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Abstract Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent β-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P

Transplantation is an effective approach for treating end-stage organ failure. There has been a long-standing interest in xenotransplantation as a means of increasing the number of available organs. In the past decade, there has been tremendous progress in xenotransplantation accelerated by the development of rapid gene-editing tools and immunosuppressive therapy. Recently, the heart and kidney from pigs were transplanted into the recipients, which suggests that xenotransplantation has entered a new era. The genetic discrepancy and molecular incompatibility between pigs and primates results in barriers to xenotransplantation. An increasing body of evidence suggests that innate immune responses play an important role in all aspects of the xenogeneic rejection. Simultaneously, the role of important cellular components like macrophages, natural killer (NK) cells, and neutrophils, suggests that the innate immune response in the xenogeneic rejection should not be underestimated. Here, we summarize the current knowledge about the innate immune system in xenotransplantation and highlight the key issues for future investigations. A better understanding of the innate immune responses in xenotransplantation may help to control the xenograft rejection and design optimal combination therapies.

BackgroundA complex interplay between different cell types in the epithelium leads to activation of the luminal acidifying capacity of the epididymis, a process that is crucial for sperm maturation and storage. Basal cells sense the luminal angiotensin II (ANG II) and stimulate proton secretion in clear cells through nitric oxide (NO). Our previous study has shown the chemokine regulated upon activation normal T-cell expressed and secreted (RANTES) was expressed in the F4/80 positive macrophages of human epididymis. The objective of this study was to explore the involvement of RANTES in regulating the luminal acidification in the rat epididymis.MethodsThe role of RANTES was investigated by in vivo perfusion with recombinant RANTES, Met-RANTES, and PBS of different pH values. Furthermore, rats vasectomy was performed to alter the epididymal luminal pH. RIA was used to measure the tissue homogenate ANG II concentration. Real time-PCR and western blot were employed to examine the expression levels of AGTR2, RANTES, CCR1, CCR5, and iNOS in epididymis.ResultsRANTES was restricted to the basal macrophages of epididymal ducts and co-localized with its receptors CCR1 and CCR5. Both V-ATPase and iNOS were up-regulated in the cauda epididymis after perfused with recombinant RANTES, while the antagonist Met-RANTES perfusion led to a complete abrogation of the increased expression of V-ATPase in the apical membrane of clear cells and iNOS in macrophages. Upon alkaline perfusion, RANTES expression was significantly increased and the apical accumulation of V-ATPase in the clear cells was induced in the cauda epididymis. The luminal pH in the cauda epididymis increased after vasectomy. The concentration of the ANG II and the expression levels of AGTR2, RANTES, CCR1, CCR5, and iNOS dropped in the cauda epididymis following vasectomy.ConclusionUpon the activation of basal cells, RANTES might induce the NO release from macrophages by interacting with its receptors, which increases proton secretion by adjacent clear cells. Thus, RANTES is possible to participate in the crosstalk among basal cells, macrophages and clear cells for the fine control of an optimum acidic luminal environment that is critical for male fertility.

In response to the demand for high sensitivity and stability during respiratory dust detection, photoacoustic spectroscopy is proposed for real-time monitoring of respiratory dust. The influence of the background noise generated by the inlet flow and the small suction pump on the experiment was analyzed, and noise reduction was carried out by physical methods such as adding a sound insulation layer to the small suction pump, as well as the Kalman filtering method was added to the LabVIEW software to further reduce the influence of noise. To carry out the detection of respirable dust in the ambient atmosphere. The detection under 0.2 μm filter membrane can filter out the effect of environmental dust, and the collection efficiency of 5 μm diameter dust is 50%; therefore, 5 and 0.2 μm filter membranes were added at the air inlet for respiratory dust detection, and two groups of experiments were carried out by using 5 and 0.2 μm filter membranes to obtain the change curve of the respiratory dust by the differential method. Through experimental validation, it is shown that the detection system can further improve the detection accuracy and stability of respiratory dust with the processing of physical noise reduction and Kalman filtering and can meet the monitoring of respiratory dust in the environmental atmosphere. [ABSTRACT FROM AUTHOR]

As one of the key part of automotive brake,the performance of brake block has a direct impact on the safety and comfort of cars. Modeling the brake block of disc brake in reverse parameterization by reverse engineering software, analyzing and optimizing the reconstructed model by CAE software. Processing the scanned point cloud by Geomagic Studio and reconstructing the CAD model of the brake block with the parametric surface function of the software, then analyzing and optimizing it by Wrokbench. The example shows that it is quick to reconstruct the CAD model of parts by using reverse parameterization method and reduce part re-design development cycle significantly.

