Photothermal modulation speckle optical coherence tomography of microvascular nondestructive imaging in vivo with high effective resolution.

To achieve non-invasive and high effective resolution microvascular imaging in vivo, photothermal modulation speckle optical coherence tomography (PMS-OCT) imaging technology is proposed in this Letter to enhance the speckle signal of the bloodstream for improving the imaging contrast and image quality in the deeper depth of Fourier domain optical coherence tomography (FD-OCT). The results of simulation experiments proved that this photothermal effect could disturb and enhance the speckle signals, because the photothermal effect could modulate the sample volume to expand and change the refractive index of tissues, leading to the change in the phase of interference light. Therefore, the speckle signal of the bloodstream will also change. With this technology we obtain a clear cerebral vascular nondestructive image of a chicken embryo at a certain imaging depth. This technology expands the application fields of optical coherence tomography (OCT) especially in more complex biological structures and tissues, such as the brain, and provides a new way, to the best of our knowledge, for the application of OCT in brain science.

High-sensitivity synchronous angio-lymphography based on a speckle spectrum contrast OCT.

To achieve accurate selection and synchronous imaging of blood vessels and lymph, a speckle spectrum contrast method (SSC) based on spectral-domain optical coherence tomography (SD-OCT) is proposed in this Letter. In this method, the time-lapse optical coherence tomography (OCT) intensity signal is transformed to the Fourier frequency domain. By analyzing the frequency spectrum of the time-lapse OCT intensity signal, a parameter called SSC signal, which represents the ratio of different intervals of the high frequency to the low frequency, is utilized to extract and contrast different types of the vessels in the biological tissues. In the SSC spectrum, the SSC signals of the static tissue, lymphatic vessels, and vascular vessels can be separated in three different frequency intervals, enabling differentiation and synchronous imaging of the lymphatic-vascular vessels. A mouse ear was used to demonstrate the feasibility and efficiency of this method. By using the SSC signal as the imaging parameter, the lymphatic and blood vessels of the mouse ear are differentiated and visualized simultaneously. This study shows the feasibility of the three-dimensional (3D) synchronous angio-lymphography based on the SSC method, which provides a tool to improve the understanding for disease research and treatment.

Sonic hedgehog promotes synovial inflammation and articular damage through p38 mitogen-activated protein kinase signaling in experimental arthritis.

Activated fibroblast-like synoviocytes (FLS) play a pivotal role in synovial inflammation and joint destruction of rheumatoid arthritis (RA). The mechanisms by which sonic hedgehog (SHH) signaling promotes RA FLS-mediated chronic inflammation and tissue damage are not fully understood. The present study aims to determine the role of SHH signaling in the pathogenesis of RA and to explore the potential mechanism(s). We found that the components of SHH signaling were highly expressed in FLS and synovial tissue from patients with RA and in the joint tissue of collagen-induced arthritis (CIA) mice. Overexpression of SHH aggravated the synovial inflammation and joint destruction of CIA and exacerbated cartilage degradation in the cartilage and RA FLS-engrafted severe combined immunodeficiency (SCID) model. Conversely, inhibition of SHH signaling significantly alleviated arthritis severity and reduced cartilage destruction caused by the invasion of RA FLS in vivo. Moreover, we found that p38 mitogen-activated protein kinase (MAPK) cascade was regulated by SHH signaling in RA FLS and the level of phospho-p38 in the joint tissue of CIA was decreased after blockade of SHH signaling. Inhibition of p38 MAPK abolished the effect of SHH overexpression on synovial inflammation and articular destruction of CIA and suppressed the aggressive properties of RA FLS, which were promoted by SHH agonist. In conclusion, our study suggests that SHH signaling aggravates synovial inflammation and joint destruction of experimental arthritis and promotes the abnormal behavior of RA FLS in a p38-dependent manner. SHH-p38 MAPK signaling could be a potential target for the treatment of RA.

