Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4.

BACKGROUND: Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol. METHODS: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a-/- and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers. RESULTS: We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells. CONCLUSIONS: We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.

Effect of inactivated COVID-19 vaccine on the negative conversion of nucleic acid in asymptomatic or mild patients with COVID-19.

BACKGROUND: Negative conversion of nucleic acid was a key factor in deciding discharge or the end of isolation of asymptomatic or mild COVID-19 patients. We aimed to explore the effect of vaccination on the time to negative conversion after Omicron infection. METHODS: This retrospective cohort study included asymptomatic or mild patients with COVID-19 admitted to Fangcang shelter Hospital from November 10, 2022 to December 2, 2022. The relationship between vaccination status and the time to negative conversion was analyzed by multiple linear regression. RESULTS: A total of 2,104 asymptomatic or mild COVID-19 patients were included in the analysis, of whom 1,963 were vaccinated. The mean time to negative conversion of no vaccination, one dose, two doses, and three doses were 12.57 (5.05), 12.18 (3.46), 11.67 (4.86) and 11.22 (4.02) days, respectively (p = 0.002). Compared with no vaccination, two doses (ß=-0.88, 95% CI: -1.74, -0.02, p = 0.045), and three doses (ß=-1.51, 95% CI: -2.33, -0.70, p < 0.001) were both associated with shorter time to negative conversion. Comparing with two doses, booster dose was associated significantly with shorter time to negative conversion (ß=-0.63, 95% CI: -1.07, -0.20, p = 0.004). Age was positively correlated with the time to negative conversion (ß = 0.04, 95% CI: 0.02, 0.05, p < 0.001). CONCLUSION: Vaccination with inactivated vaccine and booster dose can shorten the time to negative conversion of asymptomatic or mild COVID-19 patients. The significant prolongation of time to negative conversion with increasing age suggests the promotion of vaccination, especially booster dose, particularly in the elderly.

Analyte-Size-Dependent Ionization and Quantification of Monosaccharides in Human Plasma Using Cation-Exchanged Smectite Layers.

Smectite, a synthetic inorganic polymer with a saponite structure, was subjected to matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Typical organic matrix molecules 2,4,6-trihydroxyacetophenone (THAP) and 2,5-dihydroxybenzoic acid (DHBA) were intercalated into the layer spacing of cation-exchanged smectite, and the complex was used as a new matrix for laser desorption/ionization mass spectrometry. Because of layer spacing limitations, only a small analyte that could enter the layer and bind to THAP or DHBA could be ionized. This was confirmed by examining different analyte/matrix preparation methods and by measuring saccharides with different molecular sizes. Because of the homogeneous distribution of THAP molecules in the smectite layer spacing, high reproducibility of the analyte peak intensity was achieved. By using isotope-labeled (13)C6-d-glucose as the internal standard, quantitative analysis of monosaccharides in pretreated human plasma sample was performed, and the value of 8.6 ± 0.3 µg/mg was estimated.

Study on tank damage and response of adjacent tanks in full time domain of detonation.

The flammable gas volatilized from the storage medium in the tank will burn and explode under the action of an accidental ignition source. Tank explosions formed by the explosive shock wave, explosive debris will not only cause their own damage, but also on the safe operation of adjacent tanks to form a threat. Therefore, in this paper, the vertical dome roof tank is taken as the research object, the criteria of brittle fracture failure of tank materials are constructed, and the multi-field coupling calculation model of tank detonation based on TNT equivalent method is established, taking into account the fluid properties inside and outside the tank, the structure of implosion tank and adjacent tank. By analyzing the full time domain process of gas detonation in tanks under different influence factors, the response to implosion damage of tanks and adjacent tanks under the action of explosion shock wave overpressure and debris was obtained. With the increase of the liquid level, the overpressure and deformation of the shock wave of the detonation tank and adjacent tank decrease, and the type and number of fragments decrease. With the increase of the volume of the tank, the overpressure and stress of the shock wave become larger, the strain rate of the tank becomes larger, and brittle failure is more likely to occur. The types and number of fragments formed increase, but detonation fragments are not formed when the tank is full. The research results in this paper provide a theoretical basis and calculation method for preventing and controlling tank implosion accidents, as well as tank design and tank spacing layout.

