Although the interaction between tumors and tumor-associated macrophages (TAMs) has been reported to facilitate the targeted drug resistance and progression of clear cell renal cell carcinoma (ccRCC), the related mechanisms remain unknown. Here, we report that SOX17 serves as a novel tumor suppressor in ccRCC and a positive regulatory loop, SOX17low/YAP/TEAD1/CCL5/CCR5/STAT3, facilitates the ccRCC-TAM interaction. SOX17 expression was commonly downregulated and negatively correlated with TAM infiltration in ccRCC specimens, and the integration of SOX17 and TAMs with the existing clinical indicators TNM stage or SSIGN score achieved better accuracy for predicting the prognosis of ccRCC patients. AZD5438 cell line Mechanistically, SOX17 knockdown activated YAP signaling by promoting the transcription and nuclear distribution of YAP, which recruited TEAD1 to trigger CCL5 transcription. Then, CCL5 educated macrophages toward TAMs, which reciprocally enhanced ccRCC progression through CCL5/CCR5 and activated STAT3/SOX17low/YAP. However, SOX17 overexpression in ccRCC achieved the opposite effect. Thus, a positive regulatory loop, SOX17low/YAP/TEAD1/CCL5/CCR5/STAT3, was identified in the ccRCC-TAM interaction. Furthermore, targeting tumor-TAM interactions by blocking this positive regulatory network impaired the metastasis and targeted drug resistance of ccRCC in in vivo mouse models of lung metastasis and orthotopic ccRCC. These findings provide a new mechanism underlying the tumor-TAM interplay in ccRCC progression and present a potential target for inhibiting targeted drug resistance and metastasis in advanced ccRCC.

Diabetic retinopathy (DR) is related to oxidative stress and insufficient intake of dietary antioxidants may be associated with the onset and progression of DR. This study aimed to detect the association between main dietary antioxidants intake and the risk for DR.

This is a cross-sectional study of a Chinese urban population. Four hundred and fifty-five subjects with type 2 diabetes were recruited and divided into diabetic patients without retinopathy (DWR) group and DR group based on their retinal status. CSMO (clinically significant macular oedema) was diagnosed by stereoscopic photography. Demographic and lifestyle characteristics were ascertained by questionnaire. General physical and ophthalmic examinations were completed for all subjects. Dietary antioxidants were assessed by 3-day food records. Subjects who have taken any type of vitamin supplements were excluded from the study. The association of dietary antioxidants with the risk for DR was analysed by logistic regression with adjustment of other factors. The dietary antioxidants levels of the CSMO subjects and non-CSMO subjects were compared using the Wilcoxon rank sum test.

One hundred and nineteen subjects in DR group and 336 subjects in DWR group participated in the study. Only ten DR subjects had CSMO. The results showed that higher vitamin E (OR (95% CI)0.97 (0.95, 1.00), P = 0.036) and selenium (OR (95% CI)0.98 (0.96, 1.00), P = 0.017) intake appear to be the protective factors of DR. The dietary antioxidants levels of CSMO and non-CSMO subjects had no statistical differences (P > 0.05).

Dietary antioxidants intake, particularly vitamin E and selenium, were observed to have protective effects on DR.

Dietary antioxidants intake, particularly vitamin E and selenium, were observed to have protective effects on DR.Patients with acute myeloid leukaemia (AML) who lack a matched sibling or unrelated donor commonly undergo transplantation from a donor matched at 9/10 HLA-A, -B, -C, -DRB1, -DQB1 alleles, and it is unclear if a specific locus mismatch is preferable to any other. We therefore studied 937 patients with AML in complete remission transplanted using a reduced intensity conditioning regimen from an unrelated donor mismatched at a single allele. In a multivariate analysis, patient age, adverse karyotype and patient cytomegalovirus (CMV) seropositivity were correlated with decreased leukaemia free survival (LFS) and overall survival (OS). There was no significant difference in LFS or OS between patients transplanted from donors mismatched at HLA-A, -B, -C or -DRB1 in comparison to a HLA-DQB1 mismatched transplant. In a multivariate analysis, patients transplanted with a HLA-A mismatched donor had higher rates of acute graft-versus-host disease (GVHD) and non-relapse mortality (NRM) than patients transplanted with a HLA-DQB1 mismatched donor. Patient CMV seropositivity was associated with an increase in NRM and acute GVHD and reduced LFS and OS, regardless of donor CMV status. For CMV seropositive patients lacking a fully matched donor, alternative GVHD and CMV prophylaxis strategies should be considered.Clonal propagation and genetic engineering of plants requires regeneration, but many species are recalcitrant and there is large variability in explant responses. Here, we perform a genome-wide association study using 190 natural Arabidopsis accessions to dissect the genetics of shoot regeneration from root explants and several related in vitro traits. Strong variation is found in the recorded phenotypes and association mapping pinpoints a myriad of quantitative trait genes, including prior candidates and potential novel regeneration determinants. As most of these genes are trait- and protocol-specific, we propose a model wherein shoot regeneration is governed by many conditional fine-tuning factors and a few universal master regulators such as WUSCHEL, whose transcript levels correlate with natural variation in regenerated shoot numbers. Potentially novel genes in this last category are AT3G09925, SUP, EDA40 and DOF4.4. We urge future research in the field to consider multiple conditions and genetic backgrounds.Deep subsurface environments can harbour high concentrations of dissolved ions, yet we know little about how this shapes the conditions for life. We know even less about how the combined effects of high pressure influence the way in which ions constrain the possibilities for life. One such ion is perchlorate, which is found in extreme environments on Earth and pervasively on Mars. We investigated the interactions of high pressure and high perchlorate concentrations on enzymatic activity. We demonstrate that high pressures increase α-chymotrypsin enzyme activity even in the presence of high perchlorate concentrations. Perchlorate salts were shown to shift the folded α-chymotrypsin phase space to lower temperatures and pressures. The results presented here may suggest that high pressures increase the habitability of environments under perchlorate stress. Therefore, deep subsurface environments that combine these stressors, potentially including the subsurface of Mars, may be more habitable than previously thought.