Abstract The self‐renewing capacity of B1 cells infers homeostatic regulation; however, previous work suggests the low level of N‐region addition characterizing B1 cells early in life increases with age, which implies that the B1‐cell population is not a closed system. To explore this, we evaluated N‐region addition in CD5 + B1 cells generated from adult BM. Adult BM cells were marked with GFP introduced by mouse stem cell virus transduction, and were then adoptively transferred into lethally irradiated recipients. Within 2–3 months, we found GFP‐marked CD5 + B cells in the peritoneal cavities of recipients, which we demonstrate here meet a variety of criteria for B1‐cell traits including Mac‐1 surface expression; annexin, elfin, and Pax‐5 gene expression; mitogenic responsiveness to phorbol ester; and spontaneous immunoglobulin secretion. Notably, we found by single‐cell PCR that this population of BM‐derived CD5 + B1 cells expressed immunoglobulin with abundant N‐region addition (and little V H 11/V H 12 skewing), unlike CD5 + B1 cells obtained from unmanipulated animals but reminiscent of B2 cells. Further, we confirmed that native CD5 + B1 cells from older mice contain more N‐region additions than native CD5 + B1 cells from younger mice. These results suggest that adult BM progenitors contribute to the peritoneal CD5 + B1‐cell pool over time.
The recent emergence of immunotherapies is transforming cancer treatments. Although many cancer immunotherapies are finding enormous success for treating hematologic tumors, a major obstacle for the treatment of solid tumors is localizing immune cells to the tumor site. Therefore, we have developed a technology that is capable of directing immune cell migration. Specifically, we have packaged chemokines, signaling molecules that promote immune cell migration, inside polyethylene glycol decorated-liposomes. The release profiles of chemokines and other large molecules from the liposomes have been examined in serum-containing media. We have demonstrated that the liposomes are able to release chemokines to induce immune cell migration. Additionally, these liposomes have been shown in vitro to limit cancer cell growth through increased immune cell recruitment. This strategy of encapsulating chemokines within liposomes paves the way for additional cancer immunotherapies and chemokine-based therapies.
To investigate the prevalence and the risk factors of COPD in the Uyghur population in the Kashi region.From August 2018 to March 2019, we recruited participants of Uyghur ethnicity and aged ≥40 years old from the Kashi region using a combined cluster sampling and random sampling method. We collected potential risk factors using questionnaire, and conduced lung function using a portable pulmonary function instrument.A total of 2963 participants were included in this analysis, of whom 1268 were males and 1695 were females. There were 504 participants with COPD, generating a prevalence of 17.01%. With the increase of age, the prevalence of COPD in different genders increased significantly. The results of different regions were χ2= 627.89, p < 0.01, indicating significant differences in the prevalence in different regions. Among them, based on the existing survey data, it is speculated that Shache county has the highest crude prevalence, but the sample size needs to be further expanded. The participants with high age, smoking, lower BMI, high waist circumference, systolic blood pressure, fried cooking and barbecue share more COPD than those who partake of fruits and vegetables in this study.The prevalence of COPD among the Uyghur population in the Kashi region is higher than the national rural average. Among them, high age, smoking, low BMI, high waist circumference, high systolic blood pressure, cooking methods that may be stir-fried and deep-fried barbecue are risk factors for COPD, and vegetable and fruit intake may be a protective factor for COPD.
Heavy metal pollution poses significant environmental challenges, and understanding how plants and endophytic bacteria interact to mitigate these challenges is of utmost importance. In this study, we investigated the roles of endophytic bacteria, particularly
The idiopathic inflammatory myopathies represent a group of autoimmune diseases that are characterized by lymphocyte infiltration of muscle and muscle weakness. Insulin-like 6 (Insl6) is a poorly characterized member of the insulin-like/relaxin family of secreted proteins, whose expression is upregulated upon acute muscle injury. In this study, we employed Insl6 gain or loss of function mice to investigate the role of Insl6 in a T cell-mediated model of experimental autoimmune myositis (EAM). EAM models in rodents have involved immunization with human myosin-binding protein C with complete Freund's adjuvant (CFA) emulsions and pertussis toxin. Insl6-deficiency in mice led to a worsened myositis phenotype including increased infiltration of CD4 and CD8 T cells and the elevated expression of inflammatory cytokines. Insl6-deficient mice show significant motor function impairment when tested with treadmill or Rotarod devices. Conversely, muscle-specific overexpression of Insl6 protected against the development of myositis as indicated by reduced lymphocyte infiltration in muscle, diminished inflammatory cytokine expression and improved motor function. The improvement in myositis by Insl6 could also be demonstrated by acute hydrodynamic delivery of a plasmid encoding murine Insl6. In cultured cells, Insl6 inhibits Jurkat cell proliferation and activation in response to phytohemagglutinin/phorbol 12-myristate 13-acetate stimulation. Insl6 transcript expression in muscle was reduced in a cohort of dermatomyositis and polymyositis patients. These data suggest that Insl6 may have utility for the treatment of myositis, a condition for which few treatment options exist.