Polarimetric Helmholtz Stereopsis.

Helmholtz stereopsis (HS) exploits the reciprocity principle of light propagation (i.e., the Helmholtz reciprocity) for 3D reconstruction of surfaces with arbitrary reflectance. In this paper, we present the polarimetric Helmholtz stereopsis (polar-HS), which extends the classical HS by considering the polarization state of light in the reciprocal paths. With the additional phase information from polarization, polar-HS requires only one reciprocal image pair. We derive the reciprocity relationship of Mueller matrix and formulate new reciprocity constraint that takes polarization state into account. We also utilize polarimetric constraints and extend them to the case of perspective projection. For the recovery of surface depths and normals, we incorporate reciprocity constraint with diffuse/specular polarimetric constraints in a unified optimization framework. For depth estimation, we further propose to utilize the consistency of diffuse angle of polarization. For normal estimation, we develop a normal refinement strategy based on degree of linear polarization. Using a hardware prototype, we show that our approach produces high-quality 3D reconstruction for different types of surfaces, ranging from diffuse to highly specular.

Zinc-mineralized diatom biosilica/hydroxybutyl chitosan composite hydrogel for diabetic chronic wound healing.

For sustained and stable improvement of the diabetic wound microenvironment, a temperature-sensitive composite hydrogel (ZnDBs/HBC) composed of inorganic zinc mineralized diatom biosilica (ZnDBs) and hydroxybutyl chitosan (HBC) was developed. The interfacial anchoring effect between ZnDBs and HBC enhanced the mechanical strength of the hydrogel. The mechanical strength of the composite hydrogel containing 3 wt% ZnDBs was increased by nearly 2.3times. The hydrogel can be used as a carrier for sustained release of Zn2+ for at least 72 h. In diabetic rats models, ZnDBs/HBC composite hydrogel could accelerate the inflammatory process by regulating the expression of pro-inflammatory factor IL-6 and anti-inflammatory factor IL-10, and also promote tissue cell proliferation and collagen deposition, thereby restoring the normal healing process and accelerating wound healing. The wound contraction rate of the composite hydrogel group was more than 2 times that of the control group. Therefore, ZnDBs/HBC composite hydrogel has the potential to be used as a therapeutic dressing for diabetic chronic wounds.

The long-term efficacy of imatinib with hepatic resection or other local treatment for gastrointestinal stromal tumours liver metastases: a retrospective cohort study.

BACKGROUND: The liver is the most common site of metastasis from gastrointestinal stromal tumors (GISTs). The authors aimed to evaluate imatinib (IM) combined with hepatic resection (HR) or other local treatments such as radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), compared to IM monotherapy in long-term survival benefits in patients suffering from GIST liver metastases. METHODS: Our research encompassed 238 patients diagnosed with liver metastases of GISTs from January 2002 to April 2022 at the First Affiliated Hospital of Sun Yat-Sen University. The oncological outcomes of concern included overall survival (OS), progression-free survival (PFS), and liver-specific PFS. RESULTS: Of all 238 patients, 126 were treated with IM alone (IM group), 81 with IM combined with HR (IM+HR group), and 31 with IM combined with RFA/TACE (IM+RFA/TACE group). The median follow-up time was 44.83 months. The median OS in the IM group was 132.60 months and was not reached in either the IM+HR group or the IM+RFA/TACE group. The 10-year OS rate in the IM+HR group was significantly superior to the IM group and the IM+RFA/TACE group (91.9% vs. 61.1% vs. 55.2%, respectively, P =0.015), and the liver-specific PFS ( P =0.642) and PFS ( P =0.369) in the three groups showed a beneficial trend in the combined treatment group. Multivariate analyses showed that age less than or equal to 60 years (HR 0.280, P< 0.001) and IM+HR (HR 0.361, P =0.047) were independently associated with better OS. Achieving no evidence of disease through surgical intervention was independently correlated with enhanced OS (HR 0.099, P =0.034), liver-specific PFS (HR 0.388, P =0.014), and PFS (HR 0.402, P =0.004). CONCLUSIONS: In patients with GIST liver metastases, IM combined with HR might improve OS in selected patients compared with IM alone and IM combined with RFA/TACE. Achieving no evidence of disease status with surgical treatment of patients results in significant prolonging of OS, liver-specific PFS, and PFS.

