, however, is rarely studied. METHODS: BM-MSCs from green fluorescent protein transgenic male mice were transfused to irradiated recipient female C57BL/6 mice. Twenty-one days later, the female mice were inflicted with burn wounds. The size of the burned area was measured by an in vivo fluorescence imaging system, and BM-MSC chemotaxis and epithelialization were estimated by fluorescence in situ hybridization and immunofluorescence technology. The expression of CXCL12 and CXCR4 in the wound margin was detected by enzyme-linked immunosorbent assay and immunohistochemistry. The importance of CXCL12/CXCR4 signaling in BM-MSC chemotaxis was further estimated by blocking CXCR4 in vivo and in vitro. RESULTS: In vivo imaging results showed that BM-MSCs migrated to the injured margins. Fluorescence in situ hybridization and immunofluorescence technology revealed that Y chromosome-positive cells derived from green fluorescent protein transgenic mice were detected to be colocalized with keratin protein. Enzyme-linked immunosorbent assay revealed increased levels of CXCL12 and CXCR4 protein in the wound sites of BM-MSC-treated chimeric mice after burn. Immunohistochemistry also disclosed that CXCL12 levels were elevated at postburn day 7 compared with day 0. Furthermore, pretreatment of the BM-MSCs with the CXCR4 antagonist AMD3100 significantly inhibited the mobilization of BM-MSCs in vitro and in vivo, which attenuated wound closure. CONCLUSION: BM-MSC migration to the burned margins promotes the epithelialization of the wound, and mobilization of BM-MSCs is mediated by CXCL12/CXCR4 signaling.