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Background: Maintenance immunosuppression is required for suppression of alloimmunity or allograft rejection. However, continuous use of immunosuppressants may lead to various side effects, necessitating the use of alternative immunosuppressive drugs. The early secreted antigenic target of 6 kDa (ESAT-6) is a virulence factor and immunoregulatory protein of mycobacterium tuberculosis (Mtb), which alters host immunity through dually regulating development or activation of various immune cells. ESAT-6 may be a potential alternative immunosuppressant that could be utilized to suppress allograft rejection although it remains unknown whether ESAT-6 actually regulates alloimmunity. Methods: In this study, murine skin or heart allotransplantation was performed to determine the effects of ESAT-6 protein on allograft survival. Flow cytometric analyses were conducted to quantify CD4+Foxp3+ Tregs, while immunohistochemistry was carried out to observe allograft immunopathology. Western blotting was used to detect IĸBα/c-Rel signaling during Treg induction. Finally, CD4+CD25- conventional T cells were cultured to induce Tregs and their proliferation. Results: Here we found that ESAT-6 significantly extended murine skin and heart allograft survival, alleviated CD3+ T cell infiltration and increased Foxp3+ Tregs in an allograft. ESAT-6 augmented the percentage of CD4+Foxp3+ Tregs, whereas it decreased the frequency of Th1 and CD4+/CD8+ effector T cells in spleen and lymph nodes (LNs) posttransplantation. ESAT-6 also induced CD4+Foxp3+ Tregs from CD4+CD25- T cells in vitro by activating IĸBα/c-Rel signaling pathway, whereas inhibition of c-Rel signaling blocked Treg induction. Moreover, it suppressed conventional CD4+CD25- T cell proliferation in vitro in the absence of antigen-presenting cells (APCs), with an increase in IL-10 and decrease in IFN-γ production. On the other hand, it did not significantly alter DC maturation after allotransplantation. Conclusion: Thus, ESAT-6 suppresses alloimmunity and inhibits allograft rejection by inducing CD4+Foxp3+ Tregs through IĸBα/c-Rel signaling pathway. [ABSTRACT FROM AUTHOR]

A nondestructive evaluation of the hydrogen damage of materials in a hydrogen environment is important for monitoring the running conditions of various pieces of equipment. In this work, a new thermostatic electrolytic hydrogenation in situ ultrasonic test system (In Situ TEH-UT) was developed. The system operates by combining cross-correlation delay estimation and frequency domain amplitude estimation and hence improves measurement accuracy with respect to ultrasonic propagation time and amplitude, allowing in situ ultrasonic evaluation of the hydrogen-charging process in X80 pipeline steel. The experimental results show that under a 30 mA/cm2 hydrogen-charging current, the hydrogen saturation time of X80 pipeline steel is 800 min. Between 0 and 800 min, the attenuation coefficient and amplitude attenuation both demonstrate a strong linear relationship with the hydrogen-charging time. After 800 min, the attenuation coefficient and amplitude attenuation do not change further, while the attenuation coefficient fluctuates greatly. Through the characterization of the microstructures of the materials analyzed, it was found that hydrogen-induced cracks (HICs) constituted the main reason for the change in the ultrasonic parameters, and the mechanism behind the hydrogen-induced damage layer (HIDL) was determined. This study provides reference significance for clarifying the change mechanism of ultrasonic parameters under hydrogen damage conditions and determining the extent of hydrogen damage using an ultrasonic technique. [ABSTRACT FROM AUTHOR]

With the widespread application of small-sized bolts in aerospace and other fields, the demand for measuring their connection structures is increasing. Currently, although ultrasonic longitudinal wave methods are commonly used for bolt pretension stress measurement, their accuracy is limited for small-sized bolts. This paper proposes a piezoelectric acoustic resonance method (PZTAR) for small-sized bolt pretension stress measurement based on acoustic elasticity theory, ultrasonic resonance principles, and a bolt stress–strain model. The method involves analyzing the ultrasonic time-domain signals of small-sized bolts under load in the frequency domain to better evaluate the changes in the ultrasonic frequencies under different pretension stress. The effectiveness of this method is verified through pretension stress measurement experiments. The results indicate that the proposed ultrasonic resonance method achieves an average error of less than 5% for M5 specification bolts. Compared to traditional ultrasonic time delay methods, the proposed method demonstrates higher measurement accuracy. Additionally, the ultrasonic resonance method exhibits better robustness during the measurement process. [ABSTRACT FROM AUTHOR]

Bronchial asthma is a chronic inflammatory disease of the airways involving a variety of inflammatory cells and cellular components. To study the pathogenesis, treatment, and prognosis of this disease, a reliable animal model must be established. This article summarizes and evaluates the modeling methods for asthmatic animals and presents comprehensive comparison of the study of bronchial asthma animal models from different perspectives, hoping to provide a reference for researchers in the future.