Study on the calculation method and structural dynamic response of buried pipeline subjected to external explosion load based on multiphase coupling.

When the buried pipeline is subjected to the external explosion load, stress and deformation will occur. When the stress and deformation value exceed a specific range, it will affect the normal use of the buried pipeline. In this paper, a multiphase coupled model of pipeline, soil and fluid within the pipeline is established. The penalty function coupling method is used to describe the load between soil and pipeline and the fluid within the pipeline. By specifying the boundary conditions of the coupled system, the multiphase coupled global solution variational principle function of the soil-pipe-fluid is derived. According to the established multiphase coupled calculation method, the numerical simulation analysis of the response of pipeline to external explosion is carried out. The maximum error of the experimental and numerical simulation results is about 5%, which verifies the accuracy of the multiphase coupled calculation method. The soil-pipeline-fluid multiphase coupled numerical calculation model is established to analyze the response of the buried pipeline under the external explosion load. The results show that during the explosion shock wave propagating in the soil, the peak value of the explosion pressure in different positions in the soil of the gas pipeline is greater than that of the oil pipeline. As for the structural response, the maximum radial displacement value of the oil pipeline is reduced by 3.83 mm compared with the gas pipeline, the maximum stress value is reduced by 3.75%. The maximum radial displacement value of the pipeline with a fluid velocity of 1.5 m/s is 2.65 mm larger than that of the pipeline with a fluid velocity of 1 m/s, and the maximum stress value is increased by 5.72%. The deformation resistance and explosion resistance of the oil pipeline are both stronger than that of the gas pipeline. The higher the fluid velocity, the weaker the pipeline's resistance to deformation and explosion will be.

Full-Volume 3D Fluid Flow Reconstruction With Light Field PIV.

Particle Imaging Velocimetry (PIV) is a classical method that estimates fluid flow by analyzing the motion of injected particles. To reconstruct and track the swirling particles is a difficult computer vision problem, as the particles are dense in the fluid volume and have similar appearances. Further, tracking a large number of particles is particularly challenging due to heavy occlusion. Here we present a low-cost PIV solution that uses compact lenslet-based light field cameras as imaging device. We develop novel optimization algorithms for dense particle 3D reconstruction and tracking. As a single light field camera has limited capacity in resolving depth (z-dimension measurement), the resolution of 3D reconstruction on the x-y plane is much higher than along the z-axis. To compensate for the imbalanced resolution in 3D, we use two light field cameras positioned at an orthogonal angle to capture particle images. In this way, we can achieve high-resolution 3D particle reconstruction in the full fluid volume. For each time frame, we first estimate particle depths under a single viewpoint by exploiting the focal stack symmetry of light field. We then fuse the recovered 3D particles in two views by solving a linear assignment problem (LAP). Specifically, we propose an anisotropic point-to-ray distance as matching cost to handle the resolution mismatch. Finally, given a sequence of 3D particle reconstructions over time, we recover the full-volume 3D fluid flow with a physically-constrained optical flow, which enforces local motion rigidity and fluid incompressibility. We perform comprehensive experiments on synthetic and real data for ablation and evaluation. We show that our method recovers full-volume 3D fluid flows of various types. Two-view reconstruction results achieves higher accuracy than those with one view only.

Exosomal circEZH2_005, an intestinal injury biomarker, alleviates intestinal ischemia/reperfusion injury by mediating Gprc5a signaling.

