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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.

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 β0/β0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

Background: A complex interplay between the different cell types presented 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 of epididymal epithelium 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 cells of human epididymis. The objective of this study was to explore the involvement of RANTES in regulating the luminal acidification in the rat epididymis. Methods: The role of RANTES was explored by in vivo perfusion with recombinant RANTES, Met-RANTES, and PBS of different pH values. Furthermore, rat vasectomy was established to alter the epididymal luminal pH. RIA was used to measure the tissue homogenate ANG II concentration. Real time-PCR and western blot were used to detect the expression levels of AGTR2, RANTES, CCR1, CCR5 and iNOS in epididymis. Results: RANTES was restricted to the 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 perfusing with recombinant RANTES, while the antagonist Met-RANTES perfusion led to a complete abrogation of the increased expression of V-ATPase on 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 on 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 were reduced in the cauda epididymis following vasectomy. Conclusion: Activation of AGTR2 in basal cells by luminal ANG II may stimulate RANTES in basal macrophages to induce the production of NO, 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.

The traditional contact devices measure material's surface roughness by scratching its surface, which may cause surface damage and sampling error. In order to avoid these troubles, an optical measurement system is used in this paper. Considering the anisotropic and inhomogeneous surface structure of Cf/SiC composite, a multi-scale measure system must be established. Fiber bundle is the first scale to be studied, whose appropriate measurement parameters are studied here. When sampling area is 150μm×150μm and sampling step is from 0.1μm to 0.5μm, the values of 3D surface parameters Sa, Sq, Ssk and Sku are steady and their relative changes are small. 2D surface roughness Ra is adopted to select the proper sampling length. The results show that as long as the sampling length is more than 112μm, the mean value of 2D surface roughness Ra are relatively stable. The critical sampling length is about 1/7 of the standard minimum sampling length in ISO 468-1982. According to the results obtained, the research provides a useful guideline for determination on the appropriate sampling conditions of Cf/SiC composite fiber bundle surface measurement.

It has been suggested that metastasis-associated proteins 1 and 2 (MTA1 and MTA2) are capable of suppressing estrogen receptor alpha (ERα) transactivation activity in breast cancer cells. ERα, which is present in the epididymis, is a crucial mediator of maintaining the luminal environment necessary for proper sperm maturation and function. The present study was undertaken to analyze the expression profile of both MTA1 and MTA2 in the epididymis of rats and to ascertain whether MTA1/2 colocalizes with ERα in the epididymis and primary cultured epididymal epithelial cells. Reverse transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry analyses were utilized to demonstrate that MTA1 and MTA2 are expressed in the epididymis. Furthermore, these analyses revealed that MTA1 and MTA2 are predominantly localized in the nuclei of almost all epididymal epithelial cells. Immunofluorescence staining revealed that MTA1/2 colocalizes with ERα in epididymal epithelial cells. In conclusion, MTA1 and MTA2 are expressed in the epididymis of rats; these proteins colocalize with ERα in epididymal epithelial cells, suggesting that MTA1 and MTA2 may be involved in the regulation of ERα transactivation activity in the epididymis of rats to facilitate a stable environment in the lumen.

Hb A

Hb A2 (α2δ2) is one of the key components looked for in hemoglobinopathies screening programs. Therefore, quantitative and accurate method for Hb A2 value determination is essential for routine screening. Here, we report a case of Hb A2 and Hb Constant Spring (Hb CS, HBA2: c.427T>C) with Hb H-Hb CS disease that was not detected by high performance liquid chromatography (HPLC), while Hb A2 and Hb CS were clearly quantified by capillary electrophoresis (CE).

Estrogen receptors (ERs), including two sub-types ERα and ERβ, belong to the steroid hormone superfamily of nuclear receptors. ERα distributes in the male reproductive system and plays a crucial role in the regulation of male reproduction through estrogen-dependent and -independent ways. In this article, we mainly reviewed the molecular structure, mode of action and location of ERα in the male reproductive system, and explored the mechanism of ERα in regulating the male reproductive system by analyzing different animal models of disrupted ERα.

Oxidative stress plays a critical role in the process of testicular torsion and detorsion (T/D). The purpose of the present study was to investigate the protective effect of polydatin (PD) on testicular T/D injury. Rats were randomly divided into three groups, a sham group, a group subjected to 2 h torsion followed by 24 h detorsion and a group subjected to T/D and injected i.p. with 20 mg kg−1 PD 30 min before detorsion. Unilateral orchiectomy was performed after 24 h of reperfusion. Half the testes were prepared for histological examination by haematoxylin–eosin staining and the terminal deoxyribonucleotidyl transferase-mediated dUTP–digoxigenin nick end-labelling (TUNEL) technique. In the remaining tissues, levels of malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) were determined, as was the expression of several apoptosis-related proteins. Compared with the T/D group, PD pretreatment significantly ameliorated the morphological damage, lowered the Cosentino histological score and increased the mean number of germ cell layers and Johnsen’s testicular biopsy score. In addition, PD treatment markedly decreased MDA levels and upregulated CAT, GPx and SOD activity. Furthermore, PD decreased T/D-induced germ cell-specific apoptosis, attenuated the activation of caspase-3, caspase-8, caspase-9 and poly(ADP-ribose) polymerase and increased the Bcl-2/Bax ratio. The findings indicate that PD has a protective effect against testicular T/D injuries, especially at the histological, antioxidative stress and antiapoptotic levels.

113 Cd NMR spectroscopy was employed to investigate the interactions between aromatic C–H and the coordinated sulfur atom in the neutral four-coordinated cadmium(II) complexes, [Cd{S-2-(4-X-C 6 H 4 CONH)C 6 H 4 } 2 (1-MeIm) 2 ] (X=H, OMe, F and CN; 1-MeIm=1-methylimidazole). The coordinating atom set here is S 2 N 2 that is similar to the zinc and iron sites in the known metalloproteins such as zinc finger and ferredoxins, respectively. The observation of 113 Cd NMR signals in the range 480–420 ppm in chloroform at 298 K indicates that the cadmium(II) ion is bound with the S 2 N 2 donor set in solution. The complex without substituent (i.e. X=H) exhibits a 113 Cd NMR signal at 475 ppm while the analog with the strongest electron-withdrawing cyano substituent gives a signal at 424 ppm in chloroform at 298 K. The chemical shifts of cadmium(II) complexes with a variety of substituents had a linear correlation with the Hammett σ m values rather than the σ p values, although the substituents are at the para -position of the benzoyl group. The results demonstrate that there are aromatic C–H---S interactions between the protons of the benzoyl group and the coordinated sulfur atom in the cadmium(II) complexes with S 2 N 2 binding site, in addition to the NH---S hydrogen bonds which were confirmed by infrared and 1 H NMR spectroscopies.

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.