We performed a systematic study of the vibrationally resolved absorption spectra in the Q band of three metalloporphyrins (Mg, Zn, and Pd) to understand the spectral changes in this series, including both the Franck-Condon (FC) and Herzberg-Teller (HT) contributions. The ground (S0) and the lowest singlet excited (S1) states were, respectively, simulated by the static and time-dependent density functional theory, with which the Duschinsky rotation effect was considered. Different functionals and basis sets were tested and compared with experiment. Results show that the long-range corrected functional CAM-B3LYP can nicely describe the spectral fingerprints of these metalloporphyrins, while the B3LYP functional significantly underestimates the FC contributions. We found that the absorption fine structures of these molecules are mainly caused by the HT vibronic couplings. The experimentally observed enhancements to the on-site 0-0 absorption peak in the series of Mg, Zn, and Pd are nicely reproduced. Enhanced absorption intensity is caused by larger FC contributions of molecules with heavier metal ions. The structure-spectroscopy relationship was analyzed, and it was found that the smaller cavity size of the porphyrin ring can significantly enhance the oscillator strength of the S0 → S1 transition. [ABSTRACT FROM AUTHOR]

The vibrationally resolved fluorescence spectrum of a narrow-line single-molecule transducer, fused 5,15-(diphenyl)-10,20-(dibromo)porphyrin (fused-H2P) molecule, has been calculated by time-dependent density functional theory with the inclusion of both Franck-Condon and Herzberg-Teller contributions. Analytical transition dipole derivatives are used for the calculations of Herzberg-Teller terms to eliminate the possible errors caused by numerical differentials. The performance of different exchange-correlation functionals including B3LYP, ωB97X-D, and M06-2X has been examined. The comparison with the high-resolution experimental emission spectrum indicates that all three functionals can satisfactorily describe the fluorescence spectral profile, while ωB97X-D and M06-2X give slightly better excitation energy than B3LYP. Detailed analysis shows that the fluorescence spectrum is dominated by the Franck-Condon contribution, while the Herzberg-Teller term contributes mostly to its low energy tail. It is found that the size of the basis set has limited influence on the fluorescence spectrum, and a standard 6-31G(d, p) basis set is adequate for the purpose. The substitution of terthiophene side chains is found to have minor effects on the fluorescence spectrum. Our study provides unambitious assignments for all the vibronic structures in the experimental spectrum. [ABSTRACT FROM AUTHOR]

Emerging evidence has linked the gut microbiota dysbiosis to transplant rejection while memory T-cells pose a threat to long-term transplant survival. However, it's unclear if the gut microbiome alters the formation and function of alloreactive memory T-cells. Here we studied the effects of berberine, a narrow-spectrum antibiotic that is barely absorbed when orally administered, on the gut microbiota, memory T-cells, and allograft survival. In this study, C57BL/6 mice transplanted with islets or a heart from BALB/c mice were treated orally with berberine. Allograft survival was observed, while spleen, and lymph node T-cells from recipient mice were analyzed using a flow cytometer. High-throughput sequencing and qPCR were performed to analyze the gut microbiota. CD8+ T-cells from recipients were cultured with the bacteria to determine potential T-cell memory cross-reactivity to a specific pathogen. We found that berberine suppressed islet allograft rejection, reduced effector CD8+CD44highCD62Llow and central memory CD8+CD44highCD62Lhigh T-cells (TCM), altered the gut microbiota composition and specifically lowered Bacillus cereus abundance. Further, berberine promoted long-term islet allograft survival induced by conventional costimulatory blockade and induced cardiac allograft tolerance as well. Re-colonization of B. cereus upregulated CD8+ TCM cells and reversed long-term islet allograft survival induced by berberine plus the conventional costimulatory blockade. Finally, alloantigen-experienced memory CD8+ T-cells from transplanted recipients rapidly responded to B. cereus in vitro. Thus, berberine prolonged allograft survival by repressing CD8+ TCM through regulating the gut microbiota. We have provided the first evidence that donor-specific memory T-cell generation is linked to a specific microbe and uncovered a novel mechanism underlying the therapeutic effects of berberine. This study may be implicated for suppressing human transplant rejection since berberine is already used in clinic to treat intestinal infections. [ABSTRACT FROM AUTHOR]