Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor–β1

Suppressor of cytokine signaling (SOCS)3 is a major negative feedback regulator of signal transducer and activator of transcription (STAT)3-activating cytokines. Transgenic mouse studies indicate that high levels of SOCS3 in T cells result in type 2 T helper cell (Th2) skewing and lead to hypersensitivity to allergic diseases. To define the physiological roles of SOCS3 in T cells, we generated T cell–specific SOCS3 conditional knockout mice. We found that the mice lacking SOCS3 in T cells showed reduced immune responses not only to ovalbumin-induced airway hyperresponsiveness but also to Leishmania major infection. In vitro, SOCS3-deficient CD4+ T cells produced more transforming growth factor (TGF)-β1 and interleukin (IL)-10, but less IL-4 than control T cells, suggesting preferential Th3-like differentiation. We found that STAT3 positively regulates TGF-β1 promoter activity depending on the potential STAT3 binding sites. Furthermore, chromatin immunoprecipitation assay revealed that more STAT3 was recruited to the TGF-β1 promoter in SOCS3-deficient T cells than in control T cells. The activated STAT3 enhanced TGF-β1 and IL-10 expression in T cells, whereas the dominant-negative form of STAT3 suppressed these. From these findings, we propose that SOCS3 regulates the production of the immunoregulatory cytokines TGF-β1 and IL-10 through modulating STAT3 activation

Decreased Serum Free Testosterone in Workers Exposed to High Levels of Di-n-butyl Phthalate (DBP) and Di-2-ethylhexyl Phthalate (DEHP): A Cross-Sectional Study in China

BACKGROUND: Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility. OBJECTIVE: Our objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. METHODS: We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status. RESULTS: Compared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 μg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 μg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 μg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = −0.25, p = 0.03) and MEHP (r = −0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = −0.26, p = 0.002). CONCLUSION: We observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers

King Khufu’s Second Boat: Scientific Identification of Wood Species for Deckhouse, Canopy, and Forecastle

Very little published information is available on the scientific identification of wood species used in the construction of boats in ancient Egypt. This paper deals with the scientific identification of wood species used in the construction of the deckhouse, canopy, and forecastle of King Khufu’s second wooden boat (4th Dynasty—Old Kingdom) in detail. This paper also discusses the principal technological characteristics of the identified woods, considering specifically their utilization for construction of the deckhouse, canopy, and forecastle. Almost all the woods used in the boat’s deckhouse, canopy, and forecastle were made of two imported species of wood (Cedrus libani A.Rich. and Juniperus sp.), with two native species (Ziziphus spina-christi (L.) Willd. and Vachellia sp.) also identified. The analysis most surprisingly revealed the presence of Ziziphus spina-christi (L.) Willd. in 25% of the analyzed forecastle samples, which was discovered for the first time for making cross beams in the construction of boats in ancient Egypt. Another intriguing aspect of the boat’s construction is the presence of Juniperus sp., which surprisingly showed that almost 85% of the analyzed samples were Juniperus sp., used in the deckhouse’s boards, frames, and cross beams. The data let us examine the specific employment of the wood species used in the parts of the boat, which evidenced that the identified woods were suitably used for the construction of the different parts of the deckhouse, canopy, and forecastle of the boat