Identifying tuberculous pleural effusion using artificial intelligence machine learning algorithms.

BACKGROUND: The differential diagnosis of tuberculous pleural effusion (TPE) is challenging. In recent years, artificial intelligence (AI) machine learning algorithms have started being used to an increasing extent in disease diagnosis due to the high level of efficiency, objectivity, and accuracy that they offer. METHODS: Data samples on 192 patients with TPE, 54 patients with parapneumonic pleural effusion (PPE), and 197 patients with malignant pleural effusion (MPE) were retrospectively collected. Based on 28 different features obtained via statistical analysis, TPE diagnostic models using four machine learning algorithms (MLAs), namely logistic regression, k-nearest neighbors (KNN), support vector machine (SVM) and random forest (RF) were established and their respective diagnostic performances were calculated. The respective diagnostic performances of each of the four algorithmic models were compared with that of pleural fluid adenosine deaminase (pfADA). Based on 12 features with the most significant impacts on the accuracy of the RF model, a new RF model was designed for clinical application. To demonstrate its external validity, a prospective study was conducted and the diagnostic performance of the RF model was calculated. RESULTS: The respective sensitivity and specificity of each of the four TPE diagnostic models were as follows: logistic regression - 80.5 and 84.8%; KNN- 78.6 and 86.6%; SVM - 83.2 and 85.9%; and RF - 89.1 and 93.6%. The sensitivity and specificity of pfADA were 85.4 and 84.1%, respectively, at the best cut-off value of 17.5 U/L. RF was the superior method among the four MLAs, and was also superior to pfADA. The newly designed RF model (based on 12 out of 28 features) exhibited an acceptable performance rate for the diagnosis of TPE with a sensitivity and specificity of 90.6 and 92.3%, respectively. In the prospective study, its sensitivity and specificity were 100.0 and 90.0%, respectively. CONCLUSIONS: Establishing a model for the diagnosis of TPE using RF resulted in a more effective, economical, and faster diagnostic method. This method could enable clinicians to diagnose and treat TPE more effectively.

4-Octyl Itaconate Activates Nrf2 Signaling to Inhibit Pro-Inflammatory Cytokine Production in Peripheral Blood Mononuclear Cells of Systemic Lupus Erythematosus Patients.

BACKGROUND/AIMS: Increased production of multiple pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6, plays an essential pathogenic role in the progression of systemic lupus erythematosus (SLE). Recent studies have characterized itaconate as a novel and potent nuclear-factor-E2-related factor 2 (Nrf2) activator that activates Nrf2 signaling by alkylating cysteine residues on Keap1 (Kelch-like ECH-associated protein 1). METHODS: THP-1 human macrophages and peripheral blood mononuclear cells (PBMCs) of SLE patients were treated with 4-octyl itaconate (OI). Nrf2 signaling activation was tested by qPCR assay and western blotting. mRNA expression and the production of multiple pro-inflammatory cytokines were tested by qPCR and enzyme-linked immunosorbent assays, respectively. Nuclear factor (NF)-κB activation was tested by the p65 DNA-binding assay. RESULTS: We demonstrated that OI, the cell-permeable derivative of itaconate, induced Keap1-Nrf2 dissociation, Nrf2 protein accumulation, and nuclear translocation, which enabled the transcription and expression of multiple Nrf2-dependentantioxidant enzymes (heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1, and glutamate-cysteine ligase modifier subunit) in THP-1 human macrophages. OI also induced significant Nrf2 activation in SLE patient-derived PBMCs. OI pretreatment inhibited mRNA expression and the production of multiple pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in SLE patient-derived PBMCs and lipopolysaccharide (LPS)-activated THP-1 cells. OI potently inhibited NF-κB activation in SLE patient-derived PBMCs and LPS-activated THP-1 cells. Importantly, Nrf2 silencing (by targeted short hairpin RNA) or knockout (by CRISPR/Cas9 gene-editing method) almost abolished OI-induced anti-oxidant and anti-inflammatory actions in SLE patient-derived PBMCs and LPS-activated THP-1 cells. CONCLUSION: OI activates Nrf2 signaling to inhibit the production of pro-inflammatory cytokines in human macrophages and SLE patient-derived PBMCs. OI and itaconate could have important therapeutic value for the treatment of SLE.