Intestinal ischemia/reperfusion (I/R) injury is a severe clinical condition without optimal diagnostic markers nor clear molecular etiological insights. Plasma exosomal circular RNAs (circRNAs) are valuable biomarkers and therapeutic targets for various diseases, but their role in intestinal I/R injury remains unknown. Here we screen the expression profile of circRNAs in intestinal tissue exosomes collected from intestinal I/R mice and identify circEZH2_005 as a significantly downregulated exosomal circRNA. In parallel, circEZH2_005 is also reduced in the plasma of clinical cardiac surgery patients who developed postoperative intestinal I/R injury. Exosomal circEZH2_005 displays a significant diagnostic value for intestinal injury induced by I/R. Mechanistically, circEZH2_005 is highly expressed in intestinal crypt cells. CircEZH2_005 upregulation promotes the proliferation of Lgr5+ stem cells by direct interaction with hnRNPA1, and enhanced Gprc5a stability, thereby alleviating I/R-induced intestinal mucosal damage. Hence, exosomal circEZH2_005 may serve as a biomarker for intestinal I/R injury and targeting the circEZH2_005/hnRNPA1/Gprc5a axis may be a potential therapeutic strategy for intestinal I/R injury.

Carya cathayensis leaf extract attenuates ectopic fat deposition in liver, abdomen and aortic arch in ovariectomized rats fed a high-fat diet.

BACKGROUND: Carya cathayensis1is a commercially cultivated plant in the Zhejiang Province, China. Its nuts exhibit properties of tonifying kidneys and relieving asthma. There have been a few pharmacological studies addressing the function of the leaves of this plant. Our previous studies on C. cathayensis leaf extract (CCE) showed a significant inhibitory effect on weight gain in mice fed a high-fat diet, particularly in female mice. HYPOTHESIS/PURPOSE: To investigate the biological and molecular mechanisms underlying the regulation of ectopic adipose tissue deposition by CCE in ovariectomized rats fed a high-fat diet. STUDY DESIGN: Female Sprague-Dawley rats were ovariectomized and treated with CCE (50, 100, and 200 mg/kg body weight, oral) or estradiol (1 mg/kg body weight, oral) for 8 weeks. METHODS: CCE was subjected to high-performance liquid chromatography to quantify major components. Body weight gain, abdominal fat coefficient, and aortic arch fat coefficient were determined; serum was collected for biochemical analysis; tissues were collected for histopathological examination, quantitative polymerase chain reaction (Q-PCR), and western blotting. RESULTS: The total flavonoid content was determined to be 57.30% in the CCE and comprised chrysin, cardamomin, pinostrobin chalcone, and pinocembrin. Compared with the model group (OVX), CCE treatment reduced body weight gain, abdominal and aortic arch fat coefficients, serum and hepatic lipid profiles, including total cholesterol (TC), total triglycerides (TG), and free fatty acids (FFA) levels; decreased lipid droplets in liver cells; decreased fat accumulation in the aortic arch blood vessel wall and increased its smoothness; decreased the diameter of abdominal fat cells; and reduced serum leptin and adiponectin levels significantly. Serum adiponectin levels significantly correlated with serum TG and hepatic TC levels. Leptin levels positively correlated with serum TG levels and negatively correlated with hepatic TG. Leptin mRNA, peroxisome proliferator-activated receptor (PPARγ) mRNA, and protein expression levels in abdominal adipose tissue were significantly down-regulated. Adiponectin mRNA levels were slightly reduced but not significantly. CONCLUSION: CCE attenuated ectopic fat deposition induced by deficient estrogen and a high-fat diet in rats; this may be associated with activated leptin sensitivity, improved leptin resistance, and regulated adiponectin levels. CCE may improve adipose function to regulate adipocyte differentiation by down-regulating PPARγ. Overall, these results suggest that CCE is a potential phytoestrogen.

Shape and Reflectance Reconstruction Using Concentric Multi-Spectral Light Field.