Abstract Reduction of the nitrogen (N) footprint of agroecosystems is currently a hot topic in various research disciplines and fields. However, the effect of machine-plantedrice with side-deep fertilization (MRSF) on nitrogen loss and footprint of double-cropping rice fields in Hunan is still unclear. Here, we established a field experiment in which we applied various N compositions (N 135/148.5–90/99 kg ha − 1 ) to early-season rice (ESR) and late-season rice (LSR). The loss of different N forms during the whole growth period of double cropping rice was measured. The N footprint of double cropping rice in red soil region of South China was calculated by using life cycle assessment method. Compared with the conventional fertilizer (CF; N 150/165 kg ha − 1 ) treatment, the MRSF treatments significantly reduced NH 4 + -N and NO 3 − -N runoff by 26.2–40.9% and 9.0–36.5%, respectively, for ESR, and by 54.4–79.0% and 6.6–40.7%, respectively, for LSR. Moreover, relative to the CF treatment, the MRSF treatments significantly reduced leaching loss by 21.8–41.2% and 20.5–42.1%, respectively, for ESR, and 26.7–41.8% and 20.9–51.0%, respectively, for LSR. While urease activity decreased with increasing soil depth, MRSF treatments increased relative soil urease activity in the later stages of rice growth. Compared with the CF treatment, they also decreased the total N footprint by 42.3–53.5% and 45.1–57.1% for ESR and LSR, respectively. Correlation analysis further showed that mineral N loss and total N footprint increased exponentially with the N-application rate under the MRSF strategy. Overall, MRSF was found to reduce environmental risks associated with N loss caused by paddy field leaching and runoff while maintaining the topsoil N content. In this manner, MRSF can attenuate the total N footprint of double-cropping rice systems in Southern China.
Abstract Background The present study aimed to investigate the relationship between seven polymorphisms of the serine protease inhibitor‐2 (SERPINE2) gene and the risk of chronic obstructive pulmonary disease (COPD) in the Uygur population via a case–control study. Methods In total, 440 Uygur patients with COPD were included in the patient group and 384 healthy individuals were recruited in the matched control group. Data on demographic variables, smoking status, occupational dust exposure history and living conditions were collected. Polymorphism analysis was performed for seven loci of the SERPINE2 gene by mass spectrometry. Results The genotype distribution of rs16865421 showed a significant difference between the patient and control groups ( p < 0.05). Participants carrying the rs16865421‐AG heterozygous mutant genotype had a lower risk of COPD compared to those with the rs16865421‐A allele (odds ratio = 0.68, 95% confidence interval = 0.47–0.98, p = 0.041). However, no such association was found for rs1438831, rs6734100, rs6748795, rs7583463, rs840088 and rs975278. No significant interaction was observed between the genotypes and risk factors. Conclusions Polymorphisms of rs16865421‐AG carried by the Uygur population may be protective against COPD.
Transcatheter aortic valve replacement (TAVR) is a critical approach for treating patients with severe aortic stenosis (AS). A staging cardiac damage has been recently proposed that provided prognostic value in patients underwent TAVR, and left atrial volume index (LAVi) is a significant indicator of left heart damage. This study aimed to investigate the prognostic significance of LAVi in patients with severe AS after TAVR. This retrospective cohort study enrolled 553 consecutive patients with severe AS who underwent TAVR between April 2012 and October 2019 at a single center. Patients with biological valve decay after surgery, moderate-to-severe mitral stenosis, and inadequate echocardiographic image were excluded. The primary outcome was mortality at 4 years after TAVR. Several risk factors for the estimation of 4-year mortality after TAVR were analyzed, and the hazard ratios (HRs) were calculated by univariate and multivariate Cox regression analysis. A total of 500 patients [age: 74 (interquartile range, 70-78) years, and 44.4% were female] were included in our study, and 64 (12.8%) of these patients were died after the follow-up time. Compared to the survivors, the non-survivors were more likely to be older, male, and have a higher Society of Thoracic Surgeons score, a higher LAVi, and a lower serum albumin level. Results from univariate and multivariate Cox regression analysis indicated that the age [HR =1.072; 95% confidence interval (CI): 1.023-1.124; P=0.004], the LAVi level (HR =1.023; 95% CI: 1.013-1.033; P<0.001) and the serum albumin level (HR =0.862; 95% CI: 0.796-0.934; P<0.001) were the independent risk factors for the estimation of 4-year mortality after TAVR. Moreover, the mortality in patients with the highest category of LAVi (>48 mL/m2) was significantly higher than that of patients in other categories (multivariable HR =4.796; 95% CI: 1.137-20.238). In addition, Kaplan-Meier analysis revealed a reduced survival probability for those with the highest category of LAVi (P=0.003). LAVi was found to be an independent predictor of mortality in patients with severe AS after TAVR, and LAVi emerged as a risk stratification tool for prognosing the long-term clinical outcome of patients treated with TAVR.
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