[Effects of the Application of Irrigation Water Containing Zn at the Key Growth Period on the Uptake and Transport of Cd in Rice].

In this study， a field experiment was conducted to examine the effects of the application of irrigation water containing Zn at the key growth period （booting stage and filling stage） on exchangeable Cd content in the soil， Cd concentration in pore water， and Cd uptake and transport in rice in a Cd-contaminated paddy field in Liuyang City， Hunan Province. The results indicated that： ① the application of irrigation water containing Zn during the key growth period could inhibit the releasing process of exchangeable Cd from the soil into pore water. Compared with that in the control， the content of exchangeable Cd in soil was slightly changed， but the concentration of Cd in soil pore water at the mature stage was significantly reduced by 16.7%-57.6%. ② The application of irrigation water containing Zn at the key growth period could significantly reduce the Cd content in various parts of rice. Cd contents in root， stem， and brown rice with the application of irrigation water containing 20 mg·L-1 Zn before the booting and the filling stage （BF1） were significantly decreased by 56.0%， 83.8%， and 85.2%， respectively. ③ Compared with the application of 100 mg·L-1 irrigation water containing Zn， the application of 20 mg·L-1 irrigation water containing Zn significantly reduced the uptake and transport of Cd in rice， and the translocation factor （TF） of Cd from rice roots to stems was also significantly reduced by 12.5%-56.3%， with the B1 and BF1 treatments reaching significant levels. These results suggested that the application of irrigation water containing Zn could significantly reduce the uptake and accumulation of Cd in rice， and the application of 20 mg·L-1 irrigation water containing Zn before the booting and filling stage could effectively realize the safe production of Cd-contaminated paddy fields.

[Key Growth Stage of Pb Accumulation in Rice Through a Hydroponic Experiment with Pb Stress].

Pb accumulation in rice varies significantly at different growth stages. In this study, a hydroponic experiment was conducted to study the effects of exogenous Pb stress on Pb accumulation and transportation in rice plants and determine the key rice growth stages of Pb accumulation and their contribution to the Pb content in brown rice. For the hydroponic experiment, 0.5 mg ·L-1 of exogenous Pb was added to rice at different growth stages, including the tillering stage, jointing stage, booting stage, filling stage, dough stage, maturing stage, and whole growth stage (103 d) of the rice plant. Another treatment of the whole growth stage without Pb stress was established as the control. The results showed that: ① There were no significant effects of Pb stress in any single stage on the plant height, tiller number, and biomass, but the rice plant height and biomass significantly decreased under the Pb stress for the whole growth period. ② Pb contents in different tissues at the maturing stage of the rice plant were in the order of root > stem node 1 > other stem nodes > root rhizome > sti > leaf > ear > husk > brown rice. Pb contents in brown rice ranged from 0.1 to 1.2 mg ·kg-1 for all exogenous Pb treatments, and ranked in the growth stages as booting stage > jointing stage > tillering stage > filling stage > maturing stage > dough stage. ③ The relative contribution rates of Pb accumulation in the whole rice plants were relatively high during the reproductive growth period (filling stage, dough stage, and maturing stage), while those in the above-ground parts of the rice plants were relatively high during the vegetative growth stage (tillering stage, jointing stage, booting stage). ④ The booting stage was the key growth period for Pb accumulation in brown rice. Pb stress at this stage contributed 43.3% of Pb content in brown rice, followed by Pb stress at the jointing stage and the tillering stage, with contribution rates of 24.4% and 21.3%, respectively. ⑤ Water management regimes, application of amendments, or leaf resistance control techniques should be applied appropriately at the booting stage of the rice plants to reduce Pb accumulation in brown rice and to realize the safe use of rice paddies polluted with Pb.