An NO2 photoacoustic sensor system with a high reflective mirror based on a low power blue diode laser is developed in this work. The excitation power is enhanced by increasing the number of reflections. Comparing with a traditional photoacoustic system, the pool constant is improved from 300.24 (Pa⋅cm)/W to 1450.64 (Pa⋅cm)/W, and the signal sensitivity of the photoacoustic sensor is increased from 0.016 μV/ppb to 0.2562 μV/ppb. The characteristics of temperature and humidity of the new photoacoustic sensor are also obtained, and the algorithm is adjusted to provide a quantitative response and drift of the resonance frequency. The results of this research provide a new method and concept for further developing the NO2 photoacoustic sensors. [ABSTRACT FROM AUTHOR]

A simultaneous in-situ detection technique to obtain multi-optical parameters was proposed. The same 403.56 nm, low power, blue diode laser was used to conduct the cavity ring-down spectroscopy and photoacoustic spectroscopy, which were coupled. Four photoacoustic spectra were applied to the simultaneous in-situ detection of the cavity ring-down spectrum, which were systematically compared and analyzed for the first time. And the main performance of the systems varied with the arrangement of the photoacoustic pool. The results reveal that the photoacoustic response was optimized by the high reflectivity mirror with the pool constant of 1450.64 (Pα·cm)/W and the signal sensitivity of 0.2562 μv/ppb. The intensity value of the photoacoustic pool inside the cavity ring down was superimposed to 48.45% of the initial intensity. The corresponding experimental results were consistent with the theoretical analysis and shown the coupled cavity could suitable for simultaneous in-situ measurement of high concentration. The coupled two detection techniques detected different optical parameters and thus provided a new method for the simultaneous in-situ detection of the multi-optical parameters of specific atmospheric components. [ABSTRACT FROM AUTHOR]

Our previous study showed that the chemokine regulated upon activation normal T-cell expressed and secreted (RANTES) originating from the mouse epididymis bound to the midpiece of luminal spermatozoa. The present study was undertaken to investigate the association between RANTES and epididymal spermatozoa and to determine whether the association is mediated by the RANTES receptors CCR1, CCR3 or CCR5. The use of reverse transcription polymerase chain reaction (RT-PCR), immunohistochemical staining and immunofluorescent staining demonstrated that RANTES secreted by apical and narrow cells of mouse epididymal ducts was associated with luminal spermatozoa. Flow cytometric analysis and immunofluorescent labelling revealed that the association between RANTES and spermatozoa of different regions weakened gradually as the spermatozoa moved along the epididymis. Moreover, CCR1, CCR3 and CCR5 were expressed in epididymal spermatozoa and located on the head of epididymal spermatozoa, while RANTES was generally located at the midpiece. In conclusion, RANTES and its receptors were not in the same sperm location, suggesting that RANTES binding to mouse epididymal spermatozoa is independent of CCR1, CCR3 and CCR5. [ABSTRACT FROM AUTHOR]

• The dual-channel cavity photoacoustic spectroscopy instrument can be applied to simultaneous measurement of NO 2 and NO. • In order to confirm the reliability of the PAS instrument in the field atmosphere. Continuous measurement was conducted and the stability of the instrument was shown. When comparing the PAS instrument for NO 2 measurement with a CRDS instrument in the field, the results both showed a good correlation between these techniques. • In order to reduce the local noise of the system, the optimized design and test of the buffer cavity are carried out. Minimum detection limits of NO 2 and NO x were estimated to be 1.47 ppb and 1.50 ppb at an average time of 60 s with the sensitivity of 0.040 μv/ppb and 0.039 μv/ppb. • As a result, the instrument can be seen as a low-cost, simple, reliable method for the measurement NO 2 and NO x directly with good sensitivity and good time resolution in the field. The instruments developed could lead to the wider application for ambient air quality monitoring and will be useful to investigate photochemistry in the atmosphere more precisely. The levels of nitric oxide (NO) and nitrogen oxide (NO 2) are trace gases in the order of ppb, which are the main products of fossil fuel, anthropogenic combustion, natural lightning and microbial emissions, and are important for further analysis of air quality. Photoacoustic spectroscopy (PAS) technique, which is based on absorption at the wavelength of 403.65 nm, has been used for NO 2 measurements. In this study, a dual-channel PAS system for NO 2 and NO x detection is reported. The PAS method is capable of measuring species with good sensitivity and accuracy. The calibrated slopes of photoacoustic cavity A and B are 0.040 μv/ppb and 0.039 μv/ppb, respectively. And the detection limits of the developed PAS system for NO 2 and NO x measurements are estimated to be about 1.47 ppb (3σ, 60 s) and 1.50 ppb (3σ, 60 s), respectively. In order to reduce the influence of local noise, the photoacoustic cavity with multiple buffer partitions is designed and the corresponding photoacoustic frequency of the photoacoustic pool is analyzed. The sound pressure value and resonance frequency of the photoacoustic pool gradually decrease with the increase of the number of buffer partitions, but the amplitude is small. The relationship between the gas absorption cross section, volume fraction, laser power and photoacoustic excitation signal is derived. After deducting the influence of local noise, the photoacoustic response gradients of dual-channel cavities are obtained, the linear fitting of the response gradient of both cavities is good, the correlation R2 is greater than 0.99, and the fitting slope is 0.040 and 0.039 respectively. The influence of O 3 generated by photolysis of the mercury lamp is considered under different NO level conditions. An intercomparison between the system and a cavity ring-down system (CRDS) independently developed by our research group showed a good agreement for measuring the ambient atmosphere NO 2 gas. The results of NO 2 showed a linear correction factor (R2) of 0.943 in a slope of 0.944 ± 0.002, with an offset of (0.636 ± 0.021) ppb. The accuracy of NO 2 measurement by the photoacoustic spectroscopy system was verified. In addition, the simultaneous measurement of NO and NO 2 by dual-channel cavity photoacoustic spectroscopy technique was deployed. These observations indicate that NO 2 and NO concentrations can be effectively observed with the dual-channel PAS instrument. [ABSTRACT FROM AUTHOR]