Recovering the shape and reflectance of non-Lambertian surfaces remains a challenging problem in computer vision since the view-dependent appearance invalidates traditional photo-consistency constraint. In this paper, we introduce a novel concentric multi-spectral light field (CMSLF) design that is able to recover the shape and reflectance of surfaces of various materials in one shot. Our CMSLF system consists of an array of cameras arranged on concentric circles where each ring captures a specific spectrum. Coupled with a multi-spectral ring light, we are able to sample viewpoint and lighting variations in a single shot via spectral multiplexing. We further show that our concentric camera and light source setting results in a unique single-peak pattern in specularity variations across viewpoints. This property enables robust depth estimation for specular points. To estimate depth and multi-spectral reflectance map, we formulate a physics-based reflectance model for the CMSLF under the surface camera (S-Cam) representation. Extensive synthetic and real experiments show that our method outperforms the state-of-the-art shape reconstruction methods, especially for non-Lambertian surfaces.

Rapid determination of sulfonamides in chicken using two-dimensional online cleanup mode with three columns coupled to liquid chromatography-tandem mass spectrometry.

A novel method based on online cleanup mode combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established. After an automated sample cleanup system with aqueous gel column, sulfonamides in chicken were detected in multiple reaction monitoring (MRM) mode. The total run time of the system, which included automated extraction, analytical chromatography and re-equilibration, was within 30 min. Different experimental processes containing extraction, purification, separation, and detection have been evaluated respectively to obtain optimized parameters. The developed method was fully validated and the efficient and superior performance of the developed method was demonstrated. The method produced linear results for all sulfonamides from 1 to 10 ng g-1 with a linearity >0.99. The intra-day precision of the method was <8.45% while the inter-day precision was <9.11%. The matrix effect was 77.5% to 105.1%. The recovery was in the range of 72.66% to 116.7% for all sulfonamides. The limit of quantitation in the chicken was 0.6 ng g-1 and the limit of detection was 0.2 ng g-1. Compared with traditional procedures, the automated sample clean-up strategy could significantly shorten the analysis time and offer higher detectability, with the advantage of sufficient sensitivity. Also, the use of gel chromatography column employed the water phase and reduced the organic reagent to achieve the level of green chemistry.

Detection and Quantification of 4-Methylimidazole in Cola by Matrix-assisted Laser Desorption Ionization Mass Spectrometry with Fe2O3 Nanoparticles on Zeolite.

Food additives generally used in carbonated drinks, such as 4-methylimidazole (4MI), caffeine (Caf?), citric acid (CA), and aspartame (Apm), were measured by matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) using nanometer-sized particles of iron oxide (Fe2O3 NPs). The quantification of 4MI in Coca Cola (C-cola) was carried out. In order to improve the reproducibility of the peak intensities, Fe2O3 NPs loaded on ZSM5 zeolite were used as the matrix for quantification. By using 2-ethylimidazole (2EI) as the internal standard, the amount of 4MI in C-cola was determined to range from 88 to 65 µg/355 mL. The results agree with the published value (approx. 72 µg/355 mL). It was found that MALDI using Fe2O3 was applicable to the quantification of 4MI in C-cola.

Transesterification of sunflower oil to biodiesel on ZrO2 supported La2O3 catalyst.

ZrO(2) supported La(2)O(3) catalyst prepared by impregnation method was examined in the transesterification reaction of sunflower oil with methanol to produce biodiesel. It was found that the catalyst with 21 wt% loaded La(2)O(3) and calcined at 600 degrees C showed the optimum activity. The basic property of the catalyst was studied by CO(2)-TPD, and the results showed that the fatty acid methyl ester (FAME) yield was related to their basicity. The catalyst was also characterized by TG-DTA, XRD, FTIR, SEM and TEM, and the mechanism for the formation of basic sites was discussed. It was also found that the crystallite size of support ZrO(2) decreased by loading of La(2)O(3), and the model of the solid-state reaction on the surface of La(2)O(3)/ZrO(2) catalyst was proposed. Besides, the influence of various reaction variables on the conversion was investigated.