[Effects of Different Treatments with Water Management Combined with Leaf Spraying Silicon Fertilizer on Cd Accumulation in Rice].

A field experiment involving eight treatments with water management combined with leaf spraying silicon fertilizer was conducted in a paddy field heavily contaminated with Cd (2.83 mg·kg-1) to study the effects of these treatments on rice growth and Cd accumulation in different rice tissues. The results showed that:① the treatments had no significant effects on rice plant height or number of tillers, but increased the biomass of brown rice by 1.7% to 25.0%. Among the eight treatments, that of water flooding during the rice maturation period plus leaf spraying silicon fertilizer (CY) resulted in the highest amount of brown rice yield. ② The treatment of conventional water management plus leaf spraying silicon fertilizer (Si) had no significant effect on the exchangeable Cd content and TCLP extractable Cd content in soil, whereas the other treatments reduced the exchangeable Cd content by 7.8%-42.6% and the TCLP extractable Cd content by 20.0%-40.8%. ③ The Si treatment could reduce the Cd content in various rice tissues, with an overall decrease of 19.0% in brown rice. The other treatments significantly reduced the Cd content in various rice tissues. The treatment of moisture during the rice maturation period plus leaf spraying silicon fertilizer (CS) resulted in the highest reduction in the Cd content in brown rice (44.0%), and was followed by the treatments of batch-type water flooding during the entire rice growth period plus leaf spraying silicon fertilizer (JX; 36.4%), and moisture during the rice pustulation period plus leaf spraying silicon fertilizer (GS; 31.8%). ④ For paddy-fields that are contaminated with Cd to medium and heavy levels, the CS and JX treatments are recommended to manage rice production in order to significantly reduce the Cd content of brown rice whilst having little effect on the rice yield.

[Effects of Exogenous Phosphorus on Rice Growth and Cadmium Accumulation and Transportation Under Cadmium Stress].

In this study, we investigated the effects of exogenous phosphorus on the accumulation and transportation of cadmium in rice plants through a hydroponic experiment. In the experiment, the rice variety was Huanghuazhan, P solution concentrations were 10.0-45.0 mg ·L-1 that was made using NaH2PO4, and Cd solution concentrations were 0.1 mg ·L-1 and 0.2 mg ·L-1. The results showed that: ① the biomass in all parts of rice plants and contents of photosynthetic pigment (chlorophyll a, chlorophyll b, and carotenoid) increased gradually with an increase in exogenous P. ② Content of Cd in rice stems, leaves, husk, and brown rice increased gradually with an increase in the amounts of exogenous P. The content of Cd in brown rice increased by 2.8%-22.8% and 40.9%-61.8% when treated with Cd concentrations of 0.1 mg ·L-1 and 0.2 mg ·L-1 in hydroponic solutions, respectively. ③ Cd accumulation in rice plants was accelerated due to the application of exogenous P. Cd accumulating amounts increased from 395.1 µg ·plant-1 to 542.6 µg ·plant-1 and 639.6 µg ·plant-1 to 1082.0 µg ·plant-1 when treated with Cd concentrations of 0.1 and 0.2 mg ·L-1 in hydroponic solutions, respectively. ④ With an increase in the applied amounts of exogenous P, the P/Cd quality ratio in rice roots increased, while those in rice stems, leaves, husks, and brown rice decreased; meanwhile, the Cd transfer coefficients from root to stem (TFroot-stem) and stem to leaf (TFstem-leaf) increased. This showed that there was a certain synergistic effect between P and Cd in the rice parts. Finally, the application of exogenous P promoted the transfer of Cd from the rice root to other rice tissues, resulting in a synergistic effect on Cd accumulation and transportation in various rice tissues and increased Cd contents in brown rice.