Gut microbiota dysbiosis has been observed in a number of autoimmune diseases. However, the role of the gut microbiota in systemic lupus erythematosus (SLE), a prototypical autoimmune disease characterized by persistent inflammation in multiple organs of the body, remains elusive. Here we report the dynamics of the gut microbiota in a murine lupus model, NZB/W F1, as well as intestinal dysbiosis in a small group of SLE patients with active disease. The composition of the gut microbiota changed markedly before and after the onset of lupus disease in NZB/W F1 mice, with greater diversity and increased representation of several bacterial species as lupus progressed from the predisease stage to the diseased stage. However, we did not control for age and the cage effect. Using dexamethasone as an intervention to treat SLE-like signs, we also found that a greater abundance of a group of lactobacilli (for which a species assignment could not be made) in the gut microbiota might be correlated with more severe disease in NZB/W F1 mice. Results of the human study suggest that, compared to control subjects without immune-mediated diseases, SLE patients with active lupus disease possessed an altered gut microbiota that differed in several particular bacterial species (within the genera and and an unnamed genus in the family ) and was less diverse, with increased representation of Gram-negative bacteria. The/ ratios did not differ between the SLE microbiota and the non-SLE microbiota in our human cohort. SLE is a complex autoimmune disease with no known cure. Dysbiosis of the gut microbiota has been reported for both mice and humans with SLE. In this emerging field, however, more studies are required to delineate the roles of the gut microbiota in different lupus-prone mouse models and people with diverse manifestations of SLE. Here, we report changes in the gut microbiota in NZB/W F1 lupus-prone mice and a group of SLE patients with active disease.

Current influenza vaccines only confer protection against homologous viruses. We synthesized pulmonary surfactant (PS)–biomimetic liposomes encapsulating 2′,3′-cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), an agonist of the interferon gene inducer STING (stimulator of interferon genes). The adjuvant (PS-GAMP) vigorously augmented influenza vaccine–induced humoral and CD8+ T cell immune responses in mice by simulating the early phase of viral infection without concomitant excess inflammation. Two days after intranasal immunization with PS-GAMP–adjuvanted H1N1 vaccine, strong cross-protection was elicited against distant H1N1 and heterosubtypic H3N2, H5N1, and H7N9 viruses for at least 6 months while maintaining lung-resident memory CD8+ T cells. Adjuvanticity was then validated in ferrets. When alveolar epithelial cells (AECs) lacked Sting or gap junctions were blocked, PS-GAMP–mediated adjuvanticity was substantially abrogated in vivo. Thus, AECs play a pivotal role in configuring heterosubtypic immunity.

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Background The prevalence of general and abdominal obesity has increased rapidly in China. The aims of this study were to estimate the dynamic prevalence of overweight, general obesity, and abdominal obesity and the distribution of body mass index (BMI) and waist circumference (WC) among Chinese adults. Methods Data were obtained from the China Health and Nutrition Survey (CHNS). According to the suggestions of the WHO for Chinese populations, overweight was defined as a 23 kg/m2 ≤ BMI < 27.5 kg/m2 and general obesity as a BMI ≥ 27.5 kg/m2. Abdominal obesity was defined as a WC ≥ 90 cm for males and ≥ 80 cm for females. Grade 1, grade 2, and grade 3 obesity were defined as 27.5 kg/m2 ≤ BMI < 32.5 kg/m2, 32.5 kg/m2 ≤ BMI < 37.5 kg/m2, and BMI ≥ 37.5 kg/m2, respectively. Generalized estimation equations were used to estimate the prevalence and trends of overweight, general and abdominal obesity. Results This study included 12,543 participant. From 1989 to 2011, the median BMI of males and females increased by 2.65 kg/m2 and 1.90 kg/m2, respectively; and WC increased by 8.50 cm and 7.00 cm, respectively. In 2011, the age-adjusted prevalence of overweight, general obesity, and abdominal obesity were 38.80% (95% CI: 37.95–39.65%), 13.99% (95% CI: 13.38–14.59%), and 43.15% (95% CI: 42.28–44.01%), respectively, and significantly increased across all cycles of the survey among all subgroups (all P < 0.0001). The age-adjusted prevalence of grade 1–3 obesity significantly increased in total sample and sex subgroups (all P < 0.0001). For all indicators, there were significant increases in annual ORs among all subgroups (all P < 0.0001), with the exception of grade 2 obesity. Significant differences were observed in ORs across the three age groups in males. And ORs significantly decreased with age. Conclusions The age-adjusted prevalence of overweight, general obesity, and abdominal obesity significantly increased among Chinese adults from 1989 to 2011. The obesity population is trending toward an increased proportion of males and younger individuals in China.

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Src plays an important role in cell proliferation, differentiation, adhesion, and migration. Altered Src activity has been strongly implicated in the development, growth, progression, and metastasis of human cancers. We have analysed the change and regulation of Src upon cell detachment in anoikis-resistant human lung adenocarcinoma cells and compared with that of relatively normal and anoikis-sensitive epithelial cells. We found that Src activity was increased in the anoikis-resistant lung tumor cells when they were detached and cultured in suspension. The detachment-induced Src activation in the tumor cells compensates for the loss of cell survival signals caused by disruption of cell-matrix interactions and contributes to anoikis resistance of the tumor cells. Pyk2, rather than PI 3K/Akt or Erk, appears to be the key downstream effecter of Src in mediating the cell survival signals. The increased Src activity is mainly due to the phosphorylation of Tyr-419, rather than the dephosphorylation of Tyr-530 of Src protein. PDGFR, not FAK or EGFR, appears to be the upstream protein tyrosine kinase responsible for the detachment-induced Src activation in the lung tumor cells. The increased Src activity upon cell detachment may contribute to the metastasis potential of malignant tumors.

Background Atherosclerotic cardiovascular (CV) events commonly occur in individuals with a low CV risk burden. This study evaluated the ability of the triglyceride glucose (TyG) index to predict subclinical coronary artery disease (CAD) in asymptomatic subjects without traditional CV risk factors (CVRFs). Methods This retrospective, cross-sectional, and observational study evaluated the association of TyG index with CAD in 1250 (52.8 ± 6.5 years, 46.9% male) asymptomatic individuals without traditional CVRFs (defined as systolic/diastolic blood pressure ≥ 140/90 mmHg; fasting glucose ≥126 mg/dL; total cholesterol ≥240 mg/dL; low-density lipoprotein cholesterol ≥160 mg/dL; high-density lipoprotein cholesterol < 40 mg/dL; body mass index ≥25.0 kg/m2; current smoking; and previous medical history of hypertension, diabetes, or dyslipidemia). CAD was defined as the presence of any coronary plaque on coronary computed tomographic angiography. The participants were divided into three groups based on TyG index tertiles. Results The prevalence of CAD increased with elevating TyG index tertiles (group I: 14.8% vs. group II: 19.3% vs. group III: 27.6%; P < 0.001). Multivariate logistic regression models showed that TyG index was associated with an increased risk of CAD (odds ratio [OR] 1.473, 95% confidence interval [CI] 1.026–2.166); especially non-calcified (OR 1.581, 95% CI 1.002–2.493) and mixed plaques (OR 2.419, 95% CI 1.051–5.569) (all P < 0.05). The optimal TyG index cut-off for predicting CAD was 8.44 (sensitivity 47.9%; specificity 68.5%; area under the curve 0.600; P < 0.001). The predictive value of this cut-off improved after considering the non-modifiable factors of old age and male sex. Conclusions TyG index is an independent marker for predicting subclinical CAD in individuals conventionally considered healthy.

The regulation and function of the signaling adaptor protein p130(Cas) in tumor cell anchorage-independent survival, or anoikis resistance, were investigated in human lung adenocarcinoma cells. The tyrosine phosphorylation and function of p130(Cas) during cell detachment were analyzed in tumor cells and compared with that of normal epithelial cells. Cell detachment trigged rapid dephosphorylation of p130(Cas) in the nontumorigenic and anoikis-sensitive normal epithelial cells, but had no effect on the tyrosine phosphorylation of p130(Cas) in the anoikis-resistant lung adenocarcinoma cells. Further analysis revealed that the total tyrosine kinase activities associated with p130(Cas) in the lung tumor cells are anchorage-independent and are significantly higher than that in the normal cells, in which the p130(Cas)-associated tyrosine kinase activities are anchorage-dependent. Analysis of two known p130(Cas)-associated tyrosine kinases FAK and Src indicated that the regulation of tyrosine phosphorylation of FAK and Src are altered in the tumor cells. Inhibition of Src specifically abolished phosphorylation of p130(Cas) and induced anoikis. Furthermore, overexpression of dominant-negative forms of p130(Cas) also induced apoptosis. Taken together, these data suggest that p130(Cas) mediates a cell survival signal from cell-matrix interaction. Alterations in tumor cells that lead to constitutive phosphorylation of p130(Cas) can prevent cells from anoikis, hence contribute to tumor cell anchorage independence and